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Biomedical subjects

R Okun

Publications and source records attributed to R Okun.

At least 19 recordsLinked to original sources

Antihypertensive and metabolic effects of concomitant administration of terazosin and methyclothiazide for the treatment of essential hypertension.

The efficacy and safety of once-daily 2.5- or 5.0-mg methyclothiazide (MCTZ) added to once-daily 5.0-mg terazosin (TRZ) versus 5.0-mg TRZ alone was evaluated in this double-blind, multicenter study. All patients received TRZ during a 6-week titration period. Hypertensive patients (222) (mean blood pressure of 159/104 mm Hg) were randomized to one of three treatment groups: TRZ alone (N = 76); TRZ+MCTZ-2.5 mg (N = 74); and TRZ+MCTZ-5.0 mg (N = 72) for the 8-week double-blind period. Changes in the supine and standing SBP/DBP from preTRZ period were: TRZ alone (-4.8/-8.1 and -2.6/-6.1 mm Hg); TRZ+MCTZ-2.5 mg (-17.3/-12.4 and -16.0/-11.2 mm Hg); and TRZ+MCTZ-5.0 mg (-20.6/-14.4 and -23.3/-14.6 mm Hg). Blood pressure changes in the combination groups were significantly greater than those in the TRZ alone group. However, there were no statistically significant differences between the TRZ+MCTZ-2.5-mg and TRZ+MCTZ-5.0-mg groups. The combination of TRZ and MCTZ tends to mitigate the adverse effects on serum glucose, uric, potassium and lipids usually associated with thiazide diuretics. Thus, combination treatment that begins with TRZ and adds MCTZ is effective in lowering blood pressure without any significant adverse metabolic effects.

Adrenergic alpha-Antagonists↗

Prazosin versus captopril as initial therapy. Effect on hypertension and lipid levels.

A randomized, parallel group study evaluated the safety, efficacy, and effect of the alpha blocking agent prazosin and the angiotensin converting enzyme inhibitor captopril on serum lipid levels in patients with mild to moderate hypertension. Baseline evaluations were performed on 31 patients after a four-week placebo washout period. Patients were randomly assigned to receive either prazosin (n = 15) or captopril (n = 16). Daily doses were titrated as follows: for prazosin, 1 mg two times daily to maximum of 20 mg per day; for captopril, 25 mg three times daily to a maximum of 450 mg per day. If diastolic blood pressure was not adequately controlled (less than 85 mm Hg) after four weeks of monotherapy, 1 mg of polythiazide was added to the daily regimen. There were no statistically significant differences between the drug groups for the measured variables in either the parallel or crossover phase of the study. Five of 15 prazosin-treated patients and six of 16 captopril-treated patients required the addition of thiazide to achieve blood pressure control.

Adult↗

Management of hypertension in patients with concomitant diseases.

The treatment of hypertension in patients with diabetes, obstructive airway disease, impaired renal function, or congestive heart failure (CHF) is discussed. Specifically, the value of alpha 1-adrenoceptor blocking agents in such patients is reviewed. An individualized approach to therapy is required, with careful consideration of the effects of different drugs on the existing metabolic and hemodynamic situation. In diabetic individuals, commonly used step-1 agents may impair glucose tolerance; beta-adrenergic blockade may increase blood glucose levels and significantly change response to insulin-induced hypoglycemia. Diabetic patients may also be especially sensitive to side effects of some centrally acting antihypertensive agents. In patients with obstructive airway disease, beta-blockade and alpha-stimulation worsen bronchospasm; although beta-stimulants produce bronchodilatation, they often are contraindicated in hypertensive patients due to their stimulatory effects on the heart. In patients with impaired renal function, therapy for hypertension may include problems such as an increased half-life of antihypertensive agents and retention of active metabolites. In patients with CHF, if blood pressure is not normalized with diuretics, more aggressive therapy may be required. According to results of several studies discussed, the alpha 1-adrenoceptor blocking-agent prazosin appears to be a safe and effective therapy, causing a minimum of side effects, for treatment of hypertension in patients with these conditions.

Antihypertensive Agents↗

A comparison of prazosin versus nadolol in combination with a diuretic.

The comparative efficacy and effects on total body potassium of prazosin and polythiazide vs nadolol and polythiazide in the treatment of patients with mild to moderate essential hypertension unresponsive to diuretic alone were compared in an open, crossover trial involving 20 male patients. Both prazosin and nadolol reduced blood pressure to goal values in both study phases. Side effects were minor, and only 1 patient dropped out of treatment for reasons unrelated to the study drugs. Neither prazosin nor nadolol in combination with thiazide had significant additional adverse effects on total body potassium. These findings confirm that the efficacy of prazosin is equivalent to that of nadolol in the long-term management of patients with essential hypertension.

Adrenergic beta-Antagonists↗

Effectiveness of prazosin as initial antihypertensive therapy.

After nearly 10 years in clinical use, prazosin has been shown in numerous studies worldwide to be an effective antihypertensive agent over the entire range of hypertension (mild, moderate, and severe), when used alone or in multitherapy. In addition to its general effectiveness, prazosin is particularly useful in specific subpopulations of hypertensive patients, such as those with impaired renal function, those on hemodialysis, and those with concomitant heart block, bronchospasm, diabetes mellitus, or disturbed carbohydrate metabolism, hyperlipidemia, or hyperuricemia. The side effects of prazosin are usually mild and transient and seldom require discontinuation of the drug. Sexual dysfunction is uncommon. In clinical experience with 22,000 patients receiving an initial dose of 1 mg of prazosin, syncope was reported in 1 of every 667 patients (0.15%). Withholding diuretics for 1 day before initiating prazosin therapy, utilizing prazosin as first-line therapy, limiting the initial dose to 1 mg, and taking it at bedtime are all helpful in eliminating many of the initial adverse effects. Fluid retention, although rare and not as pronounced as that with other antihypertensive agents, may develop on long-term therapy and may necessitate the addition of a diuretic later on.

Blood Pressure↗

Analgesic effects of oral nalbuphine and codeine in patients with postoperative pain.

Efficacy and safety of oral nalbuphine in doses of 15 and 45 mg were compared with those of the standard oral analgesic codeine in single doses of 30 and 90 mg in 153 patients with acute postoperative pain; data on 20 more patients were excluded because they received potentially interfering medications. All patients had pain ranging from moderate to severe in intensity and most had severe pain related to orthopedic procedures or trauma. Estimates of relative potency showed that nalbuphine was three times as potent as codeine. The most common side effect was sedation, which was greatest in patients who received the higher doses of codeine and nalbuphine. The effects of oral nalbuphine are much like those of oral codeine in patients with acute postoperative pain.

Adolescent↗

A double-blind study of tienilic acid with two year follow-up of patients with mild to moderate essential hypertension.

In a double-blind study, thirty patients having mild to moderate essential hypertension were randomly assigned to a six week regimen of either tienilic acid, hydrochlorothiazide, or placebo. Blood pressure was significantly reduced with tienilic acid and hydrochlorothiazide although more so with tienilic acid. Serum uric acid declined strikingly with tienilic acid and increased significantly with hydrochlorothiazide. Serum potassium declined slightly with tienilic acid but more so with hydrochlorothiazide. Serum creatinine and blood urea nitrogen increased slightly more with tienilic acid than with hydrochlorothiazide. There were no clinical adverse effects to any of the medications during this study. Twenty-four months of continuous administration of tienilic acid revealed maintenance of blood pressure effect, but with slight increases in blood urea nitrogen, serum creatinine and uric acid and slight decreases in serum potassium as compared to six weeks administration. Tienilic acid appears to be a useful new antihypertensive agent. The hypouricaemic effect is profound and strongly suggests the need for continuing evaluation of this compound because of its unique combination of diuretic, antihypertensive and hypouricaemic properties.

Adult↗

Ticrynafen and hydrochlorothiazide in hypertension.

In a double-blind study, 28 patients having mild to moderate essential hypertension were randomly assigned to a 6-week regimen of ticrynafen, hydrochlorothiazide, or placebo. Blood pressure fell after ticrynafen and hydrochlorothiazide. Serum uric acid fell strikingly with ticrynafen whereas it rose with hydrochlorothiazide. Serum potassium declined very little with ticrynafen; much less than with hydrochlorothiazide. Serum creatinine and blood urea nitrogen rose slightly more with ticrynafen than with hydrochlorothiazide. There were no clinical adverse effects to either of the medications. Ticrynafen appears to be an effective antihypertensive with a substantial hypouricemic effect.

Adult↗

Feasibility of low-dose and intermittent chenodeoxycholic acid therapy of gallstones.

Chenodeoxycholic acid, by reducing the concentration of biliary cholesterol relative to that of bile acid and phospholipid, dissolves cholesterol gallstones. This bile acid, however, has potential dose-related hepatotoxicity and causes dose-related diarrhea. Therefore, the feasibility of low-dose and intermittent therapy was assessed by studying the induction and persistence of chenodeoxycholic acid-induced biliary lipid changes. Biliary lipid composition with each of 3 doses of chenodeoxycholic acid was determined in bile samples obtained by cholecystokinin-stimulated duodenal drainage before, after one week and one month of treatment, and up to 9 weeks after discontinuation of treatment. The lowest dose that significantly reduced the relative concentration of biliary cholesterol was 250 mg/day. A significant reduction occurred one week after initiation of treatment and was maintained for 9 weeks following discontinuation of treatment. Thus, clinical trials on low-dose and intermittent chenodeoxycholic acid therapy for gallstone prophylaxis or dissolution are warranted.

Adult↗

Long-term efficacy and safety of prazosin in essential hypertension.

The long-term efficacy and safety of prazosin plus a thiazide diuretic in severe hypertension has been evaluated in an open trial that is now in its fifth year. The combination is consistently effective in reducing diastolic blood pressure to 90 mm Hg or less. No side effects or adverse reactions have been observed except a "first-dose" fall in blood pressure, and there is no evidence of development of tolerance to the agent.

Adult↗