Final Exam Toxicology Flashcards
Cholinergic Toxidrome
SLUDGE
Salivation
Lacrimation
Urination
Defecation
Gastrointestinal Symptoms
Emesis
Triple B’s/Killer B’s
Bronchorrhea
Bradycardia
Bronchospasm
Anticholinergic Toxidrome
Sympathetic Toxidrome
Agitation
Anxiety
Bronchodilation
HTN
Mydriasis
Tachycardia
Urinary Retention
Seizures
Toxidrome Comparison
Treatment Strategies
Prevent absorption
Enhance elimination
Block effects
GI Decontamination: Activated Charcoal
Other Methods of GI Decon
Emesis
Not recommended
Gastric Lavage
Scare evidence
Use within 30-60 minutes of ingestion
Cathartics
No indication for routine use
Whole Bowel Irrigation
Large amount of osmotically balanced polyethylene glycol electrolyte lavage solution
Ingestion of toxic amount of drug that is not adsorbed to activated charcoal, ER preparations, or Body packers
When is Activated Charcoal NOT Useful
Caustic/corrosive solution
Heavy metals (iron/lead/mercury)
Alcohols
Rapidly absorbed substances
Cyanide
Organophosphates
Aliphatic hydrocarbons
Lithium
Hemodialysis
Urinary Alkalization
Opioids
Causative agents: Buprenorphine, Codeine, Fentanyl, Heroin, Hydrocodone, Hydromorphone, Meperidine, Methadone, Morphine, Oxycodone, Oxymorphone, Tapentadol, Tramadol
Mechanism of toxicity: Increased stimulation of opioid receptors
Receptor and Clinical effects
u – Analgesia, sedation, euphoria, respiratory, depression, GI dysmotility, bradycardia, pruritis, physical dependence
k – Analgesia, miosis
g – Analgesia
Opioid Overdose: Clin Presentation
Sedation
Respiratory distress
Bradycardia
Hypotension
Miosis
Emesis
Constipation
Seizures (meperidine, tramadol)
Overdose Treatment: Naloxone (Narcan)
MOA: Competitively inhibits binding of opioids to opioid receptors
Goals of therapy: Reinstitution of spontaneous ventilation
Use lower practical dose; escalate rapidly as clinically indicated
IV: 0.4-2 mg as initial dose
Repeat dose at 2-3 minute intervals
Consider other causes of toxicity if no response after 10mg of naloxone
Adverse Reaction: Withdrawal
Pharmacokinetics: T1/2 = 30-90 minutes
Benzodiazepines and Barbiturates
Benzodiazepines and Barbiturates: Clin Presentation
Benzodiazepines and Barbiturates: Management and Monitoring
Supportive Care
Maintain airway
Hemodynamic support
Minimum 24h monitoring period for overdoses on long-acting hypnotics or drugs with significant enterohepatic recirculation
Benzodiazapine Antidote: Flumazenil
MOA: Competitive benzodiazepine antagonist
Rapidly reverses sedative effect of benzodiazepines and Zolpidem
Dose:
0.2mg over 30 seconds
Repeat doses: 0.2 mg over 30 seconds repeated at 1-min intervals
Maximum Cumulative Dose: 3mg (usual total dose 1-3 mg)
Caution: May precipitate benzo withdrawal
Boxed Warning: Seizures
Caution in multi-substance overdoses
Beta Blocker & Calcium Channel Blocker Toxicity
Beta Blockers
B1 selective: Acebutolol, Atenolol, Betaxolol, Bisoprolol, Esmolol, Metoprolol, Nebivolol
Mixed: Carvedilol, Labetalol, Propranolol
Calcium Channel Blockers
Dihydropyridine: Amlodipine, Nicardipine, Nifedipine, Nimodipine
Non-dihydropyridine: Verapamil, Diltiazem
Beta Blocker & Calcium Channel Blocker Toxicity Clinical Presentation
Bradycardia
Hypotension
CCB-Specific
Vasodilatory shock
Hyperglycemia
Dihydropyridines: Reflex tachycardia in mild – moderate overdose
BB-Specific
Propranolol: Hypoglycemia, seizures, coma, and dysrhythmias
Prolonged QRS and QT intervals
Rare: Prolonged PR interval or high-grade AV block
Beta Blocker & Calcium Channel Blocker Mechanism of Toxicity
BB/CCB Supportive care
Early airway and respiratory support
Early GI decon
Activated charcoal (single dose) for all IR ingestions if within 4 hours
Whole Bowel irrigation (polyethylene glycol electrolyte mixture) for SR preparations if early and Asymptomatic
Manage Shock
Isotonic IV fluids: Limit 1-2 L to avoid fluid overload and pulmonary edema
Symptomatic bradycardia
Cutaneous and transvenous pacing
BB/CCB Pharmacotherapy PT 1 (Atropine/Calcium)
BB/CCB Pharmacotherapy PT 2 (Glucagon)
BB/CCB Pharmacotherapy PT 3 (Catecholamines)
BB/CCB Pharmacotherapy PT 4 (High-dose insulin euglycemia therapy (HIET))
Specific Pharmacotherapy
Monitoring
Observe in the ICU until bradycardia, hypotension, EKG abnormalities, and/or CNS Toxicity resolve
Beta Blockers
Toxicity from regular release beta blockers poisoning typically occurs within the first 6 hours
Sotalol: Delayed ventricular dsyrhythmias up to 9 hours post-ingestion
Observe PTs who ingest ER preparations for at least 24 Hours
Calcium Channel Blockers
If IR preparation ingestion, ensure that serial EKGs over 6-8 Hours have remained unchanged
Observe PTs who ingest ER products for at least 24 Hours, even if asymptomatic
Digoxin
Cardioactive steroid used for management of supraventricular arrhythmias and heart failure
MOA:
Inhibition of the Na/K/ATPase pump in myocardial cells
Increased intracellular Ca via Na/Ca exchange pump
Increased myocardial contractility
Digoxin Toxicity Diagnosis
Therapeutic range 0.4-2 ng/mL
Suggestion to lower upper limit 1ng/mL
Clinical presentation
Symptoms
Electrolyte abnormalities
EKG findings
Timing of Symptom onset
Acute vs chronic toxicity
Digoxin Toxicity: Clin Presentation
The Digitalis Effect
Digoxin Antidote: DigiFab
Digifab: Digoxin-specofoc antibody fragments
Binds with digoxin to decrease serum digoxin concentration (SDC)
Increased Renal clearance of Bound Digoxin
Dosing
Emperic dosing
- Acute: 10-20 vials
- Chonic: 3-6 Vials
Known Amount
-Calculate Total Body Load:
–Capsules: amount (mg) digoxin capsules ingested
–Tablets 0.8 x amount (mg) digoxin tablets ingested
-Calculate number of vials needed
–Total body load (mg)/0.5
DigiFab indications
Acetaminophen Overdose: Clinical Presentation
APAP Toxic Doses
Acute Toxicity
Single Ingestion of 150 mg/kg
Chronic Toxicity
Less well defined
Evaluate in PTs taking more than 200 mg/kg/d (or 10 g/d) in 24H
Evaluate in PTs taking more than 150 mg/kg/d (or 6 g/d) in 48H
Factors Affecting APAP Toxicity
APAP dose
Pattern of use
Acute vs Chronic alcohol ingestion
Concomitant Medication ingestion
Age
Nutritional status
Presence of Chronic liver disease
APAP Toxicity Supportive Care
GI Decon with Activated Charcoal
If within 4 hours of acute APAP ingestion
May be given after 4 hours if extended-release APAP ingestion of drugs that delay gastric emptying time
Liver Transplant
Lifesaving procedure when APAP ingestion has progressed to irreversible liver failure
Qualifying factors: Poor projected outcome and high risk of mortality based on MELD, Kings Criteria, and Apache II scores
Pharmacotherapy: N-Acetylcysteine (NAC)
Cysteine prodrug and hepatic GCH precursor
Replenishes and maintains hepatic GCH stores by providing Cysteine, which detoxifies reactive metabolites of APAP
May reduce NAPQI back to APAP by enhancing Sulfonation pathway
May reduce mortality from 5% to 0.7%
Utility of Rumack-Matthew Nomogram
Unknown Time of Ingestion: To Treat or not to Treat
If Normal APAP and Normal AST/ALT do not treat, otherwise TREAT
Treatment Duration
Decision to discontinue NAC after extending treatment beyond standard protocol length is PT specific and should be continued if:
Evidence of hepatic injury
- AST significantly above normal
- PT/INR> twice normal
- Encephalopathy
APAP metabolism is incomplete (APAP detectable)
Continue treatment with NAC until evidence of hepatic injury resolves and APAP is undetectable
Organophosphates
Agents: Malathion, Parathion, methyl parathion, diazinon
MOA/Mechanism of Toxicity: Increased concentration of acetylcholine (ACh) at muscarinic and nicotinic cholinergic synapses-> cholinergic excess
Organophosphate Clin Presentation
Management of Organophosphate Tox
Atropine MOA: Competitive antagonist of AcH at muscarinic receptors; reverses excessive secretions, miosis, bronchospasm, vomiting, diarrhea, diaphoresis, and urinary incontinence
Pralidoxime (2-PAM) MOA: Enhances regen of AChE to lower ACh concentrations and improve muscarinic and nicotinic effects
Serotonin Overview
Serotonin (5-HT): Monoamine neurotransmitter synthesized from tryptophan
5-HT1A and 5-HT2A most commonly implicated in serotonin syndrome
Found in the CNS, platelets, and GI tract
CNS: regulates appetite, memory, mood, and sexual activity
Peripherally: Assists in regulating clotting, peristalsis, and vascular tone
L-Tryptophan -> 5 Hydroxytryptamine (Serotonin)
Causative Agents
Increased Serotonin Production – L-Tryprophan
Inhibition of serotonin reuptake – Chlorpheniramine, cyclobenzaprine, dextromethorphan, meperidine, methadone, pentazocine, SSRIs, St. John’s wort, Tramadol, trazodone, TCAs
Inhibition of serotonin metabolism by MAO – Linezolid, methylene blue, phenelzine, selegiline
Increased serotonin release – Dextromethorphan, meperidine, methadone, MDMA, mirtazapine, Fentanyl, cocaine, amphetamines
Stimulation of Serotonin receptors – Buspirone, lithium, LSD, Meperidine, metoclopramide, triptans
Diagnosis
Diagnosis of exclusion – no confirmatory test
Assess exposure to serotonergic drugs in the last 5 weeks
Monitor signs/Symptoms of serotonin syndrome
Obtain Labs tox screen
SS Clin Presentation
Differential Diagnosis: SS vs Neuroleptic Malignant Syndrome (NMS)
Supportive Care of SS
Discontinue offending agent
Administer IV fluids
Control hemodynamic instability
Benzo for agitation
Implement standard cooling measures for hyperthermia
Severe toxicity may warrant sedation, paralysis &/or intubation
Pharmacotherapy for SS
Monitoring
Typically resolves within 24H of cessation of serotonergic drug
Admit and monitor 12-24 Hrs
Concern for delayed cardiotoxicity
TCA
Mechanism of Toxicity
Inhibition of Serotonin and norepinephrine reuptake at nerve terminals
Direct a adrenergic block
Membrane stabilizing effect
Anticholinergic action
TCA Clin Presentation
TCA Management
TCA Monitor
Stimulant Toxicity
Causative Agents
Amphetamines/Dextroamphetamines/Methamphetamines
Methylenedioxymethamphetamine (MDMA/Ecstasy)
Synthetic Cathinones (bath salts)
Methylphenidate
Cocaine
Stimulant OD Management/Supportive care
Toxic Alcohols
Clin Presentation of Methanol
Clin Presentation of Ethylene Glycol
Clin Presentation of Isopropanol
Mechanism of Alcohol Toxicity
Supportive care for Alcoholic Toxicity
The Role of Vitamins in Alcohol Toxicity
Treatment indications of Alcohol Toxicity
Alcohol Antidotes: Ethanol and Fomepizole
Not as helpful with isopropanol
Pharmacotherapy: Fomepizole
Pharmacotherapy: Ethanol
Co-Ingestion of Ethanol