Cardiovascular drug poisoning

Last updated: September 20, 2023

Summarytoggle arrow icon

Cardiovascular drug poisoning can occur as a result of attempted self-harm, inadvertent medication error, or changes in drug clearance, e.g., if renal insufficiency develops. Hypotension, arrhythmias, and/or neurologic changes commonly occur at toxic levels of these medications. Management often requires a clinical diagnosis to be made based on medication history and ECG changes, and the patient is treated symptomatically until the offending agent is identified. Initial symptomatic treatment may include GI decontamination, IV fluids for hypotension, atropine for bradycardia, and benzodiazepines for seizures. Definitive therapy may include a drug class-specific antidote, e.g., high-dose euglycemic insulin therapy for calcium channel blocker poisoning or digoxin immune Fab (DigiFab) for digoxin poisoning.

Overviewtoggle arrow icon

Cardiovascular drug poisoning often manifests with cardiogenic shock that may require judicious IV fluid resuscitation with vasopressors and inotropes PLUS substance-specific antidotes.

Clinical featurestoggle arrow icon

Nonspecific features common to most cases of cardiovascular drug poisoning include: [2]

Patients with severe cardiovascular drug poisoning can present with cardiogenic shock or cardiac arrest.

Managementtoggle arrow icon

Initial management [2][5]

Management of poisoning by multiple classes of cardiovascular drugs is complex; Consult a medical toxicologist and critical care specialist.

Diagnostic evaluation

Cardiovascular (CV) drug poisoning is primarily diagnosed clinically. Serum drug levels, when available, can support the diagnosis and, in some cases, help guide management.

  • Ensure the following are included in the toxicological history and physical examination:
    • CV drug ingestion details (e.g., witnesses, time, quantity, access, availability)
    • Co-ingested hemodynamically active medications or substances
    • Conditions affecting CV drug metabolism, e.g., worsening renal failure
  • Consult a toxicologist to determine individual risk as toxic dose thresholds for CV drugs can vary by poison center. [6][7]
  • Obtain ECG, CMP, and drug levels (e.g., serum digoxin). [5][8]
  • See “Toxicological risk assessment” for details.

A single pill of a cardiovascular drug formulated for adults may contain a toxic or even fatal dose for a child. [7]

GI decontamination

Do not perform whole bowel irrigation if the patient is hemodynamically unstable, has clinical signs of bowel obstruction, and/or their airway is not protected. [13]

Symptom-specific management [2]


Consider initiating VA-ECMO early in severely unstable patients. [2][5]

Bradycardia [5]

Atropine is seldom effective for medication-induced bradycardia. Temporary cardiac pacing and antidotes (e.g., high-dose glucagon) are often required. [16]

Arrhythmias [17]

Avoid Class IA and Class IC antidysrhythmic medications, as they may worsen the proarrhythmic state of the myocardium. [2][17]

Seizures [5]

Antidotes and dosagestoggle arrow icon

Calcium therapy for drug poisoning [2][16][18]

Calcium chloride is usually administered through a central line, unless the patient is hemodynamically unstable. [2]

High-dose euglycemic insulin therapy [2][16][18]

  • Indications: CCB poisoning, beta blocker poisoning
  • Administration: Titrate infusion upward every 10–15 minutes until reaching a heart rate ≥ 50/min and systolic blood pressure ≥ 90 mm Hg. [21]
  • Monitoring
    • Check blood glucose every 15–30 minutes until stable; the goal is euglycemia.
    • Check potassium every 60 minutes until stable; maintain levels of at least 2.8–3.2 mEq/L. [5]

High-dose glucagon [2][5][16][18][23]

Intravenous lipid emulsion therapy (ILE) [2][24]

Only use intravenous lipid therapy when symptoms of toxicity are refractory to more conventional therapy, e.g., if at least three vasopressors to correct hypotension. [2][24]

Methylene blue for drug poisoning [2][5][25]

Dispositiontoggle arrow icon

The following are expert-recommended best practices. Follow local protocols and consult a toxicologist to help determine individual disposition. [2][3][5][27][28]

  • Transfer unstable patients to the ICU.
  • Admit patients to a monitored bed in the following cases:
    • New arrhythmias or conduction abnormalities
    • Chronic digoxin poisoning regardless of symptoms
    • Ingestion of drugs with extended release formulations or delayed toxicity, e.g., sotalol
    • Signs or symptoms of toxicity that do not reverse in the observation period.
  • Observe stable patients based on the half-life of the ingested medication(s) and the amount ingested.
  • Consult psychiatry if the overdose was intentional.

Beta blocker poisoningtoggle arrow icon

Potentially toxic doses [7]

Discuss risk with poison control; the lowest reported toxic dose is typically higher than the maximum recommended therapeutic dose but can overlap in drugs with a narrow therapeutic index.

Maximum recommended single therapeutic oral doses for common beta blockers [7]
Adults Children
Atenolol 200 mg 2 mg/kg
Carvedilol 50 mg 0.5 mg/kg
Metoprolol 450 mg 2.5 mg/kg
Propranolol 240 mg 4 mg/kg
Sotalol 160 mg 4 mg/kg
Acebutolol 600 mg 12 mg/kg
Bisoprolol 10 mg [29] 0.14 mg/kg [30]

Bisoprolol toxicity may not follow a clear dose-response relationship. Similar toxic effects have been seen at low and high doses of exposure. [31]

A few drops of ophthalmic beta blockers (e.g., timolol) can cause significant systemic effects. [32]

Clinical features [2][5][27]


  • Life-threatening symptoms: possible as early as 30 minutes after ingestion [5]
  • Most symptoms: within the first 6 hours [5]
  • Sotalol poisoning: can cause delayed and prolonged symptoms

Signs and symptoms

Sotalol poisoning can manifest with CNS depression and vomiting. [31]

Diagnostics [2][5][27]

Management [2][14][16][27][33]

If the patient is unstable, begin interventions simultaneously rather than sequentially.

Initial management

Persistent instability after initial management

Glucagon can be used as an antidote for beta blocker poisoning. [2][5]

Sustained instability after secondary interventions

Refractory instability

Calcium channel blocker poisoningtoggle arrow icon

Potentially toxic doses [6]

Discuss risk with poison control; the lowest reported toxic dose is typically higher than the maximum recommended therapeutic dose but can overlap in drugs with a narrow therapeutic index.

Maximum recommended single therapeutic oral doses for common CCBs [6]
Adults Children
Amlodipine 10 mg 0.3 mg/kg
Diltiazem IR 120 mg 1 mg/kg
Diltiazem SR 360 mg
Verapamil IR 120 mg 2.5 mg/kg
Verapamil SR 480 mg
Nifedipine 30 mg 1 mg/kg

Clinical features [2][5][27]


  • Immediate release CCBs: within 6 hours [35]
  • Sustained-release CCBs: within 12–24 hours [35]
  • Patients who present early or have only consumed a small quantity of CCBs may be asymptomatic.

Signs and symptoms

Most clinical features of CV drug overdose can occur. Specific features depend on the agent and poisoning severity.

CCB poisoning more often results in life-threatening symptoms (e.g., profound hypotension and bradycardia) than beta blocker poisoning. [2]

Diagnostics [2][12][27]

Management [33][36][37]

If the patient is unstable, begin interventions simultaneously rather than sequentially.

Initial management

Consider GI decontamination for sustained-release CCB poisoning. [5]

Persistent instability after initial management

Where possible, use high-dose euglycemic insulin therapy rather than vasopressor infusions for severe CCB poisoning. [5]

Sustained instability after secondary interventions

The effectiveness of these agents is inconsistent.

Refractory instability

Non-ECMO extracorporeal therapy (e.g., hemodialysis) is discouraged for severe poisoning with amlodipine, diltiazem, and verapamil as these substances are not dialyzable. [38]

Digoxin poisoningtoggle arrow icon

Poisoning may result from acute digoxin overdose, reduced clearance of chronically administered digoxin, or ingestion of plants containing cardiac glycosides.

Risk factors [2][5]

Digoxin has a narrow therapeutic index. Serum concentrations of cardiac glycosides must be monitored closely because overdoses can have severe consequences.

Clinical features [2][5][8][39]

The symptoms and signs of chronic digoxin poisoning are nonspecific, with significant overlap between acute and chronic toxicity.

Potentially fatal bradyarrhythmias and/or tachyarrhythmias may occur in digoxin poisoning.

Diagnostics [2][5]

ECG [40]

Any dysrhythmia or conduction block may occur; bradyarrhythmias are as common as tachyarrhythmias.

There is no characteristic arrhythmia associated with digoxin poisoning; a wide range of arrhythmias can occur. [2]

Laboratory studies [42]

Management [2][5][40][43][44]

DigiFab is the antidote for significant acute and chronic poisoning. [2][44]

In severe digoxin poisoning, interventions such as cardiac pacing or cardioversion can trigger asystole or Vfib, as cardiac tissue may be hypersensitive to electrical and/or mechanical stimulation. [2]

Avoid class IA antiarrhythmics, e.g., quinidine, procainamide, and disopyramide. [5]

Digoxin immune Fab (DigiFab) [2][5][43]

Indications [2][5][43]

Known or suspected digoxin poisoning in patients with any of the following:

  • Cardiac arrest [5]
  • Any life-threatening or potentially life-threatening arrhythmia [5]
  • Serum potassium rapidly rising or > 5.0 mEq/L (attributable to digoxin) [2]
  • Acute ingestion > 4 mg (or > 0.1 mg/kg) in a healthy child or 10 mg in a healthy adult [5]
  • Serum digoxin concentrations > 10 ng/mL soon after acute ingestion or > 6 ng/mL steady state [2][5]
  • Serum digoxin concentration > 1.6 ng/mL AND signs or symptoms of severe digoxin toxicity [43]
  • Co-ingestion of other cardiovascular drugs

There are no absolute contraindications to DigiFab. [46]

Dosage and administration [46]

Several strategies can be used to determine the initial dose of DigiFab. Expect a clinical response in most patients within 1 hour of infusion completion. [5]

  • Unknown ingested quantity: empiric administration
    • Acute ingestion
    • Chronic ingestion
  • Known ingested quantity: ingested digoxin in mg x 2 = vials of DigiFab [2][5][46]
  • Known serum digoxin concentration: (concentration in ng/mL x patient weight in kg)/100 = vials of DigiFab

Adverse effects of Digifab include hypokalemia, loss of therapeutic effects of digoxin (e.g., rebound rapid A-fib), and occasionally, allergic reactions. [46]

Monitor for recurrence of toxicity; repeat dosing of DigiFab is occasionally required. [2]

Other antiarrhythmic drug poisoningtoggle arrow icon

Class I antiarrhythmic poisoning [5][8]

Amiodarone poisoning [5][8]

Acute overdose is rare and experience with acute amiodarone poisoning is limited; see “Adverse effects of amiodarone” for side effects of long-term therapeutic use. [8]

Antihypertensive drug poisoningtoggle arrow icon

Clonidine poisoning [2][5]

Clinical features



Nitrate poisoning [2]

Toxicity from nitrates may result from vasodilation and/or methemoglobinemia.

If the nitrates were initiated for acute coronary syndrome, use vasopressors cautiously. [2]

ACEI and ARB poisoning [5]

Toxicity is rarely life-threatening in isolated ACEI or ARB overdose.

Check for co-ingestion with other antihypertensives, e.g., beta blockers or CCBs.

Referencestoggle arrow icon

  1. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay. J Am Coll Cardiol. 2019; 74 (7): p.e51-e156.doi: 10.1016/j.jacc.2018.10.044 . | Open in Read by QxMD
  2. Kerns W. Management of β-Adrenergic Blocker and Calcium Channel Antagonist Toxicity. Emerg Med Clin North Am. 2007; 25 (2): p.309-331.doi: 10.1016/j.emc.2007.02.001 . | Open in Read by QxMD
  3. Walls R, Hockberger R, Gausche-Hill M, Erickson TB, Wilcox SR. Rosen's Emergency Medicine 10th edition- Concepts and Clinical Practice E-Book. Elsevier Health Sciences ; 2022
  4. Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. Goldfrank's Toxicologic Emergencies, 11th edition. McGraw-Hill Education ; 2019
  5. Roberts DM, Gallapatthy G, Dunuwille A, Chan BS. Pharmacological treatment of cardiac glycoside poisoning. Br J Clin Pharmacol. 2015; 81 (3): p.488-495.doi: 10.1111/bcp.12814 . | Open in Read by QxMD
  6. Levine M, Nikkanen H, Pallin DJ. The Effects of Intravenous Calcium in Patients with Digoxin Toxicity. J Emerg Med. 2011; 40 (1): p.41-46.doi: 10.1016/j.jemermed.2008.09.027 . | Open in Read by QxMD
  7. Krenz JR, Kaakeh Y. An Overview of Hyperinsulinemic-Euglycemic Therapy in Calcium Channel Blocker and β-blocker Overdose. Pharmacotherapy. 2018; 38 (11): p.1130-1142.doi: 10.1002/phar.2177 . | Open in Read by QxMD
  8. Graudins A, Lee HM, Druda D. Calcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies. Br J Clin Pharmacol. 2015; 81 (3): p.453-461.doi: 10.1111/bcp.12763 . | Open in Read by QxMD
  9. Petersen KM, Bøgevig S, Riis T, et al. High‐Dose Glucagon Has Hemodynamic Effects Regardless of Cardiac Beta‐Adrenoceptor Blockade: A Randomized Clinical Trial. J Am Heart Assoc. 2020; 9 (21).doi: 10.1161/jaha.120.016828 . | Open in Read by QxMD
  10. Gosselin S, Hoegberg LCG, Hoffman RS, et al. Evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning. Clin Toxicol. 2016; 54 (10): p.899-923.doi: 10.1080/15563650.2016.1214275 . | Open in Read by QxMD
  11. Iolascon A, Bianchi P, Andolfo I, et al. Recommendations for diagnosis and treatment of methemoglobinemia. Am J Hematol. 2021; 96 (12): p.1666-1678.doi: 10.1002/ajh.26340 . | Open in Read by QxMD
  12. Porizka M, Kopecky P, Dvorakova H, et al. Methylene blue administration in patients with refractory distributive shock – a retrospective study. Sci Rep. 2020; 10 (1).doi: 10.1038/s41598-020-58828-4 . | Open in Read by QxMD
  13. Olson KR, Erdman AR, Woolf AD, et al. Calcium Channel Blocker Ingestion: An Evidence-Based Consensus Guideline for Out-of-Hospital Management. Clin Toxicol. 2005; 43 (7): p.797-822.doi: 10.1080/15563650500357404 . | Open in Read by QxMD
  14. Wax PM, Erdman AR, Chyka PA, et al. β-Blocker Ingestion: An Evidence-Based Consensus Guideline for Out-of-Hospital Management. Clin Toxicol. 2005; 43 (3): p.131-146.doi: 10.1081/clt-62475 . | Open in Read by QxMD
  15. Olson KR, Anderson IB, Benowitz NL, et al.. Poisoning and Drug Overdose, Seventh Edition. McGraw-Hill Education / Medical ; 2017
  16. American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists. Position Paper: Single-Dose Activated Charcoal. Clin Toxicol. 2005; 43 (2): p.61-87.doi: 10.1081/clt-51867 . | Open in Read by QxMD
  17. Tenenbein M, Lheureux P, Seger D, Meulenbelt J. Position Paper: Whole Bowel Irrigation. J Toxicol Clin Toxicol. 2004; 42 (6): p.843-854.doi: 10.1081/clt-200035932 . | Open in Read by QxMD
  18. Thanacoody R, Caravati EM, Troutman B, et al. Position paper update: Whole bowel irrigation for gastrointestinal decontamination of overdose patients. Clin Toxicol. 2014; 53 (1): p.5-12.doi: 10.3109/15563650.2014.989326 . | Open in Read by QxMD
  19. Alshaya OA, Alhamed A, Althewaibi S, et al. Calcium Channel Blocker Toxicity: A Practical Approach. J Multidisc Healthcare. 2022; Volume 15: p.1851-1862.doi: 10.2147/jmdh.s374887 . | Open in Read by QxMD
  20. Albertson TE, Owen KP, Sutter ME, Chan AL. Gastrointestinal decontamination in the acutely poisoned patient. Int J Emerg Med. 2011; 4 (1).doi: 10.1186/1865-1380-4-65 . | Open in Read by QxMD
  21. Rotella JA, Greene SL, Koutsogiannis Z, et al. Treatment for beta-blocker poisoning: a systematic review. Clin Toxicol. 2020; 58 (10): p.943-983.doi: 10.1080/15563650.2020.1752918 . | Open in Read by QxMD
  22. McLean AS. Echocardiography in shock management. Crit Care. 2016; 20 (1).doi: 10.1186/s13054-016-1401-7 . | Open in Read by QxMD
  23. Barnes BJ, Hollands JM. Drug-induced arrhythmias. Crit Care Med. 2010; 38: p.S188-S197.doi: 10.1097/ccm.0b013e3181de112a . | Open in Read by QxMD
  24. St-Onge M. Cardiovascular Drug Toxicity. Crit Care Clin. 2021; 37 (3): p.563-576.doi: 10.1016/j.ccc.2021.03.006 . | Open in Read by QxMD
  25. Frithsen IL, Simpson WM Jr. Recognition and management of acute medication poisoning.. Am Fam Physician. 2010; 81 (3): p.316-23.
  26. Thompson TM, Theobald J, Lu J, Erickson TB. The general approach to the poisoned patient. Dis Mon. 2014; 60 (11): p.509-524.doi: 10.1016/j.disamonth.2014.10.002 . | Open in Read by QxMD
  27. Whelton, PK, Carey, RM et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. Hypertension. 2017; 71 (6): p.e13–e115.doi: 10.1161/hyp.0000000000000065 . | Open in Read by QxMD
  28. Bueno Gomez A, Healy M, Delle Donne G, et al. P10 Initiation of bisoprolol in paediatric patients – experience from a specialist paediatric cardiac centre. Arch Dis Child. 2023; 108 (5): p.5.2-6.doi: 10.1136/archdischild-2023-nppg.9 . | Open in Read by QxMD
  29. Lauterbach M. Clinical toxicology of beta‐blocker overdose in adults. Basic Clin Pharmacol Toxicol. 2019.doi: 10.1111/bcpt.13231 . | Open in Read by QxMD
  30. Rana MA, Mady AF, Rehman BA, et al. From Eye Drops to ICU, a Case Report of Three Side Effects of Ophthalmic Timolol Maleate in the Same Patient. Case Reports in Critical Care. 2015; 2015: p.1-4.doi: 10.1155/2015/714919 . | Open in Read by QxMD
  31. Vanden Hoek TL, Morrison LJ, Shuster M, et al. Part 12: Cardiac Arrest in Special Situations: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010; 122 (18_suppl_3): p.S829-S861.doi: 10.1161/circulationaha.110.971069 . | Open in Read by QxMD
  32. Bouchard J, Shepherd G, Hoffman RS, et al. Extracorporeal treatment for poisoning to beta-adrenergic antagonists: systematic review and recommendations from the EXTRIP workgroup. Crit Care. 2021; 25 (1).doi: 10.1186/s13054-021-03585-7 . | Open in Read by QxMD
  33. Finnel L. Tintinalli's Emergency Medicine Manual, Eighth Edition. McGraw Hill Professional ; 2017
  34. St-Onge M, Anseeuw K, et al. Experts Consensus Recommendations for the Management of Calcium Channel Blocker Poisoning in Adults. Crit Care Med. 2017; 45 (3): p.e306-e315.doi: 10.1097/ccm.0000000000002087 . | Open in Read by QxMD
  35. St-Onge M, Dubé PA, Gosselin S, et al. Treatment for calcium channel blocker poisoning: A systematic review. Clin Toxicol. 2014; 52 (9): p.926-944.doi: 10.3109/15563650.2014.965827 . | Open in Read by QxMD
  36. Wong A, Hoffman RS, Walsh SJ, et al. Extracorporeal treatment for calcium channel blocker poisoning: systematic review and recommendations from the EXTRIP workgroup. Clin Toxicol. 2021; 59 (5): p.361-375.doi: 10.1080/15563650.2020.1870123 . | Open in Read by QxMD
  37. $Proceedings of UCLA Health.
  38. Yang EH, Shah S, Criley JM. Digitalis Toxicity: A Fading but Crucial Complication to Recognize. Am J Med. 2012; 125 (4): p.337-343.doi: 10.1016/j.amjmed.2011.09.019 . | Open in Read by QxMD
  39. Ma G, Brady WJ, Pollack M, et al. Electrocardiographic manifestations: Digitalis toxicity. J Emerg Med. 2001; 20 (2): p.145-152.doi: 10.1016/s0736-4679(00)00312-7 . | Open in Read by QxMD
  40. Goldberger ZD, Goldberger AL. Therapeutic Ranges of Serum Digoxin Concentrations in Patients With Heart Failure. Am J Cardiol. 2012; 109 (12): p.1818-1821.doi: 10.1016/j.amjcard.2012.02.028 . | Open in Read by QxMD
  41. Pincus M. Management of digoxin toxicity. Aust Prescri. 2016; 39 (1): p.18-20.doi: 10.18773/austprescr.2016.006 . | Open in Read by QxMD
  42. Lapostolle F, Borron SW, Verdier C, et al. Digoxin-specific Fab fragments as single first-line therapy in digitalis poisoning. Crit Care Med. 2008; 36 (11): p.3014-3018.doi: 10.1097/ccm.0b013e31818b341c . | Open in Read by QxMD
  43. Lalonde RL, Deshpande R, Hamilton PP, McLean WM, Greenway DC. Acceleration of digoxin clearance by activated charcoal. Clin Pharmacol Ther. 1985; 37 (4): p.367-371.doi: 10.1038/clpt.1985.55 . | Open in Read by QxMD
  44. DIGIFAB® Digoxin Immune Fab FDA package insert. Updated: June 1, 2017. Accessed: July 31, 2023.
  45. Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2). McGraw-Hill Education / Medical ; 2018
  46. Di Grande A, Giuffrida C, Narbone G, et al. Management of sodium-channel blocker poisoning: the role of hypertonic sodium salts. Eur Rev Med Pharmacol Sci. 2010; 14 (1): p.25-30.
  47. Caron J, Libersa C. Adverse Effects of Class I Antiarrhythmic Drugs. Drug Saf. 1997; 17 (1): p.8-36.doi: 10.2165/00002018-199717010-00002 . | Open in Read by QxMD
  48. Yates C, Manini AF. Utility of the electrocardiogram in drug overdose and poisoning: theoretical considerations and clinical implications. Curr Cardiol Rev. 2012; 8 (2): p.137-51.doi: 10.2174/157340312801784961 . | Open in Read by QxMD

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