Toxicology Flashcards
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What effect does a toxic dose of drug have on absorption?
Absorption will be increased, and peak effect will be reached much later than with a therapeutic dose. Why? Injured GI tract absorption, slow tablet dissolution, altered GI emptying, etc.
What effect does a toxic dose of drug have on Vd?
Not much. However, the Vd can tell you if dialysis will be an effective tool for detox. With a high Vd, very little drug will remain in the plasma, so dialysis unlikely to benefit. and vice versa.
What effect does a toxic dose of drug have on clearance?
Clearance will be slowed due to saturation of enzyme pathways, possible damage to liver/kidneys.
What effect does a toxic dose of drug have on half-life?
Half life values are for published doses, so unlikely to be accurate for toxic dosage. Peak absorption may be reached much later than expected, clearance will be affected, etc.
Please name several pharmacokinetic detox methods and one pharmacodynamic method.
Pharmacokinetic methods:
slow/decrease absorption
increase/decrease enzyme activity to/from active product
Increase clearance/excretion
Pharmacodynamic method: antidote.
What are four broad interventions that will slow absorption?
Emetics, gastic lavage, chemical adsorption, osmotic cathartics.
What are some emetics? When are these contraindicated?
Syrup of ipecac.
Contraindications to use of emetic agent
Patient comatose / stuporous (lack of gag reflex risk of aspiration)
Ingestion of corrosive poisons (i.e., strong acids or alkalis)
Ingestion of CNS stimulant such as strychnine (risk of seizures)
Ingestion of petroleum distillate (risk of pneumonitis)
Pregnancy Category C: (weigh benefit vs risk, unknown if drug can cause harm)
How effective is gastric lavage/emesis at removing toxin? What are the steps?
Remove contents of stomach with nasogastric tube, rinse with saline. Removes ~30%. Best if used quickly, or with slow-dissolving agents.
What considerations are important when administering charcoal?
Should be administered without gastric emptying. Will bind Ipecac, which should be given first if used at all. Should be given with an osmotic agent like sorbitol to prevent “shitting bricks, literally.” Can even remove drugs given via IV because of reverse absorption and ion trapping. Should give in a 10:1 ratio charcoal:toxin.
What is the use for osmotic cathartics? Give specific examples.
eg Sorbitol. Create a positive osmotic gradient into the bowel to increase expulsion of GI contents. Indicated if time is >60 minutes, toxin is in coated tablets, or hydrocarbon.
Sorbitol, polyethylene glycol (colonoscopy GI emptying), magnesium sulfate or citrate, sodium sulfate.
Describe the etiology of methanol toxicity and how to treat.
Methanol is often present in poorly made moonshine. Causes blindness and death due to creation of formic acid. Ethanol dehydrogenase creates formaldehyde and formic acid. Onset is often delayed 8-36 hours due to enzyme lag. Severe metabolic acidosis within 4-12 hours.
Ideal treatment is inhibition of alcohol dehydrogenase with Fomepizole. If non available, give large quantities of EtOH to compete at active site of enzyme (BAC 0.1% ideal). Also give NaHCO3 for acidosis, gastric lavage, and/or hemodialysis.
Describe the etiology of ethylene glycol toxicity and how to treat.
Ethylene glycol (antifreeze) is metabolized to oxalic acid by alcohol dehydrogenase. Leads to acute renal failure due to formation of calcium oxalate crystal deposition in the kidneys. Onset is often delayed 8-36 hours due to enzyme lag. Severe metabolic acidosis within 4-12 hours.
Ideal treatment is inhibition of alcohol dehydrogenase with Fomepizole. If non available, give large quantities of EtOH to compete at active site of enzyme (BAC 0.1% ideal). Also give NaHCO3 for acidosis, gastric lavage, and/or hemodialysis.
Describe the 4 stages of acetaminophen toxicity.
Initial 24 hours: Symptoms do not reflect potential seriousness of intoxication (nausea, vomiting, diaphoresis, abdominal pain)
24-48 hours: Clinical indications of hepatic damage became apparent (elevated plasma aminotransferases, prothrombin time prolonged)
72-96 hours: Peak hepatotoxicity (potential for severity of hepatic necrosis can be predicted by relation between acetaminophen plasma levels and time post-ingestion along with calculated half-life)
7-8 days: Recovery if timely treatment - if specific treatment NOT received severe liver damage in 10% with 10-20% of those eventually dying of liver failure
What is diaphoresis?
Sweating
