"Dec. 14, 2012 -- Drinking a glass of beet juice may have an immediate impact on lowering blood pressure, according to a new study.
The study shows that within hours of drinking it, beet juice lowered systolic blood pressure (the top n"...
(Generic versions may still be available.)
TIMOLIDE (timolol maleate-hydrochlorothiazide)
Timolol maleate and hydrochlorothiazide have been used singly and concomitantly for the treatment of hypertension. The antihypertensive effects of these agents are additive. The two components of TIMOLIDE (timolol maleate-hydrochlorothiazide) have similar dosage schedules, and studies have shown that there is no interference with bioavailability when these agents are given together in the single combination tablet. Therefore, this combination provides a convenient formulation for the concomitant administration of these two entities.
In controlled clinical trials with TIMOLIDE (timolol maleate-hydrochlorothiazide) in selected patients with mild to moderate essential hypertension, about 90 percent had a good to excellent response. In patients with more severe hypertension, TIMOLIDE (timolol maleate-hydrochlorothiazide) may be administered with other antihypertensives such as ALDOMET* (Methyldopa) or a vasodilator.
Although the mechanisms of action of timolol maleate and hydrochlorothiazide in the treatment of hypertension have not been established, they are thought to be different; for example, hydrochlorothiazide increases plasma renin activity while timolol maleate reduces plasma renin activity.
Timolol maleate is a beta1 and beta2 (non-selective) adrenergic receptor blocking agent that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic activity.
Clinical pharmacology studies have confirmed the beta-adrenergic blocking activity as shown by (1) changes in resting heart rate and response of heart rate to changes in posture; (2) inhibition of isoproterenol-induced tachycardia; (3) alteration of the response to the Valsalva maneuver and amyl nitrite administration; and (4)reduction of heart rate and blood pressure changes on exercise.
Timolol maleate decreases the positive chronotropic, positive inotropic, bronchodilator, and vasodilator responses caused by beta-adrenergic receptor agonists. The magnitude of this decreased response is proportional to the existing sympathetic tone and the concentration of timolol maleate at receptor sites.
In normal volunteers, the reduction in heart rate response to a standard exercise was dose dependent over the test range of 0.5 to 20 mg, with a peak reduction at 2 hours of approximately 30% at higher doses.
Beta-adrenergic receptor blockade reduces cardiac output in both healthy subjects and patients with heart disease. In patients with severe impairment of myocardial function beta-adrenergic receptor blockade may inhibit the stimulatory effect of the sympathetic nervous system necessary to maintain adequate cardiac function.
Beta-adrenergic receptor blockade in the bronchi and bronchioles results in increased airway resistance from unopposed parasympathetic activity. Such an effect in patients with asthma or other bronchospastic conditions is potentially dangerous.
Clinical studies indicate that timolol maleate at a dosage of 20-60 mg/day reduces blood pressure without causing postural hypotension in most patients with essential hypertension. Administration of timolol maleate to patients with hypertension results initially in a decrease in cardiac output, little immediate change in blood pressure, and an increase in calculated peripheral resistance. With continued administration of timolol maleate blood pressure decreases within a few days, cardiac output usually remains reduced, and peripheral resistance falls toward pretreatment levels. Plasma volume may decrease or remain unchanged during therapy with timolol maleate. In the majority of patients with hypertension, timolol maleate also decreases plasma renin activity. Dosage adjustment to achieve optimal antihypertensive effect may require a few weeks. When therapy with timolol maleate is discontinued, the blood pressure tends to return to pretreatment levels gradually. In most patients the antihypertensive activity of timolol maleate is maintained with long-term therapy and is well tolerated.
The mechanism of the antihypertensive effects of beta-adrenergic receptor blocking agents is not established at this time. Possible mechanisms of action include reduction in cardiac output, reduction in plasma renin activity, and a central nervous system sympatholytic action.
Pharmacokinetics and Metabolism
Timolol maleate is rapidly and nearly completely absorbed (about 90%) following oral ingestion. Detectable plasma levels of timolol occur within one-half hour and peak plasma levels occur in about one to two hours. The drug half-life in plasma is approximately 4 hours and this is essentially unchanged in patients with moderate renal insufficiency. Timolol is partially metabolized by the liver and timolol and its metabolites are excreted by the kidney. Timolol is not extensively bound to plasma proteins; i.e., <10% by equilibrium dialysis and approximately 60% by ultrafiltration. An in vitro hemodialysis study, using 14C timolol added to human plasma or whole blood, showed that timolol was readily dialyzed from these fluids; however, a study of patients with renal failure showed that timolol did not dialyze readily. Plasma levels following oral administration are about half those following intravenous administration indicating approximately 50% first pass metabolism. The level of beta sympathetic activity varies widely among individuals, and no simple correlation exists between the dose or plasma level of timolol maleate and its therapeutic activity. Therefore, objective clinical measurements such as reduction of heart rate and/or blood pressure should be used as guides in determining the optimal dosage for each patient.
Hydrochlorothiazide is a diuretic and antihypertensive agent. It affects the renal tubular mechanism of electrolyte reabsorption. Hydrochlorothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate. The mechanism of the antihypertensive effect of thiazides may be related to the excretion and redistribution of body sodium. Hydrochlorothiazide usually does not cause clinically important changes in normal blood pressure.
Last reviewed on RxList: 1/28/2005
This monograph has been modified to include the generic and brand name in many instances.
Additional Timolide Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Get tips on handling your hypertension.