Toxicology Flashcards
Opioid toxidrome? Interventions & antidotes? How often should the antidote be given? What may require higher dosing? What best predicts response? Can this precipitate withdrawal? What other antidotes are there and how do they differ?
Largely normal VS (slightly decreased HR, BP, temp) except decreased RR (hypoventilation) –> respiratory failure. Pinpoint pupils (intense miosis). Mental status changes: lethargy, sedation, coma. Decreased bowel sounds. Interventions: Supportive – Airway/Breathing/Circulation/Substrates (Glucose, especially if altered mental status!!). Antidote: Naloxone – competitive receptor antagonist at mu, delta & kappa opiod receptors. Frequent dosing because of a short half life (15 minutes). Synthetic opioids require increased doses. Decreased RR best predicts response. Can precipitate withdrawal if already tolerant: Flu-like symptoms + yawning + piloerection – there is normal mental status and this is not life-threatening; if due to naloxone, this may only last 15-30 minutes. Other antidotes: Nalmefene, Naltrexone – these differ in pharmacokinetics and last longer and can produce a longer withdrawal state.
Benzodiazepine toxidrome? Interventions & antidotes? Can this precipitate withdrawal? What are adverse effects of the antidote?
Normal VS, depressed mental status (realize that other sedative-hypnotics [alcohol, barbiturates] will cause disinhibition –> lethargy –> stupor –> coma –> respiratory failure + ataxia, nystagmus, hypothermia). Interventions: ABCS. Antidote: Flumazenil (only for benzodiazepines!) – Competitive non-selector benzodiazepine receptor antagonist. Can precipitate withdrawal if tolerant. Seizures reported in mixed OD; not uniform in reversal of respiratory depression.
Acetaminophen (APAP) prodrome? Outline acetaminophen metabolism in the liver. Antidote? Indications? When should this be given? What are “ominous” signs of late APAP hepatotoxicity? What is included in the new criteria for this hepatotoxicity? Are these signs accurate? At this point, do we still use the antidote?
Acetaminophen has no prodrome! However, we can “map” the toxicity: Stage 1 (0.5-24 hrs) = asymptomatic, mild GI toxicity; Stage 2 (1-3 days) = LFT & renal function abnormalities +/- RUQ pain; Stage 3 (3-5 days) = Hepatic necrosis +/- renal failure; Stage 4 (4 days - 2 weeks) = Resolution of organ fxn. A reversal can occur at any stage. Normally, APAP is metabolized by liver glucoronyl transferase to form an inactive conjugate; a minor P450 pathway exists that forms toxic N-acetylbenzoquinoneimine with is inactivated by glutathione. In overdose situation, the GSH is depleted, and once this happens the metabolites can react with hepatocytes and cause centrilobular necrosis. Antidote: N-acetylcysteine (NAC) – supplies -SH to replentish GSH. Best if given within 8 hours of overdose. Indications: A level and known time of ingestion over the Rumack-Matthew nomogram (need to wait 4 hours!); signs of hepatotoxicity; when APAP level will not be available within 8 hours. Ominous signs of late APAP hepatotoxicity: (note that these are signs of dysfunction!) PT > 200 sec, Serum Cr > 3.3 mg/dl, Grade III-IV hepatic encephalopathy, Blood pH 30. The newest variable is serum lactate: > 3.0 mmol/L after 12 hours and fluids. these signs are VERY accurate and can be used to determine who is in most need of a liver transplant. At this stage, we can still use NAC, but more as an antioxidant and for improved microcirculation.
TCA prodrome? What is most concerning? Interventions & antidote? What is the end point of the antidote?
Remember that TCAs are antimuscarinic: mydriasis, hyperthermia (hot but DRY skin), increased HR, dry membranes, no bowel sounds – antimuscarinics will cause hypertension, but TCAs are also alpha blockers so they cause HYPOTENSION + “the 3 C’s+ –> Convulsions (GABA antagonist), Coma, Cardiotoxicity – the cardiotoxicity is due a sodium channel blocker which results in a widened QRS (phase 0!). Most concerning is the sodium channel blockade the subsequent risk of arrhythmia!! Intervention: Sodium to overcome the sodium channel blockade; Alkalinization to reduce TCA affinity to its myocardium receptor, with the endpoint being QRS narrowing and a blood pH not exceeding 7.55.
Anticholinergic toxidrome? Interventions & antidote? Indications? Who should this not be given in? Rapid administration can result in? When unsure of indications, what can be used?
Mydriasis, hot BUT dry skin, hyperthermia, urinary retention, decreased bowel sounds, increased HR & BP, altered mental status: delirium, hallucinations, seizures. Antidote: Physostigmine – acetylcholinesterase inhibitor (crosses the BBB!) Indications: Pure anticholinergic poisoning w/ CNS &/or PNS manifestations & no EKG findings suggestive of TCA exposure (widened QRS & RAD). This should not be given in those with TCA exposure!! – This can cause aystole due to muscarinic and cholinergic excess. Rapid administration can result in seizures. Sedative-Hypnotics can be used when unsure of indications.
Cholinergic toxidrome? What are examples of cholinergic drugs? Interventions & antidotes?
SLUDGE! Salivation, lacrimation, urination, defecation, GI distress, emesis + miosis, CNS excitation, bronchospasm, fasciculations. Cholinergic drugs: Cholinomimetics, Anticholinesterases (nerve gases, organophosphates, physostigmine, neostigmine, carbamates). Antidote: Atropine (anticholinergic) – very high doses may be needed! Atropine is only ANTIMUSCARINIC and thus wil not have any effect at nicotinic receptors. Also: Pralidoxime – regenerates AChE but must be given before aging occurs, at which point reversal is no longer possible. This also reduces the atropine requirement.
In evaluating a possible methanol or ethylene glycos (alcohol)-induced anion-gap metabolic acidosis, how can we rule out the other members of MUDPILES? Based on the osmolal gap, how can we prove toxic alcohol? Describe the metabolism of methanol and ethylene glycol. What is the antidote? What must also be done?
Uremia - Normal BUN/Cr. DKA - No ketones. Paraldehyde, phenformin (metformin), Iron/INH, Lactate - No lactate. Salicylate - No lactate (also can measure this directly). Osmolal gap > 50 = toxic OH until proven otherwise. Osmolal Gap = 2(Na) + BUN/2.8 + Glu/18 + ETOH/4.6 = (normal) -10 to 10. Methanol to Formaldehyde via ADH to Formate (formic acid) via ALDH; Ethylene glycol to Glycoaldehyde via ADH to Glycolate (Glycolic acid) via ALDH. The acid is what is toxic! Antidote: Fomepizole – a competitive inhibitor at ADH. As such, we must still hemodialyze to remove toxin and metabolite. Indications: > 25-50 mg/dL of methanol or ethylene glycol, MA, coma, hemodynamic instability.
What antihypertensives can cause bradycardia and hypotension in overdose? What happens in a CCB overdose? How do we treat a CCB overdose? What happens in a BB overdose? Which BB are we especially concerned about? What does a clonidine OD look like? What does acute digoxin toxicity look like? What predicts outcomes? Antidote?
BB, CCB, Dig, Alpha-2-agonists (clonidine, guanfacine, imidazolines). In a CCB overdose, phase 2 is affected (slowed inward calcium current) – Negative ionotrope (decreased ventricular contractility), negative chronotrope (sinus node depression), hypotension (AV node depression + vasodilation) – Of course, verapamil & diltiazem will cause hypotension and bradycardia, whereas nifedipine & other dihydropyridines will cause peripheral vasodilation with hypotension and a reflex tachycardia. To treat a CCB overdose: 1 - decrease absorption (whole bowel irrigation or activated charcoal), 2 - Increase elimination (very difficult to do), 3 - Specific antidotes: Calcium, Glucagon, High Dose Insulin (achieves an ionotropic effect), Pacing, Amrinone (PDEi), Vasopressors (dopamine, dobutamine, NE, isoproterenol), Itraeortic balloon pump, Lipid emulsion. BB overdose: B1 effects – negative ionotrope, chronotrope, slowed AV conduction, B2 effects (minimal) – bronchoconstricion, increased vascular resistance. Especially concerned about propanolol b/c it has membrane stabilizing activity and can cause a fast Na+ block and a widened QRS, it is also lipophilic and can cause mental status depression and seizures. Clonidine OD (also guanfacine, imidazolines): alpha-2 decrease CNS sympathomimetic output, there is some cross-reactivity with alpha-1 agonists – results in bradycardia, CNS depression, with pinpoint pupil – this can look VERY MUCH like an opiod OD w/ abnormal vital signs; these pts respond favorably to supportive care. Dig: HYPERKALEMIA!! hypotension, bradycardia, dysrrhythmia, death. Level of K+ predicts outcomes: >5.5 DEAD,
CNS stimulant toxidrome? PCP? Synthetic marijuana (K2/spike/spice)? LSD? In general, what are the treatments for these drugs of abuse?
CNS stimulants (cocaine, amphetamines, ephedra) Anxiety, agitation, hallucinations, seizures, hyperthermia + increased muscle activity ==> increased CK, kidney injury, can decrease blood flow to the heart, increased HR/BP, warm SWEATY skin. PCP/Ketamine/DM: Dissociative anesthetic! Synthetic marijuana: Hyperadrenergic findings, seizures, paranoia. LSD: Only adverse effects are related to the experience (no inherent toxicity). Treatment: Sedation, restraint, cooling.
