Verapamil

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Verapamil
Clinical data
Pronunciation/vɛˈræpəmɪl/
ve-RAP-ə-mil
Trade namesIsoptin, Calan, others[1]
AHFS/Drugs.comMonograph
MedlinePlusa684030
License data
Pregnancy
category
intravenous
Drug classCalcium channel blocker
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability35.1%
MetabolismLiver
Elimination half-life2.8–7.4 hours[6]
ExcretionKidney: 11%
Identifiers
  • (RS)-2-(3,4-Dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile
JSmol)
ChiralityRacemic mixture
  • N#CC(c1cc(OC)c(OC)cc1)(CCCN(CCc2ccc(OC)c(OC)c2)C)C(C)C
  • InChI=1S/C27H38N2O4/c1-20(2)27(19-28,22-10-12-24(31-5)26(18-22)33-7)14-8-15-29(3)16-13-21-9-11-23(30-4)25(17-21)32-6/h9-12,17-18,20H,8,13-16H2,1-7H3 checkY
  • Key:SGTNSNPWRIOYBX-UHFFFAOYSA-N checkY
  (verify)

Verapamil, sold under various trade names,

injection into a vein.[7]

Common side effects include headache,

non–dihydropyridine calcium channel blocker family of medications.[7]

Verapamil was approved for medical use in the United States in 1981.

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]

Medical uses

Verapamil is used for controlling

migraine headache prevention.[16]

Verapamil is also used for the treatment of

Prinzmetal variant), unstable angina (crescendo, preinfarction), and for the prevention of paroxysmal supraventricular tachycardia (PSVT).[17]

Verapamil is a

arrhythmia.[20][21]

Verapamil is also used intra-arterially to treat cerebral vasospasm.[22] Verapamil is used to treat the condition cluster headache.[23] Tentative evidence supports the use of verapamil topically to treat plantar fibromatosis.[24]

Verapamil use in people with recent onset 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]

Contraindications

Use of verapamil is generally avoided in people with severe left ventricular dysfunction,

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]

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. 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

low heart rate, atrioventricular block, rash and flushing.[4] Along with other calcium channel blockers, verapamil is known to induce gingival enlargement.[31]

Overdose

Acute overdose is often manifested by nausea,

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]

Mechanism of action

Verapamil's

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

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]

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.[35]

Pharmacokinetic details

More than 90% of verapamil is absorbed when given orally,

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
]

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.[36][37][38] Such effect was not documented in another study with ponies.[39]

Uses in cell biology

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

Hoechst 33342. Radioactively labelled verapamil and positron emission tomography can be used with to measure P-glycoprotein function.[medical citation needed
]

References

  1. ^ a b "Verapamil". www.drugs.com. Archived from the original on 1 August 2017. Retrieved 14 December 2016.
  2. ^ a b "Verapamil Use During Pregnancy". Drugs.com. 18 November 2019. Retrieved 26 March 2020.
  3. ^ "Securon SR - Summary of Product Characteristics (SmPC)". (emc). 17 May 2017. Retrieved 26 March 2020.
  4. ^ a b c d e f g h "Calan- verapamil hydrochloride tablet, film coated". DailyMed. 17 December 2019. Retrieved 26 March 2020.
  5. ^ Human Medicines Evaluation Division (14 October 2020). "Active substance(s): verapamil" (PDF). List of nationally authorised medicinal products. European Medicines Agency.
  6. ISBN 978-1-4557-0101-8
    . The elimination half-life of standard verapamil tablets is usually 3 to 7 hours,...
  7. ^ a b c d e f "Verapamil Hydrochloride". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
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  9. S2CID 28302667
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  11. ^ "Isoptin: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 26 March 2020.
  12. hdl:10665/325771
    . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  13. hdl:10665/345533
    . WHO/MHP/HPS/EML/2021.02.
  14. ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  15. ^ "Verapamil - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
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  17. PMID 30860730
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