Drug

Toxidrome

Acetaminophen

Phase 1 (0-6 hrs): nausea/vomiting Phase 2 (4-24 hrs): clinically silent, LFTs, PT rise Phase 3 (18-72 hrs): toxic hepatitis, peaks in 2-3d in pts that recover; otherwise fulminant liver failure Phase 4: full recovery of liver function

Anticholinergics (antimuscarinic)

Mydriasis, dry mouth, dry skin, tachycardia, slows GI and GU tracts (urinary retention), altered mental status (staring, mumbling, "picking" at clothes/sheets) pts look like zombies MAO inhibitors: HTN rxn with some foods Tricyclic antidepressants: - anticholinergic toxidrome + abnormal EKG (due to Na channel blockade) SSRIs, SNRIs: serotonin syndrome - neuromuscular: myoclonus, rigidity (legs>arms) - autonomic: tachycardia, hyperthermia, hyper/hypotension, diaphoresis - altered mental status: agitation, sz, coma Overdose effects: - CNS depression, sz, decr BP - QT prolongation Adverse effects: - movement disrder, distonia, parkinsonian-life effects neuroleptic malignant syndrome - muscle rigidity, hyperthermia, autonomic instability, altered MS/delirium, rhabdo

Antidepressants - MAO inhibitors - Tricyclic antidepressents

Antipsychotics

Aspirin

Primary respiratory alkalosis - stimulates brainsteam resp ctr --> breathe fast Primary anion gap metabolic acidosis Tinnitus

Beta blockers

Bradycardia and hypotension

Calcium channel blockers

Bradycardia and hypotension - hyperglycemia common

Symptoms of hypoxia Carbon monoxide "cherry red" discoloration: usually preterminal finding

Cholinesterase SLUDGE/DUMBBELS inhibitors - diaphoresis, urination, miosis, broncho - organophosphate/ - produce a lot of fluid carbamates

Cyanide

Turns off aerobic metabolism - anion gap metabolic acidosis - elevated serum lactate - coma: brain needs ATP - hypotension

Digoxin

Ethanol and sedative-hypnotics

Opioids

Miosis, CNS depression, respiratory depression

Rattlesnake envenomation

3 "flavors" of effects: 1) local tissue injury: progressive pain and swelling, extends proximally up limb 2) hematologic: decr platelets, fibrinogen, coagulopathy (incr PT/INR) - looks like DIC 3) Neurologic: paresthesias, metallic taste, muscle twitching - usually a minor issue in US snakes Tachycardia, tremor, vomiting Severe: seizures

Theophylline

Toxicokinetics/dynamics Activated by liver into toxic metabolite Small amount oxidized by CYP450 to N-acetyl-parabenzoquinoneimine (NAPQI) very reactive, short half life - results in centrilobular hepatic necrosis Toxicity occurs when glutathione stores are depleted

Antidote

N-acetylcysteine (NAC) - repletes glutathione - PO or IV, both are effective; IV shorter time, but higher incidence of anaphylactoid rxns

Supprotive: IV fluid, sedation Physostigmine: inhibits AchE - raises synaptic Ach levels to overcome blockade

Serotonin syndrome: bzd, ?cyproheptadine

NMS: alpha adrenergic block --> decr ?dantrolene, bromocriptin, BP amantadine

Overdose: 1st order elimination --> zero order - half life increases - primarily renal elimination

1. GI decontamination (activated charcoal) 2. Maintain urine output: - IV fluid bolus + infusion - urine alkalinization (ion trapping with NaHCO3) Severe cases: hemodialysis Supportive, IV fluids, atropine, vasopressors glucagon: uses Gs/cAMP, bypassing blocked beta receptors IV fluids/atropine/vasopressors, Ca salts

Hyperglycemia: need Ca to release insulin vesicles

both b-blocker and CCB toxicity: high dose insulin/ glucose, mechanical adjuncts, IABP, bypass hyperbaric O2 (controversial)

CO poisoning prevents O2 delivery

atropine - fixes muscarinic effects only pralidoxime - regenerates active AChE - muscarinic and nicotinic

Traditional antidote kit: - Amyl nitrite perles (induce methemoglobinemia) - sodium nitrite IV CN- ion binds Fe3+ in iron(induce methemoglobinemia) sulfur complex in mitochondria - sodium thiosulfate (helps normal detox) Hydroxocobalamin: - provitamin B12a binds CN -> Vit B12 Supportive: cardiac monitoring, IV access, atropine for bradycardia digoxin immune Fab: - ovine Fab antibody fragments: digifab and digibind For benzodiazepines: - flumazenil: BZD like structure that competes for GABAa Cl channel - not used empirically because it may precipitate seizures/withdrawal - primary indication: iatrogenic toxicity (when the physician overdoses the pt) Naloxone: IV/IM/ETT/neb - short acting Also naltrexone (PO), nalmefene

Antivenom: CroFab - ovine produced immune fab - very expensive!! Other antivenoms: coral snake, black widow (IgG antivenom), bark scorpion (arizona) Supportive, charcoal beta-blockers, hemodialysis

Notes

Rumack Matthew Nomogram: predicts who is at risk of liver toxicity - serum APAP level and time elapsed since ingestion - derived from acute, single ingestion

Common side effects of many medications: antihistamines, psych drugs (antidepressants, antipsychotics), urinary incontinence drugs

serotonin syndrome: more common as a drug interation, but can also occur in overdose

smoke inhalation/fires, automobile exhaust CO binds heme 250x stronger than O2

Venomous snakes through continental US; 6 in california, 3 in OC Rattlesnakes: Pit vipers - lensshaped pupil, heat sensing pit organ nearly obsolete therapy for asthma/COPD, closely related to caffeine

Drug Heavy metals

Uses

Toxidrome Mutisystem toxic effects via multiple mechanisms of action Developing CNS more susceptible: fetus/children at highest risk

Lead

>30ug/dl: neuro-cognitive - irritability, fatigue, anorexia, sleep disturbance, ataxia, tremor >100ug/dl: encephalopathy - ataxia, stupor, coma, seizure, death Batteries, ammunition (bullets), - peripheral: wrist-drop allyows, glass, paint, Hematotoxicity: gasoline - increased RBC fragility - basophilic stippling Renal: (decr uric acid excretion) "saturnine gout" Reproductive toxicity CV: HTN GI: "Lead colic", gingival lead lines toxic level: 10 ug/dL Rapid-onset gastroenteritis Rare therapeutic use Cardiopulmonary and hemotoxicity as abx, Neuro effects: ascending sensory/motor promyelocytic peripheral neuropathy, encephalopathy leukemia Delay: Mees lines (transverse white nail lines) indicated period of decr growth Semi-conductor industry, wood Chronic: preservatives, constutional symptoms, anemia, pesticides, lewisite neuropathy, skin lesions, skin/kidney/lung (CW agent) cancer

Arsenic

dental amalgam, fish/shellfish 3 flavors: 1) elemental: liquid = least toxic, vapor is well absorbed and dangerous 2) salts: corrosive, cause hemorrhagic gastritis, ATN, renal failure 3) organomercuries: neurotoxicity 10% soln in peanut oil - IM injections Erethism: neuropsychiatric effects (shyness, social withdrawal, depression, explosive anger, blushing) Classic triad: tremore, neuropsychiatric disturbance, gingivostomatitis Acrodynia: painful extremity erythema, mostly in children

Mercury

Chelation Dimercaprol

Toxicokinetics/dynamics

Antidote

Inhaled, absorbed in GI tract (children absorb more than adults, 50% vs 10-15%) - incr absorption with low dietary calcium, iron deficiency, empty stomach Binds RBCs and distributed throughout body Clearance: blood/soft tissue (1-2 months), bone (yrs-decades) Interferes with heme synthesis at multiple steps: elevated protoporphyrin levels can be detected

Terminate further exposure (determine source), supportive care (hydration) Chelation Encephalopathy: treat cerebral edema/seizures steroids/mannitol/ anticonvulsants - IV CaNaEDTA, IM dimercaprol Not encephalopathic: - succimer: primary agent (DMSA, chemet)

Notes

Retained bullets in soft tissues are generally benign - may cause more damage to remove bullet - joints near bone in CSF are more commonly associated with lead poisoning

Avoid some fish in pregnant/lactating women shark, swordfish, king mackerel, tilefish