124. Acute exogenous poisoning with medicines used to treat cardiovascular

Acute exogenous poisoning with medicines used to treat cardiovascular diseases, benzodiazepines, antipsychotics, antidiabetic, antipyretic and analgesic and antiemetic agents

The lectures have ARBs, ACEI and CCBs, so those are the three that we will consider here

Used for treatment of hypertension, HF and those with previous MI
Mechanism: directly inhibit the action of angiotensin II
Pharmacokinetics: low Vd, parent drugs are rapidly converted to active metabolites
Presentation; Hypotension (tx fluids), Bradycardia, Hyperkalemia (especially in those with renal insufficiency and in combination with NSAIDs), RARELY - acute angioedema
Diagnosis - based on history of exposure, no specific bloods, do usual tests
Treatment - no specific antidote, consider oral charcoal

Used for treatment of hypertension, HF and those with previous MI
Mechanism: blocks conversion of angiotensin I to angiotensin II thereby reducing vasoconstriction and aldosterone activity. Additionally, can cause angioedema and cough, mediated by bradykinin (which is normally broken down by angiotensin converting enzyme)
Pharmacokinetics: low Vd, parent drugs are rapidly converted to active metabolites
Presentation; Hypotension (tx fluids), Bradycardia, Hyperkalemia (especially in those with renal insufficiency and in combination with NSAIDs) ALSO acute angioedema, involving tongue, lips and face which may lead to airway obstruction, has been reported
Diagnosis - based on history of exposure, no specific bloods, do usual tests
Treatment - no specific antidote, consider oral charcoal

Used for treatment of hypertension, tachycardia, angina
Mechanism: disrupt movement of calcium through calcium channels, limiting intracellular calcium which reduces excitation of smooth and cardiac muscle leading to vasodilation and bradycardia
There are three causes of CCBs we should know about, note while the selectivity remains, it is less prominent in an OD:
Dihydropyridines (e.g. nifedipine, amlodipine) - ++ peripheral vascular activity
Benzothiazepines (e.g. diltiazem) - mixed action
Phenylalkylamines (e.g. verapamil) - ++ cardiac activity
Toxicokinetics: Good bioavailability, peak concentrations after 1-2 hours. Large Vd, and highly protein bound
Toxicodynamics: cardiotoxic syndrome more likely if co-ingested with other drugs acting on CVS. Presents within 6-8 hours, clinical features are mostly in the CVS and include bradycardia and peripheral vasodilation leading to hypotension.May also have interruption, may also have AV heart block. Lactic acidosis can occur in patients with significant hypotension, hyperkalaemia and hypocalcaemia may also occur.
Management - oral charcoal if presenting in first hour after ingestion. If bradycardic give atropine, temporary pacing may be required if significant heart block. Fluids for hypotension, add in IV calcium if no response.