View source for Verapamil hydrochloride injection clinical pharmacology

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{{Verapamil}}
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==CLINICAL PHARMACOLOGY==

===Mechanism of Action: ===

Verapamil inhibits the calcium ion (and possibly sodium ion) influx through slow channels into conductile and contractile myocardial cells and vascular smooth muscle cells. The [[antiarrhythmic ]]effect of verapamil appears to be due to its effect on the slow channel in cells of the cardiac conduction system. The vasodilatory effect of verapamil appears to be due to its effect on blockade of calcium channels as well as α receptors.

In the isolated rabbit heart, concentrations of verapamil that markedly affect [[SA]] nodal fibers or fibers in the upper and middle regions of the [[AV node ]]have very little effect on fibers in the lower[[ AV node]] (NH region) and no effect on atrial action potentials or His bundle fibers.

Electrical activity in the [[SA node|SA]] and [[AV node|AV nodes ]]depends, to a large degree, upon calcium influx through the slow channel. By inhibiting this influx, verapamil slows AV conduction and prolongs the effective refractory period within the [[AV node]] in a rate-related manner. This effect results in a reduction of the ventricular rate in patients with atrial flutter and/or atrial fibrillation and a rapid ventricular response.
By interrupting reentry at the AV node, verapamil can restore normal sinus rhythm in patients with paroxysmal [[supraventricular tachycardias]] (PSVT), including [[PSVT ]]associated with [[Wolff-Parkinson-White syndrome]].

Verapamil does not induce [[peripheral arterial spasm]].

Verapamil has a local anesthetic action that is 1.6 times that of procaine on an equimolar basis. It is not known whether this action is important at the doses used in man.

Verapamil does not alter total serum calcium levels.

===Hemodynamics:=== 
Verapamil reduces afterload and myocardial contractility. The commonly used intravenous doses of 5 to 10 mg verapamil hydrochloride produce transient, usually asymptomatic, reduction in normal systemic arterial pressure, systemic vascular resistance and contractility; left ventricular filling pressure is slightly increased. In most patients, including those with organic cardiac disease, the negative inotropic action of verapamil is countered by reduction of afterload, and [[cardiac index]] is usually not reduced. However, in patients with moderately severe to severe cardiac dysfunction ([[pulmonary wedge pressure]] above 20 mm Hg, ejection fraction less than 30%), acute worsening of heart failure may be seen. Peak therapeutic effects occur within 3 to 5 minutes after a bolus injection.

===Pharmacokinetics:=== 
Intravenously administered verapamil hydrochloride has been shown to be rapidly metabolized. Following intravenous infusion in man, verapamil is eliminated bi-exponentially, with a rapid early distribution phase (half-life about 4 minutes) and a slower terminal elimination phase (half-life 2 to 5 hours). In healthy men, orally administered verapamil hydrochloride undergoes extensive metabolism in the liver, with 12 metabolites having been identified, most in only trace amounts. The major metabolites have been identified as various N- and O-dealkylated products of verapamil. Approximately 70% of an administered dose is excreted in the urine and 16% more in the feces within 5 days. About 3% to 4% is excreted as unchanged drug.

Aging may affect the pharmacokinetics of verapamil given to hypertensive patients. Elimination half-life may be prolonged in the elderly.<ref name="dailymed.nlm.nih.gov">{{Cite web  | last =  | first =  | title = VERAPAMIL HYDROCHLORIDE INJECTION, SOLUTION [CARDINAL HEALTH] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=0c27c868-7eae-4b3e-babf-e89404ea27b7#nlm34090-1 | publisher =  | date =  | accessdate =  }}</ref>



==References==

{{Reflist|2}}

[[Category:Cardiovascular Drugs]]
[[Category:Drugs]]