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Introduction to Toxicology and Hepatotoxicity


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Therapeutic Index
Therapeutic Index = LD50 / ED50
Margin of Safety
Margin of Safety = LD1 / ED99
enzyme responsible for toxic metabolism in liver
Cytochrome 450 (CYP) 2E1
substances which induce metabolism by CYP 2E1 ( toxic metabolism in liver)
ethanol; isonizid (TB meds)

[[inhibited by cimetidine]]
Concurrent use of ethanol or isoniazid - can result in toxity at commonly used doses of (very common OTC med)?
antidote to aspirin overdose
N-acetyl-cysteine (favors glutathione synthesis; and detoxification of intermediates)
Anion gap acidosis likely causes
M ethanol P araldehyde

U remia I NH, diopathetic

D KA L actic acid

E thylene glycol

S alicylates
Contraindications to ipecac. (6)
(1) Unconsciousness

(2) CNS depression

(3) Seizure

(4) Hypotension

(5) Respiratory depression

(6) Ingestion of any drug that has the potential to cause CNS depression, respiratory depression, hypotension, seizures or mucosal injury.
indications for ipecac
none. ipecac is stupid
gastric lavage indications for toxicity
don't do it
single dose activated charcoal (SDAC) clinical usefulness for toxicity
don't work apparently
Alkaline Diuresis: indication (for tx of toxicity)
phenobarbital; salicylate overdose
· Factors favoring drug removal by dialysis
(1) High water solubility

(2) Low protein binding

(3) Low Vd
Indications for hemodialysis/hemoperfusion
(1) Severe lithium overdose or poisonings with various alcohols

(2) Progressive deterioration despite intensive supportive therapy.

(3) Severe intoxication with depression of midbrain function leading to hypoventilation, hypothermia, hypotension.

(4) Complications of coma such as pneumonia or septicemia, or existence of underlying conditions predisposing to such complications (e.g., obstructive airway disease).

(5) Impairment of normal drug excretory function in the presence of hepatic, cardiac, or renal insufficiency.

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