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| {{drugbox |
| | #REDIRECT [[Verapamil#Pharmacology]] |
| | image = Verapamil skeletal svg.png
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| |IUPAC_name = 2-(3,4-dimethoxyphenyl)-5-[2-(3,4-<br>dimethoxyphenyl)ethyl-methyl-amino]<br>-2-(1-methylethyl)pentanenitrile
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| |CAS_number = 52-53-9
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| | ATC_prefix=C08
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| | ATC_suffix=DA01
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| | PubChem=2520
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| | DrugBank=APRD00335
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| | C=27 | H=38 | N=2 | O=4
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| |molecular_weight = 454.602 g/mol
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| |bioavailability = 35.1%
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| |metabolism = [[Liver|Hepatic]]
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| |elimination_half-life = 2.8-7.4 hours
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| |excretion = [[Kidney|Renal]]: 11%
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| |pregnancy_US = C
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| |legal_status = Rx-only
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| |routes_of_administration = [[Mouth|Oral]], [[Intravenous]]
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| }}
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| {{CMG}}
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| ==[[Verapamil (patient information)|For patient information, click here]]==
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| ==Overview==
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| '''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.<ref>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</ref> 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.
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| Interestingly, one of its purified [[isomer]]s may not cause constipation (a well-known adverse effect of [[racemic]] verapamil).
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| ==Mechanism and uses==
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| Verapamil's mechanism in all cases is to block voltage-dependent Calcium channels.
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| 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.
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| 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]].
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| 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.
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| ==Pharmacokinetic details==
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| Given orally, 90–100% of Verapamil is absorbed, but due to high [[first-pass metabolism]], [[bioavailability]] is much lower (10–35%). It is 90% [[plasma protein binding|bound to plasma proteins]] and has a [[volume of distribution]] of 3–5 L/kg<sup>-1</sup>. 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.
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| Verapamil has an anti-manic effect but is rarely used for mania. It has on occasion been used 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 [[Depakote|valproic acid]] (which is high in teratogenicity) or [[lithium carbonate|lithium]] (which has a small but significant incidence of causing cardiac malformation), Verapamil is usable as an alternative, albeit presumably a less effective one.
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| ==Side effects==
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| Some possible side effects of the drug are [[headache]]s, facial flushing, [[dizziness]], [[swelling]], increased urination, and [[constipation]].
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| ==Uses in cell biology==
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| Verapamil is also used in [[cell biology]] as an [[Enzyme inhibitor|inhibitor]] of drug efflux pump proteins such as P-glycoprotein.<ref name=pgp>Bellamy WT. P-glycoproteins and multidrug resistance. ''Annu Rev Pharmacol Toxicol'' 1996; '''36''':161-83. PMID 8725386</ref> This is useful as many [[tumor]] cell lines overexpress drug efflux pumps, limiting the effectiveness of [[cytotoxic drug]]s or [[fluorescent tag]]s. It's also used in fluorescent cell sorting for [[DNA]] content, as it blocks efflux of a variety of DNA-binding [[fluorochrome]]s such as Hoechst 33342.
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| ==Notes==
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| <references/>
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| ==Sources==
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| *{{MedlinePlusDrugInfo|medmaster|a684030}}
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| *[http://emc.medicines.org.uk/emc/industry/default.asp?page=displaydoc.asp&documentid=972 Securon Summary of Product Characteristics]
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| {{Antiarrhythmic agents}}
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| {{Calcium channel blockers}}
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| [[Category:Antiarrhythmic agents]]
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| [[Category:Calcium channel blockers]]
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| [[Category:Drugs]]
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| [[ja:ベラパミル]]
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| [[pl:Werapamil]]
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