Calcium channel blocker toxicity

Calcium channel blocker toxicity
Synonyms Calcium channel blocker poisoning, calcium channel blocker overdose
A 20% lipid emulsion commonly used for calcium channel blocker toxicity
Specialty Emergency medicine
Symptoms Slow heart rate, low blood pressure, nausea, vomiting, sleepiness[1][2]
Complications Cardiac arrest[2]
Usual onset Within 6 hours[2]
Causes Too much calcium channel blockers either by accident or on purpose[3]
Differential diagnosis Beta blocker toxicity[1]
Treatment Activated charcoal, whole bowel irrigation, intravenous fluids, calcium gluconate, glucagon, high dose insulin, vasopressors, lipid emulsion[1][2]
Prognosis High risk of death[2]
Frequency > 10,000 (US)[2]

Calcium channel blocker toxicity is the taking of too much of the medications known as calcium channel blockers (CCBs) either by accident or on purpose.[3] This often causes a slow heart rate and low blood pressure.[1] This can progress to the heart stopping altogether.[2] Some CCBs can also cause a fast heart rate as a result of the low blood pressure.[4] Other symptoms may include nausea, vomiting, sleepiness, and shortness of breath.[2] Symptoms usually occur in the first six hours but with some forms of the medication may not start until 24 after hours.[2]

There are a number of treatments that may be useful.[1] These include efforts to reduce absorption of the drug including: activated charcoal taken by mouth if given shortly after the ingestion or whole bowel irrigation if an extended release formula was taken.[1] Efforts to cause vomiting are not recommended.[1] Medications to treat the toxic effects include: intravenous fluids, calcium gluconate, glucagon, high dose insulin, vasopressors and lipid emulsion.[1][2] Extracorporeal membrane oxygenation may also be an option.[1]

More than ten thousand cases of calcium channel blocker toxicity were reported in the United States in 2010.[2] Along with beta blockers and digoxin calcium channel blockers have one of the highest rates of death in overdose.[2] These medications first became available in the 1970s and 1980s.[2] They are one of the few types of medication in which one pill can result in the death of a child.[2]

Signs and symptoms

Most people who have taken too much of a calcium channel blocker, especially diltiazem, get slow heart rate and low blood pressure.[1] This can progress to the heart stopping altogether.[2] CCBs of the dihydropyridine group, as well as flunarizine, predominantly cause reflex tachycardia as a reaction to the low blood pressure.[4][5][6] For verapamil, despite it having a similar mechanism of action as diltiazem, both fast and slow heart rhythm are described.[7]

Other potential symptoms include: nausea and vomiting, a decreased level of consciousness, and breathing difficulties.[2] Symptoms usually begin within 6 hours of taking the medication by mouth.[2] With extended release formulations symptoms may not occur for up to a day.[2] Seizures are rare in adults but in children occur more often.[2]

Cause

Calcium channel blockers, also known as calcium channel antagonists, are widely used for a number of health conditions.[8] Thus they are commonly present in many people's homes. In young children one pill may cause serious health problems and potentially death.[8] The calcium channel blocker that caused the greatest number of deaths in 2010 in the United States was verapamil.[2] This agent is believed to cause more heart problems than many of the others.[2]

Diagnosis

A blood or urine test to diagnose overdose is not generally available.[2] CCB overdose may cause high blood sugar levels, and this is often a sign of how severe the problem will become.[1]

Electrocardiogram

CCB toxicity can cause a number of electrocardiogram abnormalities with a low sinus rhythm being the most common.[1] Others include: QT prolongation, bundle branch block, first-degree atrioventricular block, and even sinus tachycardia.[1]

Differential

It may not be possible to tell the difference between beta blocker toxicity and calcium channel blocker overdose based on signs and symptoms.[1]

Management

The medical management of CCB toxicity may be difficult.[1] It may not improve with the usual treatments used for a low blood pressure and a slow heart rate.[9] In those who have no symptoms or signs six hours following taking an immediate release formulation and 24 hours after taking an extended release formulation need no further medical treatment.[2]

Detoxification

Activated charcoal is recommended if it can be given within an hour or two of taking the calcium channel blockers.[1] In those who have taken an extended release formulation of a CCB but are otherwise doing fine, whole bowel irrigation with polyethylene glycol may be useful.[1] Causing vomiting by the use of medications such as ipecac is not recommended.[1]

Insulin

High doses of intravenous insulin with glucose may be useful and are a first line treatment in overdoses.[1][10] As this treatment may cause a drop in blood sugar and blood potassium levels, these should be monitored closely.[11]

Other

Intravenous calcium gluconate is considered a specific antidote. Slow heart rate can be treated with atropine and sympathomimetics. Low blood pressure is treated with vasopressors such as adrenaline.[6][7]

There is tentative clinical evidence and good theoretical evidence of the benefit of lipid emulsion in severe overdoses of CCBs.[12] Methylene blue may also be used for those with low blood pressure that does not respond to other treatments.[10]

Epidemiology

More than 10,000 cases of potential calcium channel blocker toxicity occurred in the United States in 2010.[2] When death occurs in medicine overdose, heart medications are the cause more than 10% of time.[2] The three most common types of heart medications that result in this outcome are calcium channel blockers along with beta blockers and digoxin.[2]

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Palatnick, Wesley (Feb 2014). "Emergency Department Management of Calcium-Channel Blocker, Beta Blocker, and Digoxin Toxicity". Emergency Medicine Practice. 16 (2). Archived from the original on 2014-05-14.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 Marx, John A. Marx (2014). "Cardiovascular Drugs". Rosen's emergency medicine: concepts and clinical practice (8th ed.). Philadelphia, PA: Elsevier/Saunders. pp. Chapter 152. ISBN 1455706051.
  3. 1 2 "Calcium channel blocker overdose". ADAM. 2011-01-19. Archived from the original on 5 April 2014. Retrieved 9 May 2014.
  4. 1 2 Wolfson, Allan B. (2010). Harwood-Nuss' clinical practice of emergency medicine (5th ed.). Philadelphia, PA: Lippincott Williams & Wilkins. p. 1454. ISBN 9780781789431. Archived from the original on 15 August 2016. Retrieved 28 July 2016.
  5. ↑ Mutschler, Ernst (2013). Arzneimittelwirkungen (in German) (10 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. p. 1037. ISBN 978-3-8047-2898-1.
  6. 1 2 Haberfeld, H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Adalat; Norvasc; Sibelium; Zanidip.
  7. 1 2 Haberfeld, H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Verapabene.
  8. 1 2 Olson, Kent (2011). "Calcium Channel Antagonists". Poisoning & drug overdose (6th ed.). New York: McGraw-Hill Medical. pp. Chapter 40. ISBN 0071668330.
  9. ↑ Shepherd, G (Oct 1, 2006). "Treatment of poisoning caused by beta-adrenergic and calcium-channel blockers". American Journal of Health-System Pharmacy. 63 (19): 1828–35. doi:10.2146/ajhp060041. PMID 16990629.
  10. 1 2 Graudins, A; Lee, HM; Druda, D (7 September 2015). "Calcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies". British Journal of Clinical Pharmacology. 81: 453–61. doi:10.1111/bcp.12763. PMC 4767195. PMID 26344579.
  11. ↑ Engebretsen, KM; Kaczmarek, KM; Morgan, J; Holger, JS (Apr 2011). "High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning". Clinical Toxicology. 49 (4): 277–83. doi:10.3109/15563650.2011.582471. PMID 21563902.
  12. ↑ Rothschild, L; Bern, S; Oswald, S; Weinberg, G (Oct 5, 2010). "Intravenous lipid emulsion in clinical toxicology". Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 18: 51. doi:10.1186/1757-7241-18-51. PMC 2958894. PMID 20923546.
Classification
External resources
  • St-Onge, Maude; Anseeuw, Kurt; Cantrell, Frank Lee; Gilchrist, Ian C.; Hantson, Philippe; Bailey, Benoit; Lavergne, Valéry; Gosselin, Sophie; Kerns, William; Laliberté, Martin; Lavonas, Eric J.; Juurlink, David N.; Muscedere, John; Yang, Chen-Chang; Sinuff, Tasnim; Rieder, Michael; Mégarbane, Bruno (October 2016). "Experts Consensus Recommendations for the Management of Calcium Channel Blocker Poisoning in Adults". Critical Care Medicine: 1. doi:10.1097/CCM.0000000000002087. PMC 5312725. PMID 27749343.
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