Clinical data | |
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Pronunciation | /vɛˈræpəmɪl/ ve-RAP-ə-mil |
Trade names | Isoptin, Calan, others [1] |
AHFS/Drugs.com | Monograph |
MedlinePlus | a684030 |
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Routes of administration | By mouth, intravenous |
Drug class | Calcium channel blocker |
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Pharmacokinetic data | |
Bioavailability | 35.1% |
Metabolism | Liver |
Elimination half-life | 2.8–7.4 hours [6] |
Excretion | Kidney: 11% |
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CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.000.133 |
Chemical and physical data | |
Formula | C27H38N2O4 |
Molar mass | 454.611 g·mol−1 |
3D model (JSmol) | |
Chirality | Racemic mixture |
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Verapamil, sold under various trade names, [1] is a calcium channel blocker medication used for the treatment of high blood pressure, angina (chest pain from not enough blood flow to the heart), and supraventricular tachycardia. [7] It may also be used for the prevention of migraines and cluster headaches. [8] [9] It is given by mouth or by injection into a vein. [7]
Common side effects include headache, low blood pressure, nausea, and constipation. [7] Other side effects include allergic reactions and muscle pains. [10] It is not recommended in people with a slow heart rate or heart failure. [10] It is believed to cause problems for the fetus if used during pregnancy. [2] It is in the non–dihydropyridine calcium channel blocker family of medications. [7]
Verapamil was approved for medical use in the United States in 1981. [7] [11] It is on the World Health Organization's List of Essential Medicines. [12] [13] Verapamil is available as a generic medication. [7] Long acting formulations exist. [10] In 2021, it was the 196th most commonly prescribed medication in the United States, with more than 2 million prescriptions. [14] [15]
Verapamil is used for controlling ventricular rate in supraventricular tachycardia (SVT) and migraine headache prevention. [16]
Verapamil is also used for the treatment of angina (chronic stable, vasospastic or Prinzmetal variant), unstable angina (crescendo, preinfarction), and for the prevention of paroxysmal supraventricular tachycardia (PSVT). [17]
Verapamil is a class-IV antiarrhythmic and more effective than digoxin in controlling ventricular rate. [18] Verapamil is not listed as a first line antihypertensive agent by the guidelines provided by JAMA in JNC-8. [19] However, it may be used to treat hypertension if patient has co-morbid atrial fibrillation or other types of arrhythmia. [20] [21]
Verapamil is used intra-arterially to treat cerebral vasospasm. [22] It is also used to treat cluster headaches. [23] Tentative evidence supports the use of verapamil topically to treat plantar fibromatosis. [24]
Use of verapamil in people with recent onset of type 1 diabetes may improve pancreatic beta cell function. In a meta-analysis involving data from 2 randomized controlled trials (113 patients with recent onset type-1 diabetes), Dutta et al. demonstrated use of verapamil over 1 year was associated with significantly higher C-peptide area under the curve levels at 1-year [MD 0.27 nmol/L (95%CI: 0.19-0.35); P < 0.01]. Higher C-peptide levels means better pancreatic insulin production and beta cell function. [25]
Verapamil has been reported to be effective in both short-term [26] and long-term treatment of mania and hypomania. [27] Addition of magnesium oxide to the verapamil treatment protocol enhances the antimanic effect. [28]
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. [4] It is also contraindicated in people with atrial flutter or fibrillation and an existing accessory tract such as in Wolff-Parkinson-White syndrome. [29] [4]
The most common side effect of verapamil is constipation (7.3%). While the definite mechanism by which verapamil causes constipation has not been studied, studies have been conducted to rule out mechanisms of actions that might yield this adverse effect. In a study conducted by The National Library of Medicine titled, "Effect of Verapamil on the Human Intestinal Transit", the study found that verapamil does not have an effect on upper GI transit but rather in the colon. [30]
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, diarrhea, fatigue, elevated liver enzymes, shortness of breath, low heart rate, atrioventricular block, rash and flushing. [4] Along with other calcium channel blockers, verapamil is known to induce gingival enlargement. [31]
Acute overdose is often manifested by nausea, weakness, slow heart rate, dizziness, low blood pressure, and abnormal heart rhythms. 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 μg/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. [32] [33]
Verapamil's mechanism in all cases is to block voltage-dependent calcium channels. [4] 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. Verapamil is also a Kv voltage gated potassium channel blocker. [34]
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 the coronary blood vessels, which increases the supply of blood and oxygen to the heart. They also cause dilatation of systemic peripheral vessels as well, causing a reduction in the workload of the heart. Thereby reducing myocardial oxygen consumption. [4]
Preventive therapy with verapamil is believed to work because it has an effect on the circadian rhythm and on CGRPs, as CGRP-release is controlled by voltage-gated calcium channels. [35]
More than 90% of verapamil is absorbed when given orally, [4] 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. [4] It is metabolized in the liver to at least 12 inactive metabolites (though one metabolite, norverapamil, retains 20% of the vasodilatory 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.[ medical citation needed ]
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. [36] [37] [38] Such effect was not documented in another study with ponies. [39]
Verapamil inhibits the ATP-binding cassette (ABC) transporter family of proteins found in stem cells and has been used to study cancer stem cells (CSC) within head and neck squamous cell carcinomas. [40]
Verapamil is also used in cell biology as an inhibitor of drug efflux pump proteins such as P-glycoprotein and other ABC transporter proteins. [41] [40] 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.[ medical citation needed ]
An antianginal is a drug used in the treatment of angina pectoris, a symptom of ischaemic heart disease.
Carbamazepine, sold under the brand name Tegretol among others, is an anticonvulsant medication used in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other medications and as a second-line agent in bipolar disorder. Carbamazepine appears to work as well as phenytoin and valproate for focal and generalized seizures. It is not effective for absence or myoclonic seizures.
Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance anxiety, and essential tremors, as well to prevent migraine headaches, and to prevent further heart problems in those with angina or previous heart attacks. It can be taken orally or by intravenous injection. The formulation that is taken orally comes in short-acting and long-acting versions. Propranolol appears in the blood after 30 minutes and has a maximum effect between 60 and 90 minutes when taken orally.
Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as medications to decrease blood pressure in patients with hypertension. CCBs are particularly effective against large vessel stiffness, one of the common causes of elevated systolic blood pressure in elderly patients. Calcium channel blockers are also frequently used to alter heart rate, to prevent peripheral and cerebral vasospasm, and to reduce chest pain caused by angina pectoris.
Amlodipine, sold under the brand name Norvasc among others, is a calcium channel blocker medication used to treat high blood pressure, coronary artery disease (CAD) and variant angina. It is taken orally.
Nifedipine, sold under the brand name Procardia among others, is a calcium channel blocker medication used to manage angina, high blood pressure, Raynaud's phenomenon, and premature labor. It is one of the treatments of choice for Prinzmetal angina. It may be used to treat severe high blood pressure in pregnancy. Its use in preterm labor may allow more time for steroids to improve the baby's lung function and provide time for transfer of the mother to a well qualified medical facility before delivery. It is a calcium channel blocker of the dihydropyridine type. Nifedipine is taken by mouth and comes in fast- and slow-release formulations.
Diltiazem, sold under the brand name Cardizem among others, is a nondihydropyridine calcium channel blocker medication used to treat high blood pressure, angina, and certain heart arrhythmias. It may also be used in hyperthyroidism if beta blockers cannot be used. It is taken by mouth or injection into a vein. When given by injection, effects typically begin within a few minutes and last a few hours.
Flecainide is a medication used to prevent and treat abnormally fast heart rates. This includes ventricular and supraventricular tachycardias. Its use is only recommended in those with dangerous arrhythmias or when significant symptoms cannot be managed with other treatments. Its use does not decrease a person's risk of death. It is taken by mouth or injection into a vein.
Vasospasm refers to a condition in which an arterial spasm leads to vasoconstriction. This can lead to tissue ischemia and tissue death (necrosis). Cerebral vasospasm may arise in the context of subarachnoid hemorrhage. Symptomatic vasospasm or delayed cerebral ischemia is a major contributor to post-operative stroke and death especially after aneurysmal subarachnoid hemorrhage. Vasospasm typically appears 4 to 10 days after subarachnoid hemorrhage.
Betaxolol is a selective beta1 receptor blocker used in the treatment of hypertension and angina. It is also a adrenergic blocker with no partial agonist action and minimal membrane stabilizing activity. Being selective for beta1 receptors, it typically has fewer systemic side effects than non-selective beta-blockers, for example, not causing bronchospasm as timolol may. Betaxolol also shows greater affinity for beta1 receptors than metoprolol. In addition to its effect on the heart, betaxolol reduces the pressure within the eye. This effect is thought to be caused by reducing the production of the liquid within the eye. The precise mechanism of this effect is not known. The reduction in intraocular pressure reduces the risk of damage to the optic nerve and loss of vision in patients with elevated intraocular pressure due to glaucoma.
Hydralazine, sold under the brand name Apresoline among others, is a medication used to treat high blood pressure and heart failure. This includes high blood pressure in pregnancy and very high blood pressure resulting in symptoms. It has been found to be particularly useful in heart failure, together with isosorbide dinitrate, for treatment of people of African descent. It is given by mouth or by injection into a vein. Effects usually begin around 15 minutes and last up to six hours.
Cinnarizine is an antihistamine and calcium channel blocker of the diphenylmethylpiperazine group. It is prescribed for nausea and vomiting due to motion sickness or other sources such as chemotherapy, vertigo, or Ménière's disease. Cinnarizine is one of the leading causes of drug-induced parkinsonism.
Nebivolol is a beta blocker used to treat high blood pressure and heart failure. As with other β-blockers, it is generally a less preferred treatment for high blood pressure. It may be used by itself or with other blood pressure medication. It is taken by mouth.
Lercanidipine is an antihypertensive drug. It belongs to the dihydropyridine class of calcium channel blockers, which work by relaxing and opening the blood vessels allowing the blood to circulate more freely around the body. This lowers the blood pressure and allows the heart to work more efficiently.
Flunarizine, sold under the brand name Sibelium among others, is a drug classified as a calcium antagonist which is used for various indications. It is not available by prescription in the United States or Japan. The drug was discovered at Janssen Pharmaceutica (R14950) in 1968.
Ranolazine, sold under the brand name Ranexa among others, is a medication used to treat heart related chest pain. Typically it is used together with other medications when those are insufficient. Therapeutic benefits appear smaller in females than males. It is taken by mouth.
Efonidipine (INN) is a dihydropyridine calcium channel blocker marketed by Shionogi & Co. of Japan. It was launched in 1995, under the brand name Landel (ランデル). The drug blocks both T-type and L-type calcium channels. Drug Controller General of India (DCGI) has approved the use of efonidipine in India. It is launched under the brand name "Efnocar".
Sodium channel blockers are drugs which impair the conduction of sodium ions (Na+) through sodium channels.
Anipamil is a calcium channel blocker, specifically of the phenylalkylamine type. This type is separate from its more common cousin Dihydropyridine. Anipamil is an analog of the more common drug verapamil, which is the most common type of phenylalkylamine style calcium channel blocker. Anipamil has been shown to be a more effective antiarrhythmic medication than verapamil because it does not cause hypertension as seen in verapamil. It is able to do this by bonding to the myocardium tighter than verapamil.
AH-1058 is a lipophilic antiarrhythmic calcium channel blocker synthesized by the Pharmaceutical Research Laboratories of Ajinomoto Co., Inc in Kawasaki, Japan. It is derived from cyproheptadine, a compound with known antiserotonic, antihistaminic and calcium channel blocking properties. The IUPAC name of AH-1058 is: 4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-[E-3-(3-methoxy-2-nitro) phenyl-2-propenyl]piperidine hydrochloride.
The elimination half-life of standard verapamil tablets is usually 3 to 7 hours,...