(brand names: Isoptin
) is an L-type calcium channel blocker
. It has been used in the treatment of hypertension
, angina pectoris
, cardiac arrhythmia
, and most recently, cluster headaches. Verapamil has also been used as a vasodilator
during cryopreservation of blood vessels. It is a class 4 antiarrhythmic, more effective than digoxin
in controlling ventricular rate, and was approved by the FDA
Mechanism and uses
Verapamil's mechanism in all cases is to block voltage-dependent Calcium channels.
In cardiac pharmacology, calcium channel blockers are considered class IV antiarrhythmic agents. Since Calcium channels are especially concentrated in the sinoatrial and atrio-ventricular nodes, these agents can be used to decrease impulse conduction through the AV node, thus protecting the ventricles from atrial tachyarrhythmias.
Calcium channels are also present in the smooth muscle that lines blood vessels. By relaxing the tone of this smooth muscle, calcium-channel blockers dilate the blood vessels. This has led to their use in treating hypertension and angina pectoris.
The pain of angina is caused by a deficit in oxygen supply to the heart. Calcium channel blockers like Verapamil will dilate blood vessels, which increases the supply of blood and oxygen to the heart. This controls chest pain, but only when used regularly. It does not stop chest pain once it starts. A more powerful vasodilator such as nitroglycerin may be needed to control pain once it starts.
Given orally, 90–100% of Verapamil is absorbed, but due to high first-pass metabolism
is much lower (10–35%). It is 90% bound to plasma proteins
and has a volume of distribution
of 3–5 L/kg-1
. It is metabolized in the liver to at least 12 inactive metabolites (though one metabolite, norverapamil, retains 20% of the vasodilating activity of the parent drug). As its metabolites, 70% is excreted in the urine and 16% in feces; 3–4% is excreted unchanged in urine. This is a non-linear dependence between plasma concentration and dosage. Onset of action is 1-2 hours after oral dosage. Half-life is 5-12 hours (with chronic dosages). It is not cleared by hemodialysis.
Verapamil has been reported to be effective in both short-term and long-term treatment of mania and hypomania. Addition of magnesium oxide to the verpamail treatment protocol enhances the antimanic effect. It has on occasion been used to control mania in pregnant patients, especially in the first 3 months. It does not appear to be significantly teratogenic. For this reason, when one wants to avoid taking valproic acid (which is high in teratogenicity) or lithium (which has a small but significant incidence of causing cardiac malformation), Verapamil is usable as an alternative, albeit presumably a less effective one.
Some possible side effects of the drug are headaches
, facial flushing, dizziness
, increased urination, fatigue, nausea, ecchymosis, lightheadedness, and constipation
Uses in cell biology
Verapamil is also used in cell biology
as an inhibitor
of drug efflux pump proteins such as P-glycoprotein. This is useful as many tumor
cell lines overexpress drug efflux pumps, limiting the effectiveness of cytotoxic drugs
or fluorescent tags
. It's also used in fluorescent cell sorting for DNA
content, as it blocks efflux of a variety of DNA-binding fluorochromes
such as Hoechst 33342. Verapamil has also been used to treat Chloroquine-Resistant malaria.