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Biomedical subjects

D B Hunninghake

Publications and source records attributed to D B Hunninghake.

At least 109 records · Page 6Linked to original sources
PubMed1986

Lipids and hypertension. Implications of new guidelines for cholesterol management in the treatment of hypertension.

The approach to management of cardiovascular risk factors has been greatly enhanced by the recent publication of results from several large intervention studies. This increased knowledge has led to rapid changes in perspective and to some controversies regarding cardiovascular risk management. The major cardiovascular disease risk factors are high blood pressure, elevated serum cholesterol, and cigarette smoking. In the past, physicians have paid little attention to the latter two factors, focusing primarily on severe hypertension. Initially, the pharmacologic treatment of hypertension consisted mostly of thiazide diuretics, since they were the only agents generally available that were well-tolerated by most patients. Over the past decade, however, new data from large-scale intervention studies and the development of many new classes of antihypertensive agents have considerably improved the approach to managing all three primary risk factors. Recently published results of major clinical trials are likely to further alter physicians' perspectives and influence their practice habits. This article proposes an approach to comprehensive risk management that simultaneously involves all the major risk factors, with emphasis on blood pressure and lipids. The rationale for this integrated approach is based on the following facts: Hypertension trials have not convincingly demonstrated that lowering blood pressure alone reduces the risk for coronary heart disease; Cholesterol lowering has been shown conclusively to reduce the risk of coronary heart disease; Several classes of antihypertensive agents have now been found to significantly affect blood lipids, either adversely or beneficially; and Past observational epidemiologic studies have shown a positive association between blood lipids (cholesterol and triglycerides) and blood pressure, implying that these two conditions commonly occur together. The background supporting these facts, as well as a practical approach to the treatment of hypertension that takes into consideration the management of blood lipids, is provided in this article.

Adolescent↗
PubMed1986

Influence of time intervals for cholestyramine dosing on the absorption of hydrochlorothiazide.

Ten healthy adult men participated in a study to evaluate appropriate dosing schedules of cholestyramine to minimize its effect on the absorption of hydrochlorothiazide (HCTZ). A single 8 gm dose of cholestyramine 2 hours before or after HCTZ, 75 mg po, significantly decreased the amount of HCTZ excreted unchanged in the urine over 24 hours (Ae(0-24)) by 65% (P less than 0.01) and 26% (P less than 0.05), respectively, in four subjects. Six subjects randomly received three different schedules: control, single dose of cholestyramine 4 hours after HCTZ, and multiple doses of cholestyramine (-24, -12, and +4 hours) after HCTZ. There were no significant differences in HCTZ kinetics between the control group and the subjects who received a single dose of cholestyramine. Multiple doses of cholestyramine significantly altered HCTZ kinetics, including reductions in Ae(0-24) by 35% (P less than 0.02), AUC(0-infinity) by 32% (P less than 0.01), and Cmax by 31% (P less than 0.01). We conclude that the best dosing schedule for cholestyramine is 4 hours after HCTZ, but there will still be at least a 30% to 35% decrease in the absorption of HCTZ.

Absorption↗
PubMed1986

A screening survey of dyslipoproteinemias associated with prescription drug use. The Lipid Research Clinics Program Prevalence Study.

In 10 North American study populations, we surveyed alterations in blood cholesterol, triglyceride, and high-density lipoprotein cholesterol levels associated with the use of 20 categories of prescription medications. In addition, odds ratios for use of these medication categories were determined for five of the more common dyslipoproteinemias found in these populations. Increased lipid levels were found in association with use of several categories of cardiovascular drugs as well as allopurinol and warfarin. Decreased lipid levels were found in association with anti-infective agents and thyroid hormone. Few significant lipid level alterations were found with the use of antihistamines, barbiturates, analgesics, and the phenothiazines. The associations described here must be interpreted cautiously because of limitations in the study design, particularly the confounding effects of the conditions under drug treatment. However, several drug-lipid effects are suggested that may alter lipid levels and that require experimental confirmation. These findings have implications for both clinical management of individuals with dyslipoproteinemias and in the determinants and modification of population lipid levels.

Adult↗
PubMed1985

Carotenoids and vitamin A: the effect of hypocholesterolemic agents on serum levels.

Serum total carotenoid (STC) and vitamin A levels were done as part of the biochemical screening in comparative studies of lipid lowering agents in type Ila hyperlipoproteinemic patients. STC levels were reduced following bile acid sequestering agent administration (colestipol 30 g/d) by 30% (P less than 0.01). Clofibrate and avicel placebo had inconsistent and nonsignificant effects on the STC levels. Serum vitamin A levels were not significantly altered by any of the test agents. The STC level changes were not correlated with concomitant changes in low-density lipoprotein-cholesterol (LDL-C) during any of the treatment regimens. It is suggested that STC level changes are related to alterations in the absorption of carotenoids during bile acid sequestrant administration.

Adult↗
PubMed1985

Effect of clofibrate and colestipol singly and in combination on plasma lipids and lipoproteins in type III hyperlipoproteinemia.

The effects of colestipol, clofibrate, and a combination of these two drugs on plasma lipid and lipoprotein values were evaluated in seven subjects with type III hyperlipoproteinemia. When compared to baseline, colestipol administration resulted in a significant decrease in LDL-cholesterol (146 v 99, P less than 0.01) and a significant increase in VLDL-triglycerides (260 v 399, P less than 0.05). The increases in total triglycerides (346 v 462, P = 0.09) and VLDL-C (117 v 155, P = 0.17) noted with colestipol were not statistically significant. Clofibrate administration increased HDL-C (37 v 46, P less than 0.05), and lowered VLDL-C (117 v 56, P less than 0.05), VLDL-triglycerides (260 v 144, P less than 0.05) and total triglycerides (346 v 218, P less than 0.01). The combined regimen was more effective than clofibrate in lowering total and LDL-cholesterol, and no other significant differences were noted.

Adult↗
PubMed1985

Controlled trial of acifran in type II hyperlipoproteinemia.

The hypolipidemic effects of acifran were evaluated in a randomized, double-blind, placebo-controlled study of 30 patients with type IIa hyperlipoproteinemia. Plasma lipid and lipoprotein values were determined at baseline (mean of three values), again after a 2-week single-blind period of acifran dosing, and at 2-week intervals during a 10-week period of double-blind drug dosing. At week 8, subjects who received the lower dose of acifran (100 mg t.i.d.) showed significantly lower levels of total and low-density lipoprotein cholesterol and triglycerides compared with their baseline levels (P less than 0.01) or the placebo group (P less than 0.05). At week 12, subjects who received the higher dose of acifran (300 mg t.i.d.) had an increase in high-density lipoprotein levels of 16% (P less than 0.01) and a decrease in the ratio of low- to high-density lipoproteins of 22% compared with their baseline levels (P less than 0.01). There were no significant differences in lipid responses between the two groups receiving acifran. Transient mild flushing and pruritus were experienced by some subjects, but no subject failed to complete the study because of drug intolerance or side effects. The safety and efficacy demonstrated in this short-term therapeutic trial justify additional long-term studies with acifran.

Administration, Oral↗
PubMed1985

Effect of time of administration of cholestyramine on plasma lipids and lipoproteins.

Cholestyramine was administered to 15 men with type II hyperlipoproteinemia in a dosage of 8 gm twice daily. For each subject, the p.m. dose was randomly assigned to one of four approximate time periods: mid-afternoon, 30 minutes before the evening meal, 60 minutes after the evening meal, and at bedtime. The time of the morning dose remained constant throughout the study. Each treatment period lasted eight weeks, and all participants completed all four treatment assignments. There was a significant reduction of both total plasma cholesterol (TPC) and LDL cholesterol (LDL-C) compared to baseline values (p less than 0.001) for all treatment regimens. TPC and LDL-C reduction was greatest when the p.m. dose was taken 30 minutes before the evening meal. This reduction was also significantly greater than when the p.m. dose was taken mid-afternoon (p less than 0.05). There was also a significant increase in triglycerides compared to baseline during all treatment periods (p less than 0.05). These findings indicate that the time of the p.m. dose of cholestyramine is important to obtain the maximum reduction of LDL-C. They also reveal that the most effective dosage schedule is administration immediately prior to the evening meal.

Adult↗
PubMed1984

Comparison of effectiveness of thyrotropin-suppressive doses of D- and L-thyroxine in treatment of hypercholesterolemia.

In an attempt to compare the cholesterol-lowering effects of equivalent doses of D- and L-thyroxine, 10 euthyroid, hypercholesterolemic subjects were treated with graded doses of each medication in a cross-over design using thyrotropin suppression following thyrotropin-releasing hormone administration as the end-point. The mean thyrotropin-suppressive dose of D-thyroxine was 2.4 +/- 0.66 mg per day, which resulted in mean reductions of 10 percent in total plasma cholesterol, 10 percent in plasma low-density lipoprotein cholesterol, and 11 percent in plasma high-density lipoprotein cholesterol. The mean thyrotropin-suppressive dose of L-thyroxine was 135 +/- 46 micrograms per day, which resulted in mean reductions of 7 percent in total plasma cholesterol, 6 percent in plasma low-density lipoprotein cholesterol, and 14 percent in plasma high-density lipoprotein cholesterol. The reductions in total, low-density, and high-density cholesterol achieved with D-thyroxine were not significantly different from those achieved with L-thyroxine. Neither medication produced a significant increase in heart rate or ventricular ectopy as determined by Holter monitoring. These data do not support the belief that D-thyroxine has a preferential cholesterol-lowering effect in humans when compared with equivalent doses of L-thyroxine. In addition, both D- and L-thyroxine reduced plasma high-density lipoprotein cholesterol.

Adult↗
PubMed1984

Effect of cimetidine on plasma lipids and lipoproteins.

The effect of oral cimetidine on plasma lipid and lipoprotein levels was evaluated in a double-blind crossover study in 12 normal subjects and in 12 subjects with fasting serum glucose levels greater than or equal to 140 mg% or levels after a 100-gm oral glucose dose greater than or equal to 170 mg%. Plasma cholesterol (total, high-density, low-density, and very low-density lipoprotein) and triglyceride (total and very low-density lipoprotein) concentrations in placebo and cimetidine periods did not differ. Cimetidine was associated with elevated serum creatinine and aspartate amino transferase (SGOT) levels. One subject was impotent while on cimetidine.

Adult↗
PubMed1984

Effects of cholestyramine and colestipol on the plasma concentrations of propranolol.

The effect of equivalent hypolipidaemic doses of cholestyramine (8 g) or colestipol (10 g) on the plasma concentrations of propranolol and 4'-hydroxypropranolol was studied in 12 normal volunteers following the oral administration of 120 mg of normal release propranolol tablets. When two doses of either cholestyramine or colestipol were administered prior to the propranolol, the peak plasma concentrations and area under the curve for both propranolol and the metabolite 4'-hydroxypropranolol were reduced significantly (P less than 0.05). We conclude that the drug interaction between cholestyramine or colestipol and propranolol leads to significant reductions in plasma concentrations of propranolol and 4'-hydroxypropranolol which may cause a clinically diminished effect for a given dosage. Therefore, patients should be observed when either of these resins are added to or deleted from a therapeutic regimen.

Adult↗
PubMed1984

Plasma concentrations of flecainide acetate, a new antiarrhythmic agent, in humans.

Flecainide, a new antiarrhythmic agent, was given to eight healthy men to ascertain plasma drug levels and to assess tolerance for the drug. Each subject received a single intravenous (IV) dose (0.5, 1, 1.5, or 2 mg/kg) of flecainide, and plasma levels of unchanged flecainide were measured by gas-liquid chromatography. After an initial rapid distribution phase, the drug's plasma half-life (terminal elimination phase) ranged from seven to 15 hours (mean, 11 hours); half-life was apparently independent of dose level. Immediately after IV administration, the relatively high plasma drug levels seen during the short distribution phase were associated with minor and transient side effects in some subjects receiving the two higher doses; overall, the drug was well tolerated. Plasma flecainide levels 60 minutes after administration (after distribution) ranged from 52 to 300 ng/ml and were reasonably proportional to dose level. The drug's relatively long plasma half-life in humans indicates that plasma levels will be maintained for prolonged periods; thus flecainide should provide sustained therapeutic activity in patients with cardiac arrhythmias.

Adult↗
PubMed1983

Pharmacologic therapy for the hyperlipidemic patient.

Drug therapy should be instituted only after appropriate diet treatment has been started and adequate baseline lipid and lipoprotein values are established. Nicotinic acid is useful in treating most lipoprotein disorders and the cutaneous flushing that develops during the early part of treatment is usually alleviated by aspirin. Cholestyramine and colestipol are nonabsorbable resins whose use is limited to type II hyperlipoproteinemia. Clofibrate is primarily effective in lowering triglyceride levels, but its clinical use has considerably declined following the World Health Organization study results that reported increased morbidity and mortality rates among patients receiving this drug. Based on the finding of increased mortality among a subset of patients participating in the Coronary Drug Project, dextrothyroxine is only recommended for treating patients who do not have clinically evident atherosclerotic heart disease. Probucol lowers total and low-density lipoprotein cholesterol levels, but has the undesirable effect of simultaneously reducing high-density lipoprotein levels.

Bile Acids and Salts↗
PubMed1983

A multiclinic double-blind comparison of timolol and hydrochlorothiazide alone and in combination in th e treatment of essential hypertension.

In a multicenter randomized double-blind trial, we compared the antihypertensive effects of 12 weeks of therapy using timolol maleate, a new beta-adrenergic blocking agent, alone and in combination with hydrochlorothiazide, and hydrochlorothiazide alone in 70 outpatients with mild to moderate uncomplicated essential hypertension (61 of whom completed the study). All three groups showed significant blood pressure reductions in both supine and standing positions which were most marked in the timolol-hydrochlorothiazide group (154/103 leads to 129/85 mm Hg). A good or excellent therapeutic response was obtained in 20 of 21 patients in the timolol-hydrochlorothiazide group. In 16 of 20 patients receiving timolol alone, and in 10 of 20 receiving hydrochlorothiazide alone. Adverse reactions were minimal in all treatment groups but highest in the hydrochlorothiazide group. It was concluded that timolol-hydrochlorothiazide combination is more effective than either drug alone for management of hypertension and that timolol alone or with hydrochlorothiazide is well tolerated.

Adult↗
PubMed1983

Effect of cholestyramine and colestipol on the absorption of phenytoin.

The hypocholesterolemic cation resins, cholestyramine and colestipol, have variable effects on the absorption parameters of a number of lipophillic, anion drugs. Because of the unpredictable nature of this interaction, we have assessed in human volunteers the effect of these resins on the rate and total absorption of phenytoin. Our results indicate that these resins do not affect the absorption parameters of phenytoin and that special care does not have to be exercised when these agents are co-administered.

Adolescent↗
PubMed1983

Alterations in human serum alkaline phosphatase and its isoenzymes by hypolipidemic agents: colestipol and clofibrate.

Total serum alkaline phosphatase (TSAP) determinations were done as part of the biochemical screening in comparative studies of lipid lowering agents in type lla hyperlipoproteinemic patients. TSAP determinations were made by using a modification of the Bessey-Lowry method and the Statland method. Increases in TSAP following colestipol treatment of 20% (P less than 0.05) and 32% (P less than 0.005) were seen by using the respective methods. Isoenzymatic determinations were done by employing the Statland method and all fractions were increased from baseline levels during colestipol therapy. Clofibrate was associated with 34% (P less than 0.005) and 28% (P less than 0.005) reductions in TSAP activity by using the respective methods; significant reductions in both "bone" and "other" isoenzymatic components occurred. Gamma-glutamyltransferase (gamma GT) results did not consistently reflect TSAP or "liver" isoenzyme results.

Adult↗
PubMed1982

Increased leucocyte oxidative metabolism in hyperlipoproteinaemia.

Polymorphonuclear leucocytes (PMN) from a group of subjects with hyperlipoproteinaemia (HLP) had higher oxidative metabolism with greater release of superoxide anion (O2-) than PMN from age-matched controls. Release of O2- was significantly correlated with serum cholesterol and light-density-lipoprotein-cholesterol levels, PMN from HLP subjects also has higher hexose monophosphate shunt activity and chemiluminescence than controls. A causal relation was suggested by the finding that oxidative metabolism was normal in a group of HLP subjects whose lipid levels were lowered by treatment with cholestyramine.

Arteriosclerosis↗
PubMed1982

The effect of cholestyramine and colestipol on the absorption of hydrochlorothiazide.

The effect of cholestyramine and colestipol on the absorption of a single orally administered dose of 75 mg hydrochlorothiazide was determined. Both urinary excretion and plasma levels of hydrochlorothiazide were measured. Cholestyramine or colestipol administration decreased the total urinary excretion of hydrochlorothiazide by 85 and 43%, respectively. Similar effects were also noted on plasma hydrochlorothiazide levels.

Adolescent↗