Verapamil
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| Clinical data | |
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| Routes of administration | Oral, Intravenous |
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| Pharmacokinetic data | |
| Bioavailability | 35.1% |
| Metabolism | Hepatic |
| Elimination half-life | 2.8-7.4 hours |
| Excretion | Renal: 11% |
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| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.000.133 |
| Chemical and physical data | |
| Formula | C27H38N2O4 |
| Molar mass | 454.602 g/mol g·mol−1 |
Verapamil (brand names: Isoptin, Verelan, Calan, Bosoptin) is an L-type calcium channel blocker. It has been used in the treatment of hypertension, angina pectoris, cardiac arrhythmia, and most recently, headaches.[1] 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 in 1981. Interestingly, one of its purified isomers may not cause constipation (a well-known adverse effect of racemic verapamil).
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.
Pharmacokinetic details
Given orally, 90–100% is absorbed, but due to high first-pass metabolism, bioavailability 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 has 20% of vasodilating activity of the parent drug). 70% is excreted in the urine as metabolites, 16% in feces and 3–4% unchanged in urine. Non-linear dependence between plasma concentration and dosage. Onset of action is 1-2 hours after P.O. dosage. Half-life is 5-12 hours (chronic dosages).It does not cleared by hemodialysis.
It has an anti-manic effect, but is rarely used for mania. It has on occasion been used used to control mania in a patient who is pregnant, especially in the first 3 months. Since it was used so much for hypertension, we know that it seems not to be significantly teratogenic. Thus, when one wants to avoid valproic acid/ Depakote which is high in teratogenicity, and/or avoid lithium (which has a small but significant incidence of causing cardiac malformation), verapamil is an important alternative, though, presumably less effective.
Side effects
Some possible side effects of the drug are headaches, facial flushing, dizziness, swelling, increased urination, 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.[2] 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.
Notes
- ^ Management of Cluster Headaches, (Beck et al. 2005) American Family Physician Vol 71, No.4 Full Free Text: http://www.aafp.org/afp/20050215/717.html
- ^ Bellamy WT. P-glycoproteins and multidrug resistance. Annu Rev Pharmacol Toxicol 1996; 36:161-83. PMID 8725386