Acute Poisoning Flashcards
Define median lethal dose
LD50
The dose of a chemical substance that will kill 50% of the population exposed
Define therapeutic index
Quantifies relative safety of a drug
TI = LD50/ED50
The higher the ratio, the safer the drug
List and briefly describe the types of drug-induced toxicity
Dose-dependent reactions
Drug-drug interactions
Allergic reactions
Idiosyncratic reactions
Describe mechanism of toxicity for
APAP
Formation of reactive APAP metabolites
Small proportion undergoes CYP hydroxylation to form NAPQ1 = reacts with glutathione
Depleted glutathione reserves = metabolites can no longer be detoxified
Describe the clinical presentation of APAP toxicity
Step 1 = <24 hrs
GI (N/V, anorexia, abdominal pain)
Step 2 = >24 hrs Liver damage (inc. plasma transaminases)
Step 3 = days 3-4
Liver failure, jaundice, hypoglycemia, hepatic encephalopathy
Step 4 = >5 days
Liver necrosis, spasms, collapse, respiratory depression, hepatic coma
Describe therapy for APAP toxicity
Maintain vital physiological functions
Gastric charcoal (if appropriate)
Antidote for those at risk of hepatic injury (detoxifies NAPQ1)
List mechanism of toxicity for aspirin
Mild intoxification = 150-200 mg/kg
Severe intoxification = 300-500 mg/kg
Describe clinical presentation of aspirin toxicity
Neurological =
Tinnitus, lethargy, seizures, confusion
GI = N/V
Respiratory =
Hyperventilation
Metabolic =
Activate respiratory center of medulla leads to hyperventilation and respiratory alkalosis
Interference with cellular mechanism = metabolic acidosis, generation of heat + body temperature
Describe therapy for aspirin toxicity
Maintain vital physiological functions
Gastric charcoal (if appropriate)
Sodium bicarbonate:
Alkalinization traps salicylate anions in blood and renal tubule
List mechanism of toxicity for atropine
Competitive antagonists of ACh at peripheral and central muscarinic receptors
Affects mainly exocrine glands (sweating and salivation), SM, and heart (= tachycardia)
Describe clinical presentation of atropine toxicity
Dry mouth, thirst
Tachycardia
Hyperthermia, dry, red & hot skin
Urinary retention
Restlessness, confusion, hallucinations
Seizures
Respiratory depression
Mydriasis (pupil dilation)
Describe therapy for atropine toxicity
Decontamination with activate charcoal (if appropriate)
Physostigmine: reversible inhibitor of acetylcholinesterase to inc. ACh and stimulation M receptors
List the mechanism of toxicity for cholinesterase inhibitors
Phosphorylate or carbamoylate active site of AChE
Results in increased [ACh] at cholinergic junctions
Describe clinical presentation of toxicity with cholinesterase inhibitors
D = diarrhea U = urination M = miosis M = muscle weakness
B = bradycardia B = bronchoconstriction E = excess bronchial secretion L = lacrimation
L = lousy for vision S = salivation S = sweating
Describe therapy for toxicity with cholinesterase inhibitors
Activated charcoal (if appropriate)
Atropine via IV to control signs of muscarinic excess
Pralidoxime for intoxication with organophosphate
List mechanisms of toxicity for digoxin
Na/K ATPase gets inhibited = more intracellular Na and decreased exchange of Na for Ca
Ca stores in sarcoplasmic reticulum increase
Inc. parasympathetic tone in heart = dec. AV conduction
Describe clinical presentation of digoxin toxicity
Psychiatric =
Confusion, 😴, insomnia, hallucination, delirium, seizures
Visual = impaired color vision (XANTHOPSIA)
respiratory =
dyspnea, cyanosis, inc. ventilation
GI = abdominal pain, diarrhea
CNS =
N/V, headache, vertigo, dizziness, neuralgia, muscle weakness
Cardiac =
ARRHYTHMIAs
Describe therapy for digoxin toxicity
Activated charcoal if appropriate
Correct K+ deficiency
Digoxin antibodies
Anti-arrhythmic drugs
What are methods for GI decontamination to keep the [poison] in tissues as low as possible?
Gastric emptying = gastric lavage, induced vomiting
Absorption of poison = activated charcoal
Whole bowel irrigation = PEG solution
What are contraindications of activated charcoal?
Dec. level of consciousness
Inc. risk of GI bleeding/ perforation
Ingestion of medications with low affinity for charcoal binding = Li, Fe, DDT, MeOH, EtOH
What are indications of activated charcoal?
Use within 1 hour of ingestion of potentially toxic amount of medication
What are contraindications for gastric lavage?
Dec. level of consciousness
Inc. risk of GI bleeding/perforation
What are indications for gastric lavage?
No definite indications for use
Use within 1 hour of ingestion
What are indications for whole bowel irrigation?
Ingestion of potentially toxic amounts of sustained-release, EC drugs, or medications poorly absorbed by activated charcoal
Ingestion of large quantities of illicit drugs for smuggling
