Angiotensin-converting enzyme (ACE) inhibitors are being increasingly prescribed for the treatment of hypertension and heart failure. Not only are they efficacious but the incidence of serious adverse events with ACE inhibitors is similar to that with placebo. ‘First-dose hypotension’ mainly affects the renin-dependent patient. Neutropenia and agranulocytosis have been reported rarely for the nonsulfhydryl compounds. Comparative safety data are provided for captopril, enalapril, and quinapril, a new nonsulfhydryl ACE inhibitor that has been investigated extensively in over 2,000 patients. Results show that the proportion of patients reporting associated adverse events was lower with quinapril (11 %) than with captopril (17%) or enalapril (15%). Similarly, there was a lower proportion of patients withdrawn due to adverse events with quinapril.
Hypertension is a major potential problem among the increasing number of older persons in the population, threatening their health and shortening their life expectancy due particularly to stroke and congestive heart failure (CHF). Controlled studies have shown that antihypertensive drug therapy reduces the incidence of severe CHF, stroke and cardiovascular mortality in the elderly. Special consideration should be given to altered drug metabolism, altered responses to drugs, and concomitant medications when pharmacotherapy is instituted in the elderly. Angiotensin-converting enzyme (ACE) inhibitors are acceptable in the hypertensive older patient as first-line therapy for all grades of hypertension and as second-line therapy for the patient with CHF. Use of ACE inhibitors avoids many of the symptoms and metabolic disturbances associated with beta-blockers and diuretics. Quinapril is a new non-sulphydryl ACE inhibitor whose active metabolite, quinaprilat, has a relatively short accumulation half-life compared with enalapril and lisinopril but has an enhanced affinity for the converting enzyme, allowing rapid excretion of the drug while retaining a 24-hour antihypertensive effect with once-daily dosing. Quinapril is a valuable addition to the ACE inhibitor class, with demonstrated efficacy and safety in the older patient.
1 The pharmacokinetics of isoxicam have been compared in 57 volunteers with an average age of 31.3 years and 48 elderly subjects with an average age of 71.9 years. 2 Isoxicam was given in a single daily dose of 200 mg for up to 22 days. Similar plasma concentrations were obtained in the two age groups, average maximum concentrations being 39.7 mg l‐1 in those under 65 and 38.1 mg l‐1 in the elderly. There were no significant differences in the half‐life which averaged 30.4 and 32.1 h respectively. 3 Approximately 9% of all those studied had half‐life values in excess of 50 h. The results are consistent with the possibility of genetic polymorphism of isoxicam hydroxylation. 4 It is concluded that isoxicam is suitable for use in once daily dosage and that there are no clinically significant differences in its pharmacokinetics between young and elderly subjects.
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