A 63-year-old female with non-Hodgkin's lymphoma was treated with a chemotherapeutic regimen composed of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone (R-CHOP). She was given  rituximab 600 mg plus 750 ml of 0.9% sodium chloride injection intravenous drip on the first day, at the same time treatments for hydration, alkalization, protecting visceral function, prevention of adverse reactions were given. On day 2, the patient developed an involuntary shaking limbs, a lower limbs weakness, a slightly slow reaction and an unsteady gait. MRI of the brain did not show any significant finding. On day 3, she had a fever, cognitive impairment and confusion. On day 4, the patient could not have independent feeding and defecation. Methyl prednisolone, drugs for improving microcirculation and rehydration therapy were applied. Two days later, the patient's consciousness restored. He can eat independently, defecate by himself, and his limbs and neuropsychological symptoms were relieved. Five days later, the symptoms were apparently   improved.

Two female patients, aged 61 and 48 years old, received a combined chemotherapy of irinotecan 200 mg and lonaplatin 50 mg for cervical cancer. Patient 1 developed diarrhea, grade IV arrest of bone marrow and septicemia, accompanied by septic shock on the ninth day after the second cycle of chemotherapy. Patient 2 developed diarrhea, grade IV arrest of bone marrow, accompanied by fever on the sixth day after the first cycle of chemotherapy, and then developed secondary septicemia. Antidiarrhea, anti-infection, and immune support treatment were given. Five days later, diarrhea was controlled. Ten days later for patient 1 and six days later for patients 2, white blood cell, hemoglobin and platelet count were within normal range. After twenty days for patient 1 and six days later for patients 2, septicemia was controlled.

The proton pump inhibitors (PPI) are widely used as the treatment of choice in acid-related diseases in clinic. Long term use of PPI may further induce abnormal absorption of nutrition (vitamin B12, calcium, iron, magnesium and other minerals), abnormal proliferation of gastrointestinal mucosa, infection, and abnormal bone metabolism (osteoporosis and bone fracture), and so on. Most studies on safety of long term use of PPI are retrospective cohorts or case-control studies. More prospective randomized controlled trials should be performed and good clinical evidences should be obtained for reasonable and safe use of PPI.

ObjectiveTo develop a list of potentially inappropriate medication (PIM) for the Chinese aged people and provide reference for prevention and reduce the medication risk of the aged people.MethodsBased on the PIM lists of the United States, Canada, Japan, France, Norway, Germany, South Korea and Austria, and combined with the data of serious adverse drug reactions (ADR) in the aged people collected from China National Center for ADR Monitoring, ADR monitoring center in the People′s Liberation Army, Beijing Center for ADR Monitoring and ADR data from Beijing 22 hospitals, we created a preliminary PIM list for the Chinese aged people. Using Delphi technique experts consultation was made for the initial list. Round 1 consultantation invited 32 experts, according to the expert advice to adjust the initial list, and form a revised list. Round 2 consultantation invited 38 experts, according to the expert advice to adjust revised list, and the final version of the PIM list formed. ResultsA total of 13-class 72 medications or medication classes were selected as the Chinese aged people PIM list, each medicine had 1-6 risk points. The list was divided according to the result of expert evaluation into 35 kinds of high risk medications and 37 kinds of low risk medications. In addition, according to the frequency of drug use, the medications were divided into A and B two categories, including 24 medications or medication classes as the preferred alert medications (A), 48 medications or medication classes as routinely alert medications (B).ConclusionPIM list for the Chinese aged people have been developed, which can be taken as reference to intervention and evaluation of China′s elderly medication.

ObjectiveTo analyze the clinical characteristics and risk factors of lansoprazole-induced microscopic colitis (MC).MethodsPubMed, Da-Yi medical search, CHKD and Wanfang databases were searched and articles related to MC induced by lansoprazole were collected. The patients′primary diseases, coexisting diseases, the dosage, the way of administration, combination drugs, latent period, clinical manifestations, colonoscopic findings, the treatment measures, and the outcomes were recorded and the clinical characteristics, the risk factors of MC induced by lansoprazole were analyzed.ResultsA total of 30 articles and 62 patients with MC induced by lansoprazole were retrieved. All articles were case reports and no randomized controlled trials were found. Of all the 62 patients, 22 were male (35.5%) and 40 were female (64.5%) with age from 36 to 92 years and the average age was (69±12) years; 57 patients (91.9%) were >50 years; 43 patients were with collagenous colitis (CC) (69.4%) , 18 patients (29%) were with lymphocytic colitis (LC), and one patient with LC changed into CC (1.6%). All patients were treated with oral lansoprazole. The latent period of MC induced by lansoprazole were 5d-6 years and within 1-6 months in 31 patients (60.8%) . The most common clinical manifestations were non-bloody watery diarrhea (3-10 times daily in 59 patients, >10 times daily in 3 patients). Intestinal mucosal screening was performed for all the patients and mild abnormalities or edema were observed in 37 patients, mucosal defect and mucosal laceration in 11 patients, epithelial collagen layer thickening, inflammatory cells infiltration in lamina propria, increased lymphocytes in intraepithelial spaces in 18 patients. High-risk drugs for drug-induced MC were combined use in 20 patients and the combination drugs in 13 patients were non steroidal anti-inflammatory drugs. Fifty-eight patients with mild or moderate drug-induced MC returned to normal after withdrawl of lansoprazole and treatment with omeprazole or rabeprazole sodium and 4 patients with severe drug-induced MC recovered after withdrawl of lansoprazole and treatment with glucocorticoids.ConclusionsThe clinical characteristics in patients with MC induced by lansoprazole are watery diarrhea, mild abnormality or edema of colon mucosa, and thickening in the epithelium of colonic mucosa in histopathology. Age, gender, and combined use of drugs may be related to occurrence of MC induced by lansoprazole.

ObjectiveTo observe the adverse reactions of zoledronic acid in the treatment of osteoporosis combined with rheumatic diseases and analyze the potential risk factors.MethodsMedical record data of patients with rheumatic diseases and osteoporosis who were treated with zoledronic acid during hospitalization in Xuanwu Hospital of Capital Medical University from January 2011 to December 2014 were collected and a retrospective analysis was conducted. The patients were grouped according to the occurrence of adverse reactions and their demographic characteristics, types of rheumatic diseases and medication regimen of zoledronic acid were compared. The screened risk factors for adverse reactions were analyzed by multivariate logistic regression. The results were expressed by odds ratio (OR) and 95% confidence intervals (CI).ResultsA total of 120 patients were enrolled into the study. There were 41 males and 79 females. Their ages ranged from 23 to 85 years. Of 120 patients, 64 cases (53.3%) received first infusion of zoledronic acid, 66 cases (55.0%) received the treatment with corticosteroids during hospitalization, 58 cases (48.3%) were given antipyretic analgesics before infusion of zoledronic acid and 64 cases (53.3%) received sufficient hydration before and after the infusion; 49 (40.8%) of the 120 patients were reported to have adverse reactions. All adverse reactions were of acute phase responses, including fever in 32 (65.3%), flu-like symptoms in 21 (42.9%), headache in 17 (34.7%), fatigue in 12 (24.5%), myalgia in 10 (20.4%), arthralgia in 8 (16.3%), chills in 6 (12.2%), nausea in 5 (10.2%), vomiting in 4 (8.2%), and dry cough in 1 (2.0%). No severe adverse events occurred. The incidence of adverse reactions in initial infusion patients was significantly higher than that in non-initial infusion patients［51.6% (33/64) vs. 28.6% (16/56), P=0.011］. The incidence of adverse reactions in patients with  corticosteroid therapy was significantly lower than that in patients with no corticosteroid therapy［24.2% (16/66) vs. 61.1% (33/54), P<0.001］. The patients who were given sufficient hydration before and after the infusion also had significantly lower incidence of adverse reactions than those without sufficient hydration treatments［31.2% (20/64) vs. 51.8% (29/56), P=0.023］. Multivariate logistic regression analysis suggested that initial infusion was a risk factor for adverse reactions (OR=2.631, 95%CI: 1.132-6.116, P=0.025). However, oral corticosteroid and sufficient hydration treatments before and after the infusion were protective factors (OR=0.232, 95%CI: 0.102-0.526, P<0.001; OR=0.379, 95%CI: 0.164-0.874, P=0.023).ConclusionsAcute phase responses related to zoledronic acid are common in the treatment of patients with rheumatic diseases and osteoporosis. Iniaial infusion is closely associated with adverse reactions of zoledronic acid, but oral corticosteroid and sufficient hydration treatments before and after the infusion might decrease the incidence of adverse reactions.

ObjectiveTo analyze the characteristics of highly cited papers published in Adverse Drug Reactions Journal (our journal) during 2009 to 2013， understand the hot spots of subject development and demands of readers, and improve impact and quality of our journal. MethodsThe citation frequency of papers published in our journal from 2009 to 2013 was searched in China Academic Journal Network Publishing Database (as of April 30, 2015). Price law was used to determine the highly cited papers. The main statistical parameters included total citation frequency of papers published in our journal, average citation frequency of papers, citation frequency of highly cited papers, and average citation frequency of highly cited papers. The distribution of subjects of highly cited papers, regional distribution of authors, distribution of article types, and funding  sources were analyzed descriptively.ResultsA total of 1 052 articles were searched and 736 articles were entered into the study, including 147 original articles, 85 reviews, and 504 case reports. Of the 736 articles, 517 were cited (70.2%) and the total citation frequency was 2 170 times and average citation frequency of papers was 4 times. According to the Price law, the papers which were cited ≥5 times were considered as highly cited papers in our journal during the study period. The citation frequency of 138 highly cited papers was 1 388 times which accounted for 64.0% of total frequency (2  170 times) during the study period and average citation frequency of highly cited papers was 10 times. The subjects of highly cited 138 papers are relatively centered and the top 5 subjects were antimicrobial agents (44 papers, 31.9%), Chinese Medicine (22, 15.9%), cardiovascular system drugs (19, 13.8%), antineoplastic drugs (11, 8.0%), and endocrine system drugs (5, 3.6%); there were 87 papers (63.0%) distributed in Beijing and 51 papers (37.0%) distributed in other 17 provinces or municipality directly under the central government; 33 of the highly cited 138 papers were original articles (23.9%), 29 were reviews (21.0%), and 76 were case reports (55.1%), their citation frequency was 390, 354, and 643, respectively which accounted for 28.1%, 25.5% and 46.3% of total citation frequency 1 388 times, respectively, and the average citation frequency of original articles, reviews, or case reports were 12,12, and 9, respectively. There was 1 paper supported by National funds at top 20 highly cited papers.ConclusionsAs highly cited papers published in our journal, distribution of subjects and regions were relatively centered; distribution of authors were dispersive; reviews and case reports made more contributions; and average citation frequency of original articles and reviews was higher. It is valuable to understand the above mentioned characteristics to make measures for improvement of impact and quality of our journal.

A 76-year-old male patient with acute coronary syndrome received regularly aspirin (0.1 g once daily), clopidogrel (50 mg once daily), atorvastatin calcium (20 mg once daily), and isosorbide mononitrate (10 mg twice daily) by mouth after undergoing percutaneous coronary intervention. He suffered from left lumbago with gross hematuria after 2 months of treatments. Laboratory tests showed the following values：urine occult blood(+++)，235 red blood cells per microlitre and 17 red blood cells per high power field. Urinary system ultrasonography and renal function detection showed no abnormalities. Aspirin and clopidogel were withdrawn and the symptomatic treatments were given. Two days later, the patient′s urine recovered to normal，his left lumbago was alleviated, and the red blood cell in his urine was negative. Gene polymorphism detection of cytochrome P-450(CYP)2C19 showed that the patient carried CYP2C19*17(CT) allele and CYP2C19 enzyme had ultra rapid metabolism. Aspirin was given orally and the hematuria did not appear again.

A 45-year-old man with about 10 years of drug abuse history took 96 tablets of sodium valproate sustained-release (48 g) and about 20 capsules of ziprasidone hydrochloride (＞400 mg) by himself one time. He appeared comatous and had no response to being called, then he was sent to the hospital by his family members. He presented no autonomous respiration, hypotonia of the four limbs and neck (2 level) on admission. He received symptomatic supportive treatments including tracheal intubation and ventilator assisted breathing, gastric lavage, coloclyster, fluid infusion,  diuresis, and central nervous system stimulant, immediately. Two hours later, the patient awoke. Laboratory tests revealed the following results: arterial oxygen partial pressure (PaO2) 292 mmHg (1 mmHg=0.133 kPa), lactic acid 5.70 mmol/L, D-dimer 7.8 mg/L, plasma fibrinogen degradation product (FDP) 45 mg/L. Twenty-four hours later, laboratory tests revealed the following results:  PaO2  98 mmHg, lactic acid 1.7 mmol/L, D-dimer 2.2 mg/L, FDP 19 mg/L. The trachea cannula was removed. Forty-eight hours later, his consciousness returned to normal. He could finish the common action. But he still had the symptom of  drowsiness. Seven days later, the patient could answer questions accurately. His muscular tension returned to normal. He had light drowsiness occasionally.

ObjectiveTo explore the relationships between active systemic allergic reaction induced by breviscapine injection and the drug dose and the sensitization time.MethodsActive systemic allergic reaction in guinea pigs was used as experimental method. Forty-eight guinea pigs were divided into 6 groups according to random number table: breviscapine injection 1, 5, 25 and 50 mg/kg group (the breviscapine injection group 1, 2, 3, 4), 0.9% sodium chloride injection group (the negative control group) and bovine serum albumin (BSA) control group (the positive control group). Each group comprised 8 guinea pigs. Sensitization: the guinea pigs in group 1 to 4 were given the breviscapine injection  at doses of 1, 5, 25 and 50 mg/kg (0.5 ml) by intraperitoneal injection every other day for three times, respectively. The the guinea pigs in the negative control group and the positive control group were given 0.9% sodium chloride injection (0.5 ml) and bovine serum albumin (BSA) 20 mg/kg by intraperitoneal injection every other day for 3 times, respectively. Excitation: the sensitized guinea pigs in each group were divided into 2 subgroups, each subgroup comprised 4 guinea pigs. On the 14 and 21 days after the last sensitization, the guinea pigs in breviscapine 1 to 4 subgroups received 2 times of breviscapine injection intravenously (1.0 ml), respectively. The guinea pigs in the negative and the positive control subgroups  received 2 times of control articles intravenously, respectively. The symptoms of anaphylactic reaction (pilo-erection, shiver, scratching nose, sneeze, cough, vomiturition, cyanosis, dyspnea, urinary and fecal incontinence, instability of gait or tumble, convulsion or hyperspasmia, shock and death) were observed every day during the sensitization phase. The guinea pigs′ reactions which appeared in 30 min after intravenous injections were observed and the occurrence time of allergic symptoms/signs were recorded attentively. The anaphylactic reaction was determined according to the Chinese Pharmacopoeia′s allergic reaction test. ResultsThe guinea pigs in 6 groups did not show any allergic symptoms in the sensitization phase. Within 30 min in fourteenth days′ excitation,  2, 4, 4, 4 guinea pigs developed allergic reactions in the breviscapine 1 to 4 groups, respectively. But none of them were identified as allergic reaction. The 4 guinea pigs in the positive control group were judged to have positive allergic reaction. Within 30 min of 21 days′ excitation, 4、3、4、4 guinea pigs developed allergic reactions in the breviscapine 1 to 4 groups, respectively. Only one guinea pig in the breviscapine 4 group was identified as allergic reaction. The 4 guinea pigs in the positive control group were all judged positive allergic reaction. The guinea pigs in the negative control group did not develop any allergic reactions during the 2 times of excitation. The occurrence time of allergic reactions in the breviscapine groups (within 20 min after excitation) on 21 days′ excitation was shorter than those (within 25 min after excitation) occurred on 14 days′ excitation, but the difference was not statistically significant.ConclusionsThe active systemic allergic reactions induced by breviscapine injection are associated with drug dose and sensitization time. The larger dose and longer sensitization time can increase the risk of allergic reaction and shorten the latency of allergic reaction.

A 79-year-old man received an intravenous (IV) infusion of cefoperazone sodium and sulbactam sodium 1.5 g every 12 hours with concomitant use of levofloxacin 0.5 g once daily，doxofylline injection 0.2 g via pump twice daily, and an IV push of 45 mg ambroxol injection twice daily for acute exacerbation of chronic obstructive pulmonary disease. Levofloxacin was discontinued after 7 days of treatments ambroxol and doxofylline were discontinued after 13 days of treatments. Just after completion of the infusion of cefoperazone sodium and sulbactam sodium on day 16 of treatment, the patient suddenly experienced unconsciousness, convulsion of extremities, gnathospasmus, and eyes gazing rightwards, which lasted about one minute. An IV injection of methylprednisolone sodium succinate 40 mg was given immediately and 1 minute later, his consciousness restored and symptoms relieved. And then an IV injection of sodium valproate 400 mg and sodium valproate 30 mg/h via a pump were given. On day 17, 2 hours after completion of the infusion of cefoperazone sodium and sulbactam sodium, the symptoms mentioned above appeared again. An IV push of diazepam 5 mg and sodium valproate 80 mg/h were given and 2 minutes later, the symptoms alleviated gradually. Subsequently, cefoperazone sodium and sulbactam sodium was discontinued, an IV push of sodium valproate 400 mg once daily and an oral sodium valproate 0.5 g twice daily were given. After that, he didn′t experience epilepsy seizure again.

An 81-year-old female patient with pulmonary infection was given cefoxitin 2 g by intravenous drip. After 1.5 hours of treatment, the patient self-medicated with compound glycyrrhiza oral solution 10 ml for cough. About 10 minutes later, she experienced chest tightness, dyspnea, facial flushing, hyperhidrosis, weakness of limbs and rash. Disulfiram reaction was considered. Intravenous dexamethasone 10 mg and continuous low flow oxygen were given. About 30 minutes later, the patient′s condition improved. After 2 hours, the symptoms disappeared.

A 74-year-old female patient received oral carbamazepine 0.1g thrice daily because of epilepsy after acute ischemic stroke. On the third day, the patient suddenly presented drowsiness which gradually aggravated to a state of mild coma within 30 minutes. The electrocardiogram showed that sick sinus syndrome and junctional rhythm with a heart rate of 34 beats per minute. The patient was diagnosed as Adams-Stokes syndrome which may be induced by carbamazepine. She was given an intravenous injection of atropine sulfate 0.5 mg immediately. Then atropine sulfate 1 mg in 5% glucose injection 500 ml was slowly given by intravenous drip. Two hours later, the patient regained consciousness. The electrocardiogram showed restoration of sinus rhythm with a heart rate of 48 beats per minute. Carbamazepine was withdrawn and disturbance of consciousness did not recur.

A 50-year-old male patient grinded his self-purchased blister-beetle (Mylabris) body into powder and then made it into paste for large area external use on his body skin for psoriasis. A few minutes later, the patient developed erythema and blisters on the site of medication; a few hours later, the purplish-red patches and blisters spread throughout the body, epidermis relaxed and exfoliated, and symptoms of systemic poisoning appeared. One day later, the patient developed multiple organ failure, such as respiratory failure, liver injury, kidney injury, severe hypoproteinemia, and abnormal coagulation function. Epidermolysis bullosa induced by externally application of Mylabris was diagnosed, and treatments of high-doses of pulsetherapy methylprednisolone, intravenous infusions of human immunoglobulin and human albumin, bedside hemofiltration, ventilator-assisted ventilation, and etc. were given. However, the patient′s condition deteriorated rapidly and finally he died of multiple organ failure 12-hours later.

An 82-year-old female patient with severe osteoporosis received an IV infusion of zoledronic acid 5 mg after the right hip artificial femoral head replacement. About 4 hours after the end of IV infusion, the patient presented chill, fatigue, myalgia and high fever. About 6 hours later the patient occurred nausea and vomiting. About 14 hours later the patient developed dyspnea, convulsions, loss of consciousness, and tachycardia. The results of laboratory tests showed the following results: carbon dioxide-combining power (CO2-CP)14 mmol/L, B-type natriuretic peptide (BNP) 1374.07 ng/L, prothrombin time (PT) 20 s, activated partial thromboplastin time (APTT) 37 s , alanine aminotransferase (ALT) 269 U/L, aspartate aminotransferase (AST) 279 U/L, blood urea nitrogen (BUN) 34.6 nmol/L, serum creatinine (Scr) 273 μmol/L. She was diagnosed as respiratory failure, multiple organ failure due to zoledronic acid. She was transferred to ICU, and was given a tracheal intubation with ventilator assisted breathing, she received   symptomatic treatments including those to keep heart rate and blood pressure stable, to protect the functions of liver and kidney. On day 7 in ICU, the patient recovered consciousness. The laboratory tests showed the following results: ALT 135 U/L, AST 137 U/L, BUN 35.3 nmol/L, Scr 217 μmol/L, CK-MB 2.1 μg/L. On day 53 in ICU, her heart rate was 55-86 beats/min, respiration rate was 21-25 times/min, blood pressure was 102-122/51- 69 mmHg (1 mmHg= 0.133 kPa), pulse oxygen saturation was 0.97-1.00. The results of laboratory tests were: ALT 38 U/L, AST 45 U/L, BUN 7.1 nmol/L, Scr 60 μmol/L, CK-MB 1.19 μg/L, myoglobin 0.03 μg/L and BNP 401 ng /L. On day 85 in ICU, the patient regained spontaneous respiration.

A 60-year-old woman with connective tissue disease received  cyclosporine 300 mg once daily . On day 2 of adding cyclosporine, the patient  developed pharyngalgia. On day 3, she developed hematochezia, abdominal distension and abdominal pain. On day 14, she lost her vision of both eyes,  developed attacks of binoculus transient upper left gaze twice, a slight headache, and the elevated blood pressure (150/90 mmHg). Laboratory tests showed that the cyclosporine blood concentration was 372.4 μg/L. The results of cranial MRI showed bilateral frontal, parietal, occipital and temporal lobes symmetrical multiple patchy long T1, long T2 signals, the fluid attenuated inversion recovery sequence showed high signal, which suggested the vascular edema.  The patient was diagnosed as reversible posterior encephalopathy syndrome due to cyclosporine. Cyclosporine was stopped immediately. She received an IV infusion of methylprednisolone 40 mg once daily and other symptomatic supportive treatments including deprivation of body fluids, anti-epileptic, and blood pressure control, etc. On day 5 of treatment, her vision began to recover, but she had blurred vision and visual hallucinations. On day 7 of treatment, the degree of abdominal distension and abdominal pain was relieved, vision was recovered obviously, visual hallucination disappeared. Her blood pressure returned to normal (125/86 mmHg). The result of laboratory tests showed the cyclosporine blood concentration 139.2 μg/L. The result of MRI reexamination showed that the original focus disappeared.

A 77-year-old female patient with pneumonia received an IV infusion of piperacillin sodium and tazobactam sodium 4.5 g dissolved in 0.9% sodium chloride injection 100 ml, 3 times daily. The patient′s WBC, RBC, Hb, and PLT levels were 2.0×109/L， 2.9×1012/L， 88 g/L， and 10×109/L, respectively before using the medicine. On day 4 of drug administration, her WBC, RBC, Hb and PLT were 2.0×109/L, 2.9×1012/L, 88 g/L, and 10×109/L, respectively. The result of  bone marrow smear showed decrease of nucleated cell, granulocyte series,  and  erythrocyte series′ hyperplasia. The proportion and morphology of  cells at different stages were approximately normal. She was diagnosed as acute myelosuppression associated with piperacillin sodium and tazobactam sodium. Piperacillin sodium and tazobactam sodium were stopped. On day 15 of drug withdrawal, her WBC, RBC, Hb and PLT were 4.8×109/L, 3.0×1012/L, 88 g/L, and 218×109/L, respectively.

A 65-year-old man took 4 Lianhuaqingwen capsules thrice daily by himself for upper respiratory tract infection. The patient developed facial swelling and cervical lymphadenopathy after second treatment. Laboratory examination showed the following results: alanine aminotransferase (ALT) 219 U/L,  aspartate aminotransferase (AST) 106 U/L, gamma-glutamyl transpeptidase (γ-GT) 312 U/L, alkaline phosphatase (ALP) 223 U/L, total protein 65 g/L, albumin 33 g/L, albumin-globulin ratio (A/G) 1.02, total bilirubin (TBill) 14.4 μmol/L, direct bilirubin (DBil) 6.7 μmol/L, C-reactive protein (CRP) 110.4 mg/L. drug anaphylaxis and drug-induced liver injury were diagnosed. The patient was given IV infusions of polyene phosphatidylcholine 697.5 mg, reduced glutathione 2.4 g, magnesium isoglycyrrhizinate 150 mg, sodium thiosulfate 1.28 g and intramuscular injection of dexamethasone 5 mg once daily respectively. On day 6, the laboratory tests showed the following results: ALT 69 U/L, AST 19 U/L, γ-GT 275 U/L, ALP 191 U/L, total protein 56 g/L, albumin 24 g/L, A/G 0.76, TBil 16.6 μmol/L, DBil 8.5 μmol/L, CRP 148.2 mg/L。On day 16, the facial swelling disappeared. On day 21, the laboratory tests showed the following results: ALT 53 U/L, AST 36 U/L, γ-GT 155 U/L, ALP 149 U/L, total protein 76 g/L, albumin 32 g/L, A/G 0.71, TBil 6.1 μmol/L, DBil 3.1 μmol/L, CRP 89.5 mg/L.

In recent years, club drugs are often abused by teens and young adults, The common club drugs are gamma- hydroxybutyrate, ktamime, MDMA, and flunitrazepam. This paper describes the acute toxic effects of the four drugs in order to be beneficial to the management of their poisoning in clinical practice.

Objective To explore the clinical features of tacrolimus-associated posterior rever- sible encephalopathy syndrome (PRES) in patients after kidney transplantation.　Methods Relevant databases at home and abroad were searched as of August 2020, and case reports of tacrolimus-associated PRES after kidney transplantation were collected. Clinical information including patient′s basic characteristics, tacrolimus application (such as route of administration, dose, blood concentration, drug combination regimen, etc.), and the occurrence time, clinical manifestation, imaging characteristics, intervention measures, and outcomes of PRES were extracted and analyzed by descriptive statistical method.　Results A total of 16 patients were enrolled in the study, including 7 males and 9 females, aged from 7 to 54 years with a median age of 26 years. Of them, 6 patients were <18 years old and 10 patients were ≥18 years old. Among the 16 patients, 8 received intravenous administration and 8 oral administration. Thirteen patients had records of drug combination regimen and 1, 2, and 3 immunosuppressants were combined in 3, 8, and 2 patients, respectively. PRES occurred from 3 days to 3 months after renal transplantation and 10 patients (62.5%) occurred within 1 month after operation. Eleven of 13 patients who underwent tacrolimus plasma concentrations testing did not exceed the upper limit of the treatment window when PRES occurred. The main symptoms of PRES included convulsions/seizures-like seizures (in 11 patients), visual abnormalities (in 7 patients), persistent headache (in 6 patients), and coma or disturbance of consciousness (in 6 patients). CT and/or magnetic resonance imaging were performed in all 16 patients. Imaging features of cerebral edema or vasogenic cerebral edema were found in 15 patients and the lesions located mainly in occipital lobe (13 patients), parietal lobe (12 patients), and the frontal lobe (8 patients). After discontinuation or reduction of the tacrolimus dose and/or giving symptomatic and supportive treatments for 2-44 days (the median time of 9 days), symptoms subsided in all 16 patients and imaging examination showed cerebral edema, vasogenic cerebral edema, and other lesions subsided in 15 patients.　Conclusions Tacrolimus-associated PRES mostly occurred within 3 months after renal transplantation, which was not related to the route of administration or blood concentration of tacrolimus. The clinical manifestations of tacrolimus-associated PRES were similar to those caused by other factors. After discontinuation of tacrolimus, reduction of drug dose and/or administration of symptomatic treatment, most of the symptoms disappeared quickly and the imaging changes returned to normal.

Based on the potentially inappropriate medication (PIM) criteria in older adults of the United States, Canada, Japan, France, Norway, Germany, South Korea, Austria, Thailand and Chinese Taiwan, and combined with the severe adverse drug reaction (ADR) data in the elderly of China National Center for ADR Monitoring, ADR monitoring center in the Chinese People′ s Liberation Army，Beijing Center for ADR Monitoring and drug data of people over 60 years from Beijing 22 hospitals, 3 rounds of Delphi expert consultation were made to accomplish the final criteria. The criteria was divided into high risk and low risk medications according to the experts evaluation and divided into A and B alert categories according to DDDs. Finally, criteria of potentially inappropriate medications for older adults in China was formed, including medication risk and medication risk under morbid state. A sum of 13 categories 72 medications or medication classes were selected in medication risk part, for example, neurologic medication，psychotropic medication，antipyretic, analgesic and anti-inflammatory medication and cardiovascular medication. The 72 medications were divided into 28 kinds of high risk and 44 kinds of low risk medications. The 72 medications were also divided into 24 kinds of preferred alert medications(A) and 48 kinds of routinely alert medications(B)．PIM in the elderly under morbid state contained 44 medications or medication classes under 27 kinds of morbid states, in which 35 medications under 25 morbid states of preferred alert medications (A) and 9 medications under 9 morbid states of routinely alert medications (B).

The recommendations of Guideline for Emergency Management of Anaphylaxis  answered 15 clinical questions about diagnosis, preparation for treatment, treatment measures, and post-treatment management of anaphylaxis and a total of 26 recommendations were formed. In the recommendations, the quality of evidence was divided into 4 levels: high, moderate, low, and very low. And the strength of recommendation was divided into 2 levels: strong and weak. The strength of recommendations was mainly determined by weighing the advantages and disadvantages, instead of relying on the quality of evidence. Emergency management of anaphylaxis in clinical practice could be carried out with reference to the recommendations of this guideline.

An 83-year-old male patient received moxifloxacin hydrochloride (moxifloxacin) 400-mg once daily orally for acute attack of chronic obstructive pulmonary disease. He developed scattered red rashes, accompanied by itching, on his both lower limbs 5 hours after the first dose. Next day, the rashes involved skin on the trunk, and purpura appeared on the multiple skin below the knees. Laboratory tests showed platelet count (PLT) 1×109/L，and thrombocytopenia related to moxifloxacin was considered. Moxi- floxacin was stopped and the treatments including hemostasis, anti-allergy, regulation of immune function, and platelet transfusion were given. On day 2 of drug withdrawal, his PLT was 3×109/L, and on day 4 the PLT was 35×109/L. He was transferred to a superior hospital and received the therapy including anti-immune response, platelet-raising, and hemostasis for 5 days. Then his PLT increased to 244×109/L.

通过检索Medline和中国医院数字图书馆数据库,对体内药物相互作用的发生率、发生机制、临床干预方法等内容进行综述,以期引起医务工作者的充分认识,减少药源性损害,提高临床治疗水平。

Selective serotonin reuptake inhibitors (SSRIs) are a widely used newer class of antidepressants, which can treat different types of depression. The commonly used SSRIs are fluoxatine, paroxetine, sertraline, fluvoxamine, and citalopram. The SSRIs can cause various types of adverse reactions. The main adverse reactions are gastrointestinal disorders, withdrawal reactions, sexual disturbances, and syndrome of inappropriate secretion of antidiuretic hormone (SIADH), etc. SSRIs may increase the risk of suicidal thinking and behaviour in children and adolescents, but the issue remained controversial. The recent studies have suggested that exposure to SSRIs early in pregnancy appeared to be no increase in the risk of congenital malformations; however, exposure to SSRIs late in pregnancy may incresae the risk of pulmonary hypertension and withdrawal reactions of the newborn. In general, breastfeeding with SSRIs is regarded as safe because the amount of drug is very low in breast milk. But the possibility of longterm effects on development in the infant is unknown. As for the elderly, SSRIs may increase the risk of fracture. Adverse reactions resulting from interations of SSRIs with some drugs are given below. MAOIs: serotonin syndrome; diuretics: severe hyponatremia; anticoagulants: increased risk of bleeding; NSAIDs: increased risk of upper gastrointestinal bleeding; tryptophan: serotonin syndrome; astemizole, terfenadine: ventricular arrhythmias and Q-T interval prolongation; haloperidol, maprotiline: severe extrapyramidal symptoms; lithium increase in plasma lithium concentration and lithium toxicity. Overall, SSRIs have fewer adverse effects than tricyclic antidepressants, but the SSRIs do have characteristic adverse reactions of their own. Therefore, doctors should exercise caution when prescribing SSRIs to patients in clinical practice.

太尼透皮贴剂是一种新型强效镇痛透皮缓释给药剂型,使用方法简便,不良反应较低,止痛效果好,广泛用于癌性疼痛(CP)和非癌性疼痛(NCP)的治疗。常见的不良反应有便秘、恶心、呕吐和嗜睡等。但如果使用不当或过量,可造成呼吸抑制甚至死亡。因此,使用芬太尼透皮贴剂时应正确选择适应证,掌握个体用药剂量,避免严重不良反应的发生。

秋水仙碱为抗痛风药,可有效控制关节局部的红肿热痛等炎症反应。但其治疗剂量与中毒剂量接近,在体内可被代谢为具有极强毒性的二秋水仙碱,对消化道有刺激作用,可抑制骨髓造血功能,并对神经、平滑肌有麻痹作用,甚至可引起呼吸中枢麻痹而死亡。故不宜长期或大剂量应用。出现严重不良反应须立即停药,并对症救治。

Enteral nutrition (EN) is defined as the administration of a nutrient solution orally or by means of a feeding tube with the purpose of contributing the supply of all or part of the body's nutrient requirements. EN preparations can be classified into three types: elemental type, non-elemental type, and module type. EN is usually given with feeding tube. Non-invasive tube includes nasogastric tube and nasointestinal tube, and invasive tube includes gastrostomy tube and enterostomy tube. Indications for EN include radical surgery in patients with upper alimentary tract or upper respiratory tract, tracheal intubation, esophageal stenosis, dysphagia, anorexia nervosa, largescale burning or trauma. Although considered safer than parenteral nutrition, enteral feeding is not of without complications. The common complications of EN were as follows: (1) mechanical complications such as obstructions of the feeding tube; (2) gastrointestinal complications are abdominal distension, nausea, vomiting, and diarrhea, and they can be reduced or avoided by using gastrointestinal pump or nasointestinal tube, reducing infusion speed, increasing nutrient solution temperature, and using gastrointestinal prokinetic drugs; (3) metabolic complications are mainly hyperglycaemia, and it can be treated with insulin; (4) infectious complications are mainly inhalation pneumonia caused by inhaling nutrient solution or regurgitation into the lungs presenting with sudden dyspnea, fever, increased heart rate. Attention should be paid to its gastric retention.

Methamphetamine(MA), commonly called as ice, is a stimulant of the family of phenethylamines, which is one of widely abused illicit drugs in the world. Methamphetamine increases the release and blocks the reuptake of the monoamine neurontransmitter, such as dopamine, norepinephrine, and serotonin, leading to high level of the chemicals in the synaptic cleft and inducing psychological and physical effects. Methamphetamine users may develop euphoria, increased physical activity and hypersexuality. Sudden withdrawal of methamphetamine in methamphetaminedependent subjects may result in abstinence reactions including sleep disturbance, depressed mood, anxiety, agnosia, and decreased physical activity. A methamphetamine abstinence reaction can be categoried into two phases: the acute phase (lasting 7～10 days), and the subacute phase (lasting a further 2 weeks). The relapse rates to the methamphetaminedependent subjects is rather high. Preventing the occurrence of relapse is of very important practical siginifance.

近年,甘露醇静脉及口服给药的不良反多有报告,其中过敏反应较为常见,严重者可发生过敏性休克。还可致肾损害、心血管系统损害、肺水肿、中枢神经系统反应等严重不良反应,本文仅对近五年来甘露醇应用时有关不良反应的文献进行回顾,探讨导致不良反应的相关因素,以期引起临床工作者的注意。

Strychni semen is the dried ripe seed of Strychnos nuxvomica L. The crude drug contains alkaloids, of which the main alkaloids are strychnine and brucine. Strychnine is the main toxic component of strychni semen. Generally, the oral intoxicating dose of strychnine in adults is 5～10 mg, and the oral lethal dose is 30 mg. Strychnine can cause excitation of all parts of the central nervous system. Early signs of intoxication are headache, dizziness, nausea, vomiting, anxiety, restlessness, and slight twitching. Generalized convulsion, increasing sensitivity of sense organs, trismus, risus sardonicus, opisthotonus, dysphagia, and dyspnea follow. The patients often die from respiratory arrest. The principle of therapy in strychni semen poisoning is the prevention or control of convulsions and asphyxia. Management includes gastric lavage, the administration of activated charcoal, sedation with diazepam or phenobarbital, respiration support, and symptomatic treatment. The following precautions should be taken for safe use of strychni semen: crude drug should not be used, and the dosage should conform to the dosage limit in Chinese Pharmacopoeia; strychni semen should not combine with some drugs such as spirit, poppy capsule, musk, and so on; strychni semen is contraindicated in pregnant women; strychni semen should be used with caution in patients with liver and renal function insufficiency, neurological disorders, hypertension, and heart disease; overuse and prolonged use of strychni semen should be avoided, otherwise careful monitoring should be performed; the dosage should be adjusted when using strychni semen from different producing area.

ObjectiveCompare criteria of eight countries such as United States for potentially inappropriate medications (PIM) in elderly, to provide a reference for formulating China′s PIM criteria. MethodsUsing the database and network, the authors collect the PIM criteria in elderly that has been released from the inception to December 2012. Eight countries PIM criteria were selected and their development method, expert panel′s composition and contents were compared.ResultsPIM criteria from a total of eight countries including the United States, Canada, Japan, France, Norway, Germany, South Korea and Austria were selected for the analysis. Except the United States PIM criteria has been updated to version 4 (2012), the other countries have just published their first edition. The applicable age of respective country about PIM criteria is slightly different (≥ 65 ~ ≥ 75 years). Seven countries except Japan were using the Delphi method as a research methodology. The composition of the expert panel has pharmacist, geriatrician, psychiatrist, general and family practitioner, and so on. Eight countries′ PIM criteria were not completely consistent in the content and the form, but mainly contain three parts: independent risk factors, drug-disease interactions, and drug-drug interactions. Drugs were included in PIM criteria with the following features: the elderly are proneto poisoning and adverse reactions; the benefits of treatment outweigh its potential risks for the elderly; poor efficacy or uncertain efficacy for the elderly; drugs can be replaced with similar products. ConclusionReference and learning from foreign method and experience of PIM criteria in elderly can help us to formulate a PIM criteria for China′s situation as early as possible and promote rational use of drugs.

An 87-year-old male patient was scheduled for electronic laryngoscopy examination due to pharyngeal discomfort. Before the examination, he was anesthetized locally with 10-ml dyclonine hydrochloride mucilage in his mouth and vomited out 5-minutes later. After spitting out the medicine, the patient developed shortness of breath, fatigue, and dyspnea suddenly 5-minutes later; cold sweat and syncope appeared 20-minutes later; his pulse oximeter oxygen saturation (SpO2) decreased to 0.50 and unconsciousness appeared 30-minutes later. Severe allergic reaction was diagnosed, which mainly manifested as acute respiratory failure and might be related to dyclonine hydrochloride mucilage. Endotracheal intubation and ventilator assisted ventilation were performed immediately, and anti-infection, expectorant, nutritional support, stable internal environment maintaining treatments were given at the same time. After 6 days′ treatments, the endotracheal intubation was removed and the nasal tube was used for oxygen inhalation. Then the SpO2 was 0.99 and the above-mentioned symptoms disappeared.

静脉输液是最常用的药物治疗方法,但易发生不同程度的静脉炎。输液静脉炎诱发因素主要有输液的pH值及可滴定酸度、输液的渗透压、药物的化学毒性、机械性刺激等。本文对静脉炎的诱发因素及其防治进行概述,旨在对各诱发因素采取相应的预防措施,尽量减少静脉炎的发生。

本文根据近年文献报告,对5种质子泵抑制剂的作用特点、药代动力学、不良反应及相互作用进行综合比较,为临床安全合理用药提供依据。

Smoking is one of major causes leading to death and more than five million people die from smoking each year worldwide. It has become a serious public health problem. Studies have been identified that there are more than 4000 compounds in tobacco and tobacco smoke. Among them at least 43 compounds are carcinogens. Regular smoking can cause a number of diseases like cancer, emphysema, heart disease, organ damage as well as dependence (addiction). The dependence is mainly caused by nicotine containing in tobacco. Most regular smoking are addicted to nicotine. So regular smokers stopping smoking may induce nicotine withdrawal symptoms including irritability, restlessness, dizziness, headache, difficulty sleeping, and inability to concentration. Most smokers who fail to succeed in quitting smoking is mainly related to the nicotine addiction. In view of this fact, a nicotine replacement therapy (NRT) was advanced. NRT is a way of getting nicotine slowly into the body without smoking. This help people not only to stop or reduce the symptoms of nicotine withdrawal, but also avoid the hazards from smoking. The results from the various studied have showed that NRT increase the rate of success in quitting smoking, and the risk for dependence to NRT product is small. NRT medicines are available as gums, patches, inhalers, sprays, and so on. All dosage forms of NRT medicines have adverse reactions. The severity of adverse reactions are generally mild, but their types differ across NRTs. The common adverse reactions are dizziness, headache, nausea, vomiting, and gastrointestinal discomfort. NRT can safely used for pationts with cardiovascular disease. NRT is not recommended for pregnant women, nursing mothers, and adolescents. In a word, nicotine replacement therapy is safe and effective in helping smokers stop using cigarettes. NRT products have been used in many countries worldwide as OTC. It is worthy of recommendation.

鉴于20世纪末,我国出现俗称″冰毒(甲基苯丙胺)、摇头丸(亚甲二氧基甲基苯丙胺)和K粉(氯胺酮)″的毒品滥用问题。这些毒品被称为″新型毒品″,是相对鸦片、海洛因等传统毒品的一大类滥用毒品的称谓,同海洛因等传统阿片类毒品相比,此类毒品具有精神依赖性强,而身体依赖性相对弱的特点。现主要在娱乐场所被滥用,″新型毒品″滥用的群体广泛,不仅导致严重身心损害,也影响社会安定团结。本文主要介绍了全球范围滥用的几种″新型毒品″的药理学、毒理学作用特点和滥用导致的危害。

Objective: To analyze the causes of the adverse reactions induced by Qingkailtng injection and research the ways of prevention and treatment. Methods: This article summarized 136 cases of the adverse reactions caused by Qingkailing injection in recent years, analysed the category, the clinical characteristics and causes of the adverse reactions induced by Qingkailing injection. Results: The major adverse effects of Qingkailing injection were allergic reaction type I , and were related to the allergic history and CNS diseases of the patient, diluted concentration of the drug, and other drugs combined with Qingkailing injection. Conclusion: The components and formula of Qingkailing injection should be studied in order to reduce the adverse reactions.

A 23-year-old male patient received moxifloxacin, recombinant human interferon α-2b for injection, and lopinavir and ritonavir for 7 days for novel coronavirus pneumonia. There was no abnor-malityof serum potassium. Moxifloxacin was stopped, Qingfei Paidu decoction(清肺排毒汤) was given, and then the patient′s serum potassium began to rise. On day 10 after taking the decoction, laboratory tests showed serum potassium 5.7-mmol/L and the patient was diagnosed with hyperkalemia. Insulin injection 4 U diluted to 5% glucose injection 250-ml was given once by IV infusion, and then the serum potassium decreased to 5.0-mmol/L 6 hours later and 4.6-mmol/L 2 days later. After 5 days, the serum potassium rose again and finally to 5.4-mmol/L on day 17 after taking the decoction. Insulin was given once that day and 2 days later once daily according to the previous method. Then the serum potassium decreased and did not rise again. The patient recovered from novel coronavirus pneumonia and was discharged on day 28 after hospitalization.

为了解非典型抗精神病药物引起锥体外系症状(EPS)的情况,利用Medline检索系统对已公开发表的临床随机对照试验与流行病学资料进行分析。非典型抗精神病药物间引起EPS的程度各有差异,有的与剂量相关,总体较经典的抗精神病药物发生率低,严重程度轻。但临床仍应重视锥体外系症状的预防与治疗问题。

Fluoxetine is one of the selective serotonin reuptake inhibitors, which is often used for treating depression and obsessivecompulsive disorder. Fluoxetine cardiotoxicity includes arrhythmia, torsades de pointes ventricular tachycardia, QT internal prolongation syndrome, serious cardiac damage, and death. The mechanism of cardiac adverse reactions caused by fluoxetine remains uncertain presently. Fluoxetine can cause interactions with some drugs that are metabolized by CYP2D6 leading to cardiac adverse reactions. Clinicians should exercise caution when prescribing fluoxetine to patient with cardiovascular disease, female patients, and elderly patients. ECG monitoring might be performed, if necessary.

Thrombocytopenia is a severe adverse reaction of vancomycin, which can cause hemorrhagic death. The pathogenesis of vancomycin induced thrombocytopenia (VIT) is not clear, and most studies suggest that VIT is related to vancomycin-dependent antiplatelet antibodies IgG and IgM. In vitro studies, it was found that vancomycin induced a series of changes in human platelets, resulting in activation, apoptosis, and reduction of platelets. Clinical manifestations of VIT are various degrees of bleeding. If patient was diagnosed with VIT after ruling out the influencing factors of other diseases or drugs, drug treatment should be promptly withdrawn or changed, and in severe cases, platelets transfusion, corticosteroids, immunoglobulins, rituximab, and hemodialysis should be considered.

近年来抗菌药物与乙醇相互作用致双硫仑样反应的发生呈明显增加,本文就此反应发生机制及相关抗菌药物予以分析探讨。其中主要涉及头孢菌素类、硝基咪唑类,以期引起临床医务人员和患者的共同关注,保证用药安全。

对乙酰氨基酚被认为具有较好的安全性而广泛用于感冒引起的发热、头痛以及各种疼痛的治疗。但其不良反应时有发生,并且大剂量使用易引起肝损害。因此,对乙酰氨基酚的安全性与合理使用问题有必要加以讨论。

A 53-year-old woman with urinary tract infection received an IV infusion of ceftriaxone sodium 2 g dissolved in 100 ml of 0.9% sodium chloride. She had no history of heart disease and drug allergy previously. Twenty-nine minutes after the first infusion initiation, the woman presented with facial and hand flushing followed by frothing from the mouth and cardiopulmonary arrest. Cardiopulmonary resuscitation started immediately and she received IV dexamethasone, IV adrenalin, IV dopamine, closed chest cardiac compressions, endotracheal intubation, and assisted ventilation. But resuscitation was unsuccessful and she died 30 minutes later.

Carbapenems are a class of βlactam antibiotics with a broad spectum of antibacterial activity. The commonly used carbapenems are imipenem, meropenem, ertapenem, faropenem, panipenem, doripenem, and so on. Carbapenem antibiotics could induce neurotoxicity and the incidence is about 0.01%-0.3%. The main clinical manifestations of neurotoxicity are headache, convulsions, seizures, myoclonus, and disorder of consciousness. The mechanism of neurotoxicity induced by carbapenem antibiotics is thought to be related to inhibition of the γ-aminobutyric acid (γ-GABA) binding to the receptors and interruption neural inhibitory effect of γ-GABA eventally resulting in seizures and other neurological disorders. The risk factors for neurotoxic reactions include decreased renal function, pathologic changes in CNS, and combination therapy. The prevention and treatment of neurotoxicity induced by carbapenems are as follows: it is essential to consider appropriate choice of carbapenem antibiotics according to the relationship between seizures and the different types of the antibiotics; dosage should be carefully adjusted in patients with renal failure; concomitant use with other drugs such as highdose theophylline, NSAIDs, probenecid, and so on should be avoided; the children and elderly patients should be monitored during treatment; if carbapeneminduced seizures occur, the agent should be stopped and diazepam or sodium valproate may be given if necessary; hemodialysis could be used for patients with uncontrolled seizures induced by the antibiotics.

Objective To report the clinical features of pulmonary hypertension diagnosed by echocardiography in 5 patients with novel coronavirus pneumonia (COVID-19) in order to understand the special clinical manifestations of COVID-19 and explore the possible mechanism.　Methods The echocardiographic data and clinical characteristics of COVID-19 patients complicated with pulmonary hypertension diagnosed by echocardiography in Beijing Ditan Hospital, Capital Medical University were analyzed descriptively from February 5 to March 31, 2020.　Results A total of 15 patients with severe and critical COVID-19 patients underwent echocardiography. Of them, 7 patients were diagnosed with pulmonary hypertension, 5 of which were confirmed as complications of COVID-19. Among the 5 patients, 4 were female and 1 was male, aged 62-78 years; 4 were with hypertension, 3 were with diabetes, and 1 was with coronary atherosclerotic heart disease. All 5 critically ill patients with COVID-19 were given ventilator-assisted breathing, 2 of which were given extracorporeal membrane oxygenation at the same time. According to echocardiography, the systolic pressure of pulmonary artery in 5 patients was 43-65-mmHg, with an average of 54-mmHg. The severity of pulmonary hypertension was graded as mild in 1 patient and moderate in 4 patients. During the follow-up, pulmonary artery systolic pressure gradually decreased to normal in 4 patients, and then ventilator and ECMO were withdrawn; 1 patient died due to respiratory failure and persistent pulmonary hypertension.　Conclusions Patients with COVID-19 may be complicated by pulmonary hypertension, which is often found in the critical patients. Echocardiography is an important imaging diagnostic method for pulmonary hypertension in patients with COVID-19.

Pharmaceutical excipients refer to any substances other than the active principal in the pharmaceutical preparation. Their functions are to protect, support or enhance the stability and bioavailability of the active ingredient besides formulating a dosage form. It is reckoned that 40 kinds and more of pharmaceutical excipients including over one thousand different materials are now used in the manufacturing of pharmaceutical products, such as solvents, absorbents, preservations,colouring agents, flavouring agents, thickening agents, antioxidants, and so on. In addition，new classes of excipients have been available in recent years. Pharmaceutical excipients are considered to be inert in contrast to active drug. However, adverse reactions to a wide range of excipients are now documented, such as hemolysis to propylene glycol, gasping syndrome to benzyl alcohol, etc. The safety of pharmaceutical excipients involves their toxicity, quality, and improper use. The clinicians should be aware of the adverse reactions associated with pharmaceutical excipients, and drug regulatory authority should strengthen the management of the safety of pharmaceutical excipients in order to safeguard the patient safety.

Objective: To observe the adverse reactions of etanercept in the treatment of ankylosing spondylitis (AS). Methods:A randomized, doubleblind, placebocontrolled parallel study was conducted. From April 2005 to January 2006, 52 patients with active ankylosing spondylitis were enrolled in the study, and randomly divided into the etanercept and placebo groups (26 patients in each group). The patients' average age in the etanercept group was (27.7±8.5) years, and in the placebo group was (29.7±8.1) years. The trial duration was 12 weeks. The first 6 weeks were a doubleblind phase and the second 6 weeks were an openlabel phase. During the doubleblind phase, the patients in the etanercept group received etanercept subcutaneously in a dose of 25 mg twice a week for 6 weeks and the patients in the placebo group received inactive substance subcutaneously in a dose of 25 mg twice a week for 6 weeks. During the openlabel phase, all the patients in both groups received etanercept subcutaneously in a dose of 25 mg twice a week for 6 weeks. Routine blood test was performed at week 0, 1, 2, 4, 6, 7, 8, 10, and 12, meanwhile the dermal lesion at the site of injections, the skin and its appendages reactions, infections, hematological disorders, liver enzyme levels, autoantibody response, and other adverse reactions were observed and analysed. Results: The incidence of adverse reactions in the etanercept and placebo groups was 23% and 38%, respectively; the difference was not statistically significant (P>0.05); no serious adverse reaction occurred. During the doubleblind phase, 26.9% of the patients in the etanercept group developed local dermal lesions characterized by redness and swelling, induration, and pruritus at the site of injections, and no case of such local dermal lesions was found in the placebo group; the difference between both groups was statistically significant (P<0.05). During the trial period, the incidence of the reactions at the site of injections was 34.6%. During the doubleblind phase, 6 patients (23.1%) in the etanercept group developed neutrocytopenia, but neutrocytopenia was not found in the placebo group; the difference between both groups was statistically significant (P<0.05). The difference in the other adverse reactions including upper respiratory tract infections (5 vs 7), skin reactions (6 vs 3), and increased liver enzyme levels (5 vs 8) between the etanercept and placebo groups was not statistically significant (all P＞0.05). Conclusion: Etanercept is a relatively safe agent in treatment of ankylosing spondylitis.

As stated by article 12 of the Drug Administration Law of the People′s Republic of China, the state shall construct pharmacovigilance regulations to monitor, identify, assess, and control adverse drug reactions and other harmful events related to medication. Pharmacovigilance runs throughout the whole life cycle of drug from research and development to clinical use, and the core idea is to prevent and control medication risks and ensure the safety of patients and the general public. As the main places for drug consumption and the key participants in pharmacovigilance activities, the construction of pharmacovigilance system in health facilities is an important part in the construction of national pharmacovigilance regulations. At present, we are at the initial stage of the implementation of national pharmacovigilance regulations. In order to promote the establishment of pharmacovigilance system in health facilities, domestic pharmacovigilance monitoring institutions, relevant academic groups, medical colleges and universities, periodical offices, and social welfare organizations jointly initiate the compilation of Expert consensus on construction of pharmacovigilance system in health facilities by inviting experts and scholars in relevant fields to discuss, distinguish, and analyze the important concepts on adverse drug reactions/events, medication safety, pharmacovigilance, etc., in combination with cutting-edge developments. The consensus puts forward systematic principles and methods on establishing pharmacovigilance system, expecting to provide reference to health facilities in pharmacovigilance system establishment.

ObjectiveTo investigate the feasibility of detecting adverse drug event (ADE) using Global Trigger Tool (GTT) in Chinese medical institutions.MethodsDischarged patients′ records of the Xuanwu Hospital of Capital Medical University from January 1st to December 31st 2013 were collected. After sorting by discharged date, 30 cases were selected in a half month period by a random sampling tool of Microsoft Excel 2007 software. Unqualified cases were eliminated according to the inclusion criteria (patients aged 18 and over, one time admission in 2013, and hospitalization for more than 1 day) and exclusion criteria (patients in the Department of Obstetrics, Family Planning, Rehabilitation, Oncology, Pediatrics, and day-care ward). The 20 cases were reviewed every half a month in sequence of random sampling using 35 triggers, including laboratory indexes, antidotes, clinical symptoms, and treatment measures, that were identified by GTT recommendation, relevant foreign researches, and self-experience of Xuanwu Hospital of Capital Medical University. All cases were enrolled if the number of cases which met the inclusion criteria was less than 20. The cases in whom triggers could be detected were marked as the cases with positive triggers. The cases with positive triggers-related situations were further reviewed in order to identify or exclude ADE and then the identified ADEs were classified. The positive triggers and ADEs were analyzed by Microsoft Excel 2007 software and the positive predictive values of positive triggers were calculated.ResultsTotally 465 cases were reviewed. Of them, 256 were male and 209 female with the mean age of 57 (19~92) years. The time of hospital stay was 2 to 37 days with the mean hospital stay of 10 days. Of the 465 patients, in 208 patients(44.7%)positive triggers could be detected. Of all the 35 triggers, 22 triggers (62.9%) were positive referring to 342 times. There were 18 ADEs identified involving 16 patients and the detectable rate was 3.4% (16/465). Of the 18 ADEs, 13 ADEs had their corresponding triggers containing 8 triggers. The overall positive predictive value of 22 positive triggers was 3.8%. The 18 ADEs included pneumonia (2 ADEs), liver injury (2 ADEs), chill (2 ADEs), skin rash (2 ADEs), antibiotic-associated diarrhea (1 ADE), headache (1 ADE), dizziness (1 ADE), nausea and vomiting (1 ADE), hypoglycemia (1 ADE), over-sedation (1 ADE), delirium (1 ADE), bleeding (1 ADE), leucopenia (1 ADE), and excitation (1 ADE). There were 14 ADEs of class E and 4 ADEs of class F in the 18 ADEs which referred to 21 drugs including 5 kinds of antibacterial agents, 3 kinds of blood system drugs, 3 kinds of psychotherapeutic agents, 2 kinds of cardiovascular drugs, 2 kinds of hormone drugs, 2 kinds of Chinese patent medicines, 1 kind of lipid drug, 1 kind of drug acting bone metabolism, 1 kind of antipyretic analgesic, and 1 kind of anesthetic.ConclusionsGTT could help to early detect the signals of ADEs and provide the reference evidence of preventing drug risk. It is valuable that GTT is popularized and used in Chinese medical institutions.

A 56-year-old male patient received an IV infusion of methylprednisolone 500-mg/d, which was changed to oral prednisone 40-mg/d after 3 days, for thyroid associated ophthalmopathy. Calcium carbonate, calcitriol, alendronate sodium, and esomeprazole magnesium enteric-coated tablets were given orally to prevent hormone-related adverse reactions. The renal function of the patient was normal in the past, but continued to decline after 1 month of medication. And at the end of 3 months after medication, the lowest estimated glomerular filtration rate (eGFR) was 33.1-ml/(min·1.73 m2). Renal diseases and urinary tract obstruction were excluded by routine urine analysis and color Doppler ultrasound examination of the kidneys. Kidney injury caused by esomeprazole magnesium enteric-coated tablets was considered. Then the drug was replaced by famotidine and the other drugs were continued. After 9 days, the renal function of the patient gradually recovered, with the eGFR of 74.0 ml/(min·1.73 m2) at discharge.

本文对已在临床应用的抗肿瘤药物所出现的不良反应结合文献进行复习,分常见的和少见的不良反应,并提出相应的预防及处理方法,供临床医务人员参考。

儿童处于生长发育的特殊阶段,钙是最易缺乏的营养素,钙摄入不足易引起维生素D缺乏性佝偻病,但补钙过量也可造成严重危害。近年来,儿童如何补钙一直存在争议。怎样选择含钙食品和钙剂,是否需要补充维生素D以及如何补充维生素D等问题是争议的焦点。本文对钙剂吸收、预防维生素D缺乏性佝偻病、防止补钙过量,正确选择钙剂、维生素D,补钙与铅中毒等问题进行探讨,希望儿童能科学合理的补充钙剂。

Drug-induced thrombocytopenia is defined as a platelet count lower than normal range(<100×10⁹/L) caused by a drug,resulting in bleeding and some related symptoms.Drug-induced thrombocytopenia includes at least three mechanisms such as marrow suppression,immunological and non-immunological thrombocytopenia.Drugs that have been more commonly reported to cause thrombocytopenia include cancer chemotherapy agents,heparin,quinidine,quinine,gold salts,valproic acid,and antibacterials.The incidence of thrombocytopenia induced by cancer chemotherapy agents is substantially higher than that caused by other types of drugs.Signs and symptoms associated with drug-induced thrombocytopenia are petechiae,ecchymosis,epistaxis,gingival bleeding.More significant bleeding such as gastrointestinal hemorrhage,hematauria,colporrhagia,and intracranial hemorrhage may occur.Treatment options for drug-induced thrombocytopenia include stopping the suspected causative agent;administering corticosteroids,immunog…更多lobulin or platelet transfusions;gold salt or arsenide-induced thrombocytopenia can be treated with IM dimercaprol to eliminate heavy metals.

A 79-year-old male patient was given an IV infusion of piperacillin sodium and tazobactam sodium 4.5 g once every 8 hours for head injury complicated by Escherichia coli pneumonia. Before the treatment, his white blood cell count (WBC) was 10.20×109/L, red blood cell count (RBC) was 3.58×1012/L, hemoglobin (HB) was 101-g/L, and platelet count (PLT) was 202×109/L. On day 2 of medication, his blood cell count began to decrease, with the lowest values of WBC 2.96×109/L, RBC 2.40×1012/L, Hb 66-g/L, and PLT 128×109/L, respectively. It was misdiagnosed as gastrointestinal bleeding because of positive occult blood in gastric juice of the patient at the same time. However, the patient had no obvious melena, his gastric fluid occult blood did not match the development of anemia, and there was no evidence of hemolysis or hemorrhage at other sites. The relationship between the blood cell count decrease and piperacillin sodium and tazobactam sodium was considered. The drug was discontinued and the patient′s blood cell count returned to levels before treatment 3 days later.

Pyrrolizidine alkaloids (Pas) in the plants is one of the main causes of hepatic veno-occlusive disease occurring.Cases of hepatic veno-occlusive disease or liver damage associated with Pas-containing plants or medicinal herbs have been reported in America, England, China, and many other countries. There are more than six thousands kinds of the plants that contain Pas in the whole world. The Pas are primarily found in members of four plant families, I.e. (1) Compositae family: mainly in the genera Senecio, Ligularia, Eupatorium, Gynura, and Petasites; (2) Boraginaceae family: all plants of this family; (3) Leguminosae family: mainly in the genus Crotalaria; (4) Orchidaceae family: in the genus Liparis. There are thirty-eight kinds of Pas-containing medicinal herbs in China, and twelve of them are common in clinical practice as follows: Senecio scanden, Senecio campestri, Gynura segetum, Tussilago farfara, Herba Eupatorii, Herba lycopi, Radix Asters, Lithospermum, Heliotropium, Crotalaria sessiliflora, Crotalaria pallide, Liparis. The Pas have minimal toxicity in their original form, but their metabolites have hepatoxicity. In most instances of Pas liver toxicity in adults, the daily intake was several milligrams or hundreds of milligrams. However, it has been suggested by the WHO that the lowest intake of Pas that cause veno-occlusive disease in a human is just 0.015 mg/(kg·d). For a 70 kg adult, that would correspond to 1 mg total per day. The clinical manifestations of hepatic veno-occlusive disease are mainly refractory ascites, jaundice, hepatomegalia. There are no specific therapy for hepatic veno-occlusive disease, except symptomatic therapy and supportive therapy. Recently, the glucocorticosteroid or heparin therapy for Pas intoxication is reported, but their effect and safety are still under research. The authors consider that the education and monitoring for Pas-containing plants intoxication should be strengthened in our country.

Objective To explore the clinical characteristics of immune checkpoint inhibitor- related pneumonitis (CIP) caused by pembrolizumab.　Methods We reported a case of CIP caused by pembro- lizumab admitted in Peking Union Medical College Hospital and searched case reports on CIP caused by pembrolizumab in PubMed, Embase, ScienceDirect, CNKI, VIP, and Wanfang databases (as of October 1, 2019). The main clinical data (gender, age, primary diseases, use of pembrolizumab, combination drugs, time to onset of CIP, symptoms, imaging results, CIP grade, and treatment and outcome) in all reported cases were collected and analyzed.　Results A total of 33 patients were enrolled, including 23 males and 10 females, aged from 44 to 91 years with a median age of 64 years. The primary diseases in 11 cases were melanoma, in 9 cases were lung adenocarcinoma, in 4 cases were lymphoma, in 3 cases were colon cancer, and in 6 patients were esophageal cancer, breast cancer, nasopharyngeal cancer, pulmonary pleomorphic carcinoma, pulmonary large-cell neuroendocrine carcinoma, and lung squamous cell cancer, respectively. Thirty patients received pembrolizumab as monotherapy, 1 patient received combination therapy of pembrolizumab with carboplatin and pemetrexed, and 2 patients received pembrolizumab combined with radiation therapy. Time to onset of CIP in the 33 patients was 1 day at the shortest and 2 years at the longest with a median time of 12(4, 16) weeks. The symptoms of CIP mainly were dyspnea in 19 cases, cough and expectoration in 15 cases, and fever in 9 cases. The common radiological features were ground glass opacities in 17 cases, consolidations in 11 cases, and grid-like high-density shadow in 8 cases. After the diagnosis of CIP, all patients stopped using pembrolizumab. Twenty-nine patients were treated with glucocorticoids, 19 patients received antibacterial therapy, 2 patients received human immunoglobulin, 1 patient received infliximab, and 2 patients did not receive any intervention. Of the 30 patients with known clinical outcomes, 24 patients were improved and 6 died. Among the improved patients, 6 patients underwent rechallenge with pembrolizumab and 1 of them developed CIP again.　Conclusions The clinical symptoms and radiologic features of CIP caused by pembrolizumab are lack of specificity. Constant vigilance for the presences of fever and respiratory symptoms within 12 weeks after pembrolizumab treatment is required. The CIP in most patients can be improved after drug withdrawal and additional use of glucocorticoids, but the potential fatal risk of CIP is still need to be alert to.

Objective: To investigate and analyse the rationality of use and cost of antimicrobials for prophylaxis during surgical procedures. Methods: The medical records of 83 surgical patients in a hospital were collected from the 1st to the 31st of October,2005,and the rationality of use and cost of antimicrobials was analysed. Results: The irrational use of antimicrobials during surgical procedures was as follows: The duration of antimicrobials use was more than 2 days(80/83,96.4%). The timing of the first dose was not within 2 hours before incision. The selection of antimicrobials was incorrect(54/83,65.1%). Secondly,the antimicrobials effect was influenced by inappropriate combination,dosage and dilution. In addition,the susceptibility testing was ignored. The investigation showed that the application of antimicrobials was higher(100%),while the cost of antimicrobials was reasonable,it accounted for 21.9% in total. Conclusion: It is necessary to carry out "Guidelines on Clinical Use of Antimicrobials"for some inappropriate uses of antimicrobials for prophylaxis during surgical procedures in order to improve the rational use of antimicrobials.

重组人血管内皮抑素(YH-16,商品名:恩度,ENDOSTAR),是一种多靶点的血管内皮抑制剂。具有抑制内皮细胞迁移,诱导其凋亡,发挥其抗肿瘤血管生成作用,是用于非小细胞肺癌临床治疗的靶向药物之一,可以明显提高非小细胞肺癌的治疗有效率。但YH-16的不良反应也不应忽视,尤其是对心血管系统具有一定程度的毒副反应。临床使用中应加强患者心血管系统生理状况的评价,进行心电图监测,避免与蒽环类等具有心肌毒性的化疗药物联合使用,以减少不良反应的发生。

Objective: To analyse the cases with allergic shock induced by traditional Chinese medicines for rational use of the drugs. Methods: Reports of 131 cases with allergic shock published at home during 1989-1999 were collected and the way of drug administration, dosage forms and some other aspects were sorted out and investigated. Results: Injection came first in order of the cause of allergic shock (72.52%) followed by per os (16.03 % ) , preparation for external use only (2.29% ) and others (9.16% ) . Conclusion: The rational use of the drugs with a close attention during its continuation was recommended.

A 26-year-old male patient with type 2 diabetes mellitus was given liraglutide (0.6-mg/d) on the basis of insulin combined with metformin because of the poor therapeutic effect. Four days later, the dose of liraglutide was doubled and empagliflozin (10-mg orally, once daily) was added. The next day, the patient developed nausea, vomiting, and abdominal pain accompanied by elevated serum amylase and lipase (peak levels were 1-048-U/L and 26-U/L, respectively). Acute pancreatitis was diagnosed, all hypoglycemic drugs were discontinued, and fasting, gastrointestinal decompression, intravenous fluid infusion, continuous infusion of low-dose insulin, and symptomatic treatments with lansoprazole and somatostatin were given. Three days later, the patient′s symptoms were relieved, and serum amylase and lipase levels returned to normal. Ten days later, the hypoglycemic drug was changed to subcutaneous injection of insulin aspart 30 injection (24 U in the morning and 16 U in the evening) before meals and oral metformin 0.5 g thrice daily. His blood glucose was controlled and no symptoms of pancreatitis recurred. Therefore, it was considered that the patients′ pancreatitis might be related to the combined use of liraglutide and empagliflozin.

根据近年有关研究和报道对含马兜铃酸中药的毒性成分、马兜铃酸的代谢、马兜铃酸肾病的发病机制、临床特征及其诊断方法进行综述,旨在对马兜铃酸的毒理学及马兜铃酸肾病的诊治加深认识。

A 48yearold woman was given an IV infusion of cefoperazone/sulbactam 3 g dissolved in 0.9% sodium chloride injection 250 ml for treatment of bronchitis. The patient developed difficulty breathing, agitation, lips cyanosis, and unconsciousness with an unrecordable BP about 10 minutes after starting the infusion. Cefoperazone/sulbactam was discontinued immediately. Despite treatment with oxygen inhalation, adrenaline, dexamethasone, and hydrocortisone, she died.

Objective: To analyse the causative drugs, clinical manifestations and precautions of liver damage. Methods: 111 reports of drug-induced liver damage were presented by clinical departments in the hospital from January 2000 to December 2003 and retrospectively reviewed. Results: In 111 cases there were 58 males and 53 females,with a mean age of 46.96 years(range 8-82). 77drugs were involved,mainly antibacterials (18/111 cases,accounting for 16.22%),hormones and other related substances(17/111,15.32%), drugs acting on the CNS ,traditional Chinese medicines and antineoplastics (12/111,10.81%). Classification of drug-induced liver damage was made: hepatocellular damage(40 cases,36.04%),cholestatic damage (43cases, 38.74%)and mixed type damage(28cases, 25.22%). Conclusion: Routine liver function test, early diagnosis, immediate discontinuance of the causative drug and timely treatment are the key to management of drug-induced liver damage.

本文简述抗精神失常药物所致撤药综合征的基本特征,并对抗精神病药、抗抑郁药所致撤药综合征的临床表现、发生机制与防治以及抗焦虑药引起戒断反应的高危因素、临床表现与防治作一概述。

A 24-year-old female patient took about 150 carbamazepine tablets (15 g). About 17-hours later, she was found unconscious and frequent convulsions by her family and was immediately sent to the hospital. Laboratory tests showed that the serum concentration of carbamazepine was 58.7-mg/L, creatine kinase was 411-U/L, C-reactive protein was 23.7-mg/L, and blood oxygen saturation was 0.78. Toxic encephalopathy and status epilepticus induced by carbamazepine were diagnosed. Oxygen inhalation, ECG monitoring, intravascular fluid supplement, diuresis, bedside blood filtration, and symptomatic and suppor- tive treatments were given immediately. On the 2nd day, the number of epileptic seizures decreased and the serum concentration of carbamazepine decreased to 32.9-mg/L. On the 3rd day, the patient′s consciousness recovered and seizures occurred occasionally; on the 4th day, the serum concentration of carbamazepine decreased to 12.3-mg/L, and her convulsion disappeared. After 3 days of continued treatments, the patient recovered and discharged.

A 61-year-old female patient underwent intestinal preparation before electronic colonoscopy. She took polyethylene glycol electrolytes powder (Ⅳ) in 6 times (dissolved content A 24 bags and B 24 bags in warm water 3-000-ml and then took 500-ml orally per 30-minutes). During the intestinal preparation, the patient′s urine output was about 4-500-ml, diarrhea occurred 8 times, and she vomited 2 times within 5.5-hours. The patient fell into a coma at 14:00 on the day, accompanied by limb convulsion and trismus. Laboratory tests showed that the serum sodium and potassium decreased from 140-mmol/L and 4.0-mmol/L to 120-mmol/L and 2.7-mmol/L before and after treatment, respectively. In addition, his chloride was 87.2-mmol/L and bicarbonate was 11.5-mmol/L. Blood gas analysis showed pH 7.29-mmHg, partial pressure of carbon dioxide 31-mmHg, partial pressure of oxygen 105-mmHg, and base excess -10.4-mmol/L. Metabolic acidosis was diagnosed. Head CT and MRI showed no abnormalities. Electrolyte disorder, metabolic acidosis, and hyponatremia encephalopathy due to hyponatremia caused by polyethylene glycol electrolytes powder (Ⅳ) was considered. Oxygen inhalation, continuous ECG monitoring, correction of electrolyte disorders, correction of acidosis, rehydration, and other symptomatic and supportive treatments were given immediately. After 4 hours of treatments, the vital signs of the patient were gradually stable but she was still in a coma. On the third day of treatments, the patient was conscious, her serum electrolytes returned to normal, and no seizures occurred.

Two patients receiving highdose methotrexate chemotherapy developed acute renal failure.Patient 1, a 53-year-old woman with nonHodgkin lymphoma, received highdose methotrexate chemotherapy. Initially she was infused with methotrexate 500 mg intravenously within half an hour, followed by 3500 mg via infusion pump within 24 hours. Then calcium folinate was given for rescue. The first dose of calcium folinate was 30 mg/m², followed by 15 mg/m² intramuscularly once every 6 hours for 8 doses. The patient had no history of chronic renal disease. Her renal function was normal before chemotherapy (SCr 97.1 μmol/L, BUN 4.78 mmol/L). On day 4 after chemotherapy, she developed mild edema of the face and both hands, and oliguria; her SCr increased to 151 μmol/L. Methylprednisolone, furosemide, and calcium carbonate and vitamin D3 were given; her urinary alkalinisation and monitoring of renal function were performed (a peak SCr level of 275 μmol/L). On day 13 after chemotherapy, her renal function returned to within normal range (SCr 96 μmol/L).Patient 2, a 29-year-old man with acute lymphoblastic leukemia, received highdose methotrexate chemotherapy. Initially he was infused with methotrexate 500 mg intravenously within half an hour, followed by 4500 mg via infusion pump within 24 hours. The regimen of rescue was the same as patient 1. The patient had no history of chronic renal disease. His renal function was normal before chemotherapy (SCr 86.9 μmol/L, BUN 5.35 mmol/L). On day 3 after chemotherapy, he developed generalized edema and oliguria; his SCr increased to 235 μmol/L (peak level 360 μmol/L). The symptomatic treatment was given (the regimen was the same as patient 1). On day 30 after chemotherapy, his renal function returned to within normal range（SCr 89 μmol/L）.

本共识分别从新型冠状病毒肺炎疫情防控期间居家隔离药物治疗的必要性和意义、居家消毒剂的选择和合理应用、医院处方药的相关规定、长期居家药物治疗的管理等多个维度，为大众居家期间的合理用药提供指导和帮助。

A 31-year-old male patient received moxifloxacin 400-mg orally once daily for pulmonary infection. After 9 days of treatment, the patient developed hemoptysis, hematochezia, and scattered petechia and ecchymosis on his body, with platelet count (PLT) 1×109/L. Thrombocytopenic purpura was diagnosed. Moxifloxacin were stopped and treatments such as hemostasis, recombinant human interleukin-11, and an IV infusion of concentrated platelets were given. Six days later, the patient′s petechia and ecchymosis disappeared and the PLT was 376×109/L. Bone marrow puncture result showed that it was immune thrombocytopenia.

Hepatic injury may induced by long-term use of total parenteral nutrition.The clinical presentations were elevated values of liver enzyme and bilirubin,cholestasis,fatty degeneration,and cirrhosis.The exact mechanism of TPN-induced hepatic injury is presently unknown;it may associated with the long-term fasting,imbalance of administered nutrients,and intestinal bacterial translocation.Balance of administered nutrients,use of cyclic infusion,early enteral feeding,and supplementation of some nutrients(such as choline and L-glutamine)may be beneficial to prevention and treatment of TPN-induced hepatic injury

Object iv e:To investigate kidney damage caused by low-dose of enteric-coated aspirin t ablets.Method:The outcomes of600patients tak ing aspirin(50～75mg dai ly)were retrospectively analysed from January1995to August2003in our h ospital.Results:Kid ney damage occurred in16of600cases.Its frequen cy wa s related to age of patients,dosage and treatment duration of aspirin.And imp aired renal function was returned to normal gradually when aspirin was withdrawn in them.Conclusion:Prolonged oral admi nist ration of aspirin in low-dose can cause kidney damage and ordinary exam ination of urine and renal function is suggested,especially for the elderly.

A 51-year-old male patient received an operation treatment for paranasal sinusitis induced by radiotherapy and chemotherapy of nasopharyngeal carcinoma. One oxycodone and acetaminophen tablet (each tablet contains oxycodone hydrochloride 5-mg and acetaminophen 325-mg) was given orally thrice daily before and after the operation. Pregabalin 75-mg twice daily was added because of the poor analgesic effectiveness. During the treatment, oral oxycodone hydrochloride 10-mg was given once daily by his family members for 2 days. Two days after the addition of pregabalin, the patient developed mental disorders, such as delirium, irritability, involuntary convulsions of limbs, cognitive impairment, and disorientation. All above-mentioned analgesics were discontinued and dexmedetomidine was given for pain relief and sedation. Three days later, the mental state of the patient was improved, there was no obvious delirium, the discrimination and orientation returned to normal, and dexmetomidine was discontinued. There was an obvious time correlation between the occurrence and disappearance of mental disorders and the combination of analgesic drugs. Referring to the previous literature, it was considered that the mental disorders of the patient were caused by the interaction between oxycodone and pregabalin.

A 4 years and 7 months old boy was treated with IV infusions of azithromycin 0.16 g once daily and methylprednisolone sodium succinate 32-mg once daily and oral amoxicillin and clavulanate potassium for suspension 228.5-mg twice daily for bronchopneumonia complicated with multiple co-infections with mycoplasma, viruses, and bacteria. After 6 days of treatments, the boy′s symptoms were improved and his body temperature returned to normal. On the 7th day of treatments, the boy developed rash with itching, which subsided on the same day after symptomatic treatments. Amoxicillin and clavulanate potassium and azithromycin were discontinued, but the child still developed rash every time after IV infusion of methylprednisolone sodium succinate, which could subside later that day. After withdrawal of methylprednisolone sodium succinate, the boy′s rash did not recur.

Objective: To investigate the causes of cefradineinduced hematuria in children. Methods: Clinical data from 19 children with hematuria induced by cefradine use in the community from March 2005 to March 2008 were collected. The patients’ sex and age, clinical presentation, dosage and administration of cefradine, the onset time, intensity and outcome of hematuria were investigated and analyzed. Results: Of the 19 children, 16 were males, 3 were females, and their age was ≤ 1 year (3 cases), ～3 years (10 cases), ～7 years (4 cases), and ＞7 years (2 cases). The routine dosage of cefradine was 50～100 mg/(kg·d) dissolved in 100～250 ml of sodium chloride 0.9% or glucose 5% for an IV infusion. Sixteen patients received 100 mg/(kg·d). One patient received 110 mg/(kg·d), two patients received ＜100 mg/(kg·d).The daily dosage was used as a single dose in 17 patients. Of the 19 patients, 17 developed gross hematuria and two developed microscopic hematuria. Laboratory tests showed RBC (+++～++++)/HP and urinary protein ＜0.1 g/24 h. Sixteen patients (84.2%) had normal renal function and 3 patients (15.8%) had mild elevation in SCr and BUN levels. Eighteen patients (94.7%) developed hematuria within 24 hours after receiving drug therapy. One patient’s hematuria onset was over 24 hours. After drug withdrawal, gross hematuria disappeared within 1～2 days and microscopic hematuria disappeared within 3～5 days. At 3month followup after discharge, their routine urine and renal functions normalized. Conclusion: Hematuria following an IV infusion of cefradine in childnen might be linked to the factors of large dose, high concentration, and young age.

A 59-year-old male patient received SOX chemotherapy regimen (IV infusion of oxaliplatin injection 200-mg dissolved in 5% glucose injection 250-ml for 2 hours on the first day, oral tegafur, gimeracil and oteracil potassium 60-mg once daily on day 1-14, every 3 weeks was a cycle) for gastric cancer with multiple lymph nodes metastases. One week after the infusion of oxaliplatin during the third cycle, the patient suddenly developed deafness and blurred vision. The patient was diagnosed with sudden sensorineural deafness and acute optic neuritis after otorhinolaryngologist consultation. His sudden sensorineural deafness and acute optic neuritis were considered to be associated with oxaliplatin. Chemotherapy was discontinued and the patient was given neurotrophic and microcirculation-improving medications. One 1 week later, the patient′s vision gradually returned to normal, but the deafness persisted.

A 78yearold woman was hospitalized with cerebral hemorrhage, right central hemiparalysis and pulmonary infection. On day 21 after admission, her urine and stool examinations showed fungal spore and hyphae. She was considered to have fungal infections. The woman received an IV infusion of fluconazole 0.4 g daily on day 1 of therapy, followed by fluconazole 0.2 g daily. Three days later, she developed an erythematous macular eruption with mild pruritus on her chest and abdomen. Fluconazole was stopped and changed to an IV infusion of itraconazole 0.25 g twice daily. Two days later, her erythematous macular eruption with marked pruritus progressed to cover her trunk and extremities. Itraconazole was discontinued and replaced with an IV infusion of allimin and oral chlorphenamine. Five days later, her skin eruption basically subsided.

Objective: To investigate the general pattern and characteristics of ADRs to cephalosporins and to guide rational drug use.Methods: 386 cases developing drug adverse reactions to cephalosporins ,reported in Chinese literature in the past 10 years, were analysed.Results:There were 45 cases of type A reaction and 341 cases of type B reaction, mostly with allergic reactions (35.49%)and urinary lesion (29.02%). Serious ADRs amounted to 93 cases, of which,7died. Among cephalosporins, ADRs of cefoperazone (97cases), cefradine (78 cases) and cefazolin (69 cases) accounted for 25.13% , 20.21 % and 17.88% , respectively.Conclusion:Rational use of cephalosporins should be strengthened in the clinical practice in order to prevent and reduce the occurence of ADRs.

ObjectiveTo evaluate the safety of domperidone in children.MethodsClinical studies involving domperidone used in children were searched from PubMed, Embase, Cochrane Library, Chinese Biology Medical disc, CNKI, VIP, and Wanfang Database. Adverse drug reaction information bulletins which were reported by WHO Pharmaceuticals Newsletter and National Center for adverse drug reaction monitoring were searched and adverse drug reactions (ADR)/adverse drug events (ADE) related to domperidone were collected. Websites of European Medicines Agency, Food and Drug Administration of United States, Medicines and Healthcare Products Regulatory Agency (MHRA), Health Canada, and Therapeutic Goods Administration were searched and information of risks and benefits related to domperidone treatment were collected. Randomized controlled trails (RCTs) were Meta-analyzed using RevMan 5.2 software and other data were descriptively analyzed. Correlation analysis of domperidone and adverse drug reactions was performed using evaluation criteria of WHO. Severity of ADR/ADE was evaluated using criteria CTCAE 4.03 of United States Department of Health and Human Services.ResultsA total of 9 RCTs, 1 cohort study, 4 self-controlled studies, and 24 case reports were entered in this study. Meta-analysis of 9 RCTs showed the following results. There were no statistical significance in the incidence of ADR in children between the domperidone group and the control groups of placebo, cisapride, and mosapride. The incidence of ADR in children in the domperidone group was lower than that in the metoclopramide (RR=0.44, 95%CI: 0.23-0.86, P=0.02), and higher than that in the Traditional Chinese Medicine group (RR=16.09, 95%CI: 2.01-129.04, P=0.01). There were no serious adverse events of domperidone reported in the 9 RCTs. It was showed in the self-controlled study that oral domperidone was associated with QTc prolongation in neonates. One hundred and one cases of ADR were reported in 24 case reports. Of them, 80 cases (79.2%) of ADR were mild-to-moderate (CTCAE grading 1-2), 21 cases (20.8%) of ADR were severe (CTCAE grading 3), and no ADR with CTCAE grading 4-5 was reported. The results of causality assessment on above mentioned 101 cases of ADR showed that 2 cases of ADR were associated with domperidone certainly, 76 were probably, 15 cases of ADR induced by drug overdose, and 2 cases induced by combination use of medicines that may cause the same adverse reactions. In April 2014, European Medicines Agency suggested to limit clinical indications and dosage of domperidone. In September 2014, MHRA of Britain announced that domperidone was no longer to use as over-the-counter.ConclusionsNo enough evidences to prove that the incidence of ADR induced by domperidone was higher than that by the placebo, other gastro-kinetic agents, and other conventional treatments in children. The risks of serious ADR occurrence existed in children with domperidone treatment.

A 25yearold male patient took about 60 tablets of phenobarbital and scopolamine hydrobromide by himself (each tablet contains 30mg phenobarbital and 0.2mg scopolamine hydrobromide). About 1 hour later, he developed coma with paroxysmal limb convulsions. Drug poisoning was diagnosed. The patient received gastric lavage, catharsis, and intravenous injection of midazolam 10mg for epilepsy. Six hours later, his heart rate was 53 beats/min, breathing rate was 11 times/min, and occasional convulsions and hematuria occurred. Laboratory tests showed indirect bilirubin 16.97μmol/L, total protein 54g/L, albumin 27.6g/L, and thrombin time 25.0s. Multiple organ injury was considered and blood purification treatment was given. One day later, the patient′s consciousness was restored, heart rate was 68 beats/min, breathing rate was 16 times/min, and no convulsion occurred. Laboratory tests showed indirect bilirubin 8.69μmol/L, total protein 54.7g/L, albumin 34.0g/L, and thrombin time 16.7s.

ObjectiveTo evaluate the risk factors for thrombocytopenia related to linezolid (LZD) comprehensively.MethodsThe related databases were electronically searched for the case-control studies about risk factors for LZD-associated thrombocytopenia from the inception to June 2016. The quality of the literature which was enrolled into the Meta-analysis evaluated by Newcastle-Ottawa Quality Assessment Scale (NOS), and then Meta-analysis was conducted using RevMan 5.3 software. The results are presented as odds risk (OR) and 95% confidence interval (CI).ResultsA total of 25 studies involving 4 279 patients were entered, including 1 335 in the thrombocytopenia group and 2 944 in the  none thrombocytopenia group. The NOS scores of all literature were greater than or equal to 7. The result of Meta-analysis showed that, the baseline platelet count < 200×109/L (OR=3.64, 95%CI: 1.60-8.30, P=0.002), body weight ＜50 kg (OR=2.44, 95%CI: 1.79-3.34, P< 0.001), creatinine clearance<30 ml/min (OR=1.85, 95%CI: 1.29-2.67, P< 0.001) , duration of LZD therapy > 14 days (OR=1.76, 95%CI: 1.17-2.65, P=0.006) and age≥65 years (OR=1.54, 95%CI: 1.03-2.31, P=0.04) were identified as significant risk factors for LZD-associated thrombocytopenia.ConclusionCurrent evidence shows that the severe damage to renal function, low baseline platelet count, low body weight, long-term LZD administration and advanced age are risk factors of LZD-related thrombocytopenia.

Objective To compare the occurrence and clinical characteristics of hypersensitivity reactions induced by 3 non-ionic iodine contrast media (NICMs) during percutaneous coronary intervention (PCI). Methods The patients who developed hypersensitivity reactions in iopromide, iohexol, and iodixanol application during PCI were screened out from adverse drug reaction reports of Beijing Anzhen Hospital from January 1, 2013 to December 31, 2018 and the total number of patients who underwent the PCI during that period and received the above NICMs was obtained by searching the hospital information system. The overall incidences of hypersensitivity reactions and severe hypersensitivity reactions and incidences of those induced by each of the 3 NICMs were calculated and their clinical characteristics were analyzed.　Results The overall incidences of hypersensitivity reactions and severe hypersensitivity reactions induced by the 3 NICMs were 0.603% (422/69-955) and 0.024% (17/69-955). The incidences of hypersensitivity reactions induced by iohexol, iopromide, and iodixanol were 0.418% (109/26-097), 0.364% (83/22-787), and 1.092% (230/21-071), respectively; the incidences of severe hypersensitivity reactions were 0.023% (6/26-097), 0.039% (9/22-787), and 0.009% (2/21-071), respectively. Iodixanol had a higher incidence of hypersensitivity reactions than iopromide and iohexol (both P<0.001) but the lowest incidence of severe hypersensitivity reactions, which was significantly different from that of iopromide (P=0.047). Of the 422 patients who developed hypersensitivity reactions, 327 were male and 95 were female with an average age of 59 years (range: 27-101 years). The time of hypersensitivity reactions occurrence was recorded in 373 patients and time from NICMs injection to hypersensitivity reactions occurrence were 30-minutes to 90-hours with the median time of 5 hours; hypersensitivity reactions were immediate type (latency ≤1 hour) in 127 patients (34.0%) and delayed type (latency>1 hour) in 246 patients (66.0%). The hypersensitivity reactions induced by iopromide were mainly immediate type (79.5%, 62/78), while those induced by ioxamol were mainly delayed type (87.7%, 193/220). The proportion of patients with a previous history of allergy in the immediate type patients was significantly higher than that in the delayed type patients ［15.0% (15/100) vs. 7.1% (14/197), P=0.030］. The most common clinical manifestation of hypersensitivity reactions was rash ［78.0% (329/422)］. Among 17 cases of severe hypersensitivity reactions, 15 (88.2%) were anaphylactic shock, 1 was laryngeal edema, and 1 was dyspnea, all of which were immediate type. Hypersensitivity reactions were all improved after treatments, but PCI failed to be fully performed in 6 patients due to severe hypersensitivity reactions.　Conclusions The safety of 3 NICMs for PCI was good and the incidence of hypersensitivity reactions was low; the incidence of severe hypersensitivity reactions due to iopromide was the highest. Severe hypersensitivity reactions such as anaphylactic shock might affect the performance of PCI and caution should be given.

A 62-year-old female patient received oral aspirin enteric-coated tablets 100-mg once daily, clopidogrel hydrogen sulphate tables 75-mg once daily, metoprolol tartrate tablets 18.75-mg twice daily, and rosuvastatin calcium tablets 10-mg once daily after coronary artery stent implantation regularly according to the doctor′s instructions. Several days later, the patient developed edema of hands and feet from the distal end to the proximal end of the extremities, and he developed facial edema with rash and pruritus at the edema site. After 3 days of antiallergic treatment, there was no obvious regression of edema and new rash. After careful inquiry, the patient said that he always developed edema and increased rash symptoms about 2 hours after taking metoprolol tartrate tablets. After discontinuation of metoprolol tartrate tablets for 1 day, and other drugs were continued to be used, the patient′s edema and rash were relieved on the next day, and the above symptoms reappeared when the drug was used again according to the doctor′s instructions on the same day. When the drug was stopped again, the edema and rash were obviously improved the next day.After 2 days of discontinuation, the patient took metoprolol succinate sustained-release tablets at their own discretion, and still developed edema and rash. After discontinuation of metoprolol succinate sustained-release tablets, the edema and rash disappeared completely 10 days later.

盐酸西布曲明是20世纪90年代后期开发的新型减肥药,其相关不良反应临床报道较少。本文综述了国内外对西布曲明安全性评价的有关文献,对该药的常见、少见不良反应,与其他药物的相互作用以及防治措施作一介绍,以供临床参考。

Objective: To observe the efficacy and safety of fexofenadine in treating seasonal allergic rhinitis (SAR) and chronic idiopathic urticaria (CIU). Methods: In a double-blind, double-dummy, randomized, controlled, multicenter phase Ⅱ clinical trial, the efficacy and safety of fexofenadine (60 mg twice daily) were compared with cetirizine (10 mg/d) in the treatment of SAR and CIU. The duration of treatment was 14 d for patients with SAR and 28 d for patients with CIU. Results: One hundred and forty-four patients with SAR entered the trial. Of the 144 patients, 64 receiving fexofenadine and 68 receiving cetirizine were included in PPS. The symptom score reducing index and overall effective rate in fexofenadine group were 0.719±0.182 and 85.94%, respectively. There were statistically deferences between the fexofenadine group and cetirizine group (P<0.05). One hundred and forty-four patients with CIU entered the trial. Of the 144 patients, 67 receiving fexofenadine and 68 receiving cetirizine were included in PPS. The symptoms score reducing index and overall effective rate in fexofenadine group were 0.771±0.269 and 80.60%, recpectively. There were no marked differences between the two groups (P>0.05). There were no serious adverse reactions in the two groups. The incidence of adverse reactions in the fexofenadine and cetirizine groups was 17.6% and 16.9%, respectively, and there were no significantstastistically deferences between the two groups (P>0.05). The manifestations of adverse reactions in the two groups were similar, and the main of them was drowsiness and dry mouth. There were no obvious changes of ECG after dosing in the two groups, and no significant differences of QTc before and after dosing between the two groups (P>0.05). Conclusion: Fexofenadine is an effective and safe medication for treating seasonal allergic rhinitis and chronic idiopathic urticaria.

A 27-year-old couple with suppurative tonsillitis received IV azithromycin 0.2 g．The next day，both of them presented with gross hematuria in the whole process of urination．Urinalysis revealed their presence of RBC(+)and(+++)respectively，and protein(+++)．Their liver function，renal function，and ASO were normal． A B-ultrasonic examination found no abnormality in their urinary svstem． Azithromycin was ceased immediately．After treatment with etamsylate，vitamin C，and fluid replacement，their urine became clear gradually．During 1 month of follow-up，their urine routine maintained normalization．

Rituximab is a human/mouse chimeric anti-CD20 monoclonal antibody mainly used in the treatment of non-Hodgkin’s lymphomas. The most common rituximab-caused adverse reaction is acute infusion-related reactions and serious adverse reactions are rare. This article reviews the rituximabinduced rare adverse reactions，such as acute respiratory distress syndrome, diffuse alveolar hemorrhage, cardiac arrhythmia, sudden cardiac death, chronic heart failure, progressive multifocal leukoencephalopathy, tumor lysis syndrome, and cytokine release syndrome, as well as the possible pathogenesis，clinical features, and the management in order to provide references for safe rituximab use in clinical practice.

From March 2013 to December 2018, Japan, the United Kingdom, Canada, Australia, and China successively issued guidelines on therapeutic drug monitoring of voriconazole. It is recommended in guidelines at home and abroad that voriconazole should be given a loading dose, and the blood drug concentration of patients should be monitored on the third day; when adjusting the dose, adverse events occurrence or poor efficacy, increasing or stopping the drugs that may interact, and sequential administration, the blood drug concentration should be monitored again. The clinical characteristics of voricona- zole-related adverse events have been clearly defined. After adverse reactions occur during the treatment period, the drug can be stopped or reduced according to its severity. Voriconazole is not only the substrate of cytochrome P450 (CYP) 2C9, CYP2C19 and CYP3A4, but also an inhibitor of them. We should pay attention to the interaction between voriconazole and other drugs.  In the future, further research is needed to accumulate more evidence-based medical evidences for the use of the drug in different medication purposes, different diseases or different fungal infections, Child-Pugh grade C severe liver disease, and children <2 years old, so as to provide reference for clinical individualized treatment.

Objective: To study on relationship between sulphonylureasinduced hypoglycemia and CYP2C9 genotype in patients with type 2 diabetes. Methods: The outpatients with type 2 diabetes receiving sulphonylureas treatment were enrolled in a study from November 2006 to May 2007. The patients’blood glucose levels and CYP2C9 genotype were measured. The relationship between hypoglycemia and CYP2C9 genotype was analyzed. Results: Of 146 patients with type 2 diabetes, 43 were males, 103 were females, and their ages were 23～79 years\[average age (62.5±12.4) years\]. All patients received sulphonylureas. The specific drugs and dosages were as follows: glipizide 5～10 mg/d, gliclazide 80～160 mg/d, sustainedrelease gliclazide 30～60 mg/d, glimepiride 0.5～2 mg/d, and glibenclamide 5～10 mg/d. Seventyfour cases of 146 patients developed hypoglycemia. Of the 74 cases, 19 were sulphonylureasinducedhypoglycemia and 55 were other factorinduced hypoglycemia (as a consequence of delayed meal, less intake of food, excessive exercises, and so on).Of the 146 patients, 13(8.9%) were CYP2C9*1/*3 genotype, and 7 of the 13 cases were in the hypoglycemia group, 6 were in the nonhypoglycemia group. Of 19 cases of sulphonylureasinduced hypoglycemia, 6 were CYP2C9*1/*3 genotype. Of 55 cases of other factorinduced hypoglycemia, 1 was CYP2C9*1/*3 genotype. There was a statistical difference in CYP2C9 genotype between the sulphonylureasinduced hypoglycemia group and the other factorinduced hypoglycemia group or the nonhypoglycemia group (P<0.05). Conclusion: Sulphonylureasinduced hypoglycemia occurring in patients with type 2 diabetes might link to CYP2C9 gene mutation (CYP2C9*1/*3).

Drug-induced liver injury(DILI) is one of the common adverse drug reactions. Over 1100 drugs and related substances are associated with DILI. However, there is no specific diagnostic marker to DILI so far. This paper introduces and discusses some main diagnostic criterias in order to be helpful for diagnosis of DILI in clinical practice.

ObjectiveTo explore the clinical characteristics and the warning signals of Danshen lyophilized powder injection (DLPI).MethodsThe adverse drug reaction (ADR) reports of DLPI from the ADR Spontaneous Reporting Database of Shandong Province from January 1, 2005 to December 31, 2015 were collected. The clinical characteristics of ADR were analzed by descriptive statistical method. The conceptual data and the data for each year from 2005 to 2015 were analyzed to find out the warning signals of ADR induced by DLPI by the methods of proportional reporting ratio (PRR), reporting odds ratio (ROR), and bayesian confidence propagation neural network (BCPNN).ResultsA total of 887 reports and 887 patients which comprised 460 males and 427 females with the average age of (57.7±16.6) years (3 d to 91 years) were enrolled into the analysis. The patients  whose age ≥45 years accounted for 79.59% (706/887). There were 1 281 times of ADR in 887 patients which involved mainly in skin and cardio-cerebrovascular system. Top ten in turn were erythra, pruritus, dyspnea, shiver, nausea, headache, fever, palpitation, dizziness, and injection site reactions, totally 1 152 times of ADR which accounted for 65.89% (1 152/1 281). The patients stopped to use DLPI when the ADR appeared. Of the 887 patients, 557 cases were recovered and 330 had improvement after receiving the symptomatic treatments. The results of analysis on conceptual data and the data for each year by methods of PRR, TOR, and BCPNN showed that erythra (PRR method: conceptual data, from 2008 to 2015; ROR method: conceptual data, from 2008 to 2014; BCPNN method: conceptual data), pruritus (PRR method: conceptual data, 2012, 2013, 2015; ROR method: conceptual data, 2012, 2013), dyspnea (PRR method: conceptual data, from 2008 to 2014; ROR method: conceptual data, from 2008 to 2014; BCPNN method: conceptual data, 2014), shiver (PRR method: conceptual data, from 2007 to 2009; ROR method: conceptual data, from 2011 to 2013; BCPNN method：conceptual data, 2012 and 2013) could be  warning signals of ADR induced by DLPI.ConclusionsADRs due to DLPI involve mainly skin and cardio-cerebrovascular system. Erythra, pruritus, dyspnea, and shiver can be the warning signals of ADR induced by DLPI.

本文综述分析非甾体抗炎药物的不良反应和预防措施。其常见的不良反应有胃肠道损伤、肝肾功能损害、变态反应、血液系统异常及中枢神经系统反应等。临床医师和广大患者应严格掌握适应证和禁忌证,合理选用不良反应少的品种,避免大剂量长期应用,加用胃粘膜保护剂等,以期最大限度降低不良反应的发生

Objective: To analyse the characteristics of hemolysis induced by puerarin injection. Methods: From domestic medical journals 1999-2003,16 hemolysis cases due to puerarin were collected and analysed. Results: These 16 cases comprised 12 males and 4 females, mostly over 60 years old. The dose of puerarin was 200 to 600 mg once daily and hemolysis occurred chiefly within 3-10 days of the first couse of treatment except 3 cases occurring during its re-administration. It seemed to be no difference to patients with or without a history of allergy. The main symptoms were arthralgia,generalized pain, rigor, fever and macroscopic hematuria. Hemoglobin in blood was reduced and hemoglobinuria was observed. The specific antibody for puerarin was detected with immunological test. Conclusion: Puerarin-induced hemolysis was related to many factors. Much attention should be paid in the clinical use of puerarin injection.

万古霉素以其对耐甲氧西林金葡球菌(MRSA)的良效而著称,关注其不良反应并尽量避免其发生是合理用药内容之一。本文对与万古霉素相关的红人综合征(RMS)的国内外文献进行综述。多数报道认为:RMS是在快速静脉输注万古霉素的过程中发生的、由组胺介导的一种反应。此反应以脸、颈及躯干上部斑丘疹样红斑为特征。本文对其发生机制及发生率的不同看法根据文献进行了分析,亦介绍了发生RMS后的处理方法与预防措施。

矿物类中药中可含有铅、汞、砷等重金属成分,过量应用会导致药源性铅、汞和砷等重金属中毒。临床上对重金属中毒的误诊率较高,应引起高度重视。通过仔细采集病史,拓宽临床思维,认识矿物类中药重金属中毒的临床表现,结合毒物化学成分的检测结果,可正确诊断药源性重金属中毒,并及时采取特效解毒剂驱排治疗。

Two male patients developed acute renal failure after receiving an IV infusion of andrographolide injection.The first patient, a 29-year-old patient, received an IV infusion of andrographolide 0.5 g for a fever. He developed lumbago after the infusion. His SCr was 142 μmol/L in the evening at that day. The next day, he was hospitalized and his SCr was 219 μmol/L. On day 2 of hospitalization, the patient’s SCr was 332 μmol/L. Acute renal failure was diagnosed. Fluid replacement and symptomatic therapy were given. Three days later, his SCr decreased to 244 μmol/L. On day 7 of hospitalisation, his SCr decreased to 149 μmol/L. After 9 days of hospilisation, the patient was discharged, and his lumbago disappeared. A followup 10 days after discharge, his renal function normalized.The second patient, a 25-year-old man, received an IV infusion of andrographolide 0.25 g and oral azithromycin 0.25 g for a cold. After about 4 hours of the infusion, the patient developed lumbago.The next day, his SCr was 189.7 μmol/L and his BUN was 889 μmol/L. All drugs were discontinued. On day 3, his lumbago persisted, his SCr was 214 μmol/L and his BUN was 8.8 μmol/L. After receiving supportive therapy, his SCr decreased to 138 μmol/L and his BUN decreased to 6.4 μmol/L. A followup one week after discharge, his renal function normalized.

Objective: To observe and evaluate the safety of levonorgestrelreleasing intrauterine system (LNG-IUS) in the treatment of endometriosis. Methods:A total of 59 patients with endometriosis were studied. The LNG-IUS was inserted into the uterine cavity. The acne, facial pigmentation, premenstrual mammary swelling, the body weight, and quality of life were scored and compared before and 6 months and 12 months after the insertion of the LNG-IUS. The adverse reactions to LNG-IUS were observed. Results: The acne scores before and 6 months after the insertion of the LNG-IUS were 1.00 (0.00, 3.00) and 0.00 (0.00, 2.00), respectively, the difference was not statistically significant (P>0.05); while the acne scores were 0.00 (0.00, 1.00) 12 months after the insertion of the LNG-IUS, the difference was statistically significant (P<0.01). The facial pigmentation scores before and 6 months and 12 months after the insertion of the LNG-IUS were 1.00 (0.00, 1.00); the differences were not stastically significant (all P>0.05). The premenstrual mammary swelling scores before and 6 months and 12 months after the insertion of the LNG-IUS were 220 (0.00, 4.00), 1.50 (0.00, 4.00) and 1.00 (0.00, 3.00), respectively; the differences were statistically significant (P<005, P<0.01). The body weight before and 6 months and 12 months after the insertion of the LNG-IUS were 59.00 (55.00, 64.00)kg, 59.50 (55.00, 64.00)kg, and 59.00 (54.00, 64.00)kg, respectively; the differences were not statistically significant (all P>0.05). The quality of life before the insertion of the LNG-IUS was compared with the quality of life 6 months and 12 months after the insertion of the LNG-IUS; the differences were statistically significant (all P<0.01). The intramenstrual bleeding before and 6 months and 12 months after the insertion of the LNG-IUS were 4 cases (6.78%), 16 cases (27.12%), and 14 cases (23.73%), respectively. Other adverse reactions to LNG-IUS were hair loss (1 patient) and a feeling of swelling over entire body (2 patients). Conclusion: Levonorgestrelreleasing intrauterine system is safe in treatment of endometriosis.

Objective: To investigate the the allergic shock induced by cephalosporins. Methods: Literature was retrieved from domestic medical journals 1990-2003,and 244 cases with allergic shock in 210 papers were collected and analysed. Results: Twelve cephalosporins were involved in 244 cases and 93.8% of them were caused by six cephalosporins, namely, cefazolin, cefotaxime, cephalexin, cefoperazone, ceftriaxone and cefradine. The patients with and without allergic history accounted for 24.6% and 30.3% respectively and the others were unknown in this respect. 78.7% of the cases occurred during first administration and 86.1% did within 20 minutes of drug start. The mortality rate was about 8.2%. Conclusion: Cephalosporins could result in allergic shock and much attention should be especially paid to the patients with allergic history.

Druginduced headaches refer to a headache caused either directly or indirectly by medications, which account for 5%～10% of the headaches. Mechanism of druginduced headaches is unclear. The comnon causes of drug-induced headaches are as follows: vasodilation, benign intracranial hypertension, aseptic meningitis, disulfiram-like reactions, and analgesic overuse. Clinical presentation of druginduced headaches may be accompanied by dizziness, nausea, vomiting, facial flushing, and decreased blood pressure, besides headache symptoms. The most common causative agents include NSAIDs, histamine H₂ receptor antagonists, calcium antagonists, and vasodilators. Care must be taken to distinguish a headache during drug therapy from a headache secondary to the primary disease. The symptoms of druginduced headaches may relieve after stopping the offending agents and receiving symptomatic therapy.

A 60yearold woman with coronary heart disease received intraarterial iodixanol 50 ml prior to undergoing coronary angiography. One hour after surgery, the woman experienced dizziness, nausea, severe headache, and blurred vision. Her BP was 110/70 mmHg and her cranial CT scan was normal. She was given dexamethasone, fluid replacement and symptomatic therapy. Seven hours and a half later, her symptoms resolved completely.

目的 对利巴韦林和干扰素α的不良事件（AE）进行数据挖掘，为鉴别应用这两种药物治疗新型冠状病毒肺炎（新冠肺炎）过程中出现的临床症状/体征和实验室检查异常是药物引起还是疾病本身所致提供依据。　方法 根据文献及《新型冠状病毒肺炎诊疗方案（试行第五版）》中提到的新冠肺炎症状/体征及实验室检查异常结果选出本研究关注的AE。收集2004年1月1日至2019年12月31日美国FDA不良事件报告系统（FAERS）相关数据，采用报告比值比（ROR）法对利巴韦林和干扰素α进行数据挖掘。　结果 设定时段内FAERS数据库共收到7-582-463份药物相关的有效AE报告，其中利巴韦林31-775份，干扰素α 2-345份。分析结果显示，在呼吸系统、胸及纵隔疾病中可能与利巴韦林具有相关性的AE有鼻充血、咳嗽、喉疼痛、咽部水肿、咳痰和呼吸困难，可能与干扰素α具有相关性的AE有喉疼痛和咯血；在其他系统器官分类中可能与利巴韦林和干扰素α均具有相关性的AE包括发热、寒冷感、疲乏、恶心、呕吐、腹泻、头痛、关节痛、肌痛和皮疹。在实验室检查异常AE中，与利巴韦林相关的有白细胞计数降低、血小板计数降低、天冬氨酸转氨酶升高和丙氨酸转氨酶升高；与干扰素α相关的有白细胞计数降低、淋巴细胞计数降低、血小板计数降低、天冬氨酸转氨酶升高和丙氨酸转氨酶升高。　结论 利巴韦林和干扰素α相关AE中一部分与新冠肺炎的临床表现和实验室检查异常结果相似，临床实践中应当注意鉴别。

华法林为香豆素类口服抗凝剂，临床上应用越来越广泛，但他与许多药物和食物同时服用均会发生相互作用，从而影响抗凝效果。本文对华法林与西药、中草药和食物的不良相互作用进行概述，一起能为临床安全用药提供参考依据。

Objective: To study the dose-effect and time-effect relations to spermatogenic cell apoptosis of rats induced by hydroxyurea. Methods:In the dose-effect study, 25 male Wistar rats were divided into 5 groups (5 rats in each groups). Of the 5 groups, 4 were the test groups and 1 was the control group. Each of the four test groups was administered with a different dose of hydroxyurea (100 mg/kg, 200 mg/kg, 400 mg/kg, and 600 mg/kg) by intraperitoneal injection, respectively. The control group was administered with phosphatebuffered solution 2 ml/kg. All rats were killed 12 hours after dosing. In the timeeffect study, 20 male Wistar rats were divided into 4 groups（5 rats in each groups）. Of the 4 groups, 3 were the test groups and 1 was the blank control group. The three test groups were administered with hydroxyurea 400 mg/kg by intraperitoneal injection. All rats were killed 6, 12, and 24 hours after dosing. The dead rats and their testes were weighed. The testes were fixed in Bouin's solution and then stained with hematoxylineosin. Morphological changes were observed under light microscope. The TUNEL staining of apoptotic cells and PAS staining for glycogen were performed. The number of apoptotic cells was counted and the stages of seminiferous epithelial cycle were analysed. Results: There were no significant changes in weights of body and testis 6, 12, and 24 hours after dosing compared with before dosing. The results of the doseeffect study showed the rates of apoptoticpositive seminiferous tubule and apoptotic index were markedly elevated with the increase in doses, especially in 400 mg/kg \[(38.7±2.0)% and (496.4±66.8), respectively\] (P＜0.01). The results of the timeeffect study showed the mean number of apoptoticpositive spermatogenic cell and apoptotic index reached a peak at 12 hours after dosing \[(12.9±2.10) and (496.4±66.8), respectively\] compared with the control group. TUNELpositive cells were mainly in stage Ⅰ～Ⅳ of seminiferous cycle. Conclusion: The spermatogenic cell apoptosis of rats induced by hydroxyurea is cell-specific and stage-specific.

A 72-year-old female patient received intravenous injection of furosemide injection and oral metoprolol succinate sustained-release tablets, furosemide tablets, spironolactone tablets, digoxin tablets, and isosorbide mononitrate sustained release tablets for heart failure. Continuous intravenous pumping of levosimendan 12.5-mg dissolved in 0.9% sodium chloride 45-ml at a speed of 1.5-ml/h was additionally given because of her unimproved symptoms of heart failure. After 20-hours of intravenous pumping, the patient developed unconsciousness, no response to voice stimuli, and bilateral mydriasis suddenly. The electrocardiogram monitoring showed heart rate 200 beats per minute, prolonged QT interval, and QTc period 520-ms. The laboratory tests showed serum potassium 3.02-mmol/L. She was diagnosis as Torsades de Pointes and Aspen syndrome, which were considered to be related with levosimendan. Levosimendan was stopped immediately. The treatments such as closed-chest cardiac massage, electric defibrillation, and potassium supplementation were given. Four days later, the reexamining results showed her serum potassium 4.60 mmol/L, heart rate 80 beats per minute, and QTc period 450-ms.

Selective cyclooxygenase-2 (COX-2) inhibitors are a new type of non-steroidal anti-inflammatory drugs (NSAIDs), which are used in treatment of rheumatoid arthritis and osteoarthritis. Selective COX-2 inhibitors are divided into relatively selective COX-2 inhibitors ( meloxicam, nimesulide and diclofenac acid, and others) and highly selective COX-2 inhibitors( celecoxib, rofecoxib, valdecoxib, etoricoxib，and other). The inhibitory effect of the former against COX-2 is significantly stronger than that against COX-1, but also partially inhibits COX-1 at the same time, while the latter only has strong inhibitory effect on COX-2 inhibitor. The main adverse reactions of selective COX-2 inhibitors are gastrointestinal ulcers, perforation or bleeding, damage to renal function, coagulation disorders and thrombosis. The factors associated with the mechanisms are as follows: the COX-2 inhibitors inhibit both COX-1 and COX-2 at the same time and weaken the protective effects on the gastrointestinal mucosa; the COX-2 inhibitors decrease glomerular filtration rate and increase retention of sodium and potassium; the COX-2 inhibitors inhibit CYP2C9’s activity and decrease warfarin’s metabolic rate; the COX-2 inhibitors affect the balance between thromboxane A2 (TxA2) and prostaglandin I2 (PGI2). Proton pump inhibitors should be taken with the selective COX-2 inhibitors in order to decrease the incidence of gastrointestinal adverse reactions. For the patients with hypertension or sodium retention tendencies, plasma concentration and renal function should be monitored regularly, dose of antihypertensive drugs should be adjusted and coadministration of multiple NSAIDs at the same time should be avoided. Selective COX-2 inhibitors in combination with low-dose aspirin may prevent and cure cardiovascular adverse reactions. If adverse reactions induced by selective COX-2 inhibitors are confirmed, the drug should be discontinued and the symptomatic treatment should be given.

辛伐他汀为临床较常用的降血脂药,为了解其不良反应,向临床安全用药提供参考,我们搜集国内外有关辛伐他汀不良反应的文献,进行归纳分析。辛伐他汀的主要不良反应有横纹肌溶解、记忆丧失、狼疮样综合征、急性胰腺炎、血小板减少性紫癜、勃起功能障碍、肝损害、多尿等,临床应用时应予以重视。

Pharmaceutical packaging materials refer to packaging materials and containers which come into direct contact with medicines. Present major pharmaceutical packaging materials include the following four categories: glass, rubber, plastic, and metal materials. Pharmaceutical packaging materials might interact with the medicines which are packed. Some pharmaceutical packaging materials could absorb the active ingredient in medicines, thus decreasing their curative effects, and some may release hazardous substances, thus harming the body tissues. Therefore, quality control of pharmaceutical packaging materials should be strengthened; appropriate pharmaceutical packaging materials should be selected according to characteristics of medicines; and attention should be paid to drug safety problems associated with pharmaceutical packaging materials.

Objective: To observe the efficacy and adverse reactions of Shenqifuzheng injection used in patients with breast cancer while receiving neoadjuvant chemotherapy. Methods: Clinical deta of 126 patients with local advanced breast cancer while receiving neoadjuvant chemtherapy was collected from January, 2000 to December, 2005. The 126 patients were divided randomizely into two groups: control group (61 cases) and study group (65 cases). The patients in the control group were administered with CEF regimen (CTX 500 mg/m2, d1, 8; EPI 50 mg/m2, d1, 8; 5-Fu 500 mg/m2, d1, 8). The patients in the study group were treated with CEF regimen plus Shenqifuzheng injection (intravenous infusion of 250 ml, once daily). The cycle of chemotherapy was 28 d, and total two cycles were performed for the two groups. The efficacy, the changes of T lymphocyte and NK cells, and the adverse reactions to neoadjuvant chemotherapy in the two groups were observed before and after the treatment. Results: The overall …更多effective rate of the study group and control group were 69.2% (45/65) and 49.2% (30/61) respectively, and the difference was statistically significant between the two groups (P<0.05). The T lymphocyte subsets and NK cells in the study group were elevated in varying degree in comparison with those in the control group, and the differences were significant (P<0.05). The common adverse reactions of the two groups were myelosuppression and gastrointestinal reactions, but the severity of the reactions of the study group were relative mild than that of the control group. Conclusion: Shenqifuzheng injection can elevate immune function of patients with advanced breast cancer while receiving neoadjuvant chemotherapy. It can also enhance the efficacy and decrease the adverse reactions to neoadjuvant chemotherapy

众所周知,在药物发展史上曾发生过多起重大药害事件,如磺胺酏剂(含二甘醇)事件、反应停事件等,造成成百上千患者死亡。回顾这些惨痛的药害事件,从中吸取教训,无疑有助于避免或减少这类事件的发生或重演,保障患者安全。为此,本刊特开辟“药害史”栏目,欢迎广大读者、作者向本栏目踊跃投稿。

对于是否需要补钙、如何补钙以及其安全性如何尚存在较大争议。2006年2月16日美国《新英格兰医学杂志》刊登了“补钙加维生素D与骨折危险”的研究报告,对如何补钙问题又给人们带来新的困扰。作者根据国内外资料和个人的研究,对补钙争议的相关问题提出一些看法,旨在探讨如何安全有效地补钙。

近年来,国内外有关药物引起急性胰腺炎的报道有所增加。本文介绍引起或有可能引起急性胰腺炎的药物,并对其发病机制、诊断和防治进行探讨,旨在引起对药物性胰腺炎的关注,以降低其发生率。

A 15-year-old girl received IV dexamethasone(dosage not stated)for a fever(T 38.4 ℃)2 days after the occurrence of eruption.The next day,her skin rash aggravated and she developed hemorrhagic herpes accompanied by lumbago.The third day,she developed headache,nausea,and vomiting.Laboratory tests revealed the results as follows:WBC 19.65×10⁹/L,RBC 3.65×10¹²/L,Hb 123 g/L,PLT 46×10⁹/L,ALT 4 247 U/L,AST 4 719 U/L,LDH 1 209 U/L,and CK 612 U/L.After hospitalization,the patient presented with trance,tenderness over the abdomen,percussion pain in the both renal region.Her heart rate was 130 beats/min and blood pressure was 86/60 mmHg.Laboratory tests showed the following values:WBC 17.4×10⁹/L,L 0.32,RBC 2.56×10¹²/L,Hb 93 g/L,PLT 27×10⁹/L,urine occult blood(+),PO2 11.76 mmHg,and PCO₂ 2.5 mmHg.She had a history of contacting closely with the patient with varicella within 2 weeks.She was diagnosed as varicella,varicella encephalitis,multiorgan injury,infective shock,disseminated intravascular coagulation,and metabolic acidosis.The patient was given treatments with elevation of blood pressure,blood volume expansion,hemostasis,correction of acidosis,anti-infection.But she developed haematemesis,continuous bleeding from oral and nasal cavity,anuria,blood pressure reduction,and deep coma.She died 12 hours after hospitalization.

A 41-year-old woman with adhesive ileus underwent terminal ileum resection. The woman was given intravenous injection of hemocoagulase 1 KU dissolved in 20 ml of sodium chloride 0.9% after surgery, once every two hours for three times. No adverse reactions occurred after receiving the first and second dose of the medication. However, during the third infusion, the patient abruptly developed unconsciousness, sighing respiration, cyanosis of lips, pale face, bilateral mydriasis, and cardiac arrest. The infusion was stopped immediately. She underwent closed-chest cardiac message and oxygen with assisted mask ventilation. Lidocaine, adrenaline, and atropine were given intravenously. Thirty minutes later, her heart beat and respiration recovered.

A 23-year-old woman with depression successively received fluoxetine, venlafaxine, amfebutamone and amantadine without adverse reactions. Subsequently duloxetine 60 mg was added to the regimen of amfebutamone 225 mg/d and amantadine 0.2 g/d, which was given in the morning. Two to three days later, the woman presented with redness and swelling on the dorsum of her feet without pain; her renal function and rheumatoid factor examinations were normal. Treatment with IV cefalexin was ineffective. Duloxetine was withdrawn after fourteen days of administration. Amfebutamone and amantadine were continued. The redness and swelling on the dorsum of her feet subsided 3-5 days later.

A 63yearold woman with a 4month history of diabetes took glipizide and acarbose without adverse reactions occurring. Later, the woman received oral famciclovir 0.25 g thrice daily for herpes simplex. Two hours after the first administration, she experienced dizziness, nausea, vomiting, abdominal pain, and diarrhea. Intestinal infection was excluded by stool examination. Famciclovir was withdrawn and switched to an IV infusion of aciclovir 0.5 g once daily. Glipizide and acarbose were continued. Meanwhile, fluid replacement and symptomatic therapy were given. The following day, her dizziness and gastrointestinal symptoms disappeared completely. The patient continuously received IV infusion of aciclovir for four days. Her herpes simplex was entirely crusted and she was fully cured and discharged.

Objective : To investigate adverse reactions in SARS patients treated with glucocorticoids. Method:Clinical data of460cases with SARS in Xuanwu Hospital and China-Japa n Friendship Hospital were retrospectively analysed using SPSS statistical softw are.Results:344of460cases were under glucocorticoids therapy(GT),resu lting in decreased serum potassium(17.2%)and serum calcium(32.0%) ,increased blood sugar(30.5%),psychogeny(20.1%),bacterial infec tion(53.5%),mycotic infection(14.8%),and liver impairment (60 .2%).The incidence of adverse reactions were much higher in GT group of≥3 20mg daily than group of<320mg daily,and in GT group than in non-GT gr oup.Conclusion:Glucocorti-coids should only be used with great caution in SAR S patients,that is,paying more attention to existing indications and fol-lowi ng adverse effects,taking the drug doses as low as possible,and high doses may be only used for life-threatening case.

Objective: To investigate the characteristics and causative factors of tiopronin-induced anaphylatic shock for its rational use in clinic. Methods: Domestic medicine periodicals were searched between January 2000 and June 2005, and 38 cases with tiopronin-induced anaphylatic shock were analysed. Results: Routine dosages of tiopronin were administered by intravenous infusion in all cases. 86.84% of the cases developed anaphylactic shock within 30 minutes after administration, more male than female(P<0.01). Clinical symptoms of anaphylactic shock were mainly repid decrease in blood pressure, chest distress, dyspnea and chill. Allergic reactions of skin were uncommon. 97.37% of the cases(37/38) were recovered after treatment, and most cases(81.85%, 31/38)improved within one hour. Conclusion: Physicians should attach importantce to the rational use of tiopronin in clinical practice.

Objective;To evaluate the side-effects induced by clindamycin and its safety in clinical practice. Method:According to organ/system types recommended by WHO, the adverse reactions of clindamycin in 248 cases were classified. Results; 15 organs/systems were involved and the commonest ADRs were damages of skin and its appendages, digestive system, central and peripheral nervous system. Conclusion; Clindamycin should be used with caution in patients with a history of hypersensitivity. There is a potential danger of significant diarrhoea, hematuria and respiratory depression mainly because of drug interactions.

A 44yearold woman was hospitalized after she had undergone left oviducal adenocarcinoma surgery and received the fifteenth chemotherapy. On day 2 after admission, the patient was infused with paclitaxel 180 mg intravenously, and no adverse reactions occurred. On day 3, the woman was infused with cisplatin 100 mg intravenously. After about 5 minutes of infusion, she developed palpitation, nausea, chest distress, hidrosis, and disturbance of consciousness. Her blood pressure decreased from 116/74 mmHg to 74/43 mmHg. Anaphylactic shock was diagnosed. Cisplatin was discontinued immediately, and her symptoms resolved after antianaphylactic and symptomatic treatment.

ObjectiveTo evaluate the efficacy and safety of human serum albumin in treatment of patients with ascites due to cirrhosis.MethodsCochrane Library, PubMed, EMBase, Web of Science, CBM, CNKI, VIP, Wanfang Database were searched by using keywords “ascites”, “albumin”, “cirrhosis” and “randomized controlled trials”. The full text papers of randomized controlled trials (RCT) about human albumin treatment in patients with ascites due to cirrhosis were collected. The articles were selected and evaluated according to the inclusion criteria. The related information was statistically analyzed with RevMan 5.2 software, the relative risk (RR) and 95% confidence intervals (CI) were calculated. The patients in experimental group received IV infusion of human serum albumin. The patients in control group received isotonic 0.9% sodium chloride injection or artificial colloid (such as hetastarch, dextran, polygeline etc.) or no drugs. The efficacy and safety were compared between the 2 groups.ResultsA total of 688 related articles were searched and 13 RCT were enrolled into the study finally. There were 11 articles in English and 2 in Chinese. A total of 1 152 patients were entered in the study. The results of Meta-analysis showed that the incidence of hyponatremia in the experimental group (7.67%) was lower than that in the control group (14.66%), the difference was statistically significant(RR=0.60，95%CI：0.41～0.88, P=0.008). The differences of the ascites regression rates (91.67% vs. 88.44%), the incidences of renal injury (5.12% vs. 6.93%), the incidences of infection (5.04% vs. 4.93%), the incidences of hepatic encephalopathy (5.90% vs. 5.00%), the incidences of hemorrhage of digestive tract (2.57% vs. 2.73%), the incidences of hyperpotassemia (1.09% vs. 6.45%), the rehospitalization rates (52.15% vs.61.82%), the rehospitalization rates due to ascites (38.68% vs. 41.85%), the hospital mortality (3.80% vs. 4.54%), and the total mortality rates (21.40% vs. 24.83%) between the experimental group and the control group were not statistically significant ( all P >0.05). The difference of incidence of adverse reactions between the experimental group and the control group (3.13% vs. 3.05%) was not statistically significant (P=097).ConclusionThe present study can not demonstrate the obvious differences in curative effect and safety between the therapies of IV infusion of human serum albumin and artifical colloid or chloride in treatment of patients with ascites due to cirrhosis.

The meta-analysis results of the efficacy and safety of ribavirin were reviewed. In comparing to interferon mono-therapy,the combined therapy of interferon and ribavirin had higher efficacy and higher incidence of adverse reactions in treatment of chronic hepatitis C. The efficacy of ribavirin for treating infant respiratory syncytial virus infections was not sufficiently proved,so it is necessary to conduct a larger randomized controlled trials for ribavirin.

Vaccines have made great contributions to the prevention of infectious diseases, but vaccine hesitancy is widespread in the world. The reasons for vaccine hesitancy are complex, but the main reasons are the lack of public awareness of vaccine-preventable diseases and the lack of confidence in vaccine effectiveness and safety. In the context of the continuous spread of the coronavirus disease 2019 (COVID-19) epidemic, boosting public confidence and ensuring the orderly development of the vaccination work of COVID-19 vaccines and conventional vaccines are necessary to curb the resurgence of the COVID-19 epidemic and prevent the outbreak of various infectious diseases in China. Under the current situation, the main measures to deal with vaccine hesitancy are to play the role of health care institutions, improve public health literacy, normalize the public opinion orientation of the media platform, strengthen the supervision of vaccine clinical research and production, and do a good job in surveillance and compensation for adverse events following immunization.

A 41-year-old female patient received long-term treatment with metformin, glimepiride, sitagliptin, and acarbose for type 2 diabetes mellitus. Due to elevated blood-glucose, the hypoglycemic regimen was adjusted to metformin, acarbose, and dulaglutide (1.5-mg, subcutaneously injected once a week). After each injection of dulaglutide, the patient had severe anorexia but no intervention was given because that the patient could tolerate. Empagliflozin 10-mg orally once daily were added 3 days after the first injection and then the dose was adjusted to 10-mg next day. The day after the fourth injection, the patient developed dizziness, nausea, vomiting, general fatigue, etc. Laboratory tests showed blood glucose 20-mmol/L, arterial blood pH 7.22, partial pressure of carbon dioxide 22.1-mmHg, bicarbonate concentration 8.8-mmol/L, standard bicarbonate 12-mmol/L, total carbon dioxide content 10-mmol/L, ketone body in urine (+++), and urine sugar (++++). Diabetic ketoacidosis was diagnosed. Considering that severe anorexia after the application of dulaglutide caused serious insufficient carbohydrate intake and then empagliflozin- induced diabetic ketoacidosis was stimulated, the 2 drugs were discontinued and symptomatic and supportive treatments were given. Five days later, laboratory tests showed post-lunch blood glucose 10.1-mmol/L, ketone body in urine (+), negative urine sugar, and urine pH 5.5. Empagliflozin 5-mg once daily was added and laboratory tests showed carbon dioxide binding capacity of the blood 23.2-mmol/L, urine ketones (+++), urine sugar (++++), and uric acidity 5.0 four days later. The patient insisted on leaving the hospital. After discharge, she was treated with recombinant insulin glargine, acarbose, and empagliflozin. At 1 month of follow-up, symptoms of diabetic ketoacidosis did not recur.

为了解别嘌醇的不良反应,检索《中国生物医学文献数椐库》1981～2002年间有关别嘌醇不良反应的文献进行分析。由别嘌醇引起不良反应的患者共151例,其中死亡22例(14.57%)。最常见的不良反应为皮疹,共132例(87.42%),其次是发热和肝肾损害。死亡率高,应引起注意。

A 68yearold woman with pulmonary tuberculosis was administered with IV rifamycin 0.5 g once daily, oral isoniazid 0.3 g once daily, and oral ethambutol 0.5 g thrice daily. Her routine blood tests were normal (WBC count 4.91×10⁹/L, neutrophils 0.729) before therapy. After 12 days of therapy, her WBC count and neutrophils decreased to 2.48×10⁹/ L and 0.557, respectively. Leucopenia and neutropenia were considered to be possibly rifamycinrelated. rifamycin was discontinued. Seven days later, the woman’s WBC count and neutrophils returned to within normal limits (4.41×10⁹/L and 0.622, respectively). IV rifamycin 0.5 g once daily was restarted. Seven days later, her WBC count and neutrophils decreased to 2.93×10⁹/L and 0.487, respectively. rifamycin was withdrawn again and switched to IV levofloxacin 0.2 g twice daily. Isoniazid and ethambutol were continued. Ten days later, her routine blood tests were normal.

 A small amount of commonly used and first-aid drugs stored in the inpatient wards can facilitate the temporary treatment of patients and save precious time for the treatment of critically ill patients. But there is a risk of medication errors in the link of drug storage in the inpatient wards. In order to strengthen the management of drug storage in the inpatient wards and reduce medication errors, experts in medicine, pharmacy, nursing, hospital management, and etc., were organized by Medication Safety Panel in China Core Group of International Network for the Rational Use of Drugs, Chinese Pharmacological Society Professional Committee of Drug-induced Diseases, and Adverse Drug Reactions Journal Agency, to formulate the guideline for prevention of medication errors in the link of drug storage in inpatient wards based on the Expert Consensus on Medication Error Management in China. The medication errors in the link of drug storage in the inpatient wards include improper storage of drugs, wrong drug specifications, wrong drug quantity, and wrong drug placement. The risk factors include management factors (unsound management system, no designated person or post management, or no regular inspections and supervision), process factors (no corresponding standard operation process, or only imperfect or unreasonable operation process), environmental factors (unqualified drug storage space and equipment, or no special labels), human factors (no training for personnel involved in drug use, or unreasonable staff arrangement), and drug factors (too many types and quantity of drugs in inpatient wards). The prevention strategies include technical strategies (enforcement and constraint management policies, implement of informatization and intelligence management, and formulation of standardized marks and processes, and establishment of standard catalog list and audit project list) and management strategies (establishment of management systems, provision of sufficient human resources, and enhancement of training).

本文对长效干扰素治疗慢性丙型肝炎中出现少见和严重的不良反应进行综合报道,包括少见的皮肤损害、严重的肺部损害和精神神经系统不良反应等,旨在提醒临床医生使用长效干扰素时应注意类似不良反应的发生,保证患者用药安全。

为加强奥卡西平临床应用的安全性,本文从该药的药代动力学和药效学两方面,进一步论述其产生不良反应和与其他药物相互作用的机制,供临床选用该药时参考。

Objective: To compared the antiviral effects and safety of entecavir with those of lamivudine. Methods: Thirty-three patients with no prior history of antiviral therapy were divided randomizely into two groups: entecavir group (16 cases), and lamivu- dine group (17 cases). The dosage in the entecavir group and lamivudine group was 0.5 mg/d and 100 mg/d, respectively, and the duration of therapy was 48～96 weeks. The effects of entecavir and lamivudin on HBV DNA, ALT, HBeAg/HBeAb seroconversion, and their adverse reactions were observed during the treatment. Results: The patients with undetectable serum levels of HBV DNA in the entecavir group were more than those in the lamivudine group, that is, 56.25% versus 29.41% on week 24, and 87.50% versus 29.41% on week 48 after treatment. There were no marked differences in the HBeAg negative conversion rate, HBeAg/HBeAb seroconverse rate, and the incidence of adverse reactions between the two groups. Conclusion: Entecavir is more effective in …更多inhibiting reproduction of HBV than that of lamivudine, and entecavir is similar to lamivudine in the incidence of adverse reactions;therefore, entecavir could be used for long-term treatment of the patients with chronic hepatitis B.

A 49-year-old male patient with type 2 diabetes mellitus and diabetic nephropathy received long term use of retaglinide thrice daily orally, 1-mg in the morning, 2-mg in the afternoon and 1-mg in the evening. Because of the sudden acute cerebral infarction, clopidogrel was added, on the 4th day of the medication, the fasting blood glucose in the patient decreased to 2.6-mmol/L. It was considered that the interaction of clopidogrel and repaglinide caused the increase of repaglinide plasma concentration, which resulted in severe hypoglycemia in the patient. Clinical pharmacist suggested stopping repaglinide and using insulin. The physician reduced the dosage of repaglinide to twice daily, 1-mg in the morning and 0.5-mg in the afternoon, and after 3 days the patient′s fasting blood glucose fluctuated between 4.0 and 4.5-mmol/L. Since the patient had diabetes nephropathy and renal insufficiency, which might increase the risk of hypoglycemia, repaglinide was stopped, and insulin glutamine 3 U was injected subcutaneously before meals, at the same time blood glucose was closely monitored. Fasting blood glucose fluctuated between 4.9 and 5.4-mmol/L after insulin treatment.

Sodium nitroprusside is a rapid and short-acting vasodilator.It is used in the treatment of hypertensive crises and severe heart failure.Sodium nitroprusside is rapidly metabolized into cyanide,which is further metabolized to thiocyanate.Therefore,cyanide poisoning or thiocyanate intoxication from their accumulation may occur with high-doses,prolonged administration of sodium nitroprusside.Should the patients develop metabolic acidosis,central nervous system depression,and cardiovascular instability that may consider cyanide poisoning or thiocyanate intoxication,and sodium nitroprusside should be stopped immediately.The patients should be given systematic therapy and antidote.The common antidotes are sodium nitrite,methylthioninium chloride,sodium thiosulfate,and hydroxocobalamin.The thiocyanate concentrations should be monitored if treatment continues for over than 3 days,and cyanide concentrations should also be monitored.Cyanide toxicity from sodium nitroprusside may be prevented by concomitant administration of sodium thiosulfate.The patient with renal impairment may use fenoldopam to replace sodium nitroprusside.

42year-old man with pustular psoriasis was treated with acitretin capsules 30 mg once daily. His routine blood test was basically normal before therapy. He had a RBC count of 3.65×10¹²/L, a WBC count of 9.5×10⁹/L, and a PLT count of 246×10⁹/L. One week after administration, his RBC was 3.67×10¹²/L, his WBC was 16.5×10⁹/L, and his PLT was 412×10⁹/L, respectively. Pathological examination showed thrombocytosis and bone marrow hyperplasia. An ultrasound examination showed splenomegaly. The dosage of acitretin was reduced to 15 mg/day. Three weeks later, a reexamination revealed a RBC count of 3.72×10¹²/L, a WBC count of 14.3×10⁹/L, and a PLT count of 446×10⁹/L. The dosage of acitretin was continuously reduced to 10 mg/day. Two weeks later, a reexamination revealed a RBC count of 3.48×10¹²/L, a WBC count of 10.3×10⁹/L, and a PLT count of 385×10⁹/L. No abnormal abdominal findings were observed on ultrasound examination.

本文对近年国内外发生的草药药害事件、草药不良反应的相关报道以及各国管理部门对此采取的相关措施进行了综合介绍。提出应切实加强对中药安全用药知识的宣传普及和不良反应的监测;规范中成药的说明书;做好中药质量的规范化、标准化工作。另外,应注意合理应用中成药,避免因其不正确应用或滥用而出现危害,影响中医药在国际上的声誉。

A 17-year-old man was given hydroxyethyl starch 130/0.4 sodium chloride injection 500 ml by intravenous infusion at a rate of 300 ml an hour after the operation for abdominal incised wound.About 20 minutes after the initiation of infusion,the patient developed restlessness,urticaria on the nape of his neck and his chest.After antianaphylaxis therapy,his urticaria disappeared.

Objective:To discuss clinical features and risk factors of statin-induced myopathy.Methods:The clinical symptoms and the changes in serum creatine kinase(CK) concentrations and renal function in 7 patients with statin-induced myopathy from January 2004 to December 2006 were investigated retrospectively.Results:Seven male patients aged 16～71 [average age(49±19) years] were included,and three of them were over 60 years old.Of the 7 patients,3 patients were treated with a statin alone as follows:atorvastatin 10 mg daily;atorvastatin 20 mg daily;simvastatin 20 mg daily.And 4 patients received combination therapy with a statin and fenofibrate or vitamin E nicotinate as follows:atorvastatin 10 mg daily plus fenofibrate 200 mg daily;pravastatin 20 mg daily plus fenofibrate 200 mg daily;simvastatin 20 mg daily plus vitamin E nicotinate 0.2 g three times daily;atorvastatin 20 mg daily plus vitamin E nicotinate 0.2 g three times daily.The time of onset of markedly elevated serum CK concentrations(377～910 U/L)) in the 7 patients was 5 days to 26 months after treatment with statins.In addition,muscle pain occurred in 1 patient,muscle weakness occurred in 4 patients,and elevated SCr and BUN levels occurred in 1 patient,which were 340.6 μmol/L and 50.1 mmol/L respectively.Conclusion:Statins can cause myopathy,and its clinical presentations are muscle pain,muscle weakness,and elevated serum CK concentrations.Advanced age and combination therapy with a statin and fenofibrate or vitamin E nicotinate may increase the risk of myopathy.

Objective:To observe the influence of chronic oxaliplatin neurotoxicity on Nissl bodies and substance P in dorsal root ganglion in rats.Methods:Thirty Wistar rats were randomly divided into two groups:oxaliplatin group and control group.The rats in the oxaliplatin group were given oxaliplatin 4 mg/kg twice weekly by intraperitoneal injection for 9 times altogether.The rats in the control group were given the same volume of 5% glucose.50% paw withdrawal threshold(50% PWT)was measured 2 hours after each injection.The L5 dorsal root ganglion was sliced and stained 24 hours after the last injection.The morphology of dorsal root ganglion neurons,and the morphology and integrating optical density of Nissl bodies and substance P were observed.Results:50% PWT of rats in the oxaliplatin group decreased significantly after the third injection than that in the control group(P<0.01).Neuropathological examination showed,in comparison to the control group,the area of cyton,nucleus,and nucleolus In dorsal root ganglion diminished(P<0.05,P<0.01),the proportions of decentered nucleus and polynucleolus increased(P<0.01),the integrating optical density of Nissl bodies and substance P decreased(P<0.05,P<0.01).Conclusion:The peripheral neuropathy caused by oxaliplatin is related to the changes in Nissl bodies and substance P in dorsal root ganglion neuron.

ObjectiveTo detect adverse drug reaction (ADR) signals using data mining algorithm and explore its application value.MethodsReports on adverse reactions induced by anti-infective drugs in National centor for ADR monitoring from January 2009 to December 2013 were collected and potential ADR risk signals were detected using proportional reporting ratio method (PRR), reporting odds ratio method (ROR), Medicines and Healthcare Products Regulatory Agency method (MHRA), Bayesian confidence propagation neural network method (BCPNN), and multi-item gamma Poisson shrinker method (MGPS). The results of detection using the above-mentioned 5 signal detection methods were compared.ResultsA total of 35 807 ADR reports induced by anti-infective drugs were collected, 35 759 effective reports were entered, and 834 suspected drugs were involved. In the 35 759 reports, 464 kinds of ADR were defined according to lowest level term and 21 kinds of ADR were defined according to system/organ classification. After the data cleaning, splitting, and encoding process, 6 620 reports containing suspected drug-adverse reaction combination were acquired. There were 3 966 reports (59.91%) in which suspected drug-adverse reaction combination appeared once, 937 reports (14.15%)  in which suspected drug-adverse reaction combination appeared twice, and 1 717  reports (25.94%) in which suspicious drug-adverse reaction combination appeared more than thrice. The number of ADR signals detected using PRR, ROR, MGPS, BCPNN, and MHRA was 651, 614, 306, 75, and 57, respectively; the categories of drugs were 194, 168, 124, 34 and 40, respectively; ADR types were 139, 139, 121, 35, and 40,  respectively. In the top ten risk signals, azithromycin-nausea were detected by the 5 signal detection methods, levofloxacin-pruritus were detected by PRR, ROR, MHRA, and BCPNN. The top ten signals detected by PRR were totally same as those by ROR and signals detected by other methods were various.ConclusionsPotential risk signals in ADR reports could be detected systematically and automatically using PRR, ROR, MGPS, BCPNN, and MHRA. However, each method has its own advantage and disadvantage and should be applied according to the actual situation and demand.

呼吸系统疾病是临床中常见的疾病之一,其中因药物导致的肺部疾病已逐渐引起人们的重视。药源性肺部疾病是药物不良反应的一种,具有涉及的药物范围广、疾病的种类多、发病机制复杂、起病方式差异大等特点。本文综述了可导致药物性肺炎、肺纤维化、哮喘、肺水肿、肺栓塞、肺出血、肺癌、肺动脉高压、肺血管炎等疾病的药物及可能的致病机制。提示药源性肺部疾病在其诊断、治疗、预后及其潜在的用药危险因素等方面均应引起医师足够的重视。呼吸系统疾病是临床中常见的疾病之一,其中因药物导致的肺部疾病已逐渐引起人们的重视。药源性肺部疾病是药物不良反应的一种,具有涉及的药物范围广、疾病的种类多、发病机制复杂、起病方式差异大等特点。本文综述了可导致药物性肺炎、肺纤维化、哮喘、肺水肿、肺栓塞、肺出血、肺癌、肺动脉高压、肺血管炎等疾病的药物及可能的致病机制。提示药源性肺部疾病在其诊断、治疗、预后及其潜在的用药危险因素等方面均应引起医师足够的重视。

Objective: To investigate the factors of adverse reactions induced by fat emulsion injection. Methods: 25 reports of adverse raactions due to fat emulsion injection at our hospital in 2003 were retrospectively analysed. Results: Fever was the main clinical manifestation. The reactions were related to age of patients and concentration of the drug but not related to gender of patients. Conclusion: Health professionals should pay attention to the use of fat emulsion so as to reduce the occurrence of adverse effects.

The common atypical antipsychotics are aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone. Sex differences are presented in the pharmacokinetics and adverse reactions of atypical antipsychotics. Because of the lower CYP1A2 activity in women, the plasma clozapine and olanzapine concentrations are higher in women than in men. Risperidone causes hyperprolactinaemia in women, which lead to higher incidence rates of osteoporosis and sexual dysfunction in women than in men. Studies suggest that the incidence rate of metabolic syndrome is higher in women than in men: the incidence rates of obesity, hypertension, hypertriglyceridemia and decreased HDL level in women and men are 76.3% vs 35.5%, 46.9% vs 47.2%, 42.2% vs 50.7%, 48.9% vs 63.3%, respectively; the incidence rates of hyperglycemia [≥100 mg/dl(5.55 mmol/L) and ≥110 mg/dl(6.10 mmol/L)] in women and in men are 30.0% vs 21.7% and 24.2% vs 14.1%, respectively. The incidence rates of prolonged QTc interval and extrapyramidal symptoms of atypical antipsychotics are higher in women than in men. Some atypical antipsychotics have adverse effects to the fetus.

Objective: To analyze the effects of mannitol on the plasma osmolality and outcome in patients with brain injury. Methods: According to the plasma osmolality measured on admission and within two weeks after admission, the patients were divided into two groups: hyperosmolality group and hyposmolality group. Risk factors and outcome of short-term (30 days)were analyzed between the two groups. Results: Three hundred and six patients with bran injury were administered with mannitol used for dehydration and reduction of intracranial pressure. Of 90 patients with disturbance of plasma osmolality on admission, 72 had hyperosmolality and 18 had mild hyporsmolality. Of 216 patients with normal plasma osmolality on admission, 46 developed hyperosmolality and 6 occured mild hyposmolality within 2 weeks during the treatment of manmitol used for dehydration and reduction of intracranial pressure, and the rest maintained normal plasma osmolality. Single factor analysis showed that moderate or severe brain injury (GCS≤12), diabetes mellitus, nephropathy, and high dose of mannitol were significantly associated with plasma hyperosmolality. Multiple factor analysis showed, that, with the exception of nephropathy, risk of hyperosmolality to patients with moderate and severe brain injury was 2.6 times as high as those with mild brain injury, to diabetic patients was 2.2 times as high as the nondiabetic ones, to patients receiving mannitol > 100 g daily was 1.8 times as high as those receiving mannitol ≤100 g daily and to patients receiving > 1000 g total dose of mannitol was 2.6 times as high as those receiving ≤1000 g total dose of mannitol. The survival rate of 30 days in patients with plasma hyperosmolality (39.0%) was lower than that in patients without plasma hyperosmolatity (68.9%), and the difference was statistically significant (P<0.05). Conclusion: High daily dose or cumulative dose of mannitol could induce or aggravate the changes of plasma osmolality, and affect the survival rate of short-term in patients with brain injury.

目的:探讨丁卡因表面麻醉所致全身不良反应的病因、预防和处理方法。方法:回顾性总结11例不良反应者的临床表现、处理措施和预后,提出合理的防治方法。结果:11例不良反应者通过应急措施(吸氧、静脉输液、肌注和静注地塞米松等),全部抢救成功,无1例发生意外。结论:丁卡因不良反应发生与用药过量,患者对药物低耐量以及患者精神紧张有关,严格控制药物用量,适当应用镇静药和在丁卡因溶液中加入适量的肾上腺素等措施可以预防不良反应的发生。

本文重点介绍了抗感染药物静脉滴注速度过快所致的不良反应,并就其不良反应发生的机制及防治方法进行探讨。旨在引起临床重视给药速度对患者用药安全性和有效性的影响,以减少不良反应的发生。

A 45-year-old male patient underwent craniotomy and biopsy for intracranial lesions. In order to prevent epilepsy, sodium valproate 800-mg dissolved in 0.9% sodium chloride injection 8-ml was injected intravenously after operation, and then the sodium valproate solution of this concentration was continuously pumped at a speed of 0.6-ml/h. One hour after administration, the serum lactate level of the patient increased gradually, reaching the highest level of 14.7-mmol/L, accompanied by metabolic acidosis and compensatory respiratory alkalosis, and with the lowest pH of 7.09 and the lowest base excess of -26.3. The patient fell into a coma. The hyperlactatemia and metabolic acidosis were considered to be related to sodium valproate. Sodium valproate was stopped, intravenous infusion of 5% sodium bicarbonate injection and blood purification were given at the same time. After 3 days, the lactate level of the patient returned to normal, metabolic acidosis was basically corrected, and his mind was clear.

Objective: To investigate the clinical characteristics of hematological adverse reactions induced by cinepazide in order to prevent their development. Methods: Cinepazide, adverse reaction, leucopenia, agranulocytosis, and thrombocytopenia were selected as the searchwords and PubMed(1948-2010),EMBASE (1966-2010), CBM(1978-2010), CNKI(1979-2010), VIP(1979-2010),WANFANG DATA(1989－2010) as well as Adverse Drug Reaction Monitoring Network of Beijing were searched. The literatures and the case reports of hematological adverse reactions induced by cinepazide were collected. The data were analyzed retrospectively, including characteristics of patients, drug use, as well as types, onset time, clinical manifestations, treatment and prognosis to adverse reaction. Results: A total of 14 clinical research papers and the adverse drug reaction reports were selected , 16 patients were enrolled in this study. They comprised 8 men and 8 women with average age of (73.0±11.9) years. The primary diseases were cerebral infarction (9 cases), cerebral hemorrhage (3 cases), peripheral arterial embolism (3 cases) and vertebrobasilar arterial insufficiency (1 case). Dosages of cinepazide were 160 mg/d (2 cases), 240 mg/d (2 cases), 320 mg/d (8 cases), 600mg/d (1 case) and 1 200 mg/d (3 cases), respectively. The onset time to adverse reaction induced by cinepazide was within 5 days (7 cases), 6 to 10 days (3 cases), 11 to 15 days (1 case) and more than 15 days (5 cases) after treatment, respectively. The initial symptom of adverse reactions in most patients was fever. There were 10 patients with leucopenia, 4 with agranulocytosis, 1 with thrombocytopenia and 1 with both leucopenia and thrombocytopenia，in total of 16 patients. Fifteen patients received the drug discontinuation and symptomatic treatment, 14 patients improved and 1 died. Another patient’s drug was not withdrawn. Conclusion: Cinepazide is liable to decrease leckocyte, franulocyte, and platelet. Clinical cinepazide use should be followed by a careful hematological monitoring.

ObjectiveTo explore the effect of combination of telbivudine (LdT) and adefovir dipivoxil (ADV) on renal function in patients with chronic hepatitis B (CHB).MethodsThe CHB patients with renal injury due to lamivudine (LAM) resistance and combination with ADV, who visited in First Affiliated Hospital of Zhejiang Chinese Medical University were enrolled into this study. The randomized controlled trial was performed in this study. The patients were divided into two groups by table of random number: the LAM+ADV group (original treatment was continued) and the LdT+ADV group (LAM was replaced with LdT). The levels of HBV DNA, alanine aminotransferase (ALT), serum creatinine (Scr), estimated glomerular filtration rate (eGFR), urinary beta 2-microspheres (Uβ2-MG), and serum creatine kinase (sCK) were compared between the 2 groups at baseline, 24 and 48 weeks of treatments.ResultsA total of 79 patients were enrolled into the study. There were 41 patients in the LAM+ADV group and 38 in the LdT+ADV group. The differences of sex distribution, age, body weight and the basal level between the 2 groups were not statistically significant (all P>0.05). There were no HBV DNA breakthrough in patients during 48 weeks of treatment in both groups. The differences of ALT levels at different time points in patients in the 2 groups were not statistically significant (all P>0.05). In the LAM+ADV group, the Scr levels at 24 and 48 weeks of treatment were higher than those at baseline ［(117±11), (122±12) μmol/L vs. (113±12) μmol/L］. The difference between the baseline and 48 weeks of treatment was statistically significant (P＜0.05). The levels of Scr in the LdT+ADV group at 24 and 48 weeks of treatment were lower than those at baseline ［(104±10), (99±9) μmol/L vs. (109±10) μmol/L］ (all P<0.05). The levels of eGFR in the LAM+ADV group at 24 and 48 weeks of treatment were lower than those at baseline［(68.9±12.2), (66.1±7.6）ml·min-1·1.73 m-2 vs. (70.9±8.1) ml·min-1·1.73 m-2］. The difference between the baseline and 48 weeks of treatment was statistically significant (P<0.05). The levels of eGFR in the LdT+ADV group at 24 and 48 weeks of treatment were higher than those at baseline ［(75.1±11.4), (79.6±31.1) ml·min-1·1.73 m-2 vs. (71.4±10.6) ml·min-1·1.73 m-2］ (all P<0.05). The levels of Uβ2-MG in the group of LAM+ADV at 24 and 48 weeks of treatment were higher than those at baseline［4 611(23 920, 740), 4 719 (24 109, 967) μg/L vs. 4 601(23 807, 611) μg/L］. The difference between the baseline and 48 weeks of treatment was statistically significant (P＜0.05). The levels of Uβ2- MG in the LdT+ADV group at 24 and 48 weeks of treatment were lower than those at baseline ［3 251(12 890, 220), 1 950 (10 119, 73) μg/L vs. 4 109 (24 703, 633) μg/L］. The difference between the baseline and 48 weeks of treatment was statistically significant (P＜0.05). The difference of sCK levels between the baseline and 24 and 48 weeks of treatments［(99±31), (99±36), (96±37)］were not statistically significant (all P>0.05). The sCK levels in the LdT+ADV group at 24 and 48 weeks of treatments were higher than those at baseline［(107±38), (130±56) U/L vs. (97±31) U/L］. The difference between the baseline and 48 weeks of treatment was statistically significant (P＜0.05). The differences of Scr, eGFR, Uβ2-MG, and sCK levels at baseline and 48 weeks of treatment in the 2 groups were statistically significant (all P＜0.05).ConclusionsThe therapeutic regimen of telbivudine combination with adefovir dipivoxil can improve the renal function in patients with CHB. The change of sCK level should be monitor closely during the treatment.

A 1.5yearold boy was hospitalized with chill and fever after an IV infusion of ceftriaxone sodium 1.0 g for upper respiratory tract infection. On admission, he appeared listlessness and sallow. Routine blood tests revealed the following: Hb 92 g/L, RBC 4.21×10¹²/L, MCV 68.4 fl, PCV 0.288, and Ret 0.01. On day 2 after admission, he was given an IV infusion of ceftriaxone 10 g dissolved in 100 ml of glucose 5% again. Five hours later, he developed yellowish of the skin, and further 2 hours later, dark urine and temperature of 39 ℃ occurred. Laboratory testing showed the following: Hb 45 g/L, RBC 1.83×10¹²/L，PCV 0.12, Ret 0.03, and a positive direct Coombs test. Acute hemolytic anemia was diagnosed. Ceftriaxone sodium was stopped immediately. He was treated with IV dexamathasone, IV immunoglobulin, and a red cell transfusion. His symptoms were relieved, and laboratory testing showed the following: RBC 3.60×10¹²/L，Hb 91 g/L，PCV 0.289, and Ret 0.036.

Cases with liver damage induced by flutamide and bicalutamide were collected from MEDLINE of 1990-1999 and our hospital. The two drugs' adverse reactions of liver damage happened in some countries and their adoption of appropriate measures are presented in this paper. It is suggested that patients with severe liver damage should not take flutamide and bicalutamide and that individuals with poor liver function or hepatitis history take them cautiously while examined for LFT, once a month at least.

A 16-year-old female patient with acute T-cell leukemia was going to undergo allogeneic hematopoietic stem cell transplantation. Pretreatment chemotherapy was required before operation. In order to reduce the degree of adverse reactions during the chemotherapy, the patient received treatments with ondansetron, dexamethasone, and fosaprepitant dimeglumine. After intravenous injections of ondansetron 4-mg and dexamethasone 5-mg, fosaprepitant dimeglumine 150-mg dissolved in 0.9% sodium chloride injec- tion 150-ml was intravenously pumped at a speed of 300-ml/h. Five minutes later, the patient developed sweating, foreign body sensation in pharynx, dyspnea, periumbilical pain, and vomiting. Anaphylactic reaction caused by fosaprepitant dimeglumine was considered. The drug was stopped immediately and intravenous injection of dexamethasone 5-mg and oxygen inhalation were given. Twenty minutes later, her symptoms of dyspnea and abdominal pain were relieved. Fifty minutes later, the allergic symptoms disappeared.

A 78-year-old man with facial paralysis was given nifedipine,vitamin B1,cobamamide,sodium asscinate,and Xue-saitong injection after admission.And zolpidem at bedtime was given for his inability to sleep.During the 3 days of zolpidem treatment,in the first day,the patient fell asleep within 1 hour after ingestion of zolpidem 10 mg.And 3 hours later,the man got up,walked and talked with somebody while asleep.But he had no memory of that event subsequently.In the second day,the patient took zolpidem 5 mg,and no such behaviours occurred.In the third day,he developed the behaviours again 5 hours after ingestion of zolpidem 10 mg.After discontinuation of zolpidem,the behaviours did not recur.

In 2021, a total of 19-585 cases of medication error (ME) from 275-hospitals in 28 provincial administrative regions were collected in the National Monitoring Network for Clinical Safe Medication. The number of hospitals reporting ME increased by 7.84% compared with that in 2020 (255-hospitals), and the number of reported ME cases increased by 23.57% compared with that in 2020 (15-849 cases). In 19-585 cases of ME reports, 278 (1.42%) were classified as grade A, 16-221 (82.82%) as grade B, 2-442 (12.47%) as grade C, 410 (2.09%) as grade D, 95 (0.49%) as grade E, 133 (0.68%) as grade F, 1 (<0.01%) as grade G, 4 (0.02%) as grade H, and 1 (<0.01%) as grade I. Among the 19-307 patients with ME of grade B to I, 10-528 (54.53%) were male and 8-779 (45.47%) were female; they aged from 1 day to 102 years, of which 2-236 (11.58%) were children (<18 years old), 9-794 (50.73%) were young and middle-aged people (≥18 to <60 years old), and 7-277 (37.69%) were elderly people (≥60 years old). A total of 234 patients were involved in serious MEs (grade E-I), including 129 (55.13%) males and 105 (44.87%) females, aged from 3 months to 99 years, of which 45 (19.23%) were children, 88 (37.61%) were young and middle-aged people, 101 (43.16%) were elderly people. Among the 16 patients with severe MEs caused by mistaken use of drugs, 14 were children, which was a double of the number in 2020 (7 in 2020); only 3 cases were reported for mistaken use of drugs in children from 2012 to 2019. The 278 grade A MEs did not involve person who triggered the ME and place where ME occurred. Among the 19-307 grade B-I MEs, 13-932 (72.16%) were triggered by physicians, 3-961 (20.52%) by pharmacists, 541 (2.80%) by nurses, 412 (2.13%) by patients and their family members, and 461 (2.39%) by other persons; the proportion of MEs triggered by physicians and patients and their family members increased year by year for 4 consecutive years (60.89%, 65.46%, and 68.05% in 2018, 2019, and 2020 by physicians, and 1.06%, 2.04%, and 2.08% in 2018, 2019, and 2020 by patients and their family members, respectively); 8-662 MEs (44.87%) occurred in clinics, 5-256 (27.22%) in hospital wards, 3-856 (19.97%) in pharmacies, 977 (5.06%) in pharmacy intravenous admixture services, 289 (1.50%) in the nurse stations, 239 (1.24%) in patients′ houses, 6 (0.03%) in the community health service stations, and 22 (0.11%) in other places; the proportion of ME occurred in clinics and at home increased year by year for 4 consecutive years (37.32%, 37.74%, and 43.24% in 2018, 2019, and 2020 in clinics, and 0.41%, 0.89%, and 1.02% in 2018, 2019, and 2020 at home, respectively). The top 3 contents of ME were wrong dosage, wrong drug class, and wrong administration frequency. The top 3 persons who discovered the ME were pharmacists, patients and their family members, and physicians. The top 3 factors causing ME were lack of related pharmacologic knowledge, tiredness, and insufficient training of medical workers.

近年,卡马西平临床严重不良反应时有报道,本文通过检索1994年-2003年国内相关文献,就其主要报道进行归纳,并探讨在护理工作中,如何加强对卡马西平不良反应的防治。

合理用药已经是医药专业人员非常熟习的名词。但在国内论及该主题的文献中,介绍合理用药的实践经验和案例者比比皆是,而在理论的系统性和概念的完整性方面显得较为薄弱。笔者在参考大量中外相关文献的基础上,结合多年对该主题的教学心得,拟从理论研究的角度,给“合理用药”以明确的定义,解析用药合理化的评价指标,提炼合理用药概念的特点,阐述促进全社会合理用药的意义,并从药师在临床用药中作用和职责的渐变,划分合理用药在认识论上的发展过程。

Febuxostat is a new type of selective xanthine oxidase inhibitor, which mainly be used for the treatment of hyperuricemia patients with gout symptoms. The recommended initial dose of febuxostat is 40 mg once daily. In the present, there is no sufficient evidence to demonstrate that the clinical effects of febuxostat in reducing the uric acid are better than that of allopurinol. However, it is reported that febuxostat in 80 mg has better treatment effects in gout patients with diabetes or ≥ 65 years old. The common adverse reactions of febuxostat are liver dysfunction, diarrhea, headache, nausea, rash, and so on. The differences of adverse reactions in cardiovascular system between febuxostat and allopurinol are not statistically significant.

Objective: To investigate the clinical features and causes of liver damage related to Polygonum multiflorum and its preparations in order to provide the preventive measures. Methods:The Chinese Journal Fulltext Database, Chinese Biomedical Literature Database, and Chinese Scientific and Technical Periodicals Database were searched, and the case reports of Polygonum multiflorum and its preparationrelated liver damage published in domestic literature from 1996 to 2009 were collected. The baseline characteristics of the patients, the situation of drug use, the clinical features, prognosis, and outcome of the liver damage were analysed. Results:A total of 35 patients had liver damage related to Polygonum multiflorum and its preparations. They comprised 20 men and 15 women with average age of (362 ±13.7) years. Of them, 14 received Chinese patent medicine alone, 18 received herbal pieces alone, and 3 received both Chinese patent medicine and herbal pieces. Among the patients receiving herbal pieces, 6 received raw herbal pieces, 2 received processed herbal pieces, and the others were not stated. Of the 35 patients, 18 experienced liver damage again after drug readministration, 3 might have a familial tendency to develop this disorder. The time to liver damage onset after drug administration was as follows: the shortest was 3~6 days, the longest was > 3 months, and the most was 1~4 weeks. The main clinical presentations were jaundice and abnormal liver function. The case reports of having records of liver function tests were as follows: the ALT levels in 31 patients were 102~4 584 U/L, the average level was 1 153.1 U/L; the AST levels in 25 patients were 61.5~1 937 U/L, the average level was 657.4 U/L; the average TBil levels in 29 patients were 134.9 μmol/L; the average DBil levels in 23 patients were 97.9 μmol/L. The patients with mild symptoms spontaneously recovered after drug discontinuation. Most patients were cured after receiving liverprotective treatment. Of the 35 patients, 2 improved and 33 were cured. Conclusion:Both raw and processed Polygonum multiflorum and its preparations may induce liver damage. The patients’previous history and family history of Polygonum multiflorum use should be reviewed before drug administration, the correct dose should be chosen, and the patients’liver function should be monitored during polygonum multiflorum use.

A 74yearsold women was hospitalized with acute bacillary dysentery. The patient remained in shock despite treatment with antiinfectives, fluid supplement, fluid expansion, dopamine, and metaraminol. Subsequently, she received IV Shenfu 20 ml in 5% glucose 20 ml, and then an IV infusion of Shenfu 80 ml in 5% glucose 500 ml. Thirty minutes later, her blood pressure increased from 60/40 mm Hg to 90/60 mm Hg, but she presented with arrhythmia, and her atria premature beat frequency was 8～12/min. Shenfu injection was withdrawn and changed to an infusion of hydroxyethyl starch 500 ml. Thirty minutes later, her atrial premature beats disappeared.

钩吻是毒性极强的外用中药,应用不当或误服可致中毒,有时还可致命。主要毒性成分是钩吻碱,以钩吻素子含量最高。钩吻中毒主要抑制延髓呼吸中枢,并抑制脑和脊髓的运动中枢。临床表现以呼吸系统、神经系统症状为主,可出现呼吸衰竭和呼吸肌麻痹,是钩吻中毒最常见的死因。目前尚无特效解毒剂,以对症支持治疗为主。洗胃时须注意监测呼吸情况,必要时先行气管插管再洗胃。

Objective;To investigate the adverse reactions of levofloxacin injection, including the frequency, manifestationsand the related factors. Method; A multicentre prospective study of levofloxacin injection was carried out in eight hospitals in Beijing between October 2000 and September 2001, and the collected data were analysed. Results- The adverse drug reactions occurred in 143 of 4437 inpatients (3.22%) , with 58.04% of mild type. The clinical manifestations most often involved the gastro-intestinal tract and skin. Conclusion: The adverse effects of levofloxacin injection showed generally low frequency and mild symptoms, which were associated with the dose, duration,interactions of levofloxacin administration. It should be used with care in elderly patients and in allergic subjects.

Objective: To investigate the safety of influenza vaccine. Methods: After administration of influenza vaccine in 1325 individuals in 2003 the incidence type and outcome of adverse reactions (AR) were analysed. Results: The AR incidence was 55.32% (733 / 1325) including local reactions (77.76%570 / 733) with duration median of 3 days and systemic reactions (42.43%311 / 733) with duration median of 2 days. Moderate and mild AR were in a majority the latter in particular(57.57%). Persons with AR were all cured (431) or self-cured (302). Conclusion: Influenza vaccine is safer in consideration of AR nature of mildness short duration and easy recovery.

Tenofovir is a new class of nucleotide reverse transcriptase inhibitor with effective for treating HIV-infection and chronic hepatitis B. The potential renal toxicity of tenofovir is related to renal excretion. Renal histopathology revealed tubular injury. The main clinical manifestations of renal damage are decreased phosphorus and increased serum creatinine, and Fanconi syndrome, interstitial nephritis and acute renal failure may also develop. The bone toxicity of tenofovir is secondary to renal toxicity. The clinical manifestations include muscle weakness, bone pain and bone fracture. Tenofovir caused kidney-bone damage are associated with underlying diseases, gene polymorphism, plasma drug concentration and drug interactions. Patients taking tenofovir should be regularly monitored for renal function and electrolyte. The hypophosphatemia were treated with phosphate supplementation. The drug dosage should be adjusted when creatinine clearance rate is <50 ml/min. Renal function was improved markedly after tenofovir withdrawal in some patients, but part of patients progressed to chronic kidney disease.

Orlistat, a novel non-systemic treatment for obesity, is a gastrointestinal lipase inhibitor which decreases intestinal fat absorption and promotes loss of weight. The common adverse reactions of orlistat are gastrointestinal disturbances, uncommon adverse reactions are liver damage, anaphylactic reaction, etc. The purpose of this paper is to provide basis for rational application of orlistat in clinical practice

The incidence of malformations is two to three times greater in the fetus of epileptic mothers than in the fetus of normal mothers,and antiepileptic drug is the main cause of fetal malformations.The fetal malformations are caused by not only the traditional antiepileptics,such as valproate,carbamazepine,phenobarbital,and phenytoin but also the new antiepileptics,such as lamotrigine,topiramate,oxcarbazepine,levetiracetam,and vigabatrin,which have been confirmed by the animal experiments and published case reports.The incidence of fetal malformations is 4.2% to 7.6% in pregnant women receiving antiepiletics.The malformation rate of polytherapy of antiepiletics(6.0%10.9%)is greater than that of monotherapy(3.7%6.9%).The most common clinical manifestations of fetal malformations caused by antiepileptics are craniofacial abnormalities,distal phalanges hypoplasia,congenital heart defects,microcephaly,neural tube defects,and hemorrhagic tendency.Possible mechanisms for a teratogenic action …更多of antiepileptics include causing folic acid deficiency,ion channels blockage,and neuron degeneration.The epileptic women who are pregnant or thinking about becoming pregnant should be careful of the rational choice and use of antiepileptics according to the types,frequency,and cause of seizures.During the treatment with antiepileptics,the monotherapy should be given,so far as possible,dosage should be kept to the minimum necessary to control fits,the serum concentration should be monitored,and prenatal check-up should be performed in order to reduce or avoid the occurrence of fetal malformations.

治疗心血管病常用药物在医治躯体疾病的同时,可能影响病人的性生活质量,其中用于冠心病二级预防的药物尤为明显。本文综述了近年来治疗心血管病常用药物对性功能的影响、作用机制及防治方法。

A 53yearold woman with neurasthenia and neurosis received 4 Bushenyinao capsules thrice daily and estazolam 2 mg at bedtime. After 70 days, her mental symptoms recurred, accompanied by somnolence, yellowish skin and sclera. Liver function revealed the following values: ALT 274 U/L, AST 57.0 U/L, TBiL 32.4 μmol/L, DBiL 19.8 μmol/L and routine urine tests showed bilirubin (++), urobilinogen (++), and ketone (+). Bushenyinao capsules were stopped, estazolam was continued, and liverprotective treatments were given. Three weeks later, her liver function returned to within normal range.

ObjectiveTo understand the current situation of poisoning caused by poisonous animals, poisonous plants, and poisonous mushrooms in our country in order to understand the direction of work for controlling poisoning caused by poisonous organisms and to provide scientific basis for the research on key technique for controlling poisoning.MethodsChina Hospital Knowledge Database and Wanfang Database were searched, and published literature regarding poisoning cases or events caused by poisonous animals, poisonous plants, and poisonous mushrooms in 1994-2011 was collected. The data was analyzed using retrospective descriptive epidemiological methods.ResultsThree thousand four hundred and sixty-three articles consistent with the criteria were collected and a total of 94 700 poisonous patients were reported, of which 46 110 were produced by poisonous animals, 37 172 produced by poisonous plants, and 11 418 produced by poisonous mushrooms. Poisoning mainly occurred in the south area which was abundant in various species and the case distribution was nearly consistent with that of the species. The spectrum of poison were relatively concentrated in several families, and in the number of poisoning cases caused by the top 5 poison categories, poisonous animals and poisonous plants accounted for 78.77%(36 321/46 110) and 84.03%(31 234/37 172) of total number of poisoning cases caused by the 2 kinds of poisonous organisms, respectively. The main categories of poisonous animals causing poisoning were toxic snakes, fish gall bladder, and puffer fish and main plants; the main categories of poisonous plants causing poisoning were Leguminosae and Ranunculaceae. Most poisonous mushrooms poisoning was due to unknown species which accounted for 77.09% (8802/11 418), and Amanitaceae and Boletaceae were the most common mushrooms in known poisonous mushroom poisoning. The main causes of poisoning were accidents (50.24%, 41 291/82 185) and mistaken ingestion (42.19%, 34 670/82 185) and the main route of intoxication was oral ingestion (70.34%, 66 438/94 458). The case fatality rates due to poisonous animals, poisonous plants, and poisonous mushrooms were 252%(1008/39 951), 1.66% (547/33 001), and 12.39%(1248/10 076), respectively.ConclusionsPoisoning of poisonous plants, poisonous animals, and poisonous mushrooms could cause serious damage and was characterized by higher fatality rate, significant regionalism, and relatively concentrated poisonous spectrum. Therefore, from now on, the work for controlling poisoning caused by poisonous plants, poisonous animals and poisonous mushrooms should be enhanced; surveillance system should be established; studies on the key technique for controlling poisoning should be conducted; propaganda and education on the identification, hazards, prevention of poisons should be strengthened in order to minimize the incidence of poisoning.

ObjectiveTo compare and analyze the clinical characteristics of elderly and non-elderly patients with drug-induced liver injury (DILI).MethodsThe clinical characteristics of elderly (≥60 years old) and non-elderly (<60 years old) patients with DILI who sought medical advice in section for outpatients or hospitalized in Department of Infectious Diseases, Peking University First Hospital from January 1997 to September 2015 were analyzed retrospectively.ResultsThe elderly group comprised 193 patients ［female:121(62.7%)］ with average age of (69±7)years. The non-elderly group comprised 286 patients ［female: 192(67.1%)］ with average age of (43±12)years. The time from medication to the appearance of liver injury in the elderly group was 14-60 days (the median time 30 days) and the non-elderly group was 10-60 days (the median time was 30 days)(Z=-1.267, P=0.205). There were 132 cases (68.4%) with the symptoms of weakness, 121 cases (62.7%) with yellow urine, 118 cases (61.1%) of jaundice, 33 cases (17.1%) had fever in the elderly group, respectively. There were 189 cases (66.1%) with the symptoms of weakness, 182 cases (63.6%) had yellow urine, 179 cases (62.6%) had jaundice, 46 cases (16.1%) had fever in the elderly group, respectively. There were no significant differences in incidence of the symptoms mentioned above between the two groups (all P＞0.05). The differences of peak values of alanine aminotransferase, alkaline phosphatase, and total bilirubin between the two groups were not statistically significant (all P>0.05). The case number of antinuclear antibody-positive in the elderly group were more than those in the non-elderly group［27(9.4%)］(P<0.001). There were 221 kinds of suspected drugs which ［47(24.4%)］ may cause DILI in the elderly group. The top three were traditional Chinese medicine (107, 48.4%)，cardiovascular agents (31,14.0%) and antimicrobial agents (18, 8.2%). There were 316 kinds of suspected drugs which might cause DILI in the non-elderly group. The top three were traditional Chinese medicine (154, 48.7%), antimicrobial (50, 15.8%), and non-steroidal anti-inflammatory drug (23, 7.3%). The number of  cases with DILI types of hepatocellular, cholestatic, and mixed in the elderly group and the non-elderly group were 157(81.4%), 13(6.7%), 23(11.9%) and 238(83.2%), 25(8.7%), 23 (8.1%), respectively. The differences were not statistically significant. The cases number of DILI classification of 1, 2, 3, 4, and 5 in the elderly group and the non-elderly group were 56(29.0%), 31(16.1%), 99(51.3%), 5(2.6%), 2(1.0%) and 65(22.7%), 37(12.9%), 174(60.9%), 4(1.4%), 6(2.1%), respectively. The differences were not statistically significant. The suspicious drugs were withdrawn and all the patients with DILI received the anti-inflammatory and hepatoprotection therapy after the appearance of clinical symptom. There were 14 cases in the elderly group and 34 cases in the non-elderly group received steroid therapy additionally. The course of disease in the elderly group were 27-78 days, the median time was 47 days. The course of disease in the non-elderly group were 30-87 days, the media time was 54 days (P=0.07). Of 193 patients in the elderly group, 176 cases (91.2%) were cured and improved, 14 cases (7.2%) developed chronic DILI, and 3 cases (1.6%) died. Of 286 patients in the non-elderly group, 254 cases (88.8%) were cured and improved, 24 cases (8.4%) developed chronic DILI, 7 cases (2.4%) died, and 1 case received liver transplantation. The difference of prognosis between the two groups were not statistically significant (P=0.856).ConclusionsThe traditional Chinese medicines and cardiovascular agents are the main drugs which due to DILI in elderly patients, the traditional Chinese medicines and antimicrobial are main drugs which due to DILI in non-elderly patients. In addition to the cases of accompanying with autoimmune phenomena in the elderly group are more than those in the non-elderly group, the clinical manifestations, treatment, and prognosis are similar in the elderly and non-elderly patients.

Objective: To find out the clinical indications of bifendate and the mechanism of its causing hepatic injury. Methods: Bifendate, 7.5 mg tid, was taken for 28 days in 64 patients with viral hepatitis who had the abnormal ALT and no jaundice, and their liver function changes were observed. Results: The effect of bifendate was related to the clinical types of hepatitis, the values of both AST and AST/ALT ratio before therapy. Conclusion: The protective effect of bifendate on liver remains to be studied.

Objective: To analyze allergic reactions caused by traditional Chinese medicines statistically. Method: 187 ADRs were collected from national medical journals of 1999-2001 in consideration of gender, age, time, route and clinical manifastations. Results: ADR of traditional Chinese medicines was in no relation with gender and age of patients. But it was connected with route of administration. Drugs for injection ranked first on the ADR list, accounting for 109 cases. The time of ADR occurrence ranged from three minutes to seven days when drugs being taken, mostly in the period of treatment. Main manifestations of ADR were as follows: dermoreaction (122 cases), allergic shock (26), allergic rhinitis (7), allergic asthma (6), anaphylactoid purpura (5) and drug fever (17). Conclusion: Allergic reaction is the most common ADR and should be given close attention and prevented timely.

Warfarin is an oral anticoagulant used in the treatment and prophylaxis of thromboembolic disorders.Many factors affect warfarin's anticoagulant effect(enhancement or diminishment).These factors include genetics,diseases,drugs,herbal medicines,food,etc.Several polymorphisms of CYP2C9(mainly CYP2C9^*2 and CYP2C9^*3),liver function insufficiency,hyperthyroidism,heart failure,and interactions of warfarin with aspirin,clopidogrel,miconazole,angelica,fennel,celery,pineapple,onion,and garlic enhance the anticoagulant effect of warfarin.Gene mutation of VKORC1 and interactions of warfarin with rifampicin,carbamazepine,ginseng,green tea,and plenty vitamin K-containing preparations or diets diminish the anticoagulant effect of warfarin.Further more,some drugs such as phenytoin sodium can increase as well as decrease warfarin's anticoagulant effect.Understanding of these factors affecting the anticoagulant effect of warfarin,regular monitoring of INR,and individualizing medication are beneficial to safe and effective use of warfarin.

A 21-year-old female with lumbar pain took phenylbutazone 0.2 g thrice daily and prednisone 10 mg thrice daily.About 26 days later,she developed a fever,dark urine,oedema,skin rash.Three days later,the drugs were stopped,but her symptoms continued aggravating.Nine days later,she was admitted.Her body temperature was 38.7 ℃ and pulse was 112 beats/min.She presented with severe yellowing of skin and sclera.Laboratory tests revealed the following values:Tbil 190.9 μmol/L,Dbil 132.2 μmol/L,Alb 29 g/L,Glob 31 g/L,ALT 251 U/L,AST 64 U/L,ALP 233 U/L,γ-GT 251 U/L,LDH 594 U/L,WBC 13.5×10⁹/L.A lumbar MRI showed the 3rd and 4th lumbar vertebral body tuberculosis.The patient was given the anti-infective therapy,supportive therapy,methylprednisolone pulse therapy,and plasmapheresis.But her jaundice was aggravated gradually,and she developed abdominal distention,oliguresis,deep red-cloured tabular ecchymosis on trunk and limbs.Her levels of BUN and Cr were 15.5 mmol/L and 189 μmol/L,respectively.A B-scan ultrasound displayed a great quantity of seroperitoneum.A blood routine test revealed the values as follows:WBC 1.7×10⁹/L,RBC 2.04×10¹²/L,Hb 58 g/L,PLT 19×10⁹/L.A bone marrow examination showed acute aplastic crisis.The patient died on day 9 after admission

长期、大面积外用糖皮质激素进行皮肤病治疗有可能产生诸多不良反应,近来出现了一类可以局部外用的免疫调节剂,由于其疗效好,安全性高,长期使用也不会有外用糖皮质激素所产生的副作用,是一类在皮肤科领域具有广阔应用前景的药物。

ObjectiveTo understand the current status of medication errors (ME) report in Beijing area and improve the ME monitor and report system.MethodsME cases which were reported by pharmacy departments of 22 hospitals in Beijing in 2012 were collected and analyzed. Analysis projects included category, classification, and triggering factor of ME and the number and proportion of persons who triggered or detected ME. Category A is potential error. Category B, C, and D are mild ME which did not harm patients. Category E, F, G, H, and I are severe ME which cause harm to patients even death.ResultsOne thousand one hundred and sixty-five cases of ME were totally reported by 22 hospitals in Beijing. Proportion of ME of category A, B, C, D, E, and F were respectively 5.9% (69 cases), 71.9% (837 cases), 19.3% (225 cases), 2.2% (26 cases), 0.5% (6 cases), and 02% (2 cases). ME of category G, H, and I have not been reported. In 1165 reports of ME, 1220 errors of classification were noted. Therein, the error of kinds of medications was the highest proportion which reached 27.2% (332 errors). The errors of administration route, dosage, and time respectively accounted for 12.0% (147 errors), 14.3% (175 errors), and 7.1% (86 errors). The content of unreasonable drug use was contained in the errors of kinds of medications, administration route and time. In 1165 reports of ME, 1183 triggering factors were noted. The top three factors were sound alike, prescribing errors, and look alike, whose proportions were 19.1% (226 errors), 14.0% (166 errors), and 8.3% (98 errors), respectively. In terms of the persons that triggered ME, the proportions of doctors, pharmacists, nurses, and patients or families were respectively 66.0%, 30.6%, 1.1%, and 2.3%. In terms of the persons who detected ME, doctors, pharmacists, nurses, and patients or family members respectively accounted for 14%, 88.8%, 4.6%, and 5.2%.ConclusionsThe report system of ME in Beijing had tended to be mature gradually. The operation model could be used for reference for national systems of ME monitor and report.

黄热病减毒活疫苗是由减毒17D毒种生产而成,具有良好的安全记录,但近年来美国和澳大利亚等国报道的由接种黄热病疫苗所致的嗜内脏毒性和嗜神经毒性的严重不良反应较多,甚至导致患者死亡事件的发生。引起世界各地药品管理当局的高度重视,我国每年使用黄热病减毒活疫苗(17D株)10多万人次,同样存在潜在危险。应引起有关部门特别关注。

为妊娠妇女及乳母处方非甾体抗炎药时,应谨慎权衡利弊。非甾体抗炎药作为前列腺素合成抑制剂可致凝血功能异常、子宫动脉导管收缩并延长产程。水杨酸盐对动物可致畸,但尚缺乏使人致畸的依据。孕妇使用阿司匹林可致分娩时及产前、产后出血,并致新生儿患出血性疾病。一般认为吲哚美辛对胎儿的循环有影响并能致畸,但也尚有争议。而萘普生对胎儿的循环、凝血以及肾脏功能均有影响。布洛芬、保泰松也可引起先天性缺损。因此,该类药物一般应避免使用于妊娠妇女。从物理、化学性质,药动学方面看,虽然大部分非甾体抗炎药在乳汁中的排泌率低,对乳儿的影响不大,但吲哚美辛由于半衰期长、代谢物仍有活性,乳母使用可能会使乳儿发生不良反应。而乳儿发生水杨酸盐毒性反应早有报道。乳儿肝肾功能未健全,乳母阿司匹林用量的21％又可通过乳汁被乳儿摄入,水杨酸盐应为乳母的禁忌药物。

A 48-year-old female patient was hospitalized 2 times for pseudotrichinosis. She received an IV infusion of methylprednisolone 60 mg once daily (changed to oral prednisone acetate 20 mg once daily after discharging) and oral methotrexate 10 mg once a week. After 107 days of treatments with the above-mentioned drugs, thalidomide 50 mg once daily by mouth was added because of recurrent erythra in her face and trunk. One hundred and thirty-six days later, methotrexate was withdrawn for the liver injury. Forty-eight days after receiving thalidomide, her skin rash was aggravated and accompanied by desquamation and erosion. Thalidomide was stopped. Anti-infective and anti-allergic treatments, skin protective treatments were given. Fourteen days later, her skin rash was ameliorated.

Objective To understand the effect of rational use of traditional Chinese patent medicines on medication safety.MethodsBy using cluster sampling method, the adverse drug reaction (ADR) reports about traditional Chinese patent medicines (including traditional Chinese medicine for injections) derived from the Center for ADR Monitoring of Guangdong from January 1st, 2011 to December 31st, 2011, were collected and retrospectively analyzed. The information of the patients′ gender, ages, primary diseases, the suspected drugs causing ADR, drug combination, and the situation of ADR occurrence were collected. The situation of irrational drug use in these reports at 7 aspects such as indications, syndrome differentiation treatment, medication methods, dosage, combination of traditional Chinese patent medicines, concomitant use of the traditional Chinese medicines and the Western medicines, and suitability of medication were analyzed according to the protocol of evaluation standards of traditional Chinese patent medicine prescription and the rate of irrational drug use were calculated.ResultsA total of 283 reports in accordance with the inclusion criteria were collected, which comprised 283 patients. Of them, 150 were male and 133 were female with ages from 2 months to 88 years and an average age was (44±23) years. The primary diseases ranking at the top three were respiratory system disease (71 patients), nervous system disease (45 patients), and musculoskeletal system disease (42 patients). The traditional Chinese patent medicines involved in these reports were mainly antipyretic-detoxicating agents, blood activating and stasis removing agents, and reinforcing agents. The rates of irrational drug use associated with indications, medication methods, dosage, combination of traditional Chinese patent medicines, concomitant use of the traditional Chinese medicines and the Western medicines, and suitability of medication were 27.2% (77/283), 6.0% (17/283), 7.1% (20/283), 5.3% (15/283), 6.7% (19/283), 0.7% (2/283), respectively. Fifteen patients′ medication (46.8%)did not fit the syndrome differentiation classification among the 32 reports whose differentiation of syndromes could be identified.ConclusionsThe irrational drug use has marked effect on medication safety of traditional Chinese patent medicines and maybe one of the important factors in relation to adverse reactions induced by traditional Chinese patent medicines. In clinical use of traditional Chinese patent medicines, syndrome differentiation treatment should be the primary principle, medication beyond the indications should be avoided, more attention should be paid to usage and dosage of the drugs, and combination of function-similar traditional Chinese patent medicines and pharmacological action-similar traditional Chinese and Western medicines should be used cautiously.

钙不仅是维持骨健康的基本元素,也是参与全身多系统生理功能的重要物质,补钙是防治骨质疏松症的基础措施。近期,美国WHI的研究结果对补钙引起了争议,本文认为该研究设计和实施方面的局限性影响了研究结果的可靠性和科学性,并限制了其推广价值。本文还进一步阐述了对钙的吸收,补钙与肾结石的关系,以及钙剂选择标准和专家共识意见,提出了科学、安全补钙的合理建议。

Objective: To examine the frequency and type of citations of articles published in Adverse Drug Reactions Journal and to reveal the characteristics of citations in this journal. Methods: The citations of articles published in Adverse Drug Reactions Journal from 2003 to 2007 were collected. The frequency and type of the citations, Price index, and the top cited journal were statistically analyzed with bibliometris methods. Results: From 2003 to 2007, Adverse Drug Reactions Journal contained 385 articles, and 354 of them had a total of 4 849 references, for an average of 12.6 references per article. The citation rates were 91.9%. Of the 4 849 references, 89.3% were from journals, and 7.5% were from books. The Price index was 62.9%. The citations in the top 20 cited journals in citation frequency were 22.8% of the total citations. Conclusion: The citation of articles published in Adverse Drug Reactions Journal has characteristics of a large number and a wide range. The journal is one of the important sources in drug safety information.

目的：科学、客观地评估《药物不良反应杂志》的质量。方法：运用文献计量学方法，统计分析2003-2007年《药物不良反应杂志》刊文量、刊文内容、作者信息、引用参考文献量和主要评价指标。结果：该刊30期共刊登学术论文1 228篇，专门报道药物不良反应和安全用药，学术性、实用性强；作者群在不断扩大，遍及全国31个省、市和自治区；论文合著率较高，为7158%；引用参考文献5 706篇，篇均4.65篇；主要评价指标上升幅度较大，影响因子呈快速上升趋势。在2005-2007年版《中国期刊引证报告》、《中国学术期刊综合引证报告》、《中国科技期刊引证报告》中，其影响因子均居药学期刊前列，2007年版分别为1.591，1.498和0.935，均居药学期刊首位。结论：《药物不良反应杂志》是具有鲜明特色的药学专业性学术刊物，其质量和影响力提高显著，对我国药学学科的发展、提高临床安全用药水平和促进药物安全信息的交流具有积极推动作用。

ObjectiveTo analyze the prevalence and risk factors of potentially inappropriate medication (PIM) use among elderly inpatients.MethodsThe data of patients  ≥65 years of age and hospitalized in Department of Internal Medicine in the Third People′s Hospital of Hefei from January to December in 2015 were collected and the gender, age, department, diseases that patient suffered from, hospitalization days, drug varieties used in one patient, methods of payment were recorded. The patients were divided into 2 groups: the 65-79 years old group and the  80 years old group. The utilization rate of PIM drugs, the drug varieties, the proportion of PIM use between the patients in the 2 groups were calculated. The risk factors of PIM use was analyzed by Logistic regression method.ResultsA total of 388 patients (their ages were from 65 to 79 years and their average age was (76±7) years were enrolled in this study, including 206 males and 182 females. Of the 388 patients, 278 (71.6%) patients were in the 65-79 years old group and 110 (28.4%) were in the  ≥80 years old group. The utilization rate of PIM drugs was 54.9% (213/388) and the utilization rate of high-risk PIM drugs was 28.6% (111/388). The utilization rate of PIM drugs in the 65-79 years old group was 57.9% (161/278) and 47.3% (52/110) in the ≥80 years old group (χ2=3.604, P=0.058). Among 213 patients receiving PIM drugs, 132 (62.0%) patients were prescribed with one PIM drug, and 56 (26.3%), 17 (8.0%), 6 (2.8%), 2(0.9%) patients were prescribed with 2 to 5 PIM drugs, respectively. Twenty-four PIM drugs were used in the 213 patients and 17 high-risk PIM drugs were used in 111 patients, accounting for 33.3% (24/72) of the total number of PIM drugs and 48.6% (17/35) of the high-risk PIM drugs, respectively. According to the ratio of application, the top 3 drugs were insulin, anticoagulants, sedatives and hypnotics in the 65-79 years old group and anticoagulants, sedatives and hypnotics, and theophylline in the ≥80 years old group. The results of Logistic regression showed that the main risk factors of PIM use were ages (OR=0.531, 95%CI: 0.326-0.865, P=0.011) and prescribed drugs varieties (OR=3.927, 95%CI: 2.678-5.757, P<0.001). ConclusionsThe utilization rate of PIM drugs in elderly inpatients in our hospital was higher. The risk factors of PIM use were patients′ages and drugs varieties.

ObjectiveTo understand occurrence of bleeding related to drug interactions in patients who received combined treatment with warfarin and other drugs in Department of Cardiovascular Medicine and investigate control measures.MethodsThe data of inpatients using warfarin in the Department of Cardiovascular Medicine, Peking University First Hospital from January 2012 to June 2013 were collected and analyzed retrospectively. The conditions of concomitant drugs and occurrence of bleeding possibly caused by drug interactions were recorded and the drugs which were commonly used in the Department were screened.ResultsA total of 141 patients were enrolled including 90 men aged from 21 to 83 years with an average age of (63±13) years and 51 women aged from 43 to 85 years with an average age of (65±11) years. Most protopathy was atrial fibrillation which accounted for 79.4% (112 cases). Of the 141 patients, there were 14 cases (9.9%) of slight bleeding possibly because of drug interactions including 5 cases of stool occult blood, 3 cases of dermal ecchymosis and 1 case had each of the following: operative wound bleeding, oral mucosal bleeding and blood in phlegm, colporrhagia, epistaxis, hematuresis, and gum bleeding. The occurrence of bleeding in the 14patients involved totally 9 kinds of drugs containing low molecular weight heparin (related to 9 cases), atorvastatin (related to 6 cases), amiodarone (related to 4 cases), acarbose (related to 3 cases), aspirin (related to 4 cases), propafenone (related to 3 cases), omeprazole (related to 2 cases), clopidogrel (related to 2 cases), and moxifloxacin (related to 1 case) and, of them, the highest occurrence was due to low molecular weight heparin, which accounted for 64.2%. In the 9 kinds of drugs in the 141 patients, low molecular weight heparin had the highest concomitant frequency combined with warfarin accounted for 731%(103/141) and moxifloxacin had the highest bleeding incidence accounted of 1/5.ConclusionsBleeding may be caused by drug reactions due to combination therapy with warfarin and parts of clinical common cardiovascular drugs. Positive clinical pharmaceutical care of warfarin will be of great importance in prevention of bleeding.

Objective;To observe the side-effects of thalidomide used for multiple myeloma. Method:Thalidomide-induced unwanted effects were analysed in 32 inpatients with multiple myeloma. Results; The occurrence rate of adverse reactions was 94% in all, 87.5% in alimentary system, 84.4% in neuropsychic system,and the others included sinus bradycardia, escape rhythm, drug fever, skin rashes, edema, etc. Conclusion; Thalidomide could cause gastro-intestinal and neuropsychic disturbances, which would disappear or relieve with discontinuation of administration or reduction of dose.

本文根据近年国内外文献资料,对临床常用氟喹诺酮类药物的不良反应进行了分析,并概述其不良反应的机制与化学结构的关系。其中N₁、C₅、C₇、C₈取代基与不良反应的程度相关;C₂的H、C₆的F均不可取代,与抗菌药效关系密切,与不良反应无关;C₃、C₄与DNA螺旋酶结合,也与药物间相互作用有关。经验表明,临床医师在新药应用与研究开发中了解药物不良反应的监测资料是十分重要的。

Objective: To study the effects of insulin aspart and human regular insulin on blood glucose in elderly type 2 diabetic patients with irregular food intake. Methods: Thirtythree elderly patients with type 2 diabetes mellitus \[18 men, 15 women, average age (65.82±2.85) years\] were enrolled in a clinical study from February 2006 to April 2007. They initially received regimen A (SC human regular insulin 30 minutes before each meal and SC human isophane insulin at bedtime for 4 months), followed by regimen B (SC insulin aspart 1015 minutes after meals and SC human isophane insulin at bedtime for 4 months). The fasting and 2hour postprandial (after breakfast, midday meal, and evening meal) blood glucose levels were measured twice a week. The frequency and severity of hypoglycemia as well as the changes in glycosylated haemoglobin (HbAlc) levels were observed comparatively between the two regimens. Results: The fasting and 2hour postprandial (after breakfast, midday meal, and evening meal) blood glucose levels were (7.37±4.22) mmol/L, (9.73±3.38) mmol/L, (10.23±3.96) mmol/L, and (10.85±3.36) mmol/L for regimen A, and (701±1.74) mmol/L, (9.23±1.58) mmol/L, (9.22±1.28) mmol/L, and (9.76±1.32) mmol/L for regimen B, respectively. The differences were statistically significant (all P＜0.01). The fluctuations of postprandial blood glucose were lower for regimen B than for regimen A. The difference values of HbAlc before and after treatment was (3.08±0.96)% for regimen A and (3.37±0.47)% for regimen B (P＜0.01), respectively. The frequency of hypoglycemia and the incidence of moderate-to-severe hypoglycemia were 68 cases and 36.70% for regimen A, and 21 cases and 19.05% for regimen B, respectively. The differences were statistically significant (P＜0.001). Conclusion: In elderly type 2 diabetic patients, subcutaneous injection of insulin aspart after meals can effectively decrease the blood glucose levels, reduce the fluctuation of postprandial blood glucose levels, and diminish the frequency and severity of hypoglycemia. It is a safe and effective regimen for elderly type 2 diabetic patients with irregular food intake.

A 73yearold man received a prolonged treatment with warfarin after undergoing mitral valve replacement, and his international normalized ratio（INR） was maintained between 2.0~3.0. The patient received capecitabine chemotherapy due to stomach cancer. During the second cycle of the chemotherapy, he developed hemorrhagic blisters on his feet, nose bleeding, ecchymoses on his buttock, melena, and gross hematuria, and his INR increased. Warfarin was withdrawn immediately. Bleeding stopped after administration of fresh frozen plasma replacement and vitamin K₁. The INR was maintained between 1.5~2.5 after the dosages of warfarin and capecitabine were decreased, and the chemotherapy continued and no further bleeding occurred. The increased anticoagulant effect of warfarin may be associated with the capecitabineinduced suppression of cytochrome P450 2C9 isoenzyme. A review of the literature indicates bleeding occurring in patient receiving warfarin plus capecitabine usually is within 2~6 weeks after initiation of the combined chemotherapy. The most common hemorrhage is gastrointestinal bleeding. In order to avoid bleeding occurring, prothrombin time (PT) and INR should be closely monitored, and the dosage of warfarin should be individualized.

Objective: To investigate adverse reactions caused by Ciwujia injection. Methods:Literature was retrieved from domestic medical journals 1994-2003, and 103 cases with the adverse effects in 75 papers were analysed. Results: The adverse effects were mainly anaphylactic shock (33.98%), then systemic reactions and disorders in skin and respiratory system. Conclusion: Allergy is the common adverse reaction to Ciwujai injection and close attention should be paid to it in clinical practice.

A 40-year-old female patient took ibuprofen dispersible tablets twice (0.4 g, 3-4 hours interval) by herself due to fever. One hour after the second medication, the patient developed nausea, vomiting, and small bleeding spots on skin. One day later, she developed yellowish skin and sclera. Three days later, her urine output decreased to 300-400-ml daily. Five days later, laboratory tests showed alanine aminotransferase (ALT) 3-531-U/L, aspartate aminotransferase (AST) 811-U/L, total bilirubin (TBil) 149.7-μmol/L, creatinine (Scr) 753-μmol/L, and uric acid (UA) 800-μmol/L. She was diagnosis as having severe liver injury and acute renal failure, which was considered to be associated with ibuprofen. After 6 days of treatments such as liver protection, continuous renal replacement therapy (CRRT), and fresh frozen plasma infusion, the patient′s yellowish skin and sclera were relieved and small bleeding points reduced. Laboratory tests showed ALT 513-U/L, AST 36-U/L, TBil 31.5-μmol/L, Scr 281-μmol/L, and UA 241-μmol/L. Her urine volume was 2-500-ml per day. After CRRT was stopped and liver-protective treatment was continued for 14 days, the yellowish skin subsided and the bleeding points disappeared. Laboratory tests showed ALT 55-U/L, AST 39-U/L, TBil 15.6-μmol/L, Scr 101-μmol/L, and UA 237-μmol/L, and her urine volume was 4-000-ml per day.

Objective: To observe the efficacy of tiopronin in children with liver damage caused by high dose methotrexate. Methods:In 103 cases,tiopronin injection was for the management of chemotherapy-induced liver damage. And Stronger Neo-Minophagen C was used in 42 cases as control. Results: In tiopronin group, 33 percent of cases maintained normal liver function, and the remaining developed liver damage, which would resolve if tiopronin administration continued. As for the efficacy, no statistical difference was observed between treatment group and control group(P> 0.05). Conclusion: Tiopronin can effectively prevent liver cells and improve liver function, and can be combined with methrexate in treatment of children with acute lymphoblastic leukemia.

The serotonin syndrome is a potentially life-threatening adverse reactions that results from therapeutic drug use. The mechanisms are attributed to the increase on activity of serotonergic system because 5-hydroxytryptamine (5-HT) accumulates in nervous system and 5-HT postsynaptic receptors are overactivated. The clinical feature is described as a clinical triad of mental-status changes, autonomic hyperactivity, and neuromuscular abnormalities. The syndrome often occurs in coadminstration among antidepressants or combination with other drugs. The diagnosis of the serotonin syndrome is mainly based on the clinical manifestation. Management of the serotonin syndrome involves the cessation of precipitating drugs, improvement of monitoring, control of agitation, administration of 5-HT antagonists, symptomatic treatment, the control of complication, etc. The prevention of the syndrome is more important than the treatment.

他克莫司软膏为大环内酯类免疫调节剂,是治疗特应性皮炎(AD)的非皮质类固醇类外用制剂,他克莫司可抑制钙调磷酸酶的活性及阻止多种细胞因子生成,从而抑制T淋巴细胞活化,发挥药理作用。临床用于治疗AD疗效确切,不良反应较少。本文对他克莫司软膏的药理特性、临床应用和不良反应进行概述,供临床合理应用参考。

近年,药源性肌病的报道有所增加,本文概要介绍不同类型肌病的临床表现与致病药物及其作用机制,旨在提高临床的诊断能力和安全用药水平。

Objective: To investigate the clinical characteristics of antibacterials-induced neuropsychiatric symptoms in patients with chronic renal failure. Methods: Patients with chronic renal failure treated with antibacterials, during January 1999 and December 2001,were retrospectively analysed. Results: 12 patients with chronic renal failure developed antibacterials- induced neuropsychiatric symptoms, 6 males and 6 femals, with a mean age of 64.3±9.7 years. After receiving intravenous injection daily for 1-6 days, patients presented with progressive neuropsychiatric symptoms, including extra-pyramidal system symptoms, disorientation, depressed consciousness, even coma, or apathy, agitation, hallucination, and personality changes. The very common drug involved was cephalosporins, the others were penicillins, carbopenems, quinolones and isoniazid. After withdrawal of evil agents, the neuropsychiatric symptoms disappeared within a few days. Conclusion: Antibacterial agents can cause neuropsychiatric symptoms in patients with chronic renal failure. Physicians should be aware of these potentially dangerous neurotoxicity during performing anti-infection therapy and withdrawal of the drugs whenever the adverse effects occur.

A 49-year-old male patient was treated with first-line and second-line chemotherapy regimens successively for 7 months because of Hodgkin′s lymphoma. However, the tumor failed to be well controlled. His treatment was changed to intravenous infusion of sintilimab 200-mg once every 21 days. His liver function was normal before treatment. After the second administration of sintilimab (on day 42 after the first medication), the patient developed chest distress, abdominal distension, poor appetite, and etc. Reexa- mination of liver function showed alanine aminotransferase (ALT) 1-590-U/L, aspartate aminotransferase (AST) 3-678-U/L, alkaline phosphatase (ALP) 468-U/L, gamma-glutamyl transferase (γ-GT) 399-U/L, total bilirubin (TBil) 50.1-μmol/L, and direct bilirubin (DBil) 26.8-μmol/L. Sintilimab was discontinued, but the patient′s jaundice was deteriorated. Intravenous infusion of methylprednisolone 150-mg once daily was given for 3 days, but the bilirubin reached the peak (TBil 152.6-μmol/L，DBil 109.2-μmol/L). Oral mycophenolate mofetil 0.5 g twice daily was added, the patient′s symptoms were gradually improved, and his liver function gradually recovered. After 6 days of combination use of methylprednisolone and mycophenolate mofetil, the laboratory tests showed ALT 63-U/L, AST 78-U/L, TBil 25.2-μmol/L, and DBil 12.9-μmol/L. Twenty-two dags later, his liver function returned to normal.

治疗药物监测(TDM)的目的是促进药物个体化治疗。本文通过多年的TDM实践,总结了药物剂量-血药浓度-疗效和不良反应之间的相关性,并重点举例说明TDM对各种常用药物安全应用的重要性,呼吁临床检验师、药师和医师的密切合作,运用多学科知识将TDM推向更高水平,使药物不良反应得到早期警示,以提高药物治疗的有效性和安全性。

Objective: To discuss the adverse reactions caused by traditional Chinese medicines(TCM). Method: 142 ADR reports from PLA ADR Database 2001 were used for statistical analysis. Results: The ADR frequency was increased with involement of many kinds of TCM, mostly by injection. Conclusion: Caution should be advised in administering TCM to patients because of the annual rise of its adverse reactions.

对利巴韦林的致癌、致畸和致突变作用进行了文献分析及评价,为合理安全用药提供了依据。

本文对近年来新核苷类药物治疗乙肝的研究现状进行综述,主要介绍在我国即将上市的阿德福韦、恩替卡韦抗乙肝病毒效果和临床安全性的研究概况,以及依曲西他平、替诺福韦等新开发药物的研究现状。旨在使临床医生对新核苷类药物治疗乙肝的合理性和安全性有更深刻的了解。

氨基糖苷类抗生素具有抗菌谱广,对大多数革兰阴性(G-)杆菌引起的感染疗效确切等特点。但该类药物具有个体差异大、治疗指数窄等缺点,应用不当,可引起严重不良反应。本文参考近期文献从葡萄糖转运及其代谢、第二信使、微量元素和线粒体功能等方面就氨基糖苷类抗生素耳毒性的可能机制及临床处置作一综述。

A 17yearold boy with chronic granulocytic leukemia was treated with imatinib 400 mg twice daily for about 4 months, but this had no effect. Later, imatinib was changed to dasatinib 70 mg twice daily. About one month and a half later, the patient initially presented with body temperature of 39.2℃, followed by generalized myalgia, ostalgia, and arthralgia. After treatment with 1 rectal indometacin 50 mg suppository thrice daily and an IV infusion of dexamethasone 2.5 mg, his pains lessened. Dasatinib was continued for the clinical needs of the patient. His pains reappeared, and rectal indometacin suppositories were given.

Objective: To investigate the situation of antibacterial-associated diarrhea occurring in our hospital. Methods: Forty-four patients with antibacterial-associated diarrhea in our hospital were investigated and analysed retrospectively from January to June in 2005. Results:The antibacterial-associated diarrhea accounted for 41.5% of infectious diarrhea. Most of patients with antibacterial-associated diarrhea were elderly patients and patients with liver or renal dysfunction. The common causative agents were levofloxacin, cefoperazone / sulbactam, clindamycin, and so on. All these agents were given by intravenous infusion. The initial time of onset of diarrhea occurred 2 days after the start of antibacterial drug therapy. The symptoms of diarrhea disappeared after 7 days of treatment with antifungal agents and microecological preparations. Conclusion:Intraveously administered antibacterial drugs may cause diarrhea; therefore, physicians should be care of using these drugs in treating patients, especially in elderly patients and patientswith liver or renal dysfunction, in order to avoid the occurrence of diarrhea

Three antiviral drugs, including interferon α (aerosol inhalation), lopinavir/ritonavir (oral medication), and ribavirin (intravenous infusion), are recommended by Diagnosis and Treatment of Novel Coronavirus Pneumonia (revised version, the 5th ed), which was issued by the National Health Commission of People′s Republic of China and National Administration of traditional Chinese Medicine. In addition, clinical trials on a new antiviral drug ---remdesivir which is not yet on the market has also been launched in China. Medication safety related data on treatment for infections of severe acute respiratory syndrome coronavirus, middle respiratory syndrome coronavirus, human immunodeficiency virus, lopinavir/ritonavir, and ribavirin, safety data of remdesivir in animal experiment, phase I clinical trials and clinical trials of treating Ebola virus infection, and preliminary reports of treatment in novel coronavirus pneumonia were briefly reviewed, aiming to provide evidence for clinical safety medication.

Rabbit syndrome(RS) is a tardive extrapyramidal syndrome associated with prolonged use of drugs, especially antipsychotics. The incidence of RS induced by antipsychotics ranged from 1.5% to 4.4%. The clinical characteristics of RS is fast and rhythmic involuntary movement of oral and masticatory muscles. The mechanism of RS may be associated with imbalance of the cholinergic and dopaminergic neurotransmission in the basal ganglia. RS should be distinguished from tardive dyskinesia. About treatment of RS, anticholinergic agents is the first choice. Some patients switching to an atypical antipsychotic with high anti-cholinergic properties is another treatment strategy.

妊娠结核是严重危害母婴健康的妊娠并发症之一,如果处理不当可能引起母婴的严重不良后果。了解妊娠结核的发病率、妊娠与结核病的相互影响等的最新动态,掌握妊娠结核的临床表现、诊断、药物治疗以及不良反应处理等方面的新知识,将有利于保护妊娠结核的母婴健康。

ObjectiveTo investigate the application of vancomycin in elderly inpatients.Methods
The clinical data of elderly inpatients (≥60 years) treated with vancomycin from September 2012 to November 2013 in 5 hospitals including Peking University First Hospital, Beijing Hospital, Beijing Chao-Yang Hospital, Xuanwu Hospital of Capital Medical University, and Chinese PLA General Hospital were collected. All patients were divided into normal renal function group and renal insufficiency group. The application (dosage regimen, drug utilization situation, and therapeutic drug monitoring) and clinical efficacy of vancomycin and its effects on renal function in elderly patients were retrospectively analyzed. Drug utilization index (DUI) reflected the drug utilization situation. And parameters of renal function included serum creatinine (Scr), blood urea nitrogen (BUN) and creatinine clearance rate (Ccr).ResultsA total of 149 patients were enrolled in this study comprising 60 males and 89 females with age of 60-92(76±7) years. There were 87 cases in the normal renal function group and 62 cases in renal insufficiency group. The most widely used regimen of application of vancomycin was 0.50 g once every 12 hours in the normal renal function group (29/87, 33.33%) and 0.50 g once daily in the renal insufficiency group(30/62, 48.39%). The total dosage and time of using vancomycin were respectively 2 135.15 g and 1 919.5 d. And the DUI was 0.56. Among the 149 patients, 111 cases(74.50%) underwent blood concentration monitoring and there were no statistically significant differences in constituent ratio of undergoing blood concentration monitoring between the normal renal function group and the renal insufficiency group［70.11%(61/87) vs.80.65%(50/62)，χ2=2.11，P=0.15］. In all patients undergoing blood concentration monitoring, trough concentration was detected and in 7 patients peak concentration was detected. The number of cases whose trough concentrations ＜10 mg/L was 30(49.18%) and 25 cases (50.00%) in the normal renal function group and the renal insufficiency group, respectively, and there were no statistically significant differences (χ2=2.16，P=0.54). The differences between before and after administration of vancomycin in Scr［(117±79) μmol/L vs. (119±81)μmol/L］, BUN［(10.5±5.7) mmol/L vs. (12.5±8.0) mmol/L］, and Ccr［(69±37) ml/min vs. (67±36) ml/min］ in all the 149 patients were not statistically significant(all P>0.05). The differences between before and after administration of vancomycin in Scr［(59±16)μmol vs. (70±30)μmol/L, (189±110)μmol/L vs.(203±113)μmol/L］, BUN［(7.4±3.5) mmol/L vs.(9.2±5.8) mmol/L, (14.8±6.5) mmol/L vs.(17.4±9.0) mmol/L］, and Ccr［(107±29) ml/min vs.(96±26) ml/min, (44±30) ml/min vs.(33±16) ml/min］ in the normal renal function group and the renal insufficiency group were not statistically significant (all P>0.05).ConclusionsThe use of vancomycin in elderly inpatients was relatively cautious. Dosage regimen should be adjusted timely according to the results of blood concentration and renal function tests and individualized administration should be adopted in order that the efficacy and safety could be improved.

A 44-year-old woman with varicosis received iopromide 370 100 ml,0.9% sodium chloride 40 ml,and dexamethasone 10 mg by bolus injection with a high pressure syringe at a speed of 2.5 ml/s before CT enhancement scanning examination.After intravenous injection,the patient suddenly presented with unconsciousness,respiration and cardiac arrest.He was given cardiopulmonary resuscitation,tracheal intubation,and antishock drugs immediately.Two hours later,the patient died.An autopsy showed extensive eosinophilic granulocyte infiltration in many organs and tissues,pulmonary edema,larynx and epiglottis edema.

本文根据近年来的文献综述了药物引起的皮肤色素沉着。引起皮肤色素沉着的药物有抗精神病药、抗菌药、降血压药、抗心律失常药、抗癌药等。药源性皮肤色素沉着,可能与药物的用量及应用时间有关。因此,应严格掌握药物的使用剂量及使用时间,以避免或降低药物不良反应的发生。

A 77-year-old female patient was given combined chemotherapy with paclitaxel for injection (albumin bound) and nedaplatin for ovarian malignant tumor with peritoneal metastasis. When paclitaxel for injection (albumin bound) 100-mg dissolved in 0.9% sodium chloride injection 250-ml was given intravenously for the first time, the infusion was not smooth and the drip rate was slow. After stopping infusion, the infusion device was checked and white flocculent sediment above the filter was found. Clinical pharmacists ruled out the possibility of precipitation caused by drug preparation and incompatibility contraindications, and found that the infusion device used by this patient was a precision one (the pore diameter of microporous filter was 5-μm). However, in the drug label of paclitaxel for injection (albumin bound), it was pointed out that "Use of filters with a pore size less than 15-μm may result in blockage of the filter and should not be used." On the second day, a general infusion device (filter with 20-μm pore size) was used for IV infusion of paclitaxel for injection (albumin bound) and the process was smooth and no blockage recurred.

Objective: To study the pathogenesis , prevention and management of the liver damage caused by tra-dional Chinese medicines on analysis of cases with liver damage. Methods: This article summarized 427 cases of liver damage caused by traditional Chinese medicines in the last fifteen years and surveyed incidence of liver damage caused by traditional Chinese medicines, distribution of primary diseases, and clinical characteristics. Results: Liver damage cases induced by traditional Chinese medicines were on the increase year by year , amounted to 32.6% in all cases of the drug-induced liver damage. Those traditional Chinese medicines used to treat osteoarthropathy, kidney diseases and skin diseases induced liver damage more often. Zhuanggu Guanjie Wan , Tripterygium wilfordii Hook. f., and Dioscorea bulbifera L. were the most major medicines inducing liver damage. The clinical characteristics and the pathogenesis of liver damage caused by different medicine were varient. Conclusion: Ratio...更多nal use of traditional Chinese medicines and study of their hepatotoxicity should be strengthened further in clinical practice .

A 78yearold woman with cerebral infarction received IV cinepazide maleate injection 160 mg once daily. On day 3, the woman experienced a fever; her WBC count decreased from 7.32×10⁹/L to 2.3×10⁹/L; neutrophil count decreased from 6.14×10⁹/L to 1.7×10⁹/L. Cinepazide maleate injection was withdrawn immediately, and berbamine and batilol were given. Two days later, her temperature fell to normal, and laboratory testing showed a WBC count of 2.6×10⁹/L with N 20×10⁹/L. Two weeks later, her WBC and neutrophil counts retured to normal limits. A followup period lasting two months showed that her blood routine tests remained normal.

Hepatitis C virus protease inhibitors (PIs) are one of the major categories that constitute directly acting antivirals (DAA) regimen in the treatment for hepatitis C. These drugs are mainly metabolized by liver cytochrome P450 and have potential hepatotoxicity. Population pharmacokinetic study data showed that the metabolism of PIs was slower in Asians than that in White/Caucasian subjects, and the results of clinical trials and real-world studies in Asians showed that these drugs had the risk of causing liver enzyme abnormalities and bilirubin elevations. Medical workers in our country should pay full attention to the potential risks of PIs in liver safety, and should not rely too much on safety data in Europe and America. The baseline liver disease severity should be accurately assessed before selecting the DAA regimen containing PIs and the risk of disease progression should be considered. PIs are contraindicated in patients with decompensated liver disease. For patients without cirrhosis or with compensated cirrhosis, the liver function should be closely monitored during the administration of PIs and the management of liver-related adverse events should be paid attention to.

ObjectiveTo analyze the status of medication error (ME) of outpatient pharmacy of Beijing Tongren Hospital Affiliated to Capital Medical University and to find effective prevention and control measures.MethodsAs a pilot run hospital of Beijing Municipal Health Bureau ME monitoring system, ME cases were reported since August 2011 by the hospital and ME reports were analyzed monthly to formulate prevention measures. ME cases of outpatient pharmacy, which were reported to Beijing Municipal Health Bureau, from August 2011 to March 2013 were collected. The ME cases were classified according to the ME classification standard of The National Coordinating Council for Medication Error Reporting and Prevention and the links in which ME cases occurred were analyzed. MEs that occurred from August 2011 to September 2012(the pilot operation stage of the Beijing ME monitoring system) were compared with those from October 2012 to March 2013( the operation stage of Beijing municipal bureau of clinical medication safety monitoring network). The effectiveness of prevention measures was evaluated.ResultsA total of 506 ME cases, accounting for 0.031%（506/1 636 429）of the number of outpatient prescriptions at the same time, were collected. There were 2 cases of category A (potential error problems), 462 cases of category B (errors happened but the drug was not given to patient, or the drug had been given to patient but was not taken), 42 cases of category C (patients had used the drug but not be harmed), and none of categories D-I. Among them, 459 ME cases occurred in the links of prescriptions by doctors including improper usage and dosage(75.16%, 345/459), improper administration route(12.64%, 58/459), improper drug selection(5.88%, 27/459), taking medication within comtraindication(3.05%, 14/459)，imcompatibility(2.61%, 12/459), and improper choice of solvents(0.65%, 3/459). Forty-seven ME cases occurred in the links of dispensing prescriptions by pharmacists including sound alike, look alike, adjacent locations, and so on. Aiming to the links of doctors making prescriptions, a supervision model of "four-grade prescription comment and four-grade feedback" was carried out since October 2012 and the rate of qualified prescriptions was increased effectively. The proportion of ME cases in the links of prescriptions by doctors in all the prescription cases during the same period decreased from 0.035% (398/1 139 613) in the pilot operation stage to 0.012% (61/496 816) in the operation stage. Aiming to the links of dispensing prescriptions by pharmacists, many kinds of measures were carried out to improve the identification of easily confused drugs. The incidence of ME in the links of dispensing prescriptions by pharmacists decreased from 0.004% (40/1 139 613) in the pilot operation stage to 0.001% (7/496 816) in the operation stage.ConclusionThe ME cases in outpatient pharmacy of Beijing Tongren Hospital Affiliated to Capital Medical University were mainly category B and C and mostly occurred in the links of prescriptions by doctors. The main type of ME was usage and dosage. The supervision model of "four-grade prescription comment and four-grade feedback" could effectively prevent the ME in the links of prescriptions by doctors.

ObjectiveTo explore the role of CRUSADE score for evaluating the risk of gastrointestinal bleeding due to antiplatelet agents.MethodsThe hospitalized patients with coronary heart disease and received antiplatelet therapy for more than 1 year before hospitalization in department of internal medicine in the Third People′s Hospital of Cixi, Zhejiang Province from September 2010 to September 2013 were enrolled into the study. The patients were divided into the gastrointestinal bleeding group and the non-gastrointestinal bleeding group according to whether gastrointestinal bleeding occurred due to antiplatelet agents. The CRUSADE score was evaluated in the 2 groups and the relationship between the CRUSADE score and gastrointestinal bleeding was analyzed.ResultsA total of 787 patients with coronary heart disease who received antiplatelet therapy more than 1 year were collected. Forty patients with gastrointestinal bleeding were enrolled into the gastrointestinal bleeding group. One hundred and sixty patients were enrolled into the non-gastrointestinal bleeding group by equidistant sampling method randomly. The gastrointestinal bleeding group comprised 31 male and 9 female with age from 45 to 88 (71±9) years. The non-gastrointestinal bleeding group comprised 100 male and 60 female with age from 36 to 89 (65±13) years. There was statistically significant difference in age between the 2 groups (P＜0.05). The percentage of cases of receiving aspirin enteric-coated tablets, clopidogrel hydrogen sulfate tablets, and both the above-mentioned drugs in the gastrointestinal bleeding group and the non-gastrointestinal bleeding group were 55%(22/40),10%(4/40),35%(14/40) and 54%(86/160),7%(11/160), 39%(63/160), respectively. The difference was not statistically significant (P>0.05). The percentage of cases who had history of gastroin-testinal bleeding and peptic ulcer in the gastrointestinal bleeding group and the non-gastrointestinal bleeding group were 30.0%(12/40) and 11.9%(19/160), respectively. The difference was statistically significant (P＜0.05). There were 27.5%(11/40) and 27.5%(11/40) cases with the results of CRUSADE score at high risk and very high risk in the gastrointestinal bleeding group, 8.1%(13/160) and 10.6%(17/160) cases in the non-gastrointestinal bleeding group, respectively. The difference was statistically significant (P＜0.05) .ConclusionsCRUSADE score can help to evaluate the risk of gastrointestinal bleeding in patients with coronary heart disease who received antiplatelet therapy. It is suggested that the patients with coronary heart disease as well as the CRUSADE score of high risk and very high risk should receive the combination of antiplatelet agents and the proton pump inhibitor, in order to prevent or reduce the gastroin-testinal bleeding.

Two female patients who aged 42 and 33 years with adenomyosis  and hysteromyoma, respectively  were  hospitalized for surgical treatment. They had not history of kidney disease. They developed the symptoms of nausea, vomit, hematuresis, hypourocrinia, and slight puffy swelling after the second and fourth times of IV infusion of amoxicillin and clavulanate potassium 2.4 g, respectively. Laboratory examination showed  the increase of serum creatinine (Scr) and urea nitrogen (BUN)(case 1: Scr 423 μmol/L, BUN 7.2 mmol/L；case 2：Scr 443 μmol/L, BUN 6.8 mmol/L). Amoxicillin and clavulanate potassium were stopped to use in both patients immediately and symptomatic treatments which included those for relieving vomiting, hemostasis, diuresis, and fluid infusion were given to them. The two patients were transferred to another hospital′s   nephrology department for hemodialysis on day 5 and 3 of receiving amoxicillin and clavulanate potassium, respectively. The two patients′ urine volume, levels of Scr and BUN were returned to normal on day 18 and 20 after transferring, respectively (case 1: Scr 49 μmol/L, BUN 4.1 mmol/L；case 2: Scr 55 μmol/L, BUN 5.1mmol/L).

Objective: To observe the effects of milkvetch root (Radix Astragali) on hepatotoxicity induced by cocklebur fruit (Fructus Xanthii). Methods: Sixty-five male mice were divided into following five groups (13 mice in each group): 1:1 group (cocklebur fruit 5 g/kg plus milkvetch root 5 g/kg), 1:2 group (cocklebur fruit 5 g/kg plus milkvetch root 10 g/kg), 2:1 group (cocklebur fruit 5 g/kg plus milkvetch root 2.5 g/kg), cocklebur fruit group (cocklebur fruit 5 g/kg), and control group (physiological saline). The duration of administration was 4 weeks, and the weight of mice was measured weekly. After the last administration of the medicines, the serum levels of ALT and AST were measured, the liver index was calculated, and the GSH-PX, GST, and MDA of the liver were measured. Results: The weight gain in the 1:1 groups and 2:1 groups was marked higher than that in the cocklebur fruit group (P< 0.05), the liver index was lower than that in the cocklebur fruit group (P<0.05). The serum levels of AST and ALT in the three experimental groups were lower than those in the cocklebur fruit group, and there were statistically differences in comparison of the 2:1 group with the cocklebur fruit group. The activity of GSH-PX and GST in the 1: 2 group and 2:1 group were higher than those in the cocklebur fruit group, the differences were statistically significant (P<0.05; P<0.01). The content of MDA in the 1:2 group and 2:1 group were lower than that in the cocklebur fruit group, there were stastistically differences in comparison of the 2:1 group with the cocklebur fruit group (P<0.05). Conclusion: Milkvetch root could decrease the hepatoxicity of cocklebur fruit, and the 2:1 groupis better than other ones.

静脉输液不当可引起循环超负荷、血液稀释、病原微生物污染、栓塞、静脉炎、营养物质补充不当及诱发药物过量反应等。患者病情、配制操作、配制程序、伍用药物、输液溶媒及输液速度等因素均是静脉输液应用中应认真对待的问题。静脉输液相关不良反应多,应加强安全注射的教育和管理。

本文对近年来有关克林霉素不良反应的文献资料进行归纳,其主要不良反应包括胃肠道反应、过敏反应和肝肾损害等。提示临床在用该药时严格掌握其适应证,采取正确的使用方法,并谨慎联合用药,以避免或减少不良反应的发生。

A 63-year-old male patient took tamsulosin hydrochloride sustained release capsules 0.2-mg daily and Qianliexin capsules 2 g thrice daily by himself for urinary urgency and urodynia. Twenty- five days later, he developed itchy skin, deep brown urine, nausea, fatigue, and loss of appetite. Laboratory tests showed alanine aminotransferase (ALT) 265-U/L, aspartate aminotransferase (AST) 163-U/L, total bilirubin (TBil) 155.1-μmol/L, direct bilirubin (DBil) 74.7-μmol/L, indirect bilirubin (IBil) 80.4-μmol/L, alkaline phosphatase (ALP) 261-U/L, and gamma-glutamyltransferase (γ-GT) 184-U/L. Liver biopsy showed the cholestatic liver injury. He was diagnosed as acute drug-induced liver injury, which might be related to the above 2 drugs. The above 2 drugs were stopped and oral ursodeoxycholic acid 250-mg thrice daily was given. On day 42 of drug withdrawal, laboratory tests showed ALT 368-U/L, AST 179-U/L,TBil 504.9-μmol/L, DBil 382.8-μmol/L, IBil 122.1-μmol/L, ALP 201-U/L, and γ-GT 58-U/L. On day 91 of drug withdrawal, laboratory tests showed ALT 78-U/L, AST 62-U/L, TBil 138.1-μmol/L, DBil 118.2-μmol/L, IBil 20.2-μmol/L, ALP 140 U/L, and γ-GT 31-U/L. The patient′s liver function returned to normal 135 days after drug withdrawal.

Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor used in the treatment of human immunodeficiency virus or hepatitis B virus (HBV) infection. It can effectively reduce the HBV DNA level of chronic HBV infected pregnant women, preventing HBV mother-to-child transmission. TDF has been recommended by the European Society of Liver Disease as drug of choice for HBV infection in pregnant women and designated as class B drug for pregnancy by the United States Food and Drug Administration. No adverse outcome or impact has been observed in current researches on TDF to mothers or fetus or to babies through breast feeding exposure. More in-depth and meticulous researches are needed for the safety of TDF in human pregnancy and lactation.

ObjectiveTo investigate the effect of cyclosporine on serum creatinine (Scr) levels in patients with nephrotic syndrome.MethodsThe medical record data of patients, who received the treatment with cyclosporine, diagnosed as nephrotic syndrome by renal biopsy, and hospitalized in Guangdong General Hospital from April 2010 to June 2014, were collected and retrospectively studied. Before treatment, all patients′ Scr were less than 200 μmol/L. Increase of the Scr levels by more than 10%-20%, 21%-30%, and >30% of the baseline value were defined as mild, moderate, and severe increase, respectively (severe increase of Scr is considered as renal toxicity). Changes of Scr levels before and after cyclosporine treatment, relationship between the blood concentration of cyclosporine and increase of Scr were analyzed.ResultsA total of 78 patients were enrolled in this study. Of them, 52 were males and 26 were females with age from 14 to 77 years and an average age was (43±20) years. From the results of pathological types, 14 cases had minor lesion, 12 cases had focal segmental glomerulosclerosis, and 52 cases had membranous nephropathy. The average level of Scr before treatment was (94±48) μmol/L. After one week treatment, the average level of Scr in 78 patients was (103±61) μmol/L and the difference was statistically significant compared with that before treatment (P<0.05). Of the 78 patients, 30 cases (38.5%) had increased Scr levels; mild, moderate, and severe increase was seen in 9, 11 and 10 patients respectively. The incidence of renal toxicity was 12.8% (10/78). There were no statistically significant differences in Scr levels between 1, 3, and 6 months of treatment (all P> 0.05). In patients with different pathological types including minor lesion, focal segmental glomerulosclerosis, and membranous nephropathy, the incidence of Scr increase were 28.6% (4/14), 33.3% (4/12), and 42.3% (22/52), respectively (P>0.05) and the incidence rate of renal toxicity were 7.1% (1/14), 16.7% (2/12), and 13.5% (7/52), respectively (P>0.05). The incidence of increase of Scr rose gradually with the increase of cyclospo-rine concentration. In patients with cyclosporine concentrations of ≤200 ng/ml and >200 ng/ml, the incidence of increase or severe increase of Scr were 32.2% (19/59) and 57.9%, respectively (χ2=4.008，P=0.045); the incidence of renal toxicity was 8.5% (5/59) and 26.3% (5/19), respectively (P>0.05).ConclusionsSerum creatinine may increase mildly to moderately at early stage of treatment with cyclosporine in patients with nephrotic syndrome and could be controlled effectively with timely intervention. The increase of Scr may be related to blood cyclosporin concentration. Blood cyclosporin concentration should be monitored regularly during the treatment and the drug dosage should be adjusted according to the result of monitoring.

ObjectiveTo develop primary standard of potentially inappropriate medication (PIM) in Chinese aged people under morbid state and provide the basis and guide for clinical rational drug use in aged people.MethodsStandards of PIM in aged people under morbid state of the United States, Canada, Thailand, South Korea, and the Taiwan area of China were collected and, after summarizing, removing duplication, and integrating, the first round questionnaire was designed according to Delphi method to ask for the experts′ opinions. The experts′ feedback and suggestions were organized and the second round questionnaire was designed to ask for opinions again. Authoritative coefficient, positive coefficient, coordinate coefficient, mean score, and full mark rate were calculated. The selected drugs were respectively divided into grade A (frequency ≥ 3 000) and B (frequency < 3 000) standard according to medication frequency.ResultsThirty nine and 38 experts respectively took part in the 2 rounds of Delphi method investigations, who were selected from 23 grade Ⅲa hospitals in 11 provinces and 3 municipalities directly under the central government. These experts′ specialties involved 11 clinical medical specialties including neurology, psychiatry, cardiology, gastroenterology, endocrinology, urogenital epidemiology, gerontology, general medicine, pain medicine, dermatology, and respiratory medicine and 3 pharmacy specialties including clinical pharmacy, clinical pharmacology, and hospital pharmacy. After the 2 rounds of investigations, all of the authoritative coefficients of the experts were above 0.7, all of positive coefficients were 100%, and the first coordination coefficient were 0.17 and 0.21, respectively. Meanwhile, the mean scores were 3.65 and 3.94 and the means of full mark rates were 0.15 and 0.32, respectively. The first round investigation contained 188 points of drug-induced risks of 89 species (categories) of drugs under 31 kinds of morbid states and the second round investigation contained 74 points of drug-induced risks of 44 species (categories) of drugs kinds of morbid states. These indexes listed in the second round investigation were all enrolled the primary standard of PIM in Chinese aged people under morbid state. Grade A standard contained 62 points of drug-induced risks of 35 species (categories) of drugs under 25 kinds of morbid states, and grade B standard contained 12 points of drug-induced risks of 9 species (categories) of drugs under 9 kinds of morbid states.ConclusionsThe development of primary standard of PIM in Chinese aged people under morbid state has completed preliminarily. However, the standard still needs to be improved by clinical application to be used as a powerful tool for promoting rational drug use and lowering drug-induced risks of aged people.

吉非替尼是一种口服选择性表皮生长因子受体酪氨酸激酶抑制剂,可单药用于晚期非小细胞肺癌(NSCLC)患者经化疗后继续恶化的治疗。临床研究表明吉非替尼单独应用具有明显抗肿瘤活性,可使症状减轻。吉非替尼的主要不良反应包括痤疮样皮疹、恶心、呕吐、腹泻、皮肤干燥、间质性肺炎等。多数于停药后或经对症处理即可缓解,间质性肺炎虽然罕见却可致命,值得临床高度重视。

Objective To compare the adverse reactions of oxycodone hydrochloride prolonged-　release tablets and fentanyl transdermal system in the treatment of moderate and severe cancer pain.　Methods The medical records of patients with moderate to severe cancer pain who used oxycodone hydrochloride prolonged-release tablets (oxycodone group) or fentanyl transdermal systems (fentanyl group) for more than 1 week during hospitalization in Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 2018 to December 2019 were collected. The occurrence of adverse reactions after analgesic treatments were retrospectively analyzed.　Results A total of 698 patients were enrolled in the analysis, including 535 in the oxycodone group and 163 in the fentanyl group. The incidence of adverse reactions in the oxycodone group was significantly higher than that in the fentanyl group ［72.5% (388/535) vs. 51.5% (84/163), χ2=25.139, P<0.001］. The common adverse reactions (with incidence ≥5%) in the oxycodone group were constipation, nausea/vomiting, xerostomia, drowsiness, and dizziness, while those in the fentanyl group were constipation, nausea/vomiting, and dizziness. The incidence of constipation in the oxycodone group was significantly higher than that in the fentanyl group ［60.9% (326/535) vs. 40.5% (66/163), χ2=21.209, P<0.001］. The differences in the incidence of other adverse reactions in the 2 groups were not statistically significant (all P>0.05). All adverse reactions were grade 1 or 2, which were improved after symptomatic treatments. No adverse reactions of grade 3 or more severe occurred.Conclusions Both oxycodone hydrochloride prolonged-release tablets and fentanyl transdermal system are safe during the treatment for moderate to severe cancer pain, with mild adverse reactions, which can be relieved by symptomatic treatments. Oxycodone hydrochloride prolonged-release tablets are more likely to cause constipation than fentanyl transdermal system.

A 39yearold women with an upper respiratory tract infection received an IV infusion of clindamycin, ribavirin, and Shuanghuanglian for two days. However, these had no obvious effect. And they were replaced by cefoperazone and asarone. She was administered an IV infusion of cefoperazone 2 g in 5% glucose 250 ml without adverse reactions, followed by an IV infusion of asarone 16 mg dissolved in 5% glucose 250 ml. About 5 minutes after asarone infusion start, the patient suddenly developed chest distress, dyspnea, convulsion. Subsequently, she experienced confusion, respiratory and cardiac arrest. Finally, the patient died desipite resuscitation attempts.

Ricin derived from castor beans is a potent toxin, the main machanism of its toxic effects to cells is to inhibit protein synthesis in cells and result in their death. People can be poisoned via different routes of exposure to ricin. The clinical presentations of ricin poisoning depend on the route of exposure and the dose received. The patients with severe ricin poisoning may develop multi-organ failure and death. So for no specific antidote exists for ricin. The toxin vaccine of ricin is being tried out on laboratory animal. Treatment for ricin poisoning is primarily supportive medical care to minimize the effects of the poisoning.

ObjectiveTo evaluate the risk of dyspepsia and anorexia due to glucagon-like peptide-1 receptor agonist (GLP-1 RA) in patients with type 2 diabetes mellitus (T2DM).MethodsThe electronic database of Chinese BioMedical Literature Database(CBMdisc), Chinese Medical Current Contents(CMCC), Medline, EMbase, the Cochrane Library and web site of ClinicalTrials.gov were searched from inception to May 1st 2014. Those randomized controlled trials whose inclusion criteria including patients with T2DM as the research object, comparisons of GLP-1 RA and placebo or other conventional anti-diabetic drugs as the intervention measures, and dyspepsia and anorexia as the outcomes were collected. A traditional Meta-analysis and a Network Meta-analysis were used and relational graph and rank ordering figure of all the intervention measures were drawn. ResultsA total of 42 randomized controlled trials were enrolled into this study involving 20 916 patients with T2DM and 13 kinds of intervention measures comprised 7 kinds of GLP-1 RAs (exenatide, exenatide release agent, liraglutide, lixisenatide, taspoglutide, albiglutide, and dulaglutide), 5 kinds of conventional anti-diabetic drugs (insulin, metformin, sulfonylureas, sitagliptin, and thiazolidinediones ketones), and placebo. The traditional Meta-analysis showed that, compared with placebo, the whole of GLP-1 RAs could increase the risks of dyspepsia ［odds ratio(OR)=3.04, 95% confidence interval (CI): 1.79-5.16］ and anorexia (OR=2.57, 95%CI: 1.69-3.91) and there were statistically significant differences (P<0.05). The Network Meta-analysis showed that, compared with placebo, albiglutide, exenatide, exenatide release agent, liraglutide, lixisenatide, and taspoglutide could increase the risks of dyspepsia with statistically significant differences (all P<0.05) and, of them, liraglutide was at the greatest risk and the risk was 7.69 (1/0.13) times as high as that of the placebo. Compared with insulin, metformin, sulfonylureas, sitagliptin, and thiazolidinediones ketones, GLP-1 RAs could also increase the risks of dyspepsia in the patients with T2DM and, of them, liraglutide was at the greatest risk,which was 13.58, 4.17 (1/0.24), 3.85 (1/0.26), 5.00 (1/0.20), and 3.70 (1/0.27) as high as that of insulin, metformin, sulfonylureas, sitagliptin, and thiazolidinediones ketones, respectively. Compared with placebo, dulaglutide, exenatide, liraglutide, and taspoglutide could increase the risks of anorexia with statistically significant differences (all P<0.05) and, of them, dulaglutide was at the greatest risk, 5.53 times as high as that of the placebo. Compared with insulin, sulfonylureas, thiazolidinediones ketones, and sitagliptin, GLP-1 RAs could also increase the risks of anorexia in the patients with T2DM ( all OR>1.00 except for lixisenatide versus sitagliptin ) and, of them, dulaglutide was at the greatest risk, 48.91, 16.65, 36.24, and 4.75 times as high as that of insulin, sulfonylureas, thiazolidinediones ketones, and sitagliptin, respectively. There was no statistically significant difference between two kinds of GLP-1 RAs for risks of dyspepsia and anorexia (all P>0.05). The risks of dyspepsia and anorexia due to the 13 kinds of intervention measures were ranked by rank ordering figure and liraglutide and dulaglutide were at the greatest risks.ConclusionBoth the traditional Meta-analysis and Network Meta-analysis showed that GLP-1 RAs could increase the risk of dyspepsia and anorexia in patients with T2DM.

ObjectiveTo analyze the contents related to elderly people in medication instructions of oral drugs commonly used in China.MethodsOral medicines in Department of Outpatient Pharmacy, Xuanwu Hospital of Capital Medical University were recorded using Electronic Management System of drugs and composition ratio of different kinds of drugs were calculated. The notes for elderly people in medicine instructions were extracted and compared with administration suggestion (risk points) of the same drugs described in 2012 edition of Beers Criteria.ResultsA total of 368 kinds of oral drugs in Department of Outpatient Pharmacy were collected. Of them, varieties of drugs for central nervous system ranked first (93 kinds, 25.3%), varieties of drugs for cardiovascular system ranked second (62, 16.8%), varieties of drugs for digestive system ranked third (38, 10.3%)。Of the 368 kinds of oral drugs, medication instructions of 259 drugs (70.4%) were marked with notes for elderly people; medication instructions of 75 drugs (20.4%) were marked that no related tests were performed, no reliable references were provided or not clear; medication instructions of 34 drugs (9.2%) were not marked. Eighty kinds of drugs which were used in Department of Outpatient Pharmacy in 2013 were included in 2012 Beers Criteria. Of them, 8 kinds of drugs (10.0%) were not marked notes for elderly people and other 72 kinds of drugs (90.0%) were marked. Compared with the 2012 edition of Beers Criteria, the 72 kinds of drugs used in Department of Outpatient Pharmacy were divided into 4 kinds of results: risk points were not marked (52.5%，42/80), risk points were different (25.0%，20/80), risk points were less than those marked in Beers Criteria (6.3%，5/80), and risk points were identical (6.3%, 5/80). ConclusionThe notes for elderly people in medication instructions of commonly used oral drugs in China need further improvement to ensure medication safety in elderly patients.

Objective: To analyse the causes of the adverse reactions induced by Shuanghuanglian and to study the way of their prevention and treatment. Methods: This article summarized 179 cases of the adverse reactions caused by shuanghuanglian in recent years, and analysed the classification, clinical characteristics and causes of the adverse reactions induced by Shuanghuanglian . Results: The adverse reactions of Shuanghuanglian were related to the quality of the preparation, the application of the drug and the individual factors. Conclusion: To pay great attention to the adverse reactions of shuanghuanglian .

Objective: To evaluate the safety of terazosin tamsulosin finasteride and their combination for the treatment of benign prostatic hyperplasia. Methods: Correlative databases websites and medical journals were searched for the randomized clinical trials (RCTs) controlled clinical trials(CCTs) cohort studies and case reports about the serious adverse events available. The quality of the literature was evaluated the data were extracted and meta-analyzed if appropriate or otherwise would be described. Results: Nine RCTs one CCTs and three other studies met the inclusion criteria. The meta-analysis suggested that tamsulosin had a better safety profile than terazosin in the occurrence of dizziness headache orthostatic hypotension and discontinuations due to adverse reactions. There was no statistic difference between terazosin and tamsulosin in the occurrence of other adverse events. By comparison with finasteride terazosin caused more dizziness and there was no statistic difference between terazosin and finasteride in the occurrence of impotence and decreased libido. Tamsulosin and finasteride were compared in only one trial so a meta-analysis could not be done. However the results of this trial indicated that tamsulosin seemed to be safer than finasteride. Two studies compared terazosin and finasteride with their combination and found contradictory conclusions. Conclusion: According to the analysis it is concluded that tamsulosin may have a better safety and acceptability profile than terazosin. There is not enough evidence of finasteride causing more impotence and decreased libido. The safety of tamsulosin and finasteride can not be made definitely because of the insufficiency of information.

急性感染性腹泻治疗主要包括补液和快速补充营养。而活菌制剂在其中的作用目前有两种观点,一是认为补充肠道正常菌群治疗感染性腹泻可以缩短病程,减轻症状。而另一观点认为,近年来从活菌制剂的药动学,药效学和随机应用安慰剂对照的临床试验研究提示,用活菌制剂进行额外的干预治疗并非必要,因此对活菌制剂在感染性腹泻的应用价值提出了质疑。但两种观点都提出益生元的概念,且认为活菌制剂与益生元制成合剂,即合生元是其发展方向。

Objective: To observe the myopathy following telbivudine alone and telbivudine plus adefovir or interferon administration and analyze its relative factors. Methods: Five patients with myopathy related to telbivudine alone and telbivudine plus adefovir or interferon in our hospital from January 2007 to January 2008 were investigated. The dosage and administration of the drugs, the clinical manifestation of myopathy, and the results of laboratory testing were analyzed. Results: The 5 patients were men aged 25～45 years. One patient received telbivudine 600 mg once daily for 1 month. One patient received telbivudine 600 mg twice daily for 2 months, and subsequent regimen was changed to telbivudine 600 mg once daily plus adefovir 10 mg once daily for 5 months. Three patients received telbivudine 600 mg once daily plus intramuscular injection of interferon 3×106 U every other day for 3～9 months, respectively. All five patients developed myalgia and generalized hypodynamia, and cardiac muscle was involved in one patient, and three patients presented with neurological disorders. Of 5 patients, 4 patients' CK levels were 311～900 U/L. Conclusion: Telbivudine alone and telbivudine plus adefovir or interferon might induce myopathy. And the dosage of telbivudine might be associated with the severity of myopathy in certain degrees.

A 62-year-old male patient was hospitalized with bullous pemphigoid. He received prednisone 15 mg thrice daily, loratadine 10 mg once daily, and cefradine 0.5 g thrice daily by mouth as well as symptomatic and supportive therapy. Three days later, occasional agitation appeared in the patient. However, he did not receive any treatment. Seven days later, the dose of prednisone was increased to 60 mg/d for poor control of rash. Eight days later, he experienced anxiety, dysphoria, agitation, persecutory delusion, abnormal behavior, memory loss, and occasional failure to recognise location. The dose of prednisone was then decreased to 45 mg/d. Loratadine was discontinued. He was switched to oral cyproheptadine 2 mg thrice daily, and other therapy was the same as before. One week later, the patient′s psychiatric symptoms gradually relieved and he was discharged. The dose of prednisone was gradually reduced and then stopped 45 days after discharge. The patient had no recurrence of similar psychiatric symptoms at a 3-month follow-up.

ObjectiveTo understand the characteristics of medication errors (ME) of traditional Chinese medicine in elderly patientsMethodsME reports of traditional Chinese medicine in elderly patients which were collected from International Network for the Rational Use of Drugs (INRUD) from January 1st, 2013 to November 31st, 2014 were selected and analyzed. The major types of ME, persons who triggered the ME, triggering factor, category, and persons who detected the ME were analyzed descriptively.ResultsA total of 520 ME reports were collected from 23 hospitals. The number of ME on medication usage and dosage in ME types ranked first and accounted for 48.5% (252/520), the number of deployment errors ranked second and accounted for 19.8% (103/520). In terms of the persons  triggering the ME, the percentage of physicians and pharmacists were 70.0% (333/476) and 29.4% (140/476), respectively. Triggering factors of ME were lack of knowledge of traditional Chinese medicine ［30.0% (114/380)］ and similar names of different drugs ［16.3% (62/380)］. Intermediate and primary titles of pharmacists in persons who detected ME accounted for 53.2% (271/509) and 37.5% (191/509), respectively. The ME belonging to category A, B, and C accounted for 16.0% (83/520), 68.5% (356/520), and 13.8% (72/520)］, respectively and all these errors did not do harm to patients. The errors belonging to category D and E accounted for 1.5% (8/520) and 0.2% (1/520), respectively. ConclusionsIn elderly patients, the errors in usage and dosage of traditional Chinese medicine were main types of errors and most of the ME were mild and did not do harm to patients. The triggering factor of the ME were lack of knowledge of traditional Chinese medicines in physicians and pharmacists.