Biomedical subjects

M Zisblatt

Publications and source records attributed to M Zisblatt.

16 recordsLinked to original sources

PubMed1984

The efficacy of a potassium-sparing combination of chlorthalidone and triamterene in the control of mild and moderate hypertension. I.

Chlorthalidone 25 mg/triamterene 50 mg in once-daily oral doses was as effective in reducing blood pressure as chlorthalidone 25 mg alone. The decrease in serum potassium was statistically significantly less with the combination than for chlorthalidone. There were no notable differences between the treatments in any other measure of laboratory safety or adverse reactions.

Adult↗

PubMed1984

The efficacy of a potassium-sparing combination of chlorthalidone and triamterene in the control of mild and moderate hypertension. II.

Chlorthalidone 50 mg/triamterene 50 mg in once-daily oral doses was as effective in reducing blood pressure as chlorthalidone 50 mg alone. The decrease in serum potassium was statistically significantly less with the combination than for chlorthalidone. There were no notable differences between the treatments in any other measure of laboratory safety or adverse reaction.

Adult↗

PubMed1984

Chlorthalidone-triamterene: a potassium-sparing diuretic combination for the treatment of oedema.

The efficacy of a once-daily combination of chlorthalidone 50 mg plus triamterene 50 mg or chlorthalidone 100 mg plus triamterene 100 mg was compared to that of chlorthalidone 50 mg or 100 mg. This double-blind study was carried out in eighty-eight patients over a treatment period of 12 weeks. All patients entered the active medication period of 12 weeks after a placebo run-in period of 3 to 7 days, during which pretibial or malleolar pitting oedema averaging 2 to 4 mm developed. All patients started at the lower doses, i.e. forty-one started on chlorthalidone 50 mg plus triamterene 50 mg and forty-seven started on chlorthalidone 50 mg. The protocol provided for doubling the dose (but not for reducing it thereafter) at any time during the 12-week period when control of oedema was deemed inadequate. Eight of the combination therapy patients and sixteen of those on chlorthalidone required the higher doses. By Week 12, 96% of the chlorthalidone plus triamterene patients and 100% of the chlorthalidone patients had shown a reduction of at least 2 mm in depth of pits, and 92% and 72%, respectively, had complete disappearance of oedema. The decreases in pitting oedema were paralleled by mean weight losses of 2.4 kg and 3.1 kg, respectively, for the combination treatment group and the chlorthalidone group. Average serum potassium levels throughout the 12-week treatment period were 3.70 mEq/L for the patients taking the combination compared to 3.41 mEq/L of those taking chlorthalidone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1984

Indapamide, a new antihypertensive/diuretic agent, in the treatment of patients with edema.

A multicenter, double-blind, parallel-group study of 219 patients with pitting edema of various causes was undertaken to determine the efficacy and safety of indapamide, administered orally (PO) in a 2.5-, 5-, or 10-mg once-daily dose, as compared with hydrochlorothiazide, administered PO in a 100-mg once-daily dose. Efficacy was evaluated by determining each patient's weight and degree of pitting edema periodically during 12 weeks of active treatment. Lessening of edema was measured by changes in the depth of pitting in the pretibial area, ten to 14 inches below the patella. The depth of pitting was assigned an arbitrary number between 0 and 4, with 0 equivalent to no edema and 4 equivalent to more than 6 mm of pitting edema. After one week of treatment, the mean reduction of pitting edema from baseline, using the 0 to 4 scale, was 1.6 (30%) in both the indapamide (mean of the three groups) and hydrochlorothiazide groups. There were no significant differences among the three dosage levels of indapamide. After 12 weeks of treatment the mean decrease from baseline was 1.8 (34%), indicating a stable reduction of edema. The mean weight loss at one week was 2.5 kg for the three indapamide groups and 2.6 kg for the hydrochlorothiazide group; this loss was maintained for the 12 weeks of the study. The mean decreases in weight and pitting edema were clinically and statistically significant (P less than 0.05) for both medications.

Antihypertensive Agents↗

PubMed1983

Long-term experience with indapamide.

Indapamide, 2.5 mg administered once daily for periods up to 36 months, was found to be safe and effective for the long-term control of mild to moderate hypertension. The effects of hydrochlorothiazide, 50 mg, and indapamide, 2.5 mg, were studied in two randomized, double-blind, multicenter trials. Data from the two multicenter trials (20 study sites) were pooled for purposes of comparison. Significant reductions in systolic and diastolic blood pressure, with patients in both supine and standing positions, occurred in both groups within the first 8 weeks of treatment. This effect was maintained throughout the active treatment period. Success, as determined by the therapeutic success rate (percentage of patients with decreases of standing phase V diastolic blood pressure of at least 10 mm Hg or to below 90 mm Hg), occurred in 53% of the patients given hydrochlorothiazide and in 56% of the indapamide-treated patients. During the study period, the nature, frequency, and severity of adverse reactions were similar for both groups. There was no clinically significant difference between the treatment groups for the laboratory assessments. Patients who completed the multicenter trials were eligible for participation in an ongoing long-term extension study of the safety of indapamide. Data are available for periods up to 36 months and demonstrate neither augmentation of clinical or laboratory adverse effects nor any potentially harmful indicators that could be attributed to prolonged treatment.

Adult↗

PubMed1983

Indapamide in the stepped-care treatment of obese hypertensive patients.

A double-blind study was carried out in obese patients with moderately severe hypertension to assess the efficacy and tolerability of 2.5 mg indapamide as a once-a-day Step 1 drug compared to 50 mg hydrochlorothiazide also as a once-a-day Step 1 drug; to assess the efficacy and tolerability of a fixed daily dose of 2.5 mg indapamide administered concomitantly with methyldopa starting at 500 mg daily; and to compare the findings of efficacy and tolerability of 2.5 mg indapamide daily with those of 50 mg hydrochlorothiazide daily as Step 1 agents when methyldopa is the Step 2 drug. Twenty-nine patients completed the study and were evaluated. Nine patients achieved the study criterion of reduction of average standing diastolic pressure to 90 mmHg or less when treated with Step 1 medication only. Twenty patients required the addition of methyldopa to their Step 1 medication: 10 patients took 2.5 mg indapamide with an average constant daily dose of 1100 mg methyldopa and 10 patients took 50 mg hydrochlorothiazide with an average constant daily dose of 1575 mg methyldopa to achieve blood pressure control. All groups had mean diastolic pressure controlled at or below the 90 mmHg criterion during the period of constant methyldopa dosage for those patients who required Step 2 therapy. There were no significant differences between groups with respect to diastolic pressure during the constant dosage period. The indapamide patients required significantly (p less than 0.05) less methyldopa than did the hydrochlorothiazide patients in order to maintain satisfactory control of diastolic blood pressure. The number of responders was greater in the 2.5 mg indapamide + methyldopa group than it was in the 50 mg hydrochlorothiazide + methyldopa group, and responses were achieved more rapidly in the former group than in the latter. Indapamide (2.5 mg per day) was effective and well tolerated when used alone or as Step 1 medication in combination with methyldopa as Step 2 medication, and it compared favourably in this regard with hydrochlorothiazide.

Adult↗

PubMed1983

Multi-centre clinical investigation of indapamide in the United States: a review.

Indapamide, a new indoline antihypertensive agent, has been the subject of a worldwide programme to develop this drug for general clinical use. The results are described of the multi-centre U.S. clinical programme demonstrating the effectiveness and tolerance of indapamide for the treatment of hypertension. All work was conducted under U.S. Federal Food and Drug Administration guidelines, and resulted recently in a New Drug Application. A total of 1891 subjects or patients participated in 27 separate studies conducted by 91 investigators. In controlled clinical trials comparing 2.5 mg indapamide once daily with 50 mg hydrochlorothiazide once daily for 40 weeks in patients with mild to moderate essential hypertension, indapamide produced a reduction of supine blood pressure of -9.5/-14.3 mmHg as compared with -7.6/-11.4 mmHg for hydrochlorothiazide. In combination with methyldopa, propranolol, clonidine, guanethidine and hydralazine, indapamide consistently produced a greater decrease in arterial pressure than did those agents given alone. Indapamide added to these step-care agents did not result in a meaningful increase in adverse reactions. Indapamide has been the subject of a long-term safety study in which over 100 hypertensive patients have been followed up for 2 years or longer. During this period of time, indapamide was well tolerated and remained effective. No biochemical, electrocardiographic or ophthalmological changes were associated with its use. Other studies with indapamide are discussed describing the systemic and renal haemodynamic effects, pharmacokinetic properties and special safety studies conducted with this agent. The use of indapamide in patients with hepatic or renal impairment is reviewed in detail.

Antihypertensive Agents↗

PubMed1983

Inhibition of compound 48/80 induced mediator release following oral administration of tiaramide hydrochloride in normal subjects.

The ability of tiaramide hydrochloride (RHC 2592) to inhibit cutaneous reactivity was studied using 11 normal volunteers. After repeated administration tiaramide hydrochloride inhibited cutaneous mast cell mediator release induced by compound 48/80 while not affecting histamine-induced cutaneous reactivity. This is the first demonstration in man of an oral agent with such an effect.

Administration, Oral↗

PubMed1983

Preliminary report on the effects of tiaramide on the ice cube test in patients with idiopathic cold urticaria.

Three subjects diagnosed as having idiopathic acquired cold urticaria were studied to assess the ability of orally administered tiaramide to inhibit the wheal induced following cold challenge with ice cubes placed in contact with the skin, and to establish the safety of multiple doses of 250 mg, q.i.d., for one week administered after a single oral dose of 500 mg. Two subjects completed the study. One subject was known to be unresponsive to antihistamines for allergy and the second was intolerant of antihistamines due to side effects. A third subject discontinued treatment due to an adverse reaction experienced while on the study medication. The skin of the forearm of each subject was exposed to cold stimuli for 1, 2, 3, 4, and 5 minutes by placing five ice cubes on the ventral surface at one minute intervals, and removing all simultaneously five minutes after contact with the first cube. The challenge sites were observed for ten minutes and the area of the wheal, intensity of edema and the time of contact necessary to induce the skin response were recorded. The results of this provocative test following the single and multiple dosage administration of tiaramide were compared to baseline skin responses. After one week of tiaramide treatment at 250 mg, q.i.d., both subjects who completed the study had a markedly attenuated skin response to cold challenge and no adverse effects. Our results suggest that absorbable compounds that can inhibit mast cell degranulation may be efficacious in cold urticaria and of particular value in treating patients who do not respond to standard therapy.

Adult↗

PubMed1973