Verapamil

Last updated

Verapamil
Verapamil structure.svg
Verapamil-from-xtal-Mercury-3D-bs.png
Clinical data
Pronunciation /vɛˈræpəmɪl/
ve-RAP-ə-mil
Trade names Isoptin, Calan, others [1]
AHFS/Drugs.com Monograph
MedlinePlus a684030
License data
Pregnancy
category
Routes of
administration 		By mouth, intravenous
Drug class Calcium channel blocker
ATC code
Legal status
Legal status
  • UK: POM (Prescription only) [3]
  • US: ℞-only [4]
  • EU:Rx-only [5]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 35.1%
Metabolism Liver
Onset of action 1 to 2 hours (oral); 3 to 5 minutes (IV bolus) [6] [7]
Elimination half-life 2.8–7.4 hours [8]
Excretion Kidney: 11%
Identifiers
  • (RS)-2-(3,4-Dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.000.133 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C27H38N2O4
Molar mass 454.611 g·mol−1
3D model (JSmol)
Chirality Racemic 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 Yes check.svgY
  • Key:SGTNSNPWRIOYBX-UHFFFAOYSA-N Yes check.svgY
   (verify)

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. [9] It may also be used for the prevention of migraines and cluster headaches. [10] [11] It is given by mouth or by injection into a vein. [9]

Contents

Common side effects include headache, low blood pressure, nausea, and constipation. [9] Other side effects include allergic reactions and muscle pains. [12] It is not recommended in people with a slow heart rate or heart failure. [12] 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. [9]

Verapamil was approved for medical use in the United States in 1981. [9] [13] It is on the World Health Organization's List of Essential Medicines. [14] [15] Verapamil is available as a generic medication. [9] Long acting formulations exist. [12] In 2022, it was the 188th most commonly prescribed medication in the United States, with more than 2 million prescriptions. [16] [17]

Medical uses

Verapamil is used for controlling ventricular rate in supraventricular tachycardia (SVT) and migraine headache prevention. [18]

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). [19]

Verapamil is a class-IV antiarrhythmic and more effective than digoxin in controlling ventricular rate. [20] Verapamil is not listed as a first line antihypertensive agent by the guidelines provided by JAMA in JNC-8. [21] However, it may be used to treat hypertension if patient has co-morbid atrial fibrillation or other types of arrhythmia. [18] [22]

Verapamil is used intra-arterially to treat cerebral vasospasm. [23] It is also used to treat cluster headaches. [24] Tentative evidence supports the use of verapamil topically to treat plantar fibromatosis. [25]

Use of verapamil in people with recent onset of type 1 diabetes may improve pancreatic beta cell function. In a 2023 meta-analysis [26] 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. [26]

Verapamil has been reported to be effective in both short-term [27] and long-term treatment of mania and hypomania. [28] Addition of magnesium oxide to the verapamil treatment protocol enhances the antimanic effect. [29]

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. [4] It is also contraindicated in people with atrial flutter or fibrillation and an existing accessory tract such as in Wolff-Parkinson-White syndrome. [30] [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. A study by The National Library of Medicine called "Effect of Verapamil on the Human Intestinal Transit" found that verapamil affects the colon but not the upper gastrointestinal tract. [31]

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. [32]

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. [33] [34]

Mechanism of action

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. Specific conditions that fall under the definition of atrial tachyarrhythmias are atrial fibrillation, atrial flutter, multifocal atrial tachycardia, paroxysmal supraventricular tachycardia, and so on. [35] [36] [37]

Verapamil is also a Kv voltage gated potassium channel blocker. [38]

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]

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. [39]

Pharmacokinetic details

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 to 2 hours after oral dosage, and 3 to 5 minutes after intravenous bolus dosage. [6] [7] Half-life is 5–12 hours (with chronic dosages).[ 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 ]

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. [40] [41] [42] Such effect was not documented in another study with ponies. [43]

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. [44]

Verapamil is also used in cell biology as an inhibitor of drug efflux pump proteins such as P-glycoprotein and other ABC transporter proteins. [45] [44] 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 ]

Related Research Articles

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.

<span class="mw-page-title-main">Sinus node dysfunction</span> Medical condition

Sinus node dysfunction (SND), also known as sick sinus syndrome (SSS), is a group of abnormal heart rhythms (arrhythmias) usually caused by a malfunction of the sinus node, the heart's primary pacemaker. Tachycardia-bradycardia syndrome is a variant of sick sinus syndrome in which the arrhythmia alternates between fast and slow heart rates.

<span class="mw-page-title-main">Antiarrhythmic agent</span> Heart rhythm medication

Antiarrhythmic agents, also known as cardiac dysrhythmia medications, are a class of drugs that are used to suppress abnormally fast rhythms (tachycardias), such as atrial fibrillation, supraventricular tachycardia and ventricular tachycardia.

<span class="mw-page-title-main">Amlodipine</span> Medication against high blood pressure

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.

<span class="mw-page-title-main">Amiodarone</span> Antiarrhythmic medication used for various types of irregular heartbeats

Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of cardiac dysrhythmias. This includes ventricular tachycardia, ventricular fibrillation, and wide complex tachycardia, atrial fibrillation, and paroxysmal supraventricular tachycardia. Evidence in cardiac arrest, however, is poor. It can be given by mouth, intravenously, or intraosseously. When used by mouth, it can take a few weeks for effects to begin.

<span class="mw-page-title-main">Ventricular tachycardia</span> Abnormally fast rhythm of the hearts ventricles

Ventricular tachycardia is a cardiovascular disorder in which fast heart rate occurs in the ventricles of the heart. Although a few seconds of VT may not result in permanent problems, longer periods are dangerous; and multiple episodes over a short period of time are referred to as an electrical storm. Short periods may occur without symptoms, or present with lightheadedness, palpitations, shortness of breath, chest pain, and decreased level of consciousness. Ventricular tachycardia may lead to coma and persistent vegetative state due to lack of blood and oxygen to the brain. Ventricular tachycardia may result in ventricular fibrillation (VF) and turn into cardiac arrest. This conversion of the VT into VF is called the degeneration of the VT. It is found initially in about 7% of people in cardiac arrest.

<span class="mw-page-title-main">Diltiazem</span> Calcium channel blocker medication

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 given by injection into a vein. When given by injection, effects typically begin within a few minutes and last a few hours.

<span class="mw-page-title-main">Flecainide</span> Antiarrhythmic medication

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.

<span class="mw-page-title-main">Supraventricular tachycardia</span> Abnormally fast heart rhythm

Supraventricular tachycardia (SVT) is an umbrella term for fast heart rhythms arising from the upper part of the heart. This is in contrast to the other group of fast heart rhythms – ventricular tachycardia, which start within the lower chambers of the heart. There are four main types of SVT: atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia (PSVT), and Wolff–Parkinson–White syndrome. The symptoms of SVT include palpitations, feeling of faintness, sweating, shortness of breath, and/or chest pain.

<span class="mw-page-title-main">Sotalol</span> Medication

Sotalol, sold under the brand name Betapace among others, is a medication used to treat and prevent abnormal heart rhythms. Evidence does not support a decreased risk of death with long term use. It is taken by mouth or given by injection into a vein.

<span class="mw-page-title-main">AV nodal reentrant tachycardia</span> Medical condition

AV-nodal reentrant tachycardia (AVNRT) is a type of abnormal fast heart rhythm. It is a type of supraventricular tachycardia (SVT), meaning that it originates from a location within the heart above the bundle of His. AV nodal reentrant tachycardia is the most common regular supraventricular tachycardia. It is more common in women than men. The main symptom is palpitations. Treatment may be with specific physical maneuvers, medications, or, rarely, synchronized cardioversion. Frequent attacks may require radiofrequency ablation, in which the abnormally conducting tissue in the heart is destroyed.

<span class="mw-page-title-main">Catheter ablation</span> Removal or termination of an electrical pathway from parts of the heart

Catheter ablation is a procedure that uses radio-frequency energy or other sources to terminate or modify a faulty electrical pathway from sections of the heart of those who are prone to developing cardiac arrhythmias such as atrial fibrillation, atrial flutter and Wolff-Parkinson-White syndrome. If not controlled, such arrhythmias increase the risk of ventricular fibrillation and sudden cardiac arrest. The ablation procedure can be classified by energy source: radiofrequency ablation and cryoablation.

<span class="mw-page-title-main">Sinus tachycardia</span> Sinus rhythm with a rate that is higher than normal

Sinus tachycardia is a sinus rhythm of the heart, with an increased rate of electrical discharge from the sinoatrial node, resulting in a tachycardia, a heart rate that is higher than the upper limit of normal.

<span class="mw-page-title-main">Paroxysmal supraventricular tachycardia</span> Episodes of abnormally fast heart rhythm

Paroxysmal supraventricular tachycardia (PSVT) is a type of supraventricular tachycardia, named for its intermittent episodes of abrupt onset and termination. Often people have no symptoms. Otherwise symptoms may include palpitations, feeling lightheaded, sweating, shortness of breath, and chest pain.

<span class="mw-page-title-main">Ivabradine</span> Heart medication

Ivabradine, sold under the brand name Procoralan among others, is a medication, which is a pacemaker current (If) inhibitor, used for the symptomatic management of heart-related chest pain and heart failure. Patients who qualify for use of ivabradine for coronary heart failure are patients who have symptomatic heart failure, with reduced ejection volume, and heart rate at least 70 bpm, and the condition not able to be fully managed by beta blockers.

<span class="mw-page-title-main">Ranolazine</span> Drug used to treat angina

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.

Sodium channel blockers are drugs which impair the conduction of sodium ions (Na+) through sodium channels.

<span class="mw-page-title-main">Landiolol</span> Chemical compound

Landiolol (INN) is an ultra short-acting, β1-superselective intravenous adrenergic antagonist, which decreases the heart rate effectively with less negative effect on blood pressure or myocardial contractility. In comparison to other beta blockers, landiolol has the shortest elimination half-life, ultra-rapid onset of effect, and predictable effectiveness with inactive metabolites. The pure S-enantiomer structure of landiolol is believed to develop less hypotensive side effects in comparison to other β-blockers. This has a positive impact on the treatment of patients when reduction of heart rate without decrease in arterial blood pressure is desired. It is used as landiolol hydrochloride.

<span class="mw-page-title-main">Tiapamil</span> Chemical compound

Tiapamil is a calcium antagonist or calcium channel blocker. It is an experimental drug that has never been marketed.

<span class="mw-page-title-main">Arrhythmia</span> Group of medical conditions characterized by irregular heartbeat

Arrhythmias, also known as cardiac arrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults – is called tachycardia, and a resting heart rate that is too slow – below 60 beats per minute – is called bradycardia. Some types of arrhythmias have no symptoms. Symptoms, when present, may include palpitations or feeling a pause between heartbeats. In more serious cases, there may be lightheadedness, passing out, shortness of breath, chest pain, or decreased level of consciousness. While most cases of arrhythmia are not serious, some predispose a person to complications such as stroke or heart failure. Others may result in sudden death.

References

  1. 1 2 "Verapamil". www.drugs.com. Archived from the original on 1 August 2017. Retrieved 14 December 2016.
  2. 1 2 "Verapamil Use During Pregnancy". Drugs.com. 18 November 2019. Archived from the original on 30 October 2024. Retrieved 26 March 2020.
  3. ↑ "Securon SR - Summary of Product Characteristics (SmPC)". (emc). 17 May 2017. Archived from the original on 26 March 2020. Retrieved 26 March 2020.
  4. 1 2 3 4 5 6 7 8 "Calan- verapamil hydrochloride tablet, film coated". DailyMed. 17 December 2019. Archived from the original on 26 March 2020. 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. Archived from the original (PDF) on 30 October 2024.
  6. 1 2 "Verapamil". Archived from the original on 30 October 2024. Onset of Action[...]Oral: Immediate release: 1 to 2 hours (Singh 1978); IV bolus: 3 to 5 minutes
  7. 1 2 Singh 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. PMID   346345.
  8. ↑ 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. ISBN   978-1-4557-0101-8. The elimination half-life of standard verapamil tablets is usually 3 to 7 hours,...
  9. 1 2 3 4 5 6 "Verapamil Hydrochloride". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
  10. ↑ Tfelt-Hansen PC, Jensen RH (July 2012). "Management of cluster headache". CNS Drugs. 26 (7): 571–580. doi:10.2165/11632850-000000000-00000. PMID   22650381. S2CID   22522914.
  11. ↑ Merison K, Jacobs H (November 2016). "Diagnosis and Treatment of Childhood Migraine". Current Treatment Options in Neurology. 18 (11): 48. doi:10.1007/s11940-016-0431-4. PMID   27704257. S2CID   28302667.
  12. 1 2 3 World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. hdl: 10665/44053 . ISBN   9789241547659.
  13. ↑ "Isoptin: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Archived from the original on 30 October 2024. Retrieved 26 March 2020.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ "The Top 300 of 2022". ClinCalc. Archived from the original on 30 August 2024. Retrieved 30 August 2024.
  17. ↑ "Verapamil Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Retrieved 30 August 2024.
  18. 1 2 Koda-Kimble and Young's Applied Therapeutics: The Clinical Use of Drugs (10th ed.). USA: LWW. 2012. pp. 497, 1349. ISBN   978-1609137137.
  19. ↑ Fahie S, Cassagnol M (2023). "Verapamil". StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. PMID   30860730. Archived from the original on 10 April 2023. Retrieved 6 November 2023.
  20. ↑ Srinivasan V, Sivaramakrishnan H, Karthikeyan B (2011). "Detection, isolation and characterization of principal synthetic route indicative impurities in verapamil hydrochloride". Scientia Pharmaceutica. 79 (3): 555–568. doi:10.3797/scipharm.1101-19. PMC   3163365 . PMID   21886903.
  21. ↑ James PA, Oparil S, Carter BL, et al. (February 2014). "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. 311 (5): 507–520. doi: 10.1001/jama.2013.284427 . PMID   24352797.
  22. ↑ Beck E, Sieber WJ, Trejo R (February 2005). "Management of cluster headache". American Family Physician. 71 (4): 717–724. PMID   15742909. Archived from the original on 13 November 2015. Retrieved 4 November 2015.
  23. ↑ Jun P, Ko NU, English JD, et al. (November 2010). "Endovascular treatment of medically refractory cerebral vasospasm following aneurysmal subarachnoid hemorrhage". American Journal of Neuroradiology. 31 (10): 1911–1916. doi:10.3174/ajnr.A2183. PMC   4067264 . PMID   20616179.
  24. ↑ Drislane F, Benatar M, Chang BS, et al. (1 January 2009). Blueprints Neurology. Lippincott Williams & Wilkins. pp. 71–. ISBN   978-0-7817-9685-9. Archived from the original on 8 June 2013. Retrieved 14 November 2010.
  25. ↑ Young JR, Sternbach S, Willinger M, et al. (17 December 2018). "The etiology, evaluation, and management of plantar fibromatosis". Orthopedic Research and Reviews. 11: 1–7. doi: 10.2147/ORR.S154289 . PMC   6367723 . PMID   30774465.
  26. 1 2 Dutta D, Nagendra L, Raizada N, et al. (May–June 2023). "Verapamil improves One-Year C-Peptide Levels in Recent Onset Type-1 Diabetes: A Meta-Analysis". Indian J Endocrinol Metab. 27 (3): 192–200. doi: 10.4103/ijem.ijem_122_23 . PMC   10424102 . PMID   37583402.
  27. ↑ 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. PMID   6439057.
  28. ↑ Giannini AJ, Taraszewski R, Loiselle RH (December 1987). "Verapamil and lithium in maintenance therapy of manic patients". Journal of Clinical Pharmacology. 27 (12): 980–982. doi:10.1002/j.1552-4604.1987.tb05600.x. PMID   3325531. S2CID   34536914.
  29. ↑ Giannini AJ, Nakoneczie AM, Melemis SM, et al. (February 2000). "Magnesium oxide augmentation of verapamil maintenance therapy in mania". Psychiatry Research. 93 (1): 83–87. doi:10.1016/S0165-1781(99)00116-X. PMID   10699232. S2CID   18216795.
  30. ↑ "Securon 2.5 mg/ml IV Intravenous Injection - Summary of Product Characteristics (SmPC)". (emc). 24 November 2016. Archived from the original on 26 March 2020. Retrieved 26 March 2020.
  31. ↑ 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. PMID   1587197. S2CID   1007332.
  32. ↑ Steele RM, Schuna AA, Schreiber RT (April 1994). "Calcium antagonist-induced gingival hyperplasia". Annals of Internal Medicine. 120 (8): 663–664. doi:10.7326/0003-4819-120-8-199404150-00006. PMID   8135450. S2CID   41746099.
  33. ↑ 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. PMID   16615674. S2CID   10351499.
  34. ↑ Baselt R (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, California: Biomedical Publications. pp. 1637–39.
  35. ↑ Ahmad F, Abu Sneineh M, Patel RS, et al. (June 2021). "In The Line of Treatment: A Systematic Review of Paroxysmal Supraventricular Tachycardia". Cureus. 13 (6): e15502. doi: 10.7759/cureus.15502 . PMC   8261787 . PMID   34268033.
  36. ↑ 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. PMID   20926952.
  37. ↑ 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.
  38. ↑ 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. PMID   18505444. S2CID   205457755.
  39. ↑ 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. PMID   31339562. S2CID   198193843.
  40. ↑ 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. PMID   6704142.
  41. ↑ 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. PMID   3864783. S2CID   10911875.
  42. ↑ 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. PMID   2296179.
  43. ↑ 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. PMID   8116206.
  44. 1 2 Song J, Chang I, Chen Z, et al. (July 2010). "Characterization of side populations in HNSCC: highly invasive, chemoresistant and abnormal Wnt signaling". PLOS ONE. 5 (7): e11456. Bibcode:2010PLoSO...511456S. doi: 10.1371/journal.pone.0011456 . PMC   2897893 . PMID   20625515.
  45. ↑ Bellamy WT (1996). "P-glycoproteins and multidrug resistance". Annual Review of Pharmacology and Toxicology. 36: 161–183. doi:10.1146/annurev.pa.36.040196.001113. PMID   8725386.
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