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Verapamil, sold under various trade names, is a medication used for the treatment of high blood pressure, chest pain from not enough blood flow to the heart, and supraventricular tachycardia. It may also be used for the prevention of migraines and cluster headaches. It is given by mouth or by injection into a vein.

Common side effects include headache, low blood pressure, nausea, and constipation. Other side effects include allergic reactions and muscle pains. It is not recommended in people with a slow heart rate or heart failure. It is believed to cause problems for the baby if used during pregnancy. It is in the non-dihydropyridine calcium channel blocker family of medications.

Verapamil was approved for medical use in the United States in 1981. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Verapamil is available as a generic medication. The wholesale cost in the developing world is about 1.71 to 2.70 USD per month. In the United States a month of treatment costs 25 to 50 USD. Long acting formulations exist.


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Medical uses

Verapamil is used for controlling ventricular rate in supraventricular tachycardia and migraine headache prevention. It is a class-IV antiarrhythmic and more effective than digoxin in controlling ventricular rate. Verapamil is not listed as a first line agent by the guidelines provided by JAMA in JNC-8. However, it may be used to treat hypertension if patient has co-morbid atrial fibrillation or other types of arrhythmia.

Verapamil is also used intra-arterially to treat cerebral vasospasm. Verapamil is used to treat the condition cluster headache.


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Contraindication

Use of verapamil is generally avoided in people with severe left ventricular dysfunction, hypotension (systolic blood pressure less than 90 mm Hg), cardiogenic shock, and hypersensitivity to verapamil.


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Side effects

The most common side effect of Verapamil is constipation (7.3%). Other side effects include: dizziness (3.3%), nausea (2.7%), low blood pressure (2.5%), and headache 2.2%. Other side effects seen in less than 2% of the population include: edema, congestive heart failure, pulmonary edema, fatigue, elevated liver enzymes, shortness of breath, low heart rate, atrioventricular block, rash and flushing.

Along with other calcium channel blockers, verapamil is known to induce gingival hyperplasia.

Overdose

Acute overdose is often manifested by nausea, asthenia, bradycardia, dizziness, hypotension, and cardiac arrhythmia. Plasma, serum, or blood concentrations of verapamil and norverapamil, its major active metabolite, may be measured to confirm a diagnosis of poisoning in hospitalized patients or to aid in the medicolegal investigation of fatalities. Blood or plasma verapamil concentrations are usually in a range of 50-500 ?g/l in persons on therapy with the drug, but may rise to 1-4 mg/l in acute overdose patients and are often at levels of 5-10 mg/l in fatal poisonings.


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Mechanism of action

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 atrioventricular 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 lining 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 high blood pressure and angina pectoris. The pain of angina is caused by a deficit in oxygen supply to the heart. Calcium channel blockers like verapamil 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

More than 90% of verapamil is absorbed when given orally, 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. It takes 1 to 2 hours to reach peak plasma concentration after oral administration. 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 nonlinear 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. It is excreted in human milk. Because of the potential for adverse reaction in nursing infants, nursing should be discontinued while verapamil is administered.

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 verapamil treatment protocol enhances the antimanic effect. It has on occasion been used to control mania in pregnant patients, especially in the first three 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.


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Veterinary use

Intra-abdominal adhesions are common in rabbits following surgery. Verapamil can be given postoperatively in rabbits which have suffered trauma to abdominal organs to prevent formation of these adhesions. Such effect was not documented in another study with ponies.


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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 is also used in fluorescent cell sorting for DNA content, as it blocks efflux of a variety of DNA-binding fluorophores such as Hoechst 33342. Radioactively labelled verapamil and positron emission tomography can be used with to measure P-glycoprotein function.


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Research

As of 2015, a clinical trial of verapamil in diabetes was under way.


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Trade names

Verapamil is sold under many trade names worldwide.

Source of the article : Wikipedia



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