Toxicology Flashcards
Basic Principles of Toxocology
- Keep ingestion on your radar
- Obtain a detailed hx
- Be familiar with common toxidromes
Lab evals
-Glucose
-CBC
-Extended electrolytes
-Lactate
-ABG (carboxyhemoglobin, methemoglobin)
-Acetaminophen and salicylate levels
-Ethanol
-Urine drug screen
-Pregnancy test
ECG
-Many toxin cause cardiotoxic affects
-QRS widening
-Tall R-waves
-QTc prolongation
Sodium Channel Blockers
-TCAs
-Cocaine
-Benadryl
-Flexeril
-Tegretol
-Propafenone
-Flecainide
-Sodium bicarbonate if QRS <120 msec (50-100 mEq bolus, then infusion 150 mEq/Liter D5W at 150 ml/hour
Serum pH 7.45-7.55;
Check pH and K+ q 2 hours)
Agitation Management
-Benzodiazepines
-Avoid Haldol
b/c
—impairs heat dissipation
—Prolongs QTc
—worsens anticholinergic toxicity
—lower seizure threshold
Classic toxidromes
-Opioids
-Sedatives/Hypnotics
-Sympathomimetic
-Hallucinogenic
-Serotonin
-Anticholinergic/cholinergic
-Acetaminophen
-Salicylates
-BB/Ca Channel blockers
Opioids
-Bind to opioid receptors such as Mu, Kappa, Delta
-Ex: morphine, fentanyl, tramadol, methadone, heroin, meperidine, hydrocodone, oxycodone, hydromorphone
-CNS Depression, hypoventilation, miosis, hotn, rhabdomyolysis if found down, noncardiognic pulmonary edema w/ progression of ARDS
Opioid Tx
-O2, airway support, naloxone
-Nalmefene is similar to narcan but has longer half life at 10 hours. Naloxone is the preferred choice
Naloxone (Narcan)
-Mu receptor antagonist. Pushed opioids out of the receptors and binds them to themselves.
-half life is 1 hours.
-Don’t push all at once, slowly awaken patient
-0.04 to 0.4 mg IV every 2-3 minutes; repeat dose or increase to 2 mg if inadequate
-If no response with 5-10 mg, probably not opioid overdose
-Continuous infusion 0.05 mg/hour
Naloxone (Narcan) Precautions
-May precipitate acute withdrawal symptoms and seizures
-May lead to pulmonary edema
-CNS depression may return after initial improvement due to short half life
Sedatives/Hypnotics
-Benzos, ethanol, barbiturates, zolpidem
-Cause anesthesia with diminished reflex activity and loss of awareness
-CNS depression
-Hyporeflexia
-Depressed respiratory rate with large quantities
-Hypothermia
-Hotn
-mild bradycardia
-Ataxia
-Pupils normal
Sedative & Hypnotics Tx
-Supportive, o2 and airway, ETOH monitoring, benzos: Flumazenil
Flumazenil
-0.2 mg IV, followed by 0.3 mg, 0.5 mg if no effect
-Max 3 mg/hour
-If 5 mg in one hour ineffective, likely to be something other than benzodiazepine
-Half life: 54 minutes
Flumazenil Precautions
-Black box warning: increased risk of seizures, especially in patients w/ concurrent sedative-hypnotic withdrawal
-Re-sedation may occur
-May precipitate benzo withdrawal
Sympathomimetics
-Designer drugs, PCP, ecstasy, cocaine, synthetic cathinone, ephedrine, beta-adrenergic agonists, amphetamines, caffeine
-Increase activity of alpha & beta receptors
-Found in the skin, eyes, heart, GI tract, lungs, exocrine glands
-Cause: tachycardia, htn, tachypnea, agitation (at someone or something)
-Diaphoresis, mydriasis, seizures, arrhythmias
Sympathomimetics Tx
-No antidote
-Keep patient safe
-Tx: Benzodiazepines
0.02 to 0.06 mg/kg IV every 2-6 hours
Patient dependent!
-Sodium bicarbonate infusion for cardiac stabilization
(50-100 mEq bolus, then infusion 150 mEq/Liter D5W at 150 ml/hour)
Serotonergics
-Serotonergics are agents that modify the effect of serotonin in the body
-Psychedelic stimulants, Dextromethorphan, SSRIs, TCAs, MAOIs, Buspirone, lithium, meperidine, linezolid, ecstasy
-Clinical triad: autonomic instability (HR, temp increase), agitated delirium, neuromuscular agitation (hyperreflexia, clonus)
-Akathisia, tremor, diaphoresis, diarrhea, rhabdomyolysis, pupils normal
Serotonergics Tx
-Supportive care, d/c all serotonergic agents (tramadol, fentanyl). IV fluids, avoid restraints, active cooling
-Benzos, propofol +/- paralytics, Cyproheptadine vs Chlorpromazine, Precedex
—-Benzos are the cornerstone of tx
Cyproheptadine
-Serotonergic tx
-Nonspecific serotonin antagonist.
-histamine-1 receptor antagonist with nonspecific 5-HT1A and 5-HT2A antagonistic properties.
-Initial dose of 12 mg, followed by 2 mg every 2 hours until desired clinical response.
-Needs further research
-Only oral form
Chlorpromazine
-Serotonergic tx
-Not well studied. Not recommended.
-Antipsychotic agents with 5-HT2A antagonist activity.
-Exact mechanism of action is unknown, though is thought to have mild anti-serotonin activity.
Dexmedetomidine hydrochloride (Precedex)
-Alpha-2 adrenergic agonist with sedative characteristics.
-Loading dose 1 mcg/kg over 10 minutes
-Maintenance for < 24 hours 0.15 to 1.5 mcg/kg/hr
-Maintenance for > 24 hours 0.2 to 0.7 mcg/kg/hr
-Monitor for bradycardia and hypotension
Anticholinergics
-Meds association w/ parasympathetic nervous system
-Innervates the eyes, heart, respiratory system, skin, GI/GU, sweat glands
-Diphenhydramine, TCAs, Antipsychotics, jimson weed, angels trumpet, antiparkinsonian, atropine, nightshade (belladonna)
-Tachycardia, hyperthermia, variable BP, Tachypnea, mydriasis, redirectable delirium.
Anticholinergic Tx
-Supportive cares
-Monitor for seizures, treat with Benzodiazepines
-Cardiac monitoring for prolonged QRS, QTc
-Avoid haloperidol (seizure, dysrhythmias, qtc prolongation)
-Physostigmine: contraindicated in TCAs
Physostigmine
-Anticholinergic tx
-Crosses the BBB to inhibit cholinesterase and makes more acetylcholine available
-2 mg IV (slowly, 1 mg/min)
-May repeat dose for life threatening signs
-Works quickly, half life 4.9 hours
-Monitor for bradycardia and convulsions if administered too quickly
-Excessive cholinergic effects may occur
Cholinergics
-Activates the muscarinic acetylcholine receptors
-Nerve gas, insecticides, physostigmine, donepezil, muscarinic mushrooms
-Defecation, Urination
Miosis, Bradycardia
-Bronchospasm, emesis, lacrimation, secretions, seizures.
Cholinergic Tx
-Decontamination, d/c agent, supportive therapy, IV fluids, atropine (even w/ tachycardia), glycopyrolate
-Atropine
-Pralidoxime
Atropine for Cholinergic tx
-2 to 3 mg IV/IM/SQ; may repeat in 20 to 30 minutes
-Titrate based on HR, PR interval, symptoms
-In intubated ICU patients: initial dose 20 mg IV in combination with pralidoxime 2 g IV loading dose
Acetaminophen Metabolism
-rapidly absorbed from the stomach and small intestine.
-Serum levels peak in 1-2 hours, level 5-20 ug/ml, plasma peak in 4 hours.
-Elimination half-life is 2 hours, unless hepatic dysfunction, then up to 17 hrs.
-Excess acetaminophen is metabolized via the CYP enzymes to the hepatotoxic reactive metabolite N-acetyl-p-benzoquinoneimine (NAPQI).
Risk factors for acetaminophen toxicity
-underlying hepatic or renal disease
-older age, restricted diet, compromised immune system nutritional status
-Ethanol ingestion, Tobacco smoking
Isoniazid (INH), Rifampin
Phenytoin, Phenobarbital
Barbiturates, Carbamazepine, Trimethoprim-sulfamethoxazole (TMP-SMZ), Zidovudine
Phase 1: First 24 hours of acetaminophen toxicity
-Asymptomatic
Anorexia, nausea, vomiting, malaise
Phase 2: 18-72 hrs after ingestion (if untreated) acetaminophen toxicity
-RUQ pain, anorexia, nausea, vomiting
Tachycardia and hypotension
Phase 3: 72-96 hrs (if untreated) acetaminophen toxicity “hepatic phase”
Nausea, vomiting, abdominal pain
Hepatic necrosis/synthetic dysfunction
— Jaundice, encephalopathy, coagulopathy, hypoglycemia, LFTs extremely elevated and peak (AST>10000), acute renal failure possible
Phase 4: 4 days to 3 days post-ingestion acetaminophen toxicity
-Either death, complete recovery or transplant
-May take several months for complete hepatic recovery
Acetaminophen Tx
-Charcoal (within 4 hours of ingestion)
-N-acetylcystine IV or PO
IV Loading dose (41-99 kg): 150 mg/kg IV over one hour
IV Maintenance: 50 mg/kg over 4 hours; 100 mg/kg over 16 hours
Oral: 140 mg/kg PO initial dose; then 70 mg/kg every 4 hours over 16 hours
-WI vs MN
Discontinuation of N-acetylcystine
INR
Acetaminophen undetectable
Transaminases decreasing
Salicylate toxicity
-Medical emergency
-Early/mild symptoms: Tinnitus, vertigo, nausea, vomiting, diarrhea
-Late/severe symptoms: Encephalopathy (from agitation to lethargy), hyperpyrexia, noncardiac pulmonary edema
-Symptoms present in 1-2 hrs after ingestion (enteric coated)
Salicylate tx
-Admit for ingestions of 150 mg/kg or greater OR TOXICITY
-Decontamination
-intubation
-Volume status
-Alkalinization of urine
-Supplemental glucose
Ca channel blockers/Beta blockers
-bradycardia, hotn, dysrhytmias, shock
-Propranolol is the most toxic beta-blocker and the most frequently used in suicide attempts worldwide.
-Historically treated with IV fluids, inotropes, pacing, glucagon, lipids
-Evidence suggests that high dose insulin therapy may be beneficial in refractory cardiogenic shock secondary to CCB and BB overdose
MOA Ca Channel blocker toxicity
-Disrupt fatty acid metabolism and create relative insulin resistance in the myocardium
MOA of BB toxicity
Interfere with myocyte metabolism, and inhibits pancreatic insulin release.
Goals of toxicology insulin dosing
-Maintain CO & Perfusion
-Titrate off vasopressors
-Glucose 150-250 mg/dL
-K 2.5-3
-Ical 5-6 mg/dL
-Give Ca
-Bolus dextrose, followed by infusion of D50 at 150 ml/hr
-Regular insulin IV, bolus dose 1 unit/kg-Max dose (10 unites/kg/hr)
Anion Gap
Na – (Cl + HCO3)
-Normal 4-12 mmol/L
-Total cations: Sodium
-Total anions: chloride, bicarbonate
-Methanol, metformin
-Ethylene glycol
-Toluene
-Alcoholic ketoacidosis
-Lactic acidosis
-Aminoglycosides
-Cyanide, carbon monoxide
-Isoniazid, iron
-Diabetic ketoacidosis
-Generalized seizure-producing toxins
-Aspirin
-Paraldehyde, phenformin
Anion Gap Mnemonics
Methanol
Uremia
Diabetic ketoacidosis
Paraldehyde
Isoniazid/Iron
Lactate
Ethylene glycol
Salicylate
Osmolar Gap
-Take with anion gap
-detects unmeasured compounds in the serum
-Normal value < 10
-High osmolar gap can indicate the presence of an extra solute, such as methanol or ethylene glycol
Osmolar Gap Mnemonic
-Methanol
-Ethylene glycol
-Diuretics (osmotic diuretics like mannitol)
-Isopropyl alcohol
-Ethanol
