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]
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 (systolicblood pressure less than 90 mm Hg), cardiogenic shock, and hypersensitivity to verapamil.[4] It is also contraindicated in people with atrial flutterorfibrillation 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]
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]
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]
^Human Medicines Evaluation Division (14 October 2020). "Active substance(s): verapamil"(PDF). List of nationally authorised medicinal products. European Medicines Agency.
^Schroeder JS, Frishman WH, Parker JD, Angiolillo DJ, Woods C, Scirica BM (2013). "Pharmacologic Options for Treatment of Ischemic Disease". Cardiovascular Therapeutics: A Companion to Braunwald's Heart Disease. Elsevier. pp. 83–130. doi:10.1016/b978-1-4557-0101-8.00007-2. ISBN978-1-4557-0101-8. The elimination half-life of standard verapamil tablets is usually 3 to 7 hours,...
^ abcdef"Verapamil Hydrochloride". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
^World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
^World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
^Drislane F, Benatar M, Chang BS, Acosta J, Tarulli A (1 January 2009). Blueprints Neurology. Lippincott Williams & Wilkins. pp. 71–. ISBN978-0-7817-9685-9. Archived from the original on 8 June 2013. Retrieved 14 November 2010.
^Wilimowska J, Piekoszewski W, Krzyanowska-Kierepka E, Florek E (2006). "Monitoring of verapamil enantiomers concentration in overdose". Clinical Toxicology. 44 (2): 169–171. doi:10.1080/15563650500514541. PMID16615674. S2CID10351499.
^Baselt R (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, California: Biomedical Publications. pp. 1637–39.
^Wang SP, Wang JA, Luo RH, Cui WY, Wang H (September 2008). "Potassium channel currents in rat mesenchymal stem cells and their possible roles in cell proliferation". Clinical and Experimental Pharmacology & Physiology. 35 (9): 1077–1084. doi:10.1111/j.1440-1681.2008.04964.x. PMID18505444. S2CID205457755.
^Petersen AS, Barloese MC, Snoer A, Soerensen AM, Jensen RH (September 2019). "Verapamil and Cluster Headache: Still a Mystery. A Narrative Review of Efficacy, Mechanisms and Perspectives". Headache. 59 (8): 1198–1211. doi:10.1111/head.13603. PMID31339562. S2CID198193843.
^Elferink JG, Deierkauf M (January 1984). "The effect of verapamil and other calcium antagonists on chemotaxis of polymorphonuclear leukocytes". Biochemical Pharmacology. 33 (1): 35–39. doi:10.1016/0006-2952(84)90367-8. PMID6704142.
^Azzarone B, Krief P, Soria J, Boucheix C (December 1985). "Modulation of fibroblast-induced clot retraction by calcium channel blocking drugs and the monoclonal antibody ALB6". Journal of Cellular Physiology. 125 (3): 420–426. doi:10.1002/jcp.1041250309. PMID3864783. S2CID10911875.
^Steinleitner A, Lambert H, Kazensky C, Sanchez I, Sueldo C (January 1990). "Reduction of primary postoperative adhesion formation under calcium channel blockade in the rabbit". The Journal of Surgical Research. 48 (1): 42–45. doi:10.1016/0022-4804(90)90143-P. PMID2296179.
^Baxter GM, Jackman BR, Eades SC, Tyler DE (1993). "Failure of calcium channel blockade to prevent intra-abdominal adhesions in ponies". Veterinary Surgery. 22 (6): 496–500. doi:10.1111/j.1532-950X.1993.tb00427.x. PMID8116206.