Toxicology & Toxidromes study guide previews.

Max daily dose generally ≤ 4 g/day (many institutions prefer ≤ 3 g. Depending on medications, sometimes even ≤ 2 g/day. Why it matters include Acetaminophen (APAP) overdose is the leading cause of acute liver failure (ALF) in the U.S. and other highincome countries. Risk factors for toxicity at lower doses includes chronic alcohol use, malnutrition or prolonged fasting, chronic illness/frailty, enzymeinducing drugs (e.g., rifampin, carbamazepine, phenytoin), underlying liver disease.

Combination opioid/APAP products are common culprits; beware extendedrelease (ER) formulations. Normal metabolism include Glucuronidation/sulfation (~90-95%) leading to nontoxic; CYP2E1 (~5-10%) leading to NAPQI (toxic intermediate). Massive ingestions can cause early lactic acidosis and coma before aminotransferases rise (mitochondrial toxicity). Stage I (0-24 h): N/V, pallor, diaphoresis; labs may be normal. Stage III (72-96 h): Peak hepatotoxicity: jaundice, coagulopathy, hypoglycemia, lactic acidosis, AKI, encephalopathy; AST/ALT often >1000-10,000 IU/L; possible death. Stage IV (4 d-2 wks): Recovery with complete hepatic regeneration in survivors (labs normalize over days-weeks) or continued decompensation without treatment/transplant.

If ≤ 4 h from ingestion include Consider activated charcoal 1 g/kg (max 50 g) if protected airway. Charcoal may still help up to 8 h for ER products. Labs include APAP level, AST/ALT, bilirubin, INR/PT, BMP, glucose, lactate, gas, ammonia, pregnancy test, ethanol level, salicylate level.

Indications includes hypertension, ischemic heart disease, arrhythmias, heart failure, migraine, essential tremor, thyrotoxicosis. Cardioselective (β1): metoprolol, atenolol, bisoprolol (selectivity is dosedependent; lost in overdose). Lipophilicity includes propranolol, metoprolol, carvedilol are lipophilic leading to CNS toxicity (seizures/coma); atenolol/nadolol are hydrophilic. Why it matters includes bB overdose can cause rapid cardiovascular collapse and neurotoxicity. Management hinges on early decontamination, glucagon, HIET, vasopressors, and targeted adjuncts (bicarbonate, lipid emulsion, ECMO). Common among cardiovascular drug overdoses; propranolol frequently implicated in severe/CNStoxic cases.

Mortality increases with delayed recognition, ER formulations, coingestants (sedatives, calcium channel blockers), and lipophilic/MSA agents. β1 blockade: decreased inotropy/chronotropy leading to bradycardia, hypotension, AV block, cardiogenic shock. β2 blockade: peripheral vasoconstriction, bronchospasm, hypoglycemia (decreased glycogenolysis/gluconeogenesis - differentiates from calcium channel blockers), especially in children. MSA (Nachannel blockade): QRS widening, ventricular arrhythmias (notably propranolol). Cardiac includes sinus bradycardia, junctional rhythms, AV block, hypotension/shock; possible ventricular dysrhythmias (MSA) or torsades (sotalol). Neurologic includes lethargy, coma, seizures (lipophilic agents; often early and abrupt in propranolol OD).

Respiratory includes bronchospasm (β2 blockade), apnea with CNS depression. Timeline includes iR often within 1-2 h; ER may have delayed onset (6-12+ h) and prolonged course (≥24 h). Labs includes bMP (K, creatinine), glucose q15-30 min initially, Mg, phosphate; ABG/VBG (pH, lactate); LFTs and troponin as indicated. ECG includes rate/rhythm, PR/QRS/QT intervals (look for QRS widening with MSA agents; QT prolongation with sotalol). Largebore IVs; consider arterial line and central access in shock.

decreased β-adrenergic receptor activity leading to decreased cAMP leading to decreased chronotropy, inotropy, conduction. Blockade of L-type calcium channels leading to decreased calcium influx leading to impaired cardiac contractility, conduction, and vascular tone. High-dose insulin euglycemia therapy (HIET) for refractory cases.

Two main classes include Dihydropyridines (DHPs): e.g., amlodipine, nifedipine. Potent vasodilators, less cardiac suppression, Nondihydropyridines (nonDHPs): verapamil, diltiazem. Greater cardiac effects (negative inotropy, chronotropy, and dromotropy), Available in immediaterelease (IR) and sustainedrelease (SR/ER) formulations, and CCB overdose is highly lethal and often requires aggressive ICU care, including advanced therapies like highdose insulin euglycemia therapy (HIET) and extracorporeal support.

CCBs account for a significant proportion of cardiovascular drug overdoses and are among the most lethal prescription overdoses. Mortality includes up to 30-40% in severe cases despite therapy. Sustainedrelease formulations are especially dangerous due to delayed onset and prolonged toxicity. Block Ltype calcium channels in myocardium, vascular smooth muscle, and pancreatic beta cells.

Effects include decreased contractility, bradycardia, AV block (esp. nonDHPs), hypotension, distributive shock (esp. DHPs), inhibition of calciumdependent insulin release leading to hypoinsulinemia, hyperglycemia, metabolic acidosis, and Severe toxicity may produce cardiogenic shock, refractory hypotension, metabolic acidosis, and multiorgan failure.

Hydroxocobalamin, a form of vitamin B12, is traditionally used for cyanide toxicity. However, in recent years, it has emerged as a rescue vasopressor for vasoplegic shock, particularly in cases refractory to conventional vasopressors. Its vasoconstrictive properties are tied to nitric oxide (NO) scavenging.

Primary effect (as vasopressor) include Scavenges nitric oxide (NO): Hydroxocobalamin binds NO and reduces its vasodilatory effects and decreased NO leading to decreased soluble guanylate cyclase (sGC) activation leading to decreased cGMP leading to decreased vasodilation leading to increased vascular tone.

Secondary effects include May bind hydrogen sulfide (H₂S), another endogenous vasodilator, Reduces availability of carbon monoxide (another vasodilator), and May enhance response to endogenous or exogenous catecholamines.

Importantly, many cases are associated rather than purely caused by metformin - meaning metformin often worsens lactic acidosis in the setting of another acute illness. Key concept include metformin accumulation plus a lactate-generating stressor. Typical patient includes older adult on metformin who becomes dehydrated, septic, or hypotensive and develops AKI. Inhibits Complex I of the electron transport chain. Shifts metabolism toward anaerobic pathways leading to increased lactate. Clinical pearl include Metformin alone rarely causes severe lactic acidosis - it amplifies lactate when clearance or perfusion is impaired.

Methylene blue acts as a selective inhibitor of nitric oxide (NO)-mediated vasodilation through two major mechanisms Inhibition of nitric oxide synthase (NOS) leading to decreased NO production, Inhibition of soluble guanylyl cyclase (sGC) leading to decreased cyclic GMP (cGMP) leading to decreased smooth muscle relaxation, and Reverses vasoplegia by reducing pathological vasodilation, increasing systemic vascular resistance (SVR), and raising mean arterial pressure (MAP).

Methylene blue is not a first-line agent but may be considered as a rescue therapy in Vasoplegic shock (especially post-cardiopulmonary bypass or liver transplant) and Septic shock refractory to catecholamines and vasopressin. The onset is usually within 30 minutes.

Neuroleptic malignant syndrome (NMS) is a rare but life-threatening neurologic and hypermetabolic emergency associated with dopamine blockade or abrupt dopamine withdrawal. Early recognition is critical because delayed diagnosis increases morbidity and mortality. It can also occur after abrupt withdrawal of dopaminergic therapy. NMS is primarily caused by severe central dopamine dysfunction.

Opioid toxicity is one of the most common and immediately reversible causes of respiratory failure in emergency and critical care. This is a discussion for healthcare providers, not patients or the general public! None of this is medical advice.

The key danger is not the altered mental status itself. The key danger is include Respiratory depression leading to hypercapnia leading to hypoxemia leading to cardiac arrest. These are important because recurrent toxicity can occur after initial naloxone response. Opioids primarily act on mu-opioid receptors in the central nervous system.

Salicylate poisoning is one of the classic toxicologic emergencies that can deteriorate rapidly despite initially reassuring vital signs or laboratory values. Patients can appear deceptively stable until they suddenly decompensate. Clinical status matters more than serum level alone. Understanding the physiology is critical because many management decisions - especially around airway management - are based on preserving the patient’s compensatory mechanisms.

Serotonin syndrome is a potentially life-threatening toxidrome caused by excessive serotonergic activity within the central and peripheral nervous system. Early recognition is critical because the syndrome can deteriorate rapidly over hours. It is often caused by combining multiple serotonergic agents.

Serotonin Syndrome vs NMS introduces the clinical pattern, physiology, and bedside decisions that matter for emergency and critical care practice.

Common substances include cocaine, methamphetamine, MDMA (ecstasy), bath salts (synthetic cathinones), pseudoephedrine, ephedrine, ADHD stimulants (amphetamine, methylphenidate), synthetic stimulants (e.g., mephedrone), designer drugs, and Sympathomimetic toxicity is common in ED presentations, can mimic other toxidromes, and may progress to lifethreatening hyperthermia, arrhythmias, seizures, or multiorgan failure.

High morbidity/mortality from cardiac complications (MI, arrhythmia, stroke) and hyperthermia. MDMA/ecstasy linked to raves/parties and severe complications: hyperthermia, hyponatremia, serotonin syndrome overlap. CNS stimulation leading to agitation, seizures, psychosis; dopamine surge leading to euphoria/addiction.

Bedside assessment may show tachycardia, hypertension, hyperthermia, tachypnea, agitation, anxiety, psychosis, seizures, mydriasis, diaphoresis, tremor, rhabdomyolysis (muscle rigidity, prolonged agitation), AKI, and both cause mydriasis, tachycardia, agitation - but sympathomimetic patients are diaphoretic, while anticholinergic patients are dry.