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Biomedical subjects

W Flamenbaum

Publications and source records attributed to W Flamenbaum.

At least 19 recordsLinked to original sources
PubMed1996

Pharmacokinetic interactions of moricizine and diltiazem in healthy volunteers.

Sixteen healthy male volunteers completed a nonrandomized, sequential, three-phase study. The three phases were 1) moricizine at 250 mg every 8 hours for 7 days with 12 days washout; 2) diltiazem at 60 mg every 8 hours for 7 days; and 3) concomitant administration of moricizine at 250 mg and diltiazem at 60 mg every 8 hours for 7 days. The plasma concentration-time profiles were obtained at the end of each phase for moricizine, diltiazem (with its metabolites desacetyl-diltiazem and N-desmethyl-diltiazem), and both when administered together. Under steady-state conditions, there was a two-way (opposing) pharmacokinetic drug interaction when moricizine and diltiazem were coadministered in healthy volunteers. Both maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve from time 0 to the end of administration (AUC tau) of moricizine increased significantly by 88.9% and 121.1%, respectively. Oral clearance (Clo) decreased by 54%. The terminal half-life (t1/2) of moricizine was not affected, however (2.1 +/- 0.5 hours versus 2.4 +/- 0.7 hours). It is believed that these changes were due to the inhibition of hepatic metabolism by diltiazem, which resulted in an increased systemic availability of moricizine. Moricizine had opposite effects on the pharmacokinetics of diltiazem. Moricizine decreased the Cmax of diltiazem significantly (by 36%) and increased Clo by 52%. A small but statistically significant decrease in the t1/2 from 4.6 +/- 1.3 hours to 3.6 +/- 0.7 hours was observed. Despite this result, no remarkable changes (e.g., in Cmax, AUC, or t1/2) were found for the two major diltiazem metabolites desacetyl-diltiazem and N-desmethyl-diltiazem. It appears that the pharmacokinetic interaction of moricizine and diltiazem was metabolic. With the increase in moricizine concentrations and the decrease in diltiazem concentrations, adjustments in dose may be required to achieve optimal therapeutic response when coadministering both agents.

Adolescent↗
PubMed1994

Comparison of the efficacy and tolerability of an angiotensin converting enzyme inhibitor (lisinopril) versus a calcium channel antagonist (diltiazem SR) in the treatment of moderate to severe hypertension.

One hundred and ten patients (mean age 50.6 years) with moderate to severe essential hypertension (DBP between 105 and 116 mmHg) were randomised to eight weeks of double-blind treatment with lisinopril (n = 56) or diltiazem SR (n = 54). Fourteen patients withdrew from therapy; six patients withdrew because of adverse events (lisinopril, n = 3; diltiazem SR, n = 1) and lack of BP control (lisinopril, n = 1; diltiazem SR, n = 1). Both monotherapies were titrated upward (lisinopril 20-40 mg daily, diltiazem SR 120-180 mg twice daily) to achieve an office DBP < 90 mmHg. Hydrochlorothiazide (HCTZ; 25 mg daily) was added to monotherapy after week 4 if patients did not reach the BP goal (i.e. non-responders). After four weeks of therapy, 72% of patients (74 of 103) were nonresponders. At eight weeks of therapy, 66 patients (lisinopril, n = 32; diltiazem SR, n = 34) had received HCTZ. At week 8, 53% of lisinopril and 36% of diltiazem SR patients met the response criteria. Mean office DBP decreased from baseline -18.1 +/- 8.6 mmHg for lisinopril patients and -15.9 +/- 10.1 mmHg for diltiazem SR patients at week 8. Lisinopril was as effective as diltiazem in reducing systolic and diastolic office BP at week 4 (p > 0.1). Likewise, at weeks 4 and 8, no statistically significant differences were detected between treatments (p > 0.05) for systolic and diastolic ambulatory BP averaged over 24 hours. Both treatments were well tolerated and showed important antihypertensive efficacy in patients with moderate to severe BP elevation.

Blood Pressure↗
PubMed1994

Lower dose diuretic therapy in the treatment of patients with mild to moderate hypertension.

Indapamide (Lozol), an indoline antihypertensive drug with diuretic and vasodilating activities, was evaluated in 195 patients with mild to moderate essential hypertension (sitting DBP between 95 and 110 mmHg) in a multicentre, randomised, double-blind, parallel-group design trial. A four week single-blind placebo wash-out period was followed by an eight week double-blind period. Patients were randomised to indapamide 1.25 mg/day or to placebo. The primary efficacy endpoint was the mean change in sitting DBP from baseline to week 8. Ninety patients in the placebo group (93%) and 82 patients (84%) in the indapamide group completed the eight weeks of double-blind therapy. Indapamide produced a mean (SE) decrease in sitting DBP of 7.4 (0.63) mmHg (from 100.1 to 92.8 mmHg) compared with a decrease of 3.6 (0.75) mmHg (from 99.6 to 95.8 mmHg) produced by placebo (p < 0.0001). Indapamide and placebo also produced mean decreases in standing DBP of 6.8 (0.75) and 2.8 (0.77) mmHg, respectively (p = 0.0002), in sitting SBP of 11.1 (1.18) and 3.2 (1.35) mmHg, respectively (p = 0.0001) and in standing SBP of 11.4 (1.29) and 4.0 (1.43) mmHg, respectively (P = 0.0002). Reduction in BP of > or = 10 mmHg or to a DBP of < or = 90 mmHg was more frequent (P = 0.0005) among indapamide (46.6%) compared with placebo (23.7%) treated patients. During the eight week double-blind treatment period, incidence rates for all adverse experiences and for drug-related adverse experiences were similar between the two treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Dose ranging efficacy and safety of subcutaneous sumatriptan in the acute treatment of migraine. US Sumatriptan Research Group.

Sumatriptan, a specific serotonin1-like receptor agonist, was studied in the acute treatment of migraine. Two hundred forty-two adult migraineurs participated in a randomized, double-blind study in which one dose of 1, 2, 3, 4, 6, or 8 mg of subcutaneous sumatriptan succinate was evaluated in sequential ascending fashion. At each dose level, a placebo group was included. Efficacy was defined as reduction of moderate or severe pain to mild or no pain, without the use of rescue medication. Headache relief rates showed an approximate dose-response relationship and at 1 hour were as follows: placebo, 24%; 1 mg, 43%; 2 mg, 57%; 3 mg, 57%; 4 mg, 50%; 6 mg, 73%; and 8 mg, 80%. Relief of nausea and improvement in clinical disability were also approximately dose related. Adverse events were dose related; the most common types were injection site reactions and tingling. The 6-mg dose was as effective as the 8-mg dose but was associated with fewer adverse effects and so is optimal.

Adult↗
PubMed1989

Hypertension, changes in high-density lipoproteins and antihypertensive therapy.

The risk for development of coronary heart disease (CHD) is related to a number of factors. Among these, both hypertension and various lipid abnormalities have been shown to play an important role. A clear inverse relation between high-density lipoprotein (HDL) cholesterol and CHD has been observed in numerous observational and short studies. Pharmacologic treatment of hypertension has been shown to reduce dramatically some of the sequelae of high blood pressure--renal failure, cerebrovascular accidents and congestive heart failure. However, a consistent reduction in associated CHD has not been demonstrated, and the dissociation between reducing blood pressure and reduction in CHD has not been definitively explained. One of the suggested explanations relates to alterations in blood lipid levels that may be induced by certain antihypertensive agents. Changes in HDL cholesterol levels or other lipid alterations due to antihypertensive therapy could modify the beneficial effects achieved by the direct reduction of blood pressure. If so, antihypertensive agents could be subclassified as atherogenic or antiatherogenic depending on the associated changes in lipid levels. Therefore, the antihypertensive agents of choice for patients whose cholesterol levels are a concern would be those that reduce the CHD risk factor of hypertension without compromising the risk factor associated with a patient's lipid profile.

Antihypertensive Agents↗
PubMed1989

Celiprolol in systemic hypertension.

The safety and efficacy of orally administered celiprolol, a new beta 1-selective adrenergic blocking drug with peripheral beta 2-agonist properties, were assessed in 91 patients with mild to moderate systemic hypertension (supine diastolic blood pressure [BP] 95 to 114 mm Hg without medication) using a placebo-controlled, double-blind, randomized, titration-to-effect study design. All patients received placebo for 4 weeks and were then randomized to receive placebo (n = 46) or once-daily celiprolol (n = 45), which was titrated every 2 weeks (200, 400, 600 mg/day) over a 6-week period to achieve a reduction in supine diastolic BP to less than or equal to 90 mm Hg. Plasma lipids and lipoproteins were also assessed at baseline, during placebo and after randomization to active therapy in a subgroup of patients. Compared with placebo, celiprolol reduced supine and standing BP (reduction of supine BP -0.4/-2.1 mm Hg with placebo, -5.7/-6.4 with celiprolol, p less than 0.05; reduction of standing BP -1.7/-1.0 with placebo, -7.2/-4.9 with celiprolol, p less than 0.05). Supine heart rate was reduced by 6.8 beats/min with celiprolol compared with 2.0 beats/min with placebo (p less than 0.05). No differences were seen when the effects of placebo and celiprolol on plasma lipoproteins were compared. Celiprolol is a safe, effective and well tolerated once-daily antihypertensive drug and has no detrimental effects on plasma lipids.

Antihypertensive Agents↗
PubMed1989

Beta-blockers and hypertension.

While there is general agreement on the natural history, pathology, and pathophysiology of hypertension, there continues to be controversy over the selection of specific antihypertensive agents. All antihypertensive agents will, by definition, lower blood pressure, and factors beyond side effects and other difficulties associated with therapy form the basis of selecting specific agents. One of these factors is the effect of a given drug on core organ function. Propranolol was the first beta-adrenoceptor-blocking agent introduced for the treatment of hypertension. Initiation of therapy with propranolol may result in a decline in blood pressure more at the expense of cardiac function due to a concomitant rise in total peripheral resistance. Furthermore, propranolol may result in a decline in both glomerular filtration rate (GFR) and renal blood flow (RBF). In contrast, cardioselective beta-blockers or those with intrinsic sympathomimetic activity may not adversely affect renal function. It had been predicted that nadolol, a noncardioselective beta-blocker without intrinsic sympathomimetic activity, should result in decreased renal function. In contrast, observations demonstrated a preservation or improvement in both RBF and GFR, suggesting the presence of an alternative effective mechanism. Recent additions to the beta-adrenolytic group of antihypertensive agents include drugs with concurrent beta-blockade and vasodilation. This vasodilatation may be achieved through agonist properties resulting in lesser increases in vasomotor tone and smaller, if any, decreases in cardiac output. Alternatively, vasodilation may be achieved by concomitant alpha-adrenoceptor blockade, such as with labetalol. This agent preserves GFR and RBF during therapy of hypertension, in patients with normal as well as diminished renal function and hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1988

Epoprostenol (PGI2, prostacyclin) during high-risk hemodialysis: preventing further bleeding complications.

The frequency of hemodialysis-associated hemorrhage was studied prospectively in two successive, parallel, heparin-controlled studies using epoprostenol (PGI2; average dose, 4.1 ng/kg.min) as the sole antithrombotic agent. Sixty-three patients with active or recently active bleeding underwent 163 hemodialysis treatments in each of which prospective bleeding risk was assessed. PGI2 was associated with up to 50% overall reduction in the frequency of bleeding, particularly in the highest risk circumstances. PGI2 also allowed successful completion of the full, prospectively prescribed hemodialysis time in the most treatments (82% versus 93% with heparin). Furthermore, the efficiency of hemodialysis using PGI2, as indicated by the reduction in concentration of blood urea nitrogen and serum creatinine, was equal to that using heparin, even though there was a tendency toward modest reduction in residual volume of the hollow fiber dialyzer and slightly more frequent early termination of treatment from dialyzer clotting with PGI2. No severe vasodilatory side effects of PGI2 were observed during these studies. Hypotension was equally frequent during hemodialysis with heparin as with PGI2. The current results suggest that PGI2 should be considered as a substitute for heparin during high-risk hemodialysis because PGI2 may reduce the incidence of dialysis-associated bleeding without severe adverse side effects.

Adolescent↗
PubMed1987

Treatment of hypertension in the elderly.

The objective of treating the elderly patient with hypertension should be to reduce blood pressure to safe levels (systolic blood pressure less than 180 mm Hg), while minimizing adverse effects and changes in life-style. If the clinician considers the unique physiologic, pharmacologic, and psychosocial characteristics of this population, he will be successful in attaining these goals.

Aged↗
PubMed1986

Diuretic use in the elderly: potential for diuretic-induced hypokalemia.

The more potent "loop" diuretics are being used with increasing frequency. The elderly constitute a growing portion of the population undergoing treatment with diuretics. The alterations in renal function and pharmacokinetics in the elderly (over 60 years of age) may result in the development of certain adverse effects. In patients over 70 years old, there is a progressive decline in overall renal function, resulting in a more than 50% decrease in glomerular filtration rate. Most of the pharmacokinetic changes in the elderly consist of alterations resulting in enhanced plasma levels of any given drug; diminished hepatic drug extraction, detoxification/metabolism or prodrug conversion; decreased renal excretion of drug; and diminished volume of distribution of drug. Adverse reactions to diuretics may be grouped into metabolic changes (e.g., hypokalemia), physiologic alteration (e.g., volume contraction), toxic manifestation (e.g., interstitial nephritis) and allergic or idiosyncratic phenomena (e.g., rash or thrombocytopenia). There is general agreement that significant hypokalemia, particularly among elderly patients receiving digitalis glycosides, is significant and requires therapy. Diuretic-associated hypokalemia reflects the potency and duration of action of a diuretic, factors modulating potassium balance including dietary intake and concurrent medical processes. The short duration of action and greater natriuresis relative to kaliuresis characteristic of loop diuretics may result in a lesser degree of hypokalemia than that seen with traditional thiazide diuretics.

Aged↗
PubMed1986

Obesity and hypertension. Demonstration of a "floor effect".

Weight loss has a role in the treatment of essential hypertension. With the use of a medically supervised protein-sparing supplemented fast and a behavioral program, the changes in blood pressure as a result of weight loss in 135 obese hypertensive subjects were examined. Subjects' weight, blood pressure, and antihypertensive medication intake were recorded at baseline, at conclusion of supplemented fast, and at follow-up. Significant weight loss accompanied by decrements in blood pressure occurred in all subjects. Reductions in the number of antihypertensive medications also occurred. Although the correlations between changes in weight and blood pressure were significant, their moderate size suggests the amount of weight loss accounted for a relatively small part of the blood pressure reduction. Given the large weight losses in the majority of subjects, there appears to be a degree of weight loss beyond which further decrements in blood pressure will not occur ("floor effect"). Maintenance of blood pressure reductions at realimentation/follow-up suggests that weight loss, and not the supplemented fast, results in decreased blood pressure and medication level.

Adult↗
PubMed1986

Isolated hypoaldosteronism and abnormalities in renin, kallikrein, and prostaglandin.

To further define the pathophysiology of the syndrome of acquired isolated hypoaldosteronism, we determined plasma concentrations of active and inactive renin and urinary kallikrein and prostaglandin E2 excretion rates in 11 patients with the syndrome, 12 patients with similar serum creatinine levels, but without hyperkalemia, and in 12 normotensive patients with normal renal function and low plasma renin activities (PRA). Ten of 11 patients with the syndrome had low baseline PRA, and, unlike the control groups, six of 11 failed to double their PRA after furosemide stimulation. There were also consistent abnormalities in the percentage of inactive renin, no patient having a value less than and no control subjects having a value greater than 65%. Seven of 11 patients had prostaglandin E2 excretion rates lower than either control groups. Urinary kallikrein excretion rates in the patients with isolated hypoaldosteronism were significantly lower than in the control groups, but increased in response to therapy with fludrocortisone.

Adult↗
PubMed1985

Effect of zinc supplementation on hyperprolactinaemia in uraemic men.

Zinc and prolactin levels were measured in 32 male haemodialysis patients; 12 were receiving 50 mg zinc per day as zinc acetate and 20 were not. Zinc-treated patients had significantly higher plasma zinc levels (134 +/- 10 micrograms/dl v 88 +/- 2 micrograms/dl) and lower serum prolactin levels (11 +/- 4 ng/ml v 29 +/- 7 ng/ml) than untreated patients. Plasma zinc and serum prolactin were inversely related in zinc-treated and untreated patients (r = -0.79, p less than 0.001).

Adult↗
PubMed1985

The changing spectrum of heroin-associated nephropathy.

Thirty-five renal biopsies were performed on heroin abusers at our institution between January 1977 and June 1983 as part of the evaluation of unexplained heavy proteinuria. Twenty-eight patients (80%) had histopathologic diagnoses of either focal segmental glomerulosclerosis or renal amyloidosis. Patients having a diagnosis of renal amyloidosis were older (P = 0.025), had a longer history of heroin abuse (P = 0.05), and 13/14 demonstrated clear evidence of chronic subcutaneous suppurative lesions. The remaining seven patients demonstrated a spectrum of disease similar to that seen in the nonaddicted population. We compared the clinical and biopsy characteristics of patients evaluated between 1977 and 1980 with those seen between 1981 and 1983. The relative incidences of renal amyloidosis and focal glomerulosclerosis changed significantly (P = 0.025). Whereas 29% of patients in the early series had renal amyloidosis and 57% had focal glomerulosclerosis, the relative incidences in the later series were 48% and 29%, respectively. The development of renal amyloidosis in our patients appears to be related to a longer duration of heroin abuse with increased incidence of subcutaneous injection of the narcotic. Chronic, suppurative skin ulcerations tend to occur at the site of injection, resulting in a persistent acute-phase inflammatory state important for the initiation and potentiation of secondary amyloidosis.

Adult↗