Calcium channel blocker toxicity

Medical condition

Calcium channel blocker toxicity

Other names| 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 for 24 hours or more.[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 bring about 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

[edit]

Most people who have taken too much of a calcium channel blocker, especially diltiazem, get slow heart rate and low blood pressure (vasodilatory shock).[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]

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] Hypocalcaemia may also occur.[7]

## Cause

[edit]

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

[edit]

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

[edit]

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

[edit]

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

[edit]

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] Those who have no symptoms or signs six hours following taking an immediate release formulation and 24 hours after taking an extended release formulation generally need no further medical treatment.[2]

### Detoxification

[edit]

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

[edit]

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

[edit]

Intravenous calcium gluconate or calcium chloride is considered a specific antidote.[12] Slow heart rate can be treated with atropine and sympathomimetics. Low blood pressure is treated with vasopressors such as adrenaline.[6][13]

There is tentative clinical evidence and good theoretical evidence of the benefit of lipid emulsion in severe overdoses of CCBs.[14] Methylene blue may also be used for those with low blood pressure that does not respond to other treatments.[10]

## Epidemiology

[edit]

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

[edit]

1. ^ a b c d e f g h i j k l m n o p q r s Palatnick, Wesley (Feb 2014). "Emergency Department Management of Calcium-Channel Blocker, Beta Blocker, and Digoxin Toxicity". Emergency Medicine Practice. 16 (2): 1–19, quiz 19-20. PMID 24883458. Archived from the original on 2014-05-14.
2. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z 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 978-1455706051.
3. ^ a b "Calcium channel blocker overdose". ADAM. 2011-01-19. Archived from the original on 5 April 2014. Retrieved 9 May 2014.
4. ^ a b 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. ^ a b Haberfeld, H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Adalat; Norvasc; Sibelium; Zanidip.
7. ^ Soar, J; Perkins, GD; Abbas, G; Alfonzo, A; Barelli, A; Bierens, JJ; Brugger, H; Deakin, CD; Dunning, J; Georgiou, M; Handley, AJ; Lockey, DJ; Paal, P; Sandroni, C; Thies, KC; Zideman, DA; Nolan, JP (October 2010). "European Resuscitation Council Guidelines for Resuscitation 2010 Section 8. Cardiac arrest in special circumstances: Electrolyte abnormalities, poisoning, drowning, accidental hypothermia, hyperthermia, asthma, anaphylaxis, cardiac surgery, trauma, pregnancy, electrocution". Resuscitation. 81 (10): 1400–33\. doi:10.1016/j.resuscitation.2010.08.015. PMID 20956045.
8. ^ a b Olson, Kent (2011). "Calcium Channel Antagonists". Poisoning & drug overdose (6th ed.). New York: McGraw-Hill Medical. pp. Chapter 40. ISBN 978-0071668330.
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. ^ a b 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 (3): 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. S2CID 32138463.
12. ^ "Calcium channel blocker poisoning". UpToDate. Retrieved 2019-07-09.
13. ^ Haberfeld, H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Verapabene.
14. ^ 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.

## External links

[edit]

Classification|

* ICD-10: T46.1X1A
* ICD-9-CM: 972
* MeSH: D062787
* DiseasesDB: 3971

|

External resources|

* MedlinePlus: 002580
* eMedicine: article/2184611

* 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. 45 (3): e306 – e315. doi:10.1097/CCM.0000000000002087. PMC 5312725. PMID 27749343.

* v
* t
* e

* Poisoning
* Toxicity
* Overdose

* Poison
* History

Inorganic|

| Metals|

| Toxic metals|

* Beryllium
* Cadmium
* Lead
* Mercury
* Nickel
* Thallium
* Tin

|

Dietary minerals|

* Chromium
* Cobalt
* Copper
* Iron
* Manganese
* Zinc

Other non-toxic metals|

* Silver1

Metalloids|

* Arsenic

Nonmetals|

* Sulfuric acid
* Selenium
* Chlorine
* Fluoride

Organic|

| Phosphorus|

* Pesticides
* Aluminium phosphide
* Organophosphates

|

Nitrogen|

* Cyanide
* Nicotine
* Nitrogen dioxide poisoning

CHO|

* alcohol
* Ethanol
* Ethylene glycol
* Methanol
* Carbon monoxide
* Oxygen
* Toluene

Pharmaceutical|

| Drug overdoses|

| Nervous|

* Alcohol
* Anticholinesterase
* Aspirin
* Barbiturates
* Benzodiazepines
* Cocaine
* Lithium
* Opioids
* Paracetamol
* Serotonergic substances
* Tricyclic antidepressants

|

Cardiovascular|

* Digoxin
* Dipyridamole

Vitamin poisoning|

* Vitamin A
* Vitamin D
* Vitamin E
* Megavitamin-B6 syndrome

Biological2|

| Fish / Seafood|

* Ciguatera
* Haff disease
* Ichthyoallyeinotoxism
* Scombroid
* Shellfish poisoning
* Amnesic
* Diarrhetic
* Neurotoxic
* Paralytic

|

Other vertebrates|

* Amphibian
* Batrachotoxin
* Bombesin
* Bufotenin
* Physalaemin
* Birds
* Coturnism
* Mammal
* Snakes / Snake venom
* Alpha-Bungarotoxin
* Ancrod
* Batroxobin

Arthropods|

* Arthropod bites and stings
* Bee sting / Bee venom
* Apamin
* Melittin
* Scorpion venom
* Charybdotoxin
* spider venom
* Latrotoxin / Latrodectism
* Loxoscelism
* Tick paralysis

Plants / Fungi|

* Cinchonism
* Ergotism
* Fish toxins
* Lathyrism
* Locoism
* Mushroom
* Strychnine

Related topics|

* Bite and Stinger
* plant
* Cnidocyte
* Venomous animals
* Poisonous animals
* Deadly fungus
* Mycotoxicology

Miscellaneous|

* Antibiotic
* EPA list of hazard
* Lists of poisonings
* List of types of poison
* Pollution

1Silver is generally non-toxic metal, but in large doses it can lead to argyria, which is rare.
2 including venoms, toxins, foodborne illnesses.

* Category
* Commons
* WikiProject

* v
* t
* e

Antidotes (V03AB)

Nervous
system|

| Alcohol intoxication|

* Metadoxine
* Thiamine

|

Barbiturate
overdose|

* Bemegride
* Ethamivan

Benzodiazepine
overdose|

* Cyprodenate
* Flumazenil

GHB overdose|

* Physostigmine
* SCH-50911

Nerve agent /
Organophosphate
poisoning|

* Atropine#
* Biperiden
* Diazepam#
* Oximes
* Obidoxime
* Pralidoxime
* see also: Cholinesterase

Opioid overdose|

* Diprenorphine
* Doxapram
* Nalmefene
* Nalorphine
* Naloxone#
* Naltrexone

Reversal of
neuromuscular blockade|

* Sugammadex

Circulatory
system|

| Beta blocker|

* Glucagon

|

Digoxin toxicity|

* Digoxin immune fab

Anticoagulants|

* against direct Xa inhibitors (Andexanet alfa)
* against heparin (Protamine#)

Other|

| Arsenic poisoning|

* Dimercaprol#
* Succimer

|

Cyanide poisoning|

* 4-Dimethylaminophenol
* Hydroxocobalamin
* nitrite
* Amyl nitrite
* Sodium nitrite#
* Sodium thiosulfate#

Hydrofluoric acid|

* Calcium gluconate#

Methanol /
Ethylene glycol
poisoning|

* Primary alcohols: Ethanol
* Fomepizole

Paracetamol toxicity
(Acetaminophen)|

* Acetylcysteine#
* Glutathione
* Methionine#

Toxic metals (cadmium

* lead
* mercury
* thallium)

* Dimercaprol#
* Edetates
* Prussian blue#

Other|

* iodine-131
* Potassium iodide
* Methylthioninium chloride#
* oxidizing agent
* Potassium permanganate
* Prednisolone/promethazine

Emetic|

* Copper sulfate
* Ipecacuanha
* Syrup of ipecac

* #WHO-EM
* ‡Withdrawn from market
* Clinical trials:
* †Phase III
* §Never to phase III

*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template