Verapamil is aclass-IV antiarrhythmic and more effective thandigoxin in controlling ventricular rate.[19] Verapamil is not listed as a first line antihypertensive agent by the guidelines provided byJAMA in JNC-8.[20] However, it may be used to treat hypertension if patient has co-morbidatrial fibrillation or other types ofarrhythmia.[17][21]
Use of verapamil in people with recent onset oftype 1 diabetes may improve pancreatic beta cell function. In a 2023 meta-analysis[25] 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 higherC-peptide area under the curve levels. 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 ofmania andhypomania.[27] Addition ofmagnesium 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 withatrial flutter orfibrillation and an existing accessory tract such as in Wolff-Parkinson-White syndrome.[29][4]
The most common side effect of verapamil isconstipation (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 incolonic transit but does not affectupper gastrointestinal transit.[30]
Acute overdose is often manifested by nausea,weakness,slow heart rate, dizziness, low blood pressure, andabnormal 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 thesmooth 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 treatinghigh blood pressure andangina pectoris. The pain of angina is caused by a deficit in oxygen supply to the heart.
Calcium channel blockers like verapamil dilate thecoronary 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 thecircadian rhythm and onCGRPs, as CGRP-release is controlled by voltage-gated calcium channels.[38]
More than 90% of verapamil is absorbed when given orally,[4] but due to highfirst-pass metabolism,bioavailability is much lower (10–35%). It is 90%bound to plasma proteins and has avolume 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 to 2 hours after oral dosage, and 3 to 5 minutes after intravenous bolus dosage.[6][7] Biphasic or triphasic following IV administration; terminal elimination half-life is 2–8 hours.[39] Plasma half-life of 2–8 or 4.5–12 hours after single oral dose or multiple oral doses, respectively.[medical citation needed] It is not cleared by hemodialysis.[medical citation needed] It is excreted in human milk.[medical citation needed] 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.[40][41][42] Such effect was not documented in another study with ponies.[43]
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.[44]
^Human Medicines Evaluation Division (14 October 2020)."Active substance(s): verapamil"(PDF).List of nationally authorised medicinal products. European Medicines Agency. Archived fromthe original(PDF) on 30 October 2024.
^ab"Verapamil". Archived fromthe original on 30 October 2024.Onset of Action[...]Oral: Immediate release: 1 to 2 hours (Singh 1978); IV bolus: 3 to 5 minutes
^abSingh BN, Ellrodt G, Peter CT (March 1978). "Verapamil: a review of its pharmacological properties and therapeutic use".Drugs.15 (3):169–197.doi:10.2165/00003495-197815030-00001.PMID346345.
^Schroeder JS, Frishman WH, Parker JD, et al. (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. Retrieved8 December 2016.
^World Health Organization (2023).The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization.hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
^abKoda-Kimble and Young's Applied Therapeutics: The Clinical Use of Drugs (10th ed.). USA: LWW. 2012. pp. 497, 1349.ISBN978-1609137137.
^Fahie S, Cassagnol M (2023)."Verapamil".StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing.PMID30860730.Archived from the original on 10 April 2023. Retrieved6 November 2023.
^Drislane F, Benatar M, Chang BS, et al. (1 January 2009).Blueprints Neurology. Lippincott Williams & Wilkins. pp. 71–.ISBN978-0-7817-9685-9.Archived from the original on 8 June 2013. Retrieved14 November 2010.
^Giannini AJ, Houser WL, Loiselle RH, et al. (December 1984). "Antimanic effects of verapamil".The American Journal of Psychiatry.141 (12):1602–1603.doi:10.1176/ajp.141.12.1602.PMID6439057.
^Krevsky B, Maurer AH, Niewiarowski T, et al. (June 1992). "Effect of verapamil on human intestinal transit".Digestive Diseases and Sciences.37 (6):919–924.doi:10.1007/BF01300391.PMID1587197.S2CID1007332.
^Wilimowska J, Piekoszewski W, Krzyanowska-Kierepka E, et al. (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.
^Delaney B, Loy J, Kelly AM (June 2011). "The relative efficacy of adenosine versus verapamil for the treatment of stable paroxysmal supraventricular tachycardia in adults: a meta-analysis".Eur J Emerg Med.18 (3):148–52.doi:10.1097/MEJ.0b013e3283400ba2.PMID20926952.
^Soohoo MM, Stone ML, von Alvensleben J, et al. (2021). "Management of Atrial Tachyarrhythmias in Adults with Single Ventricle Heart Disease".Current Treatment Options in Pediatrics.7 (4):187–202.doi:10.1007/s40746-021-00231-w.
^Wang SP, Wang JA, Luo RH, et al. (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, et al. (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, et al. (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, et al. (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, et al. (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.
