dihydropyridines and Cough

Candesartan, an AT(1) receptor antagonist, has been reported to have no association with persistent cough in subjects with hypertension, but there has been no study on the safety of its administration to hypertensive patients with symptomatic asthma. The aim of this study was to compare the adverse effects of candesartan and calcium antagonists on cough, pulmonary function, and bronchial hyperresponsiveness in these patients.. Sixty mildly to moderately hypertensive patients with bronchial asthma received either candesartan (n=30) or the calcium antagonists nifedipine or manidipine (n=30) for 6 months. The candesartan group included 5 subjects with a history of ACE inhibitor-induced cough. There were no differences between the 2 groups in patient characteristics, ACE gene polymorphism, pulmonary function, or bronchial hyperresponsiveness to methacholine. Control of hypertension was the primary end point; new cough detected by self-administrated questionnaire and an increase in cough frequency by visual analog scale were the second end point. No patient complained of persistent cough. Neither mean visual analog scale score nor pulmonary functions changed during this study. Bronchial hyperresponsiveness had a tendency to improve in the candesartan group, but there was no difference between the 2 groups.. Incidence, frequency, and severity of persistent cough, pulmonary functions, and bronchial hyperresponsiveness did not change in either the candesartan or calcium antagonist group. It is suggested that candesartan is as effective and safe as calcium antagonists in the treatment of hypertension associated with symptomatic asthma.

Topics: Adult; Aged; Antihypertensive Agents; Asthma; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Bronchial Hyperreactivity; Calcium Channel Blockers; Cough; Dihydropyridines; Female; Genetic Testing; Humans; Hypertension; Incidence; Male; Methacholine Chloride; Middle Aged; Nifedipine; Nitrobenzenes; Pain Measurement; Peptidyl-Dipeptidase A; Piperazines; Polymorphism, Genetic; Respiratory Function Tests; Tetrazoles; Treatment Outcome

The efficacy and tolerability of combination therapy using Lisinopril (5-20 mg om) and Isradipine (1.25 mg-2.50 mg bd) was assessed in 29/50 Chinese subjects, whose blood pressures were not controlled on Isradipine alone. The addition of Lisinopril produced approximately two-fold reductions in blood pressure compared to Isradipine alone, increasing the responder rate of the original cohort of 50 subjects by 18% and normalization rate, by 32%. No significant changes in haematological or biochemical parameters, CXR or ECG, were observed. However, use of Lisinopril in our subjects was associated with a high incidence of cough (48%), possibly limiting its use in this population.

Topics: Adult; Aged; Antihypertensive Agents; Cough; Dihydropyridines; Drug Therapy, Combination; Enalapril; Female; Humans; Hypertension; Isradipine; Lisinopril; Male; Middle Aged

Two pilot studies for prescription-event monitoring in Japan (J-PEM) were launched in 1997 and 1998. Here we present data regarding adverse events that were reported in the second pilot J-PEM study where losartan was compared with ACE inhibitors and dihydropyridine calcium channel antagonists.. We conducted a cohort study with a concurrent control. METHODS/PATIENT GROUP: Study subjects prescribed losartan, an ACE inhibitor or a calcium channel antagonist were identified from prescriptions in hospital or community pharmacies. Events and other information were collected from doctors and pharmacists by mailed questionnaires. Events were coded and analysed using the Medical Dictionary for Regulatory Activities (MedDRA) terminology. Crude event rates were calculated and compared between patients treated with losartan and those receiving control drugs. When the difference was statistically significant, the event was further examined in several ways, including follow-up studies and by comparison with the data of the UK PEM study on losartan.. Pharmacists were sent 4344 questionnaires and returned 3591 (83%), while doctors were sent 3517 questionnaires and returned 1380 (39%). In the doctors' data, the adverse event rate for losartan treatment was greater than that for ACE inhibitors and/or calcium channel antagonists for the following seven events: headache, palpitations, anaemia, insomnia, feeling abnormal, increased blood pressure and asthma. Most of these are known adverse drug reactions (ADRs) of losartan except for two events: increased blood pressure and asthma. In pharmacists' data, the event rate for losartan was significantly greater than that for control drugs for the following ten events: hot flushes, abnormal hepatic function, oedema, peripheral swelling, decreased blood pressure, increased blood pressure, rhinitis, contact dermatitis, dry skin and heat rash. The first five events were known ADRs of losartan but the other five were not. When the two sets of data were combined, the rate of an additional event, increased blood creatinine phosphokinase, which is a known ADR of losartan, was significantly greater than that for the control drugs. The six events that were not documented as ADRs for losartan were not judged to be ADRs based on the results of follow-up studies and comparison with the UK PEM study on losartan. The crude rate of cough with losartan treatment was similar to that with calcium channel antagonists, but was significantly less than that with ACE inhibitors.. No novel safety problems were found in this observational cohort study on losartan. The rates of some known ADRs differed significantly between patients treated with losartan and those in the control groups.

Topics: Aged; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Chi-Square Distribution; Cohort Studies; Cough; Dihydropyridines; Drug Monitoring; Exanthema; Female; Humans; Japan; Losartan; Male; Middle Aged; Pilot Projects; Surveys and Questionnaires