Verapamil - How It Works
Clinical pharmacology details from the US FDA-approved label: how Verapamil works in your body, how it's absorbed, how long it stays active, and how it's eliminated.
CLINICAL PHARMACOLOGY Verapamil hydrochloride and trandolapril have been used individually and in combination for the treatment of hypertension.
For the four dosing strengths, the antihypertensive effect of the combination is approximately additive to the individual components.
Verapamil Component Verapamil is a calcium channel blocker that exerts its pharmacologic effects by modulating the influx of ionic calcium across the cell membrane of the arterial smooth muscle as well as in conductile and contractile myocardial cells.
Verapamil exerts antihypertensive effects by decreasing systemic vascular resistance, usually without orthostatic decreases in blood pressure or reflex tachycardia.
During isometric or dynamic exercise, verapamil does not alter systolic cardiac function in patients with normal ventricular function.
Verapamil does not alter total serum calcium levels.
Trandolapril Component Trandolapril is de-esterified to its diacid metabolite, trandolaprilat.
Both inhibit angiotensin-converting enzyme (ACE) in human subjects and in animals.
Trandolaprilat is about 8 times more potent than trandolapril.
ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor, angiotensin II.
Angiotensin II also stimulates aldosterone secretion by the adrenal cortex.
Inhibition of ACE results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and to decreased aldosterone secretion.
The latter decrease may result in a small increase of serum potassium.
In controlled clinical trials, treatment with trandolapril and verapamil hydrochloride extended-release tablets resulted in mean increases in potassium of 0.1 mEq/L (see PRECAUTIONS ).
Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity (PRA).
ACE is identical to kininase II, an enzyme that degrades bradykinin.
Whether increased levels of bradykinin, a potent vasodepressor peptide, play a role in the therapeutic effect of trandolapril and verapamil hydrochloride extended-release tablets remains to be elucidated.
While the mechanism through which trandolapril lowers blood pressure is believed to be primarily suppression of the renin-angiotensin-aldosterone system, trandolapril has an antihypertensive effect even in patients with low renin hypertension.
Trandolapril is an effective antihypertensive in all races studied.
Both black patients (usually a predominantly low renin group) and non-black patients respond to 2 to 4 mg of trandolapril.