"The U.S. Department of Health and Human Services today launched an annual challenge designed to identify and honor clinicians and health care teams that have helped their patients control high blood pressure and prevent heart attacks and strokes."...
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.
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, a-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.
Pharmacokinetics And Metabolism
Visken ® (pindolol) is rapidly and reproducibly absorbed (greater than 95%), achieving peak plasma concentrations within 1 hour of drug administration. Visken® (pindolol) has no significant first-pass effect. The blood concentrations are proportional in a linear manner to the administered dose in the range of 5-20 mg. Upon repeated administration to the same subject, variation is minimal. After a single dose, intersubject variation for peak plasma concentrations was about 4fold (e.g., 45-167 ng/mL for a 20 mg dose). Upon multiple dosing, intersubject variation decreased to 2-2.5 fold. Visken® (pindolol) is only 40% bound to plasma proteins and is evenly distributed between plasma and red cells. The volume of distribution in healthy subjects is about 2 L/kg.
Visken ® (pindolol) undergoes extensive metabolism in animals and man. In man, 35%-40% is excreted unchanged in the urine and 60%-65% is metabolized primarily to hydroxy-metabolites which are excreted as glucuronides and ethereal sulfates. The polar metabolites are excreted with a half-life of approximately 8 hours and thus multiple dosing therapy (q.8H) results in a less than 50% accumulation in plasma. About 6%-9% of an administered intravenous dose is excreted by the bile into the feces.
The disposition of Visken ® (pindolol) after oral administration is monophasic with a half-life in healthy subjects or hypertensive patients with normal renal function of approximately 3-4 hours. Following t.i.d. administration (q.8H), no significant accumulation of Visken® (pindolol) is observed.
In elderly hypertensive patients with normal renal function, the half-life of Visken ® (pindolol) is more variable, averaging about 7 hours, but with values as high as 15 hours.
In hypertensive patients with renal diseases, the half-life is within the range expected for healthy subjects. However, a significant decrease (50%) in volume of distribution (V D) is observed in uremic patients and VD appears to be directly correlated to creatinine clearance. Therefore, renal drug clearance is significantly reduced in uremic patients, resulting in a significant decrease in urinary excretion of unchanged drug. Uremic patients with a creatinine clearance of less than 20 mL/min generally excreted less than 15% of the administered dose unchanged in the urine.
In patients with histologically diagnosed cirrhosis of the liver, the elimination of Visken ® (pindolol) was more variable in rate and generally significantly slower than in healthy subjects. The total body clearance of Visken® (pindolol) in cirrhotic patients ranged from about 50-300 mL/min and was directly correlated to antipyrine clearance. The half-life ranges from 2.5 hours to greater than 30 hours. These findings strongly suggest that caution should be exercised in dosage adjustments of Visken® (pindolol) in such patients.
The bioavailability of Visken ® (pindolol) is not significantly affected by co-administration of food, hydralazine, hydrochlorothiazide or aspirin. Visken® (pindolol) has no effect on warfarin activity or the clinical effectiveness of digoxin, although small transient decreases in plasma digoxin concentrations were noted.
Last reviewed on RxList: 2/13/2008
This monograph has been modified to include the generic and brand name in many instances.
Additional Visken Information
Visken - User Reviews
Visken User Reviews
Now you can gain knowledge and insight about a drug treatment with Patient Discussions.
Report Problems to the Food and Drug Administration
Get tips on handling your hypertension.