Verapamil

Overview

Verapamil, sold under various trade names, 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. It may also be used for the prevention of migraines and cluster headaches. It is given by mouth or by injection into a vein.[1–4] WP

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 fetus if used during pregnancy. It is in the non–dihydropyridine calcium channel blocker family of medications.[2][5][6] WP

Verapamil was approved for medical use in the United States in 1981. It is on the World Health Organization's List of Essential Medicines. Verapamil is available as a generic medication. Long acting formulations exist. In 2023, it was the 177th most commonly prescribed medication in the United States, with more than 2 million prescriptions.[2][5][7–10] WP

Uses, dosage and effects

Medical uses

Verapamil is used for controlling ventricular rate in supraventricular tachycardia (SVT) and migraine headache prevention.[11] WP

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).[12] WP

Verapamil is a class-IV antiarrhythmic and more effective than digoxin in controlling ventricular rate. Verapamil is not listed as a first line antihypertensive 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.[11][13][14][15] WP

Verapamil is used intra-arterially to treat cerebral vasospasm. It is also used to treat cluster headaches. Tentative evidence supports the use of verapamil topically to treat plantar fibromatosis.[16][17][18] WP

Use of verapamil in people with recent onset of type 1 diabetes may improve pancreatic beta cell function. In a 2023 meta-analysis involving data from two randomized controlled trials (113 patients with recent onset type-1 diabetes), it was demonstrated that the use of verapamil over one year was associated with significantly higher C-peptide area under the curve levels. Higher C-peptide levels means better pancreatic insulin production and beta cell function.[19] WP

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.[20][21][22] WP

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.[23–26] WP

Risks and side effects

Contraindications

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. It is also contraindicated in people with atrial flutter or fibrillation and an existing accessory tract such as in Wolff-Parkinson-White syndrome.[27][28] WP

Side effects

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. A 1992 study found that verapamil causes a delay in colonic transit but does not affect upper gastrointestinal transit.[29] WP

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. Along with other calcium channel blockers, verapamil is known to induce gingival enlargement.[27][30] WP

Overdose

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.[31][32] WP

Pharmacology

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. Specific conditions that fall under the definition of atrial tachyarrhythmias are atrial fibrillation, atrial flutter, multifocal atrial tachycardia, paroxysmal supraventricular tachycardia, and so on.[27][33][34][35] WP

Verapamil is also a Kv voltage gated potassium channel blocker.[36] WP

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. WP

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.[27] WP

Cluster headaches

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.[37] WP

Chemistry

Formula

C27H38N2O4 PC

CAS number

52-53-9 PC

Molar mass (g/mol)

454.6 PC

IUPAC name (computed by PubChem)

2-(3,4-dimethoxyphenyl)-5-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]-2-propan-2-ylpentanenitrile PC

SMILES

CC(C)C(CCCN(C)CCC1=CC(=C(C=C1)OC)OC)(C#N)C2=CC(=C(C=C2)OC)OC PC

InChIKey

SGTNSNPWRIOYBX-UHFFFAOYSA-N PC

PubChem CID

2520

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other Verapamil
2. Other Verapamil Hydrochloride
3. Journal / agency Tfelt-Hansen PC, Jensen RH. Management of cluster headache. CNS Drugs. July 2012. doi:10.2165/11632850-000000000-00000 · PMID 22650381
4. Journal / agency Merison K, Jacobs H. Diagnosis and Treatment of Childhood Migraine. Current Treatment Options in Neurology. November 2016. doi:10.1007/s11940-016-0431-4 · PMID 27704257
5. Other WHO Model Formulary 2008. 2009
6. Other Verapamil Use During Pregnancy. 18 November 2019
7. Journal / agency Isoptin: FDA-Approved Drugs
8. Other The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). 2023
9. Other Top 300 of 2023
10. Other Verapamil Drug Usage Statistics, United States, 2014 - 2023
11. Other Koda-Kimble and Young's Applied Therapeutics: The Clinical Use of Drugs. 2012
12. Journal / agency Fahie S, Cassagnol M. StatPearls [Internet]. 2023. PMID 30860730
13. Journal / agency Srinivasan V, Sivaramakrishnan H, Karthikeyan B. Detection, isolation and characterization of principal synthetic route indicative impurities in verapamil hydrochloride. Scientia Pharmaceutica. 2011. doi:10.3797/scipharm.1101-19 · PMID 21886903 · PMC3163365
14. Journal / agency James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, Smith SC, Svetkey LP, Taler SJ, Townsend RR, Wright JT, Narva AS, Ortiz E. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. February 2014. doi:10.1001/jama.2013.284427 · PMID 24352797
15. Journal / agency Beck E, Sieber WJ, Trejo R. Management of cluster headache. American Family Physician. February 2005. PMID 15742909
16. Journal / agency Jun P, Ko NU, English JD, Dowd CF, Halbach VV, Higashida RT, Lawton MT, Hetts SW. Endovascular treatment of medically refractory cerebral vasospasm following aneurysmal subarachnoid hemorrhage. American Journal of Neuroradiology. November 2010. doi:10.3174/ajnr.A2183 · PMID 20616179 · PMC4067264
17. Other Drislane F, Benatar M, Chang BS, Acosta J, Tarulli A. Blueprints Neurology. 1 January 2009
18. Journal / agency Young JR, Sternbach S, Willinger M, Hutchinson ID, Rosenbaum AJ. The etiology, evaluation, and management of plantar fibromatosis. Orthopedic Research and Reviews. 17 December 2018. doi:10.2147/ORR.S154289 · PMID 30774465 · PMC6367723
19. Journal / agency Dutta D, Nagendra L, Raizada N, Bhattacharya S, Sharma M. Verapamil improves One-Year C-Peptide Levels in Recent Onset Type-1 Diabetes: A Meta-Analysis. Indian J Endocrinol Metab. May–Jun 2023. doi:10.4103/ijem.ijem_122_23 · PMID 37583402 · PMC10424102
20. Journal / agency Giannini AJ, Houser WL, Loiselle RH, Giannini MC, Price WA. Antimanic effects of verapamil. The American Journal of Psychiatry. December 1984. doi:10.1176/ajp.141.12.1602 · PMID 6439057
21. Journal / agency Giannini AJ, Taraszewski R, Loiselle RH. Verapamil and lithium in maintenance therapy of manic patients. Journal of Clinical Pharmacology. December 1987. doi:10.1002/j.1552-4604.1987.tb05600.x · PMID 3325531
22. Journal / agency Giannini AJ, Nakoneczie AM, Melemis SM, Ventresco J, Condon M. Magnesium oxide augmentation of verapamil maintenance therapy in mania. Psychiatry Research. February 2000. doi:10.1016/S0165-1781(99)00116-X · PMID 10699232
23. Journal / agency Elferink JG, Deierkauf M. The effect of verapamil and other calcium antagonists on chemotaxis of polymorphonuclear leukocytes. Biochemical Pharmacology. January 1984. doi:10.1016/0006-2952(84)90367-8 · PMID 6704142
24. Journal / agency Azzarone B, Krief P, Soria J, Boucheix C. Modulation of fibroblast-induced clot retraction by calcium channel blocking drugs and the monoclonal antibody ALB6. Journal of Cellular Physiology. December 1985. doi:10.1002/jcp.1041250309 · PMID 3864783
25. Journal / agency Steinleitner A, Lambert H, Kazensky C, Sanchez I, Sueldo C. Reduction of primary postoperative adhesion formation under calcium channel blockade in the rabbit. The Journal of Surgical Research. January 1990. doi:10.1016/0022-4804(90)90143-P · PMID 2296179
26. Journal / agency Baxter GM, Jackman BR, Eades SC, Tyler DE. Failure of calcium channel blockade to prevent intra-abdominal adhesions in ponies. Veterinary Surgery. 1993. doi:10.1111/j.1532-950X.1993.tb00427.x · PMID 8116206
27. Journal / agency Calan- verapamil hydrochloride tablet, film coated. 17 December 2019
28. Other Securon 2.5 mg/ml IV Intravenous Injection - Summary of Product Characteristics (SmPC). 24 November 2016
29. Journal / agency Krevsky B, Maurer AH, Niewiarowski T, Cohen S. Effect of verapamil on human intestinal transit. Digestive Diseases and Sciences. June 1992. doi:10.1007/BF01300391 · PMID 1587197
30. Journal / agency Steele RM, Schuna AA, Schreiber RT. Calcium antagonist-induced gingival hyperplasia. Annals of Internal Medicine. April 1994. doi:10.7326/0003-4819-120-8-199404150-00006 · PMID 8135450
31. Journal / agency Wilimowska J, Piekoszewski W, Krzyanowska-Kierepka E, Florek E. Monitoring of verapamil enantiomers concentration in overdose. Clinical Toxicology. 2006. doi:10.1080/15563650500514541 · PMID 16615674
32. Other Baselt R. Disposition of Toxic Drugs and Chemicals in Man. 2008
33. Journal / agency Ahmad F, Abu Sneineh M, Patel RS, Rohit Reddy S, Llukmani A, Hashim A, Haddad DR, Gordon DK. In The Line of Treatment: A Systematic Review of Paroxysmal Supraventricular Tachycardia. Cureus. June 2021. doi:10.7759/cureus.15502 · PMID 34268033 · PMC8261787
34. Journal / agency Delaney B, Loy J, Kelly AM. The relative efficacy of adenosine versus verapamil for the treatment of stable paroxysmal supraventricular tachycardia in adults: a meta-analysis. Eur J Emerg Med. June 2011. doi:10.1097/MEJ.0b013e3283400ba2 · PMID 20926952
35. Journal / agency Soohoo MM, Stone ML, von Alvensleben J, Jacobsen R. Management of Atrial Tachyarrhythmias in Adults with Single Ventricle Heart Disease. Current Treatment Options in Pediatrics. 2021. doi:10.1007/s40746-021-00231-w
36. Journal / agency Wang SP, Wang JA, Luo RH, Cui WY, Wang H. Potassium channel currents in rat mesenchymal stem cells and their possible roles in cell proliferation. Clinical and Experimental Pharmacology & Physiology. September 2008. doi:10.1111/j.1440-1681.2008.04964.x · PMID 18505444
37. Journal / agency Petersen AS, Barloese MC, Snoer A, Soerensen AM, Jensen RH. Verapamil and Cluster Headache: Still a Mystery. A Narrative Review of Efficacy, Mechanisms and Perspectives. Headache. September 2019. doi:10.1111/head.13603 · PMID 31339562

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.