Calcium Channel Blocker Toxicity Medication

Updated: Jul 14, 2017
  • Author: B Zane Horowitz, MD, FACMT; Chief Editor: Michael A Miller, MD  more...
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Medication

Medication Summary

Initial management for a symptomatic calcium channel blocker overdose includes cardiovascular support with intravenous (IV) fluids and, if necessary, vasopressors. In addition, basic gastrointestinal [GI] decontamination is used selectively in overdose situations.Calcium administration only partially overcomes channel blockade and can be tried as a first-line agent; however, in all severe cases, vasopressors are needed. Glucagon also reportedly partially improves blood pressure and heart blockade, but rarely restores cardiac hemodynamics to normal. Therefore, despite the notion that calcium and glucagon are “antidotes,” vasopressor therapy with norepinephrine is required in most cases with hypotension. Additionally, high-dose insulin has been established as an effective therapy for calcium channel blocker overdose with cardiogenic shock. Intralipid infusion therapy should be used in patients who are deteriorating despite vasopressor therapy.

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Antidotes, Other

Class Summary

Activated charcoal adsorbs ingested medication remaining in the GI system and creates a concentration gradient to "pull back" medication circulating in the blood stream. Cathartics increase GI transit time.

Activated charcoal (Actidose-Aqua, EZ-Char, Kerr Insta-Char)

Activated charcoal is used in emergency treatment for poisoning caused by drugs and chemicals. A network of pores adsorbs 100-1000 mg of drug per gram. Administer it as soon as possible after poison ingestion. Repeated doses may help to lower systemic levels of ingested compounds, especially sustained-release preparations. In adults , activated charcoal is usually administered with sorbitol in alternating doses. Sorbitol should be avoided in children.

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Calcium Salts

Class Summary

These agents theoretically increase calcium's concentration gradient, overcoming the channel blockade and driving calcium into the cells. Calcium is given to reverse hypotension and improve cardiac conduction defects.

Calcium chloride

Calcium chloride moderates nerve and muscle performance by regulating the action potential excitation threshold.

Calcium gluconate

Calcium gluconate moderates nerve and muscle performance and facilitates normal cardiac function.

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Alpha/Beta Adrenergic Agonists

Class Summary

These agents augment blood pressure by stimulating dopamine, alpha-adrenergic receptors, and beta-adrenergic receptors. This extracellular effect is transduced across the cell membrane and activates adenylyl cyclase in the cell to form cyclic adenosine monophosphate (cAMP). The activation induces calcium inflow from the endoplasmic reticulum, which initiates muscle cell contraction. Sympathomimetics lead to vasoconstriction and increased cardiac inotropy, chronotropy, and dromotropy.

Norepinephrine (Levophed)

Norepinephrine stimulates beta1- and alpha-adrenergic receptors, which, in turn, increase cardiac muscle contractility, heart rate, and vasoconstriction. As a result, systemic blood pressure and coronary blood-flow increases. Mix 4 mg in 500 mL of 5% dextrose in water (D5W) to yield 8 mcg/mL.

Epinephrine (Adrenalin)

Epinephrine has alpha-agonist effects, which include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypotension, and vascular permeability. The drug's beta-agonist effects include bronchodilatation, chronotropic cardiac activity, and positive inotropic effects. Mix 1 mg in 250 mL D5W to yield 4 mcg/mL.

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Alpha Adrenergic Agonists

Class Summary

These agents increase peripheral vasoconstriction.

Phenylephrine

This agent does not have beta-adrenergic activity. It produces systemic arterial vasoconstriction, which, in turn, increases systolic and diastolic blood pressure while potentially reducing heart rate and cardiac output.

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Posterior Pituitary Hormones

Class Summary

Agents in this category cause contraction of smooth muscle of all parts of the vascular bed, especially the small arterioles, capillaries, and venules, with less effect on the smooth musculature of the large veins.

Vasopressin (Pitressin)

Vasopressin has vasopressor and antidiuretic hormone (ADH) activity. It promotes smooth muscle contraction throughout the vascular bed of the renal tubular epithelium (vasopressor effects). Vasoconstriction is increased in splanchnic, portal, coronary, cerebral, peripheral, pulmonary, and intrahepatic vessels.

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Inotropic Agents

Class Summary

In hypotensive patients, dopamine can be administered to support the heart rate. Failure to respond to the maximal dose of dopamine should prompt the addition of norepinephrine.

Dopamine

Dopamine activates dopamine receptors first, then beta1 receptors, and then alpha1 receptors. A low dose of 0.5-3 mcg/kg/min activates dopamine receptors and causes splanchnic vasodilation. An intermediate dose of 3-7.5 mcg/kg/min activates beta1 receptors, increasing cardiac inotropy and chronotropy. High doses of 7.5 mcg/kg/min or greater activate alpha1 receptors, causing vasoconstriction.

Doses of greater than 20 mcg/kg/min are unlikely to produce additional effects; therefore, the addition of a second agent (eg, norepinephrine) is probably indicated at that time. Mix 400 mg of dopamine in 250 mL D5W to yield 1600 mcg/mL.

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Glucose-Elevating Agents

Class Summary

Glucagon uses a different receptor than that used by sympathomimetics to stimulate intracellular cAMP production, increasing cardiac conduction and contractility. Glucagon has positive inotropic and chronotropic effects, which may be useful for treating bradycardia caused by calcium channel blockers.

Glucagon (GlucaGen)

Glucagon binds to a specific cell surface receptor found on cardiac myocytes and stimulates adenyl cyclase via G proteins. This results in the release of intracellular cAMP, thereby increasing phosphorylation of L-type calcium channels and calcium influx into cells.

One study showed that glucagon performed its action on cardiac function best in a normocalcemic environment. Mix glucagon with 0.9% sodium chloride (NaCl) to yield 1 mg/mL (1 U = 1 mg); do not use the diluent (propylene glycol) supplied with the single-dose ampule.

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Anticholinergic Agents

Class Summary

Atropine, an anticholinergic medication, works by blocking muscarinic acetylcholine receptors. Use of this drug theoretically lets the sympathetic characteristics of the autonomic nervous system prevail over the parasympathetic system. This action increases cardiac chronotropy.

Atropine IV

This agent blocks muscarinic acetylcholine receptors. It increases the heart rate and dries secretions.

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Antidiabetics, Insulins

Class Summary

Case reports of patients treated with high-dose insulin are beginning to support the use of this drug in calcium channel blocker toxicity. Insulin increases cardiac output and may increase survival as long as plasma glucose levels are monitored and supplemented with exogenous dextrose. To date, no prospective human trials have been published supporting this practice.

Insulin regular (Humulin R, Novolin R)

Calcium channel blockers inhibit the production of islet cells and the secretion of insulin and block free fatty acid uptake by the heart muscle. High-dose insulin may augment myocyte uptake of glucose during times of stress induced by calcium channel blocker overdose. Insulin's action provides additional metabolic support to improve cardiac contractility.

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Laxatives, Osmotic

Class Summary

Osmotic laxatives cause cathartic actions in the GI tract, increasing bowel transit time.

Polyethylene glycol (Colyte, MoviPrep, CoLyte, GoLYTELY)

Polyethylene glycol is a bowel irrigation solution with electrolyte and osmotic effects that has cathartic actions in the GI tract. It increases bowel transit time and interrupts enterohepatic circulation, yet it causes minimal net water and electrolyte shifts.

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