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calcium channel blocker (CCB)

Indications: 1) hypertension a) isolated systolic hypertension in the elderly b) hypertension in blacks 2) supraventricular tachycardia 3) atrial fibrillation/flutter (diltiazem, verapamil) 4) angina a) angina pectoris & angina pectoris prophylaxis b) Prinzmetal's angina c) unstable angina 5) hypertrophic cardiomyopathy 6) left ventricular diastolic dysfunction [6] 7) cluster headache 8) Raynaud's phenomenon 9) essential tremo 10) subarachnoid hemorrhage 11) premature labor [6] Contraindications: - left ventricular systolic dysfunction (sytoliv heart failure)* * amlodipine may be OK Adverse effects: 1) lower extremity edema, pedal edema - diuretics (including loop diuretics) are ineffective in treating calcium channel blocker (CCB)-induced edema [13] - CCB-induced edema is due to arteriolar vasodilation rather than excess plasma volume - ACE inhibitors & ARBs can counteract CCB-induced edema - CCB-induced arteriolar vasodilation causes edema by increasing capillary pressure - ACE inhibitors or ARBs can lower that increased capillary pressure by decreasing postcapillary resistance [14] 2) bradycardia 3) tachycardia 4) orthostatic hypotension 5) constipation 6) GERD via lowering of esophageal sphincter tone 7) urinary retention via relaxation of bladder smooth muscle 8) eczema, pruritus (especially chronic therapy in elderly) - generally occurs about 3 months after starting drug [1,4] 9) long-term use of calcium channel blocker associated with > 2-fold increased risk of breast cancer in postmenopausal women [5] - no association with increased risk for breast cancer [7] 10) in older adults > 66 years of age, prescription of calcium-channel blocker associated with increase likelihood of later prescription of loop diuretic [11] Overdose: - tetrad of hypotension, bradycardia, hyperglycemia, metabolic acidosis - hypotension due to - diminished Ca+ influx into ventricular muscle, resulting in negative inotropy - diminshed Ca+ influc into vascuclar smooth muscle, resulting in diminished systemic vascular resistance - bradycardia due to block of Ca+ channels in the sinoatrial node & AV node - hyperglcemia due to diminished insulin secretion from beta cells of pancreatic islets - metabolic acidosis due to tissue hypoperfusion, lactic acidosis, & putative dysfunction of pyruvate dehydrogenase [12] Management of overdose: 1) asymptomatic patients who may have ingested a lethal dose of calcium channel blocker should be observed for 24 hours 2) activated charcoal should be considered for up to 1 hour after ingestion [10] 3) supportive therapy: a) IV access b) continuous cardiac monitoring 4) bradycardia a) atropine generally not useful (not vagally mediated) - recommended in [10] for bradycardia b) glucagon recommended in [2], but not in [3] c) ventricular pacing 5) hypotension a) calcium gluconate 3-9 g IV through peripheral line b) calcium chloride 1-2 g IV over 10 minutes through a central venous catheter is alternative (caution: sclerosing agent) c) high-dose insulin euglycemia therapy - 1 unit/kg bolus followed by 1 unit/kg/hour - with dextrose as needed - close serum potassium monitoring [10] - up to 10 units/kg for refractory cases [10] d) norepinephrine &/or epinephrine [10] e) dobutamine for cardiogenic shock [10] - do not use dopamine or vasopressin for cardiogenic shock f) intra-aortic balloon pump g) consider adding extracorporeal membrane oxygenation [10] Drug interactions: - calcium channel blockers nefedipine, amlodipine, & felodipine in combination with clarithromycin or erythromycin may result in hypotension & acute renal failure [9] Mechanism of action: 1) blocks entry of calcium into cells 2) inhibits contractility of smooth muscle 3) dilation of blood vessels - increases coronary perfusion 4) reduction in blood pressure - decreases afterload 5) beneficial effect of diastolic relaxation 6) negative inotropic effects (diltiazem, verapamil) 7) diltiazem & verapamil block the AV node; dihydropyridine CCBs do NOT

Interactions

drug interactions drug adverse effects (more general classes)

Related

antiarrhythmic agent, Group IV

Specific

amlodipine (Norvasc, Amlocard, Amvaz) bepridil (Vascor, Angopril, Cordium) clevidipine (Cleviprex) dihydropyridine Ca+2 channel blocker (CCB) diltiazem (Cardizem, Dilacor, Tiazac, Cartia, Angiotrofin, Dilcontin) felodipine (Plendil) flunarizine (Sibelium) isradipine (DynaCirc) lercanidipine (Zanidip) manidipine nicardipine (Cardene, Cardene SR) nifedipine (Procardia, Adalat) nilvadipine nimodipine (Nimotop, Numalize) nisoldipine (Sular) nitrendipine non-dihydropyridine Ca+2 channel blocker (CCB) norverapamil; arverapamil; verapamil (Isoptin, Calan, Verelan, Covera-HS, Iproveratril, Dilacorin, Cardioprotect)

General

vasodilator agent

Properties

References

  1. Joly P et al, Chronic eczematous eruptions of the elderly are associated with chronic exposure to calcium channel blockers: Results from a cases-control study. J Invest Dermatol 2007, 127:2766 PMID: 17713574 - Stern RS Chronic medication use and inflammatory skin diseases: The power and limitations of the case-control study. J Invest Dermatol 2007, 127:2709 PMID: 18007690 - Prescriber's Letter 15(4): 2008 Calcium Channel Blockers (CCBs) and Eczema Detail-Document#: 240402 (subscription needed) http://www.prescribersletter.com
  2. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 18. American College of Physicians, Philadelphia 2009, 2012, 2018.
  3. The Washington Manual of Medical Therapeutics, 33rd edition Foster C et al (eds) Lippincott, Williams & Wilkins, Philadelphia, 2010, pg 971
  4. Summers EM et al. Chronic eczematous eruptions in the aging: Further support of an association with exposure to calcium channel blockers. JAMA Dermatol 2013 May 1 PMID: 23636109 http://archderm.jamanetwork.com/article.aspx?articleid=1684846
  5. Li CI, Daling JR, Tang MT et al Use of Antihypertensive Medications and Breast Cancer Risk Among Women Aged 55 to 74 Years. JAMA Intern Med. August 5, 2013 PMID: 23921840 http://archinte.jamanetwork.com/article.aspx?articleid=1723871 - Coogan PF Calcium-Channel Blockers and Breast Cancer.A Hypothesis Revived. JAMA Intern Med. August 5, 2013 PMID: 23921818 http://archinte.jamanetwork.com/article.aspx?articleid=1723870
  6. Deprecated Reference
  7. InterMountain Health Care. Study deputes previous claims that calcium channel blocker meds cause breast cancer. http://intermountainhealthcare.org/hospitals/imed/services/heart-institute/about/Pages/news.aspx?NewsID=1867
  8. Makani H, Bangalore S, Romero J et al Peripheral edema associated with calcium channel blockers: incidence and withdrawal rate--a meta-analysis of randomized trials. J Hypertens. 2011 Jul;29(7):1270-80. PMID: 21558959
  9. Paauw DS Dangerous and Deadly Drug Combinations Medscape. June 30, 2016 http://www.medscape.com/features/slideshow/dangerous-drug-combinations
  10. Lindberg DM Consensus Guidelines for Calcium Channel Blocker Poisoning. NEJM Journal Watch. Oct 14, 2016 Massachusetts Medical Society (subscription needed) http://www.jwatch.org - St-Onge M, Anseeuw K, Cantrell FL et al. Experts consensus recommendations for the management of calcium channel blocker poisoning in adults. Crit Care Med 2016 Oct 3 PMID: 27749343 http://journals.lww.com/ccmjournal/pages/articleviewer.aspx?year=9000&issue=00000&article=96757&type=abstract
  11. Savage RD, Visentin JD, Bronskill SE et al. Evaluation of a common prescribing cascade of calcium channel blockers and diuretics in older adults with hypertension. JAMA Intern Med 2020 Feb 24; PMID: 32091538 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2761272
  12. NEJM Knowledge+ - DeWitt CR, Waksman JC. Pharmacology, pathophysiology and management of calcium channel blocker and beta-blocker toxicity. Toxicol Rev 2004; 23:223 PMID: 15898828
  13. Rochon PA et al. Association of a calcium channel blocker and diuretic prescribing cascade with adverse events: A population-based cohort study. J Am Geriatr Soc 2024 Feb; 72:467. PMID: 38009803 https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.18683
  14. Makani H, Bangalore S, Romero J, Wever-Pinzon O, Messerli FH. Effect of Renin-Angiotensin System Blockade on Calcium Channel Blocker- Associated Peripheral Edema. Am J Med. 2011 Feb;124(2):128-35 PMID: 21295192 https://www.amjmed.com/article/S0002-9343(10)00745-X/fulltext

Component-of

calcium channel blocker/HMG CoA reductase inhibitor