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Previous studies have documented potentially adverse effects of diuretics and beta-blocking agents on plasma lipid profiles. This study was designed to establish the effects on lipid profiles of the angiotensin-converting enzyme inhibitors lisinopril and enalapril, alone and in combination with hydrochlorothiazide (HCTZ), the calcium-channel blocker nitrendipine, HCTZ, and hydralazine. After a two-week, single-blind, placebo phase, 77 patients with essential hypertension were given active agent as monotherapy in a double-blind fashion for 8-20 weeks. The dose of each agent was titrated to achieve diastolic blood pressure less than 90 mm Hg. At the end of placebo and treatment phases, plasma was analyzed for triglycerides, total cholesterol, and high-(HDL), and low-density lipoprotein (LDL) cholesterol. Overall, few changes in lipid contents were noted. Total cholesterol decreased during therapy with hydralazine but increased in patients receiving the combination of lisinopril and HCTZ. HDL cholesterol was depressed in those taking HCTZ alone and in combination with lisinopril. LDL cholesterol was lowered during therapy with hydralazine but was otherwise unaffected by all other agents. None of the agents evaluated significantly affected triglyceride concentrations. Thus, monotherapy with lisinopril, enalapril, and nitrendipine do not affect plasma lipid concentrations. Hydralazine lowers total and LDL cholesterol. If these findings are confirmed in trials with larger numbers of patients, these effects on lipid profiles may influence choice of agent in the therapy of essential hypertension.

This study describes sustained efficacy and safety of lofexidine in hypertensive patients. Twenty-one male patients (mean age 55 +/- 9 yr) who had previously completed a short-term trial of lofexidine entered this open-label trial. The daily dose of lofexidine was titrated over three months to a maximum of 1.6 mg or an erect diastolic blood pressure less than 90 mm Hg. Hydrochlorothiazide was added when necessary. Thereafter, each patient was evaluated for blood pressure (BP) response, compliance, side effects, hepatic, renal, or hematological abnormalities every three months for two years. Sustained BP reduction with lofexidine was achieved but not without concomitant diuretic therapy. There were no clinically important changes in heart rate or hepatic, renal, or hematological profiles. Side effects were frequent but severe enough to warrant discontinuation in only four patients. The side-effect profile was similar to that of clonidine. We recommend concurrent diuretic use to maximize effectiveness of lofexidine.

Twenty patients with essential hypertension, who were receiving a diuretic plus propranolol qid, were instructed to take their entire daily requirement of propranolol as a single morning dose. Blood pressure was measured in standing and supine positions at the end of a dosing interval. Patients were questioned about the occurrence of specific propranolol side effects during each of four bi-weekly evaluations. Mean blood pressure on once-daily propranolol did not differ significantly from that observed on propranolol qid. Daily doses of propranolol ranged from 80-320 mg. Side effects were infrequent and mild. We conclude that propranolol may be administered as a single daily dose to patients with hypertension whose blood pressure already has been controlled on a qid regimen.

A universally accepted description of appropriate therapy for treatment of congestive heart failure (CHF) has yet to be agreed upon, especially in the elderly. Numerous studies have provided data that question use of a digitalis glycoside as the agent of choice in treatment of chronic CHF. Several clinicians have suggested that diuretics, particularly thiazide diuretics, be used as initial agents in the treatment of this condition. Evidence now demonstrates that drug therapy with enalapril or the combination of hydralazine and isosorbide dinitrate reduces the mortality related to chronic CHF. Additional studies are required to clarify respective roles of diuretics, digitalis glycosides, and vasodilators in the management of chronic CHF.

The ability of a dosing regimen of intravenous theophylline to achieve therapeutic serum theophylline concentrations was evaluated. Intravenous theophylline was administered to 25 adult patients with acute bronchospasm using dosing guidelines 20 percent higher than FDA recommendations. The dose of theophylline was determined by assignment to one of four clinical categories. Blood samples for determination of serum theophylline concentrations were collected 12 and 24 hours after initiation of a constant infusion. Differences between mean observed and target theophylline concentrations did not achieve statistical significance. All patients in categories 1 and 2 achieved therapeutic concentrations of theophylline. Most of those with subtherapeutic levels were smokers suffering from multiple diseases. We conclude that current FDA recommendations for dosing intravenous theophylline are unreliable for routine use in category 3 and 4 patients. Further work is necessary to evaluate these recommendations in pediatric and category 1 and 2 patients.

Lisinopril is a new, nonsulfhydryl angiotensin-converting enzyme inhibitor approved for the treatment of hypertension. After oral administration, 25-29 percent of the dose is absorbed intact; biotransformation is not required for pharmacological activity. Onset of action occurs one to two hours after administration, with effects still present 24 hours later. The major route of elimination is through renal excretion and an elimination half-life of 12.6 hours has been reported in normotensive individuals. In patients with impaired renal function (creatinine clearance less than or equal to 30 ml/min) a longer half-life and accumulation have been observed. Lisinopril 20-80 mg/d has been shown to be as effective as hydrochlorothiazide, nifedipine, and beta-blocking agents in the treatment of essential hypertension. Its efficacy in renovascular hypertension has also been demonstrated. In congestive heart failure (CHF) doses of 2.5-20 mg/d appear to provide hemodynamic effects comparable to those of captopril. Dizziness and cough have been the most frequently reported side effects; rash and proteinuria have also been reported in a small number of patients. Interactions with diuretics, potassium supplements, and possibly with nonsteroidal antiinflammatory agents may occur. Lisinopril appears to be similar in efficacy to other antihypertensive agents in the treatment of essential hypertension and to captopril in the treatment of CHF. Whether lisinopril is safer or more effective than captopril or enalapril in the treatment of hypertension or CHF requires further investigation. Prolonged duration of action of lisinopril allows once daily dosing, unlike captopril for which dosing is required every 8-12 hours or enalapril which may necessitate twice daily dosing.

Initial treatment of elderly hypertensive patients with an angiotensin-converting enzyme inhibitor is currently discouraged due to such patients' typical low-renin profile. To validate this principle, we studied 38 elderly males (aged greater than or equal to 65 years) with mild to moderate hypertension, comparing hemodynamic responses to and subjective impressions of enalapril or hydrochlorothiazide (HCTZ). After gradual withdrawal of existing antihypertensive therapy and a four-week, single-blind placebo period, each patient was randomized in a double-blind fashion to receive either enalapril 10-20 mg/d or HCTZ 12.5-25 mg/d for two to four weeks. Combination therapy with both agents was employed if either alone failed to reduce seated diastolic BP to less than or equal to 90 mm Hg. Equivalent proportions of patients receiving enalapril or HCTZ (8 of 19 and 10 of 19, respectively; p = ns) responded with significant reductions in systolic and diastolic BP in seated and standing positions. Combination therapy was most effective in patients receiving HCTZ prior to enalapril. In patients receiving enalapril before HCTZ, BP changes were minimal. No adverse effects were observed in the enalapril group but occurred in an equivalent fraction of patients in the other groups (4 of 10 HCTZ alone, 6 of 20 enalapril + HCTZ; p = ns). We conclude that enalapril may be considered a reasonable monotherapeutic antihypertensive agent in some elderly patients. Combination with HCTZ is beneficial in patients who fail to respond adequately to HCTZ alone.

Previous research has suggested that concurrent administration of antacid and cimetidine results in lower than expected plasma levels of cimetidine. Because these studies were all of single-dose design, this study was undertaken to determine the nature of the interaction after repeated administration of both drugs. There was no statistically significant difference demonstrated for any of the pharmacokinetic parameters evaluated in the study. Based on these findings, the previous recommendation that administration of antacid and cimetidine be separated in time may not be necessary.