calcium channel blocker (CCB)
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Indications
- hypertension
- isolated systolic hypertension in the elderly
- hypertension in blacks
- supraventricular tachycardia
- atrial fibrillation/flutter (diltiazem, verapamil)
- angina
- hypertrophic cardiomyopathy
- left ventricular diastolic dysfunction[6]
- cluster headache
- Raynaud's phenomenon
- essential tremo
- subarachnoid hemorrhage
- premature labor[6]
Contraindications
* amlodipine may be OK
Adverse effects
- 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]
- bradycardia
- tachycardia
- orthostatic hypotension
- constipation
- GERD via lowering of esophageal sphincter tone
- urinary retention via relaxation of bladder smooth muscle
- eczema, pruritus (especially chronic therapy in elderly)
- 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]
- in older adults > 66 years of age, prescription of calcium-channel blocker associated with increase likelihood of later prescription of loop diuretic[11]
- 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]
- hypotension due to
Management of overdose:
- asymptomatic patients who may have ingested a lethal dose of calcium channel blocker should be observed for 24 hours
- activated charcoal should be considered for up to 1 hour after ingestion[10]
- supportive therapy:
- IV access
- continuous cardiac monitoring
- bradycardia
- atropine generally not useful (not vagally mediated)
- recommended in[10] for bradycardia
- glucagon recommended in[2], but not in[3]
- ventricular pacing
- atropine generally not useful (not vagally mediated)
- hypotension
- calcium gluconate 3-9 g IV through peripheral line
- calcium chloride 1-2 g IV over 10 minutes through a central venous catheter is alternative (caution: sclerosing agent)
- 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]
- 1 unit/kg bolus followed by 1 unit/kg/hour
- norepinephrine &/or epinephrine[10]
- dobutamine for cardiogenic shock[10]
- do not use dopamine or vasopressin for cardiogenic shock
- intra-aortic balloon pump
- 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]
- drug interaction(s) of calcium channel blockers with ARBs
- drug interaction(s) of calcium channel blockers with ACE inhibitors
- drug interaction(s) of calcium channel blockers with diuretics
- drug interaction(s) of calcium channel blockers with erythromycin
- drug interaction(s) of calcium channel blockers with clarithromycin
- drug interaction(s) of beta-adrenergic receptor antagonists with calcium channel blockers
- drug interaction(s) of NSAIDs & antihypertensives
Mechanism of action
- blocks entry of calcium into cells
- inhibits contractility of smooth muscle
- dilation of blood vessels - increases coronary perfusion
- reduction in blood pressure - decreases afterload
- beneficial effect of diastolic relaxation
- negative inotropic effects (diltiazem, verapamil)
- diltiazem & verapamil block the AV node; dihydropyridine CCBs do NOT
More general terms
More specific terms
- 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)
Additional terms
Component of
References
- ↑ 1.0 1.1 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/18007690
Prescriber's Letter 15(4): 2008 Calcium Channel Blockers (CCBs) and Eczema Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=240402&pb=PRL (subscription needed) http://www.prescribersletter.com - ↑ 2.0 2.1 Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 18. American College of Physicians, Philadelphia 2009, 2012, 2018.
- ↑ 3.0 3.1 The Washington Manual of Medical Therapeutics, 33rd edition Foster C et al (eds) Lippincott, Williams & Wilkins, Philadelphia, 2010, pg 971
- ↑ 4.0 4.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23636109 <Internet> http://archderm.jamanetwork.com/article.aspx?articleid=1684846
- ↑ 5.0 5.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23921840 <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23921818 <Internet> http://archinte.jamanetwork.com/article.aspx?articleid=1723870 - ↑ 6.0 6.1 6.2 Deprecated Reference
- ↑ 7.0 7.1 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
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/21558959
- ↑ 9.0 9.1 Paauw DS Dangerous and Deadly Drug Combinations Medscape. June 30, 2016 http://www.medscape.com/features/slideshow/dangerous-drug-combinations
- ↑ 10.0 10.1 10.2 10.3 10.4 10.5 10.6 10.7 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27749343 <Internet> http://journals.lww.com/ccmjournal/pages/articleviewer.aspx?year=9000&issue=00000&article=96757&type=abstract - ↑ 11.0 11.1 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: https://www.ncbi.nlm.nih.gov/pubmed/32091538 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2761272
- ↑ 12.0 12.1 NEJM Knowledge+
DeWitt CR, Waksman JC. Pharmacology, pathophysiology and management of calcium channel blocker and beta-blocker toxicity. Toxicol Rev 2004; 23:223 PMID: https://www.ncbi.nlm.nih.gov/pubmed/15898828 - ↑ 13.0 13.1 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: https://www.ncbi.nlm.nih.gov/pubmed/38009803 https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.18683
- ↑ 14.0 14.1 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: https://www.ncbi.nlm.nih.gov/pubmed/21295192 https://www.amjmed.com/article/S0002-9343(10)00745-X/fulltext