Description

Disclaimer: Content is for educational exam preparation only and does not constitute medical advice. Medicine changes quickly; always verify with current, local guidelines before applying to patient care.

I. General Toxicology Principles

Elimination and Decontamination

Toxins that are Dialyzable: Toxins are dialyzable if they have:

• Low molecular weight.
• Low volume of distribution (low lipid binding).
• Low protein binding.
• Rapid equilibration.
• Low clearance.

Pneumonic for Dialyzable Toxins (ISTUMBLED):

• Isopropyl alcohol.
• Salicellates.
• Theophiline.
• Ureia.
• Metformin or Methanol.
• Barbbiterates.
• Lithium.
• Ethylene glycol.
• Valproic acid.

Activated Charcoal (AC) — Mainstay Decontamination

• Toxins NOT bound by AC:
• Metals (heavy metals, iron, lithium).
• Solvents.
• Caustics.
• Alcohols.
• Pesticides.

Whole Bowel Irrigation (WBI) Indications: Used for toxins that activated charcoal does not bind, or things that stick around for a long time:

• Body packers.
• Bezoars.
• Sustained release formulations.
• Metals or paint with lead.

Multi-Dose Activated Charcoal (MDAC) Indications (Pneumonic: Doubled dose activated charcoal can bind drugs quite tightly):

• Dilantin (Phenytoin).
• Digoxin
• Aspirin.
• Cyclic (TCAs).
• Carbamazepine.
• Barbbiterates.
• Dapsone.
• Quinine.
• Theophiline.

Diagnostic Gaps and Acidosis

Causes of Anion Gap Metabolic Acidosis:

• KULT mnemonic: Ketones, Uremia, Lactate, Toxins.
• A CAT MUD PILES mnemonic:
• AKA (alcoholic ketoacidosis).
• Cyanide, carbon monoxide
• Acetaminophen.
• Toluene.
• Methanol or metformin.
• Uremia.
• DKA (diabetic ketoacidosis).
• Paraldehyde.
• Isoniazid (INH) or iron.
• Lactic acid.
• Ethylene glycol.
• Salicellates (aspirin).

Toxins Causing Osmolar Gap ONLY (Initially):

• These are usually alcohols and sugars, prior to being metabolized to their toxic metabolite.
• Glycerol.
• Sorbitol.
• Acetone.
• Toxic alcohols (initially).

Differentials

Drugs that can Cause Seizures (mnemonic: Otis Campbell):

• Organophosphates or oral anti-glycemic agents.
• TCAs.
• Isoniazid (INH) or insulin.
• Sympathomimetics or salicellates.
• Cocaine, carbon monoxide, cyanate, cyanide, or chlorinated hydrocarbons.
• Amphetamines, anticholinergics, antidepressants.
• Methanol or methyl xanthines.
• PCP or propranolol (beta blocker that readily crosses the BBB).
• Benzo withdrawal or bupropion.
• Ethanol withdrawal or ethylene glycol.
• Lithium, lidocaine, lead, or lindane.

Differential for Altered Mental Status (AEIOU Tips):

• Alcohol, acidosis.
• Electrolytes or encphylopathy.
• Infection.
• Opioids or overdose.
• Uremia.
• Trauma.
• Insulin.
• Psychosis.
• Seizure or stroke.

Low and Slow Differential (BRADI):

• Brash (e.g., hyperkalemia).
• Reduced oxygen, temperature, glucose, or thyroid.
• ACS.
• Drugs (beta blockers, calcium channel blockers, clonidine, digoxin, or cholinergics).
• Infection (e.g., CNS infections or Lyme).

Anticholinergics

Anticholinergic Drugs (Pneumonic: A poop b****

• Atropine.
• Plants (gyosonweed, deadly nightshade, mandrake).
• Optho drugs (cyclopentolate).
• Oxybutynin.
• Phenytoin.
• Benztropine.
• Ipratropium.
• TCAs.
• Carbamazepine.
• H1 blockers (Benadryl or Gravol).

Anticholinergic Toxidrome:

• Dry, hot, tachycardic, crazy/delirious, mydriasis (dilated pupils).

Anticholinergic Treatment:

• Supportive care.
• Single dose activated charcoal (if seeds ingested).
• Benzos for agitation or hyperthermia.
• Cooling (mainstay).
• Physostigmine: Can be used for delirium but is strictly contraindicated if there is:
• TCA overdose.
• AV block.
• Bradycardia.
• Seizures.
• Glaucoma.

II. Specific Toxins and Overdoses

A. Tylenol (Acetaminophen - APAP)

Toxic Dosing and Levels:

• Toxic dose: Over 150 mg/kg.
• Severe massive ingestion: Over 500 mg/kg.
• Treatment line (Nomogram): Over 1,000 µmol/L at 4 hours post-ingestion.

Metabolism and Mechanism:

• Metabolized 15% via the CYP450 pathway to NAPQI (toxic metabolite).
• NAPQI causes hepatic zone 3 death.
• N-acetylcysteine (NAC) Mechanism: Increases sulfation, acts as a precursor and substitute for glutathione (which helps metabolize NAPQI), and is a free radical scavenger.

Stages/Phases of Toxicity:

1. Pre-injury (0 to 12 hours): Nausea, vomiting, malaise. High APAP level, normal AST/ALT.
2. Liver Injury (8 hours to 36 hours): Nausea, vomiting, right upper quadrant tenderness, increased AST/ALT (AST rises first).
3. Liver Failure (2 to 4 days maximum): Signs of liver failure, ARDS, sepsis, cerebral edema, hepatorenal syndrome, coagulopathy.
4. Recovery (After 4 days): Liver can completely regenerate if the patient survives.

NAC Treatment Indications (mnemonic: 1824):

• 1: Over ~1,000 µmol/L at the 4-hour mark on the nomogram.
• 8: If you Will not have an APAP level by 8 hours (start treatment within 8 hours).
• 24: Any APAP detectable after 24 hours.
• Chronic Ingestion: AST is two times normal or APAP is over 200 (consult toxicology).

NAC Dosing (21-Hour Three-Bag Protocol):

• Load: 150 mg/kg over 1 hour.
• Bag 2: 12.5 mg/kg per hour over 4 hours.
• Bag 3: 6.25 mg/kg per hour over 16 hours.

NAC Stopping Criteria:

• AST is less than 100 and downtrending.
• No detectable APAP.
• No symptoms.
• Coagulation levels are normal.

Dialysis Indications for Tylenol:

• Level over 6,620 at 4 hours.
• pH less than 7.3.
• End organ failure:
• Creatinine over 350.
• Lactate over 3.5.
• Encephalopathy.

Modified King's College Transplant Criteria:

• If after resuscitation, pH is still less than 7.3.
• OR, meeting all three of the following criteria:
• Creatinine over 291.
• INR over 6.5.
• Grade III encephalopathy (at least).

B. Aspirin (Salicylates)

Toxic Dosing and Levels:

• Therapeutic dose: 15 mg/kg.
• Toxic dose: 150 mg/kg.
• Severe dose: 500 mg/kg.
• Potentially toxic level: Over 2.2 millimoles per liter.
• Metabolism changes from first order to zero order kinetics above 2.2 millimoles per liter.

Key Mechanism (Acid-Base and pH):

• Aspirin causes respiratory alkalosis (medullary stimulation/tachypnea) and metabolic acidosis (uncoupling oxidative phosphorylation, inhibiting Kreb cycle). But also respiratory acidosis (aLOC) and metabolic alkalosis (vomiting).
• At a low pH, aspirin is unionized and crosses the blood-brain barrier.
• At a high pH, aspirin is ionized and trapped in urine/blood.

Treatment and Dosing:

• Correct dehydration and ensure potassium is over 4.5.
• Multi-dose activated charcoal every 2 to 4 hours.
• Urine Alkalinization Goals:
• Goal urine pH: 7.5 to 8.
• Max blood pH tolerated: 7.55.
• Alkalinization Recipe:
• 3 amps of bicarb into a liter of D5W.
• Run at 2 to 3 mLs/kg per hour.
• Add potassium (often 40 mEq) into the bag.
• Monitoring: Check aspirin levels every 2 hours with VBG; check urine pH hourly.

Dialysis Indications for Aspirin:

• Level over 7.2 in an acute ingestion.
• Level over 2.9 in a chronic ingestion.
• pH less than 7.2.
• End organ failure (acute renal failure, altered level of consciousness, acute lung injury, liver injury, or seizures).

Disposition:

• Check aspirin level every 2 hours until three levels are less than 2.2 (without the bicarb infusion).
• Patient must be asymptomatic and have normal pH.

C. Toxic Alcohols (Ethylene Glycol and Methanol)

General Alcohol Metabolism:

• Alcohol -> (Alcohol Dehydrogenase (ADH)) -> Aldehyde -> (Aldehyde Dehydrogenase (ALDH)->Acid.

Ethylene Glycol (EG)

• Major Toxic Metabolite: Oxalic Acid
• Worrisome Metabolite Level: Over 10 millimoles
• Treatment Level (Actual Alcohol): Over 3.23 mmol/L
• Dialysis Level (Actual Alcohol): Over 8 mmol/L
• Key Toxicity: Calcium oxalate crystals (leading to Acute Tubular Necrosis/ATN and hypocalcemia).

Methanol

• Major Toxic Metabolite: Formic Acid
• Worrisome Metabolite Level: Over 16.67 mmol/L
• Treatment Level (Actual Alcohol): Over 6.24 mmol/L
• Dialysis Level (Actual Alcohol): Over 15.6 mmol/L
• Key Toxicity: Ocular phase (snowstorm vision) and CNS symptoms (specifically putaminal necrosis).

Other Toxic Alcohols:

• Isopropyl Alcohol: Causes an osmolar gap but no anion gap. Treatment is supportive (fluids for hypotension, PPI for gastritis). Dialysis for refractory hypotension or coma.
• Diethylene Glycol: Causes lifelong renal failure. Managed like EG or Methanol.
• Propylene Glycol: Increases lactic acid. Treated with fomepizole or hemodialysis.

Treatment (EG & Methanol):

1. Decontamination: No role for GI decontamination.
2. Acidosis Correction: Correct acidosis to over 7.3 (may need bicarb).
3. ADH Inhibition (Fomepizole):
   • Fomepizole Dose: Load with 15 mg/kg, then 10 mg/kg BID.
   • Fomepizole Indications (If suspicious, treat if two of five met):
   • Acidosis less than 7.3.
   • Anion gap over 16.
   • Bicarb less than 18.
   • Osmolar gap greater than 10.
   • Urine oxalate crystals.
   • Treat immediately if: Level confirmed (Methanol > 6.24, EG > 3.23) or ingestion confirmed + osmolar gap > 10.
4. Co-Factors:
   • Ethylene Glycol: Vitamin B1 and B6.
   • Methanol: Vitamin B2.

Dialysis Indications for Toxic Alcohols:

• Specific toxic level (Methanol > 15.6, EG > 8).
• Acidosis less than 7.3.
• End organ dysfunction: Renal failure, vision loss, hyperkalemia, or hemodynamic instability.

D. Ethanol and Withdrawal

Ethanol Levels (in Millimoles):

• 5: Decreased fine motor function.
• 10: Impaired judgment (legal limit).
• 20: Gait instability.
• 30: Lethargy.
• 60: Coma.
• 80: Respiratory depression.
• Metabolism: Zero order kinetics at 5 millimoles per hour.

Wernicke's Encephalopathy:

• Triad: Ataxia, Ophthalmoplegia, Altered level of consciousness.
• Dose (Vitamin B1): 500 mg TID.

Alcohol Withdrawal Stages:

1. Autonomic Hyperactivity (0 to 24 hours): Tremor, nausea, vomiting, sweating.
2. Neuronal Excitement (1 to 2 days): Seizures, confusion.
3. Delirium Tremens (DT) (2 to 4 days): Hallucinations (lack insight), profound autonomic dysfunction, delirium.

CIWA-Ar Protocol (Scoring System Components):

• Scoring: Each mark has 0 to 7 points.
• Treatment Threshold: Over 10 points.
• Severe Withdrawal Threshold: Over 20 points.
• Components (Short NAP): Sweating, Hallucinations (tactile, visual, auditory), reduced intake, Orientation, Tremor, Nausea/Vomiting, Anxiety, Agitation, Pain (in the head).

Treatment of Severe Withdrawal (Dosing):

• Benzodiazepines (First Line): Diazepam (preferred for long half-life, 48 hours) or Lorazepam (12 hour half-life).
• Lorazepam: 1 to 4 mg IV.
• Diazepam: 5 to 10 mg IV (or PO for mild withdrawal).
• Barbiturates (Phenobarbital): Bolus 130 mg to 260 mg IV.
• Adjunctive: Thiamine (B1), Magnesium, and cooling (if hyperthermic).

Discharge Criteria:

• 6 hours post their last seizure.
• Less than two seizures total.
• Normal workup (normal head CT if seizure occurred).
• CIWA of less than 10 twice.

E. Antidepressants (TCAs and Others)

General Antidepressant Toxic Dose: 10 mg/kg.

Tricyclic Antidepressants (TCAs):

• Mechanism: Blocks norepinephrine/serotonin re-uptake, anticholinergic effect, blocks sodium/potassium channels, alpha 1 blocker (hypotension), blocks histamine/GABA receptors.
• ECG Findings:
• Tachycardic.
• QRS may be over 100 ms (considered wide).
• QTc may be greater than 500 ms.
• Terminal R wave in aVR that is more than 3 mm.
• Treatment (Dosing):
• Single dose activated charcoal.
• Sodium Bicarb: Indicated if QRS > 100, seizures, acidemia, hypotension, or dysrhythmias.
• If pH gets high (7.55), switch to 3% normal saline to aid QRS widening.
• Phenytoin or Lidocaine for dangerous arrhythmias.

Specific Antidepressants:

• Citalopram (SSRI): Higher seizure rate. Monitor for 12 hours.
• Venlafaxine (SNRI): Most worrisome SNRI due to extended release. Monitor for 24 hours.
• Bupropion (Wellbutrin):
• Overdose risk: Over 4.5 grams has a 50% risk of seizure.
• Monitoring: Definitely needs 24 hours of monitoring.

MAOIs (Tyramine Syndrome):

• Caused by eating old or fermented foods (beer, wine, aged cheese/meats) while taking MAOI.
• Symptoms: Headache, hypertension, diaphoresis.
• Treatment: Treat blood pressure (if over 200 or symptomatic) with Phentolamine or Nitroprusside.
• MAOI overdose requires monitoring for 24 hours.

F. Cardiac Toxins

Digoxin:

• Normal level: 0.9 to 1.4 nanomoles per liter (or 0.5 to 1.1 nanograms per mL).
• Arrhythmia risk: 50% will have arrhythmias at 2.5 nanograms per mL.

Digifab (Digoxin Immune Fab) Indications:

• Ventricular dysrhythmias or bradyarrhythmias affecting blood pressure.
• Potassium over 5.
• Co-ingestion with another cardiotoxic drug.
• Dose over 10 mg (adult) or 4 mg (child).
• Level over 7.68 millimoles per liter

Digifab Dosing:

• Empirical Dosing (Vials):
• Arrest: 20 vials bolus.
• Acute overdose: 10 vials.
• Chronic overdose: 6 vials.
• Stable: 1 vial.
• Calculated Dosing (Vials):
• Vials = (Dose of digoxin in mg x 0.8 [bioavailability]) / 0.5 (mg bound per vial).
• Observation: Patients need observation for at least 12 hours.

Calcium Channel Blockers (CCBs) and Beta Blockers (BBs):

• Toxic Dose: BBs (e.g., propranolol) over 1 mg/kg. Non-DHP CCBs (e.g., verapamil) 5 mg/kg.
• Dialyzable BBs (SANTA): Sotalol, Atenolol, Nadolol, Timolol, and Acebutolol.
• Monitoring: At least 6 hours (non-extended release) or 24 hours (extended release).

Treatment (High-Dose Insulin and Calcium Dosing):

• Supportive
• Calcium: 1 to 2 grams of Calcium Chloride, or triple that dose of Calcium Gluconate.
• May be followed by an infusion of 20 mg/kg per hour.
• Glucagon (if taken BBs): 10 mg IV.
• Euglycemic High-Dose Insulin (EHDI):
• Insulin run at 1 to 10 units/kg per hour.
• Run with D10 at 5 mLs/kg per hour (or as needed to maintain euglycemia).

Clonidine:

• Treatment: Fluids, pressors, and Naloxone (start at 0.1 mg, double dose as needed).
• Disposition: Monitor for 4 hours (asymptomatic) or 24 hours (symptomatic).

G. Serotonin Syndrome

Hunter Criteria (Requires Tremor or Clonus):

1. Spontaneous clonus (meets criteria alone).
2. Inducible clonus PLUS one of: agitation or diaphoresis
3. Occular clonus PLUS one of: agitation or diaphoresis,
4. Inducible OR ocular clonus PLUS hypertonia, and hyperthermia.
5. Tremors and hyperreflexia.

Treatment:

• Cooling.
• Benzodiazepines.
• Treat hypertension with Phentolamine or Nitroprusside.
• Cyproheptadine 12 mg PO (although evidence supporting benefit is noted as lacking).

H. Caustics

Types of Necrosis:

• Acids: Coagulation necrosis (painful, less penetration, leads to eschar formation).
• Alkaline agents: Liquefaction necrosis and saponification (less pain, deeper penetration).

Endoscopy Timing:

• Ideal: Delayed (after 12 to 24 hours) to better differentiate the degree of injury.
• Urgent (within 12–24 hours): If patient has vomiting, drooling, stridor, or dyspnea.

Degrees of Injury (Burn Classes/Risk of Stricture):

1. Grade 1: Edema and hyperemia (superficial injuries, no risk of strictures).
2. Grade 2: Ulcers begin to form.
   • Grade 2A (Non-circumferential): 15% risk of stricture.
   • Grade 2B (Circumferential): 75% risk of stricture.
3. Grade 3: Transmural or perforation (90% risk of stricture).

Analogy for Toxic Alcohol Management: Treating toxic alcohol overdose is like dealing with a dangerous factory that turns raw materials (EG/Methanol) into harmful pollutants (Oxalic/Formic Acid). You need to immediately hit the "stop" button on the machinery (giving Fomepizole to inhibit ADH) and then use "cleanup crew" co-factors (B vitamins) to neutralize the existing pollution, while performing "heavy industrial scrubbing" (dialysis) if the pollutant levels are already dangerously high or causing internal damage.