Toxicology - Antihypertensives, Synthetic Cannabinoids, Aspirin/Salicylates, Digoxin, Sympathomimetics Flashcards

Question

* TOXIC DOSE * - Aspirin / Salicylates

Answer 1

Acute overdose ́ **Greater than 150mg/kg** ́ **Life threatening > 500mg/kg** Chronic overdose ́ Less clearly established ́ Greater toxicity at lower doses ́ Oil of wintergreen ́ 98% methyl salicylate ́ 98g/100ml ́ 20.4ml = 20g life threatening for 70kg adult ́ 5.1ml = 5g life threatening for 10kg child ́ 1.5ml = seek medical attention for 10kg child

Answer 2

Absorption ́ Aspirin ́ Absorption can be delayed (pylorospasm, enteric coated, **concretions/bezoars**) ́ Other salicylates ́ Absorption varies according to the dosage form ́ Methyl salicylate will be absorbed quickly Distribution ́ Protein binding 50-90% (decreased in OD) ́ Vd = 0.1-0.2 L/kg (small), larger in acidosis Elimination ́ Hepatic and renal: normal half life 2-4 hours Overdose ́ Michaelis-Menten kinetics ́ Half life extends Significant overdose ́ Renal elimination plays a greater role

Answer 3

Metabolic acidosis ́ Salicylic acid (minor) ́ **Uncoupled oxidative phosphorylation (major)**

Answer 4

Respiration ́ Potent stimulatory effects on respiratory drive ́ Tachypnea/hyperpnea GI ́ Disrupts mucosal barrier ́ n/v, hemorrhagic gastritis, volume depletion CNS ́ Neuronal energy depletion, **hypoglycorrachia (neuroglycopenia)** - decreased BG in CNS, but not necessarily in the bloodstream ́ Tinnitus, altered mental status, hyperpyrexia, tachycardia, fever, coma, seizures Other ́ Non-cardiogenic pulmonary edema (chronic), renal and hepatic injury

Answer 5

Acid / Base ́ EARLY: respiratory alkalosis (direct stimulation) ́ MIDDLE: mixed metabolic acidosis and respiratory alkalosis ́ LATE/PRETERMINAL: metabolic and respiratory acidosis Electrolytes ́ hypo or hyperglycemia, (CNS hypoglycemia) ́ increased fluid and electrolyte losses ́ increased anion gap (MUDPILERS. S = Salicylates) Urine ́ urine ketones will be positive

Answer 6

́ Acute overdose may be present ́ Slower, more insidious onset ́ N/V, **tinnitus**, dyspnea, hyperthermia, neurologic manifestations ́ More common to be misdiagnosed Delirium, dementia, encephalopathy Pulmonary edema more common Increased PT/LFTs ́ Lower levels will produce toxic effects ́ Enlarged volume of distribution

Answer 7

́ Airway, breathing, circulation - ABCs ́ ***maintain ventilation – do not intubate*** ́ Multiple serum salicylate levels ́ Enhance elimination ́ multiple doses of activated charcoal 1 g/kg (loss of 10:1 ratio) ́ urine alkalization (pH > 7.5) ́ hemodialysis ́ Treat adverse effects ́ seizures, cerebral edema, hypoglycemia, dysrhythmias

Answer 8

Concentrated lump of aspirin/Salicylates which slowly releases salicylates over time in the GI tract

Answer 9

Alkalize the urine to make H+A- cross to the urine, become ionized to attempt to neutralize it, and then the ions can’t cross back into the bloodstream Significantly higher urinary clearance with increasing Urinary Alkylinization Is a learning objective! (1 of 2 for the aspirin lecture)

Answer 10

́ **Give dextrose (even if normal glucose levels)** ́ 0.5-1g/kg ́ Fluid maintenance ́ Serum pH 7.45 – 7.55 ́ **150mEq SODIUM BICARBONATE in D5W at twice maintenance rate** ́ Urine pH > 7.5 ́ Maintain potassium ́ Monitor Mental status, urine and blood pH, salicylate levels, fluid and electrolytes q 2-4 hours

Answer 11

́ Serum level ́ Acute: > 100mg/dL ́ Lower threshold in impaired kidney function ́ Chronic > 60mg/dL ́ Neurologic deterioration ́ Seizures ́ Intractable acidosis ́ pH < 7.20 ́ Renal failure ́ Pulmonary edema **Continue hemodialysis until**: -Clear improvement in patient -Salicylate level < 19mg/dL -HD completed for 4-6 hours and levels not obtainable

Answer 12

Gastrointestinal system - Nausea, vomiting, diarrhea Central nervous system - Headaches, confusion, delirium - Visual (halos/colors) Metabolic derangements - Hyperkalemia Predistribution - Nausea, vomiting - Hyperkalemia Post-distribution - Hypotension - Bradycardia - Dysrhythmias - Death

Answer 13

Acute, single ingestions Normal organ function **K+ > 5.5mEq/dL = all died** **K+ < 5.0mEq/dL = all survived** K+ 5.0 - 5.5mEq/dL = mixed Digoxin Cardiac ECG - **Prolonged PR interval** - Salvador Dali’s mustache

Answer 14

Cardiac - Decreased conduction - Enhanced automaticity - Classic rhythms: PVC’s bidirectional ventricular tachycardia, atrial tachycardia with block **any rhythm except rapidly conducting SVT’s**

Answer 15

Gastrointestinal decontamination - Activated charcoal, repeat doses in renal failure Hyperkalemia - Digoxin specific FAB fragments ; Temporizing measures **Digoxin specific FAB fragments (Digifab)** - Derived from sheep ; Digoxin-specific antibody formed - Fc fraction (antigenic) cleaved - Increased volume of distribution - Less allergy Digifab dose: 1 vial binds 0.5mg digoxin ingested. Unknown amount? —> 10 vials Digifab In Practice… - Give 2 vials and titrate to effect - Give Q1 hour if no response seen Without digibind – **phenytoin** is the antidysrhythmic classically of choice

Answer 16

Potassium > 5 mEq/L Level > 20 mcg/L Progressing signs of toxicity

Answer 17

Less common to present with typical manifestation and potassium is unhelpful Digifab indications are soft and include: - Post-distribution level of > 6 mcg/L (~6 after last ingestion) - Progressing or severe signs of toxicity Unknown digoxin dose (#Digifab vials): - 5 in adults - 3 in children In practice… Give 1-2 vials and titrate to effect Give Q1 hour if no response seen

Answer 18

Inhibition of norepinephrine and dopamine reuptake, or increased release of neurotransmitters “Uppers”

Answer 19

Cocaine, Amphetamines, Bath Salts, Pseudoephedrine, Nootropics (said to promote intelligence) NO ANTIDOTE Supportive Care • Elimination strategies (i.e. activated charcoal) • **Benzodiazepines** • Anti-hypertensives • Fluids • Anti-psychotics (if agitated or combative - haloperidol or olanzapine) • Electrolyte management • Ice baths (Temp too high—> Cool them down quickly • Sodium bicarbonate (if acidosis present) Bupropion and Pseudoephedrine have similar chemical structures

Answer 20

Sympathomimetic Typical Line = 20-30 mg ́ **Ingestion of 1 gram is likely to be fatal** ́ Euphoria, seizures, dysrhythmias, hypertension ́ Coronary artery spasm myocardial infarction ́ Adulterants ́ Levimasole: neutropenia, vasculitis, purpura ́ Body Packers ́ **Management: Benzodiazepines, supportive care**

Answer 21

Mechanism of action: releases catecholamines ́ Clinical manifestations: adrenergic ́ Similar to cocaine though longer lasting ́ Agitation, seizures, hyperthermia, hypertension, delirium ́ Management: benzodiazepines, barbituates, anti- hypertensives ́ Supportive care

Answer 22

Syntheticcathinones ́ Agitation ́ Tachycardia ́ Insomnia ́ Paranoia ́ Seizures ́ Violent, unpredictable behavior ́ Management: Supportive are

Answer 23

Clinical Effects • Benzodiazepines Airway protection • Intubation Hyperthermia • Ice packs • Cool fluids • Antipyretics (may or may not work) • Benzodiazepines Dysrhythmias • Sodium bicarbonate • Lidocaine Rhabdomyolysis • Fluids