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Visken®
T1999-39
89003701
Visken ®
(pindolol)
tablets, USP
Rx only
DESCRIPTION
Visken® (pindolol), a synthetic beta-adrenergic receptor blocking agent with intrinsic sympathomimetic activity is 1-(Indol-4-yloxy)-3-(isopropylamino)-2-propanol.
Its structural formula is:
Pindolol is a white to off-white odorless powder soluble in organic solvents and aqueous acids. Visken® (pindolol) is intended for oral administration.
5 mg and 10 mg Tablets
Active Ingredient: pindolol
Inactive Ingredients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, and pregelatinized starch.
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CLINICAL PHARMACOLOGY
Visken® (pindolol) is a non-selective beta-adrenergic antagonist (beta-blocker) which possesses intrinsic sympathomimetic activity (ISA) in therapeutic dosage ranges but does not possess quinidine-like membrane stabilizing activity.
PHARMACODYNAMICS
In standard pharmacologic tests in man and animals, Visken® (pindolol) attenuates increases in heart rate, systolic blood pressure, and cardiac output resulting from exercise and isoproterenol administration, thus confirming its beta-blocking properties. The ISA or partial agonist activity of Visken® (pindolol) is mediated directly at the adrenergic receptor sites and may be blocked by other beta-blockers. In catecholamine-depleted animal experiments, ISA is manifested as an increase in the inotropic and chronotropic activity of the myocardium. In man, ISA is manifested by a smaller reduction in the resting heart rate (4-8 beats/min) than is seen with drugs lacking ISA. There is also a smaller reduction in resting cardiac output. The clinical significance of this observation has not been evaluated and there is no evidence, or reason to believe, that exercise cardiac output is less affected by Visken® (pindolol).
Visken® (pindolol) has been shown in controlled, double-blind clinical studies to be an effective antihypertensive agent when used as monotherapy, or when added to therapy with thiazide-type diuretics. Divided dosages in the range of 10-60 mg daily have been shown to be effective. As monotherapy, Visken® (pindolol) is as effective as propranolol, α-methyldopa, hydrochlorothiazide, and chlorthalidone in reducing systolic and diastolic blood pressure. The effect on blood pressure is not orthostatic, i.e. Visken® (pindolol) was equally effective in reducing the supine and standing blood pressure.
In open, long-term studies up to 4 years, no evidence of diminution of the blood pressure-lowering response was observed.
An average 3-pound increase in body weight has been noted in patients treated with Visken® (pindolol) alone, a larger increase than was observed with propranolol or placebo. The weight gain appeared unrelated to blood pressure response and was not associated with an increased risk of heart failure, although edema was more common than in control patients. Visken® (pindolol) does not have a consistent effect on plasma renin activity.
The mechanism of the antihypertensive effects of beta-blocking agents has not been established, but several mechanisms have been postulated: 1) an effect on the central nervous system resulting in a reduced sympathetic outflow to the periphery, 2) competitive antagonism of catecholamines at peripheral (especially cardiac) adrenergic receptor sites, leading to decreased cardiac output, 3) an inhibition of renin release. These mechanisms appear less likely for pindolol than other beta-blockers in view of the modest effect on resting cardiac output and renin.
Beta-blockade therapy is useful when it is necessary to suppress the effects of beta-adrenergic agonists in order to achieve therapeutic goals. However, in certain clinical situations, (e.g., cardiac failure, heart block, bronchospasm), the preservation of an adequate sympathetic tone may be necessary to maintain vital functions. Although a beta-antagonist with ISA such as Visken® (pindolol) does not eliminate sympathetic tone entirely, there is no controlled evidence that it is safer than other beta-blockers in such conditions as heart failure, heart block, or bronchospasm or is less likely to cause those conditions. In single dose studies of the effects of beta-blockers on FEV1, Visken® (pindolol) was indistinguishable from other non-cardioselective agents in its reduction of FEV1, and its reduction in the effectiveness of an exogenous beta agonist.
Exacerbation of angina and, in some cases, myocardial infarction and ventricular dysrhythmias have been reported after abrupt discontinuation of therapy with beta-adrenergic blocking agents in patients with coronary artery disease. Abrupt withdrawal of these agents in patients without coronary artery disease has resulted in transient symptoms, including tremulousness, sweating, palpitation, headache, and malaise. Several mechanisms have been proposed to explain these phenomena, among them increased sensitivity to catecholamines because of increased numbers of beta receptors.
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