circumstances

toxicokinetics

pathophysio

ANTIPYRETICS & ANALGESICS SALICYLATE (ASPIRIN) - antipyretic,analgesic (central) + anti-inflammatory (peripheral) - inhibition of PG synthesis 1. Accidental - coloured flavoured tablets children - mixed dose preparation = common in many over the counter & topical preparation 2. Suicidal = adults, adolescent - cheap, painless, available 3. Homicidal (uncommon dt bitter taste & big dose needed) Absorption : - rapidly absorbed but maybe be delayed dt i) pylorospasm retards absorption ii) formation of concretion with large dose Metabolism : in the liver into salicyl uric acid + other metabolites Excretion : by the kidney Toxic dose: 200-300mg/kg body weight 1. METABOLIC ACIDOSIS i) serum salicylate stimulate resp centre hyperventilation resp alkalosis (transient) kidney excrete bicarbonate, Na, K, water & Ca = compensate resp alkalosis metabolic acidosis *systemic acidosis helps salicylate to cross BBB ii) interference of Krebs cycle accumulation or organic metabolites metabolic acidosis acidotic breathing iii) vomiting,, fever, sweating dehydration ketosis metabolic acidosis 2. HYPOGLYCEMIA - salicylate enhance G6P activity stimulate peripheral utilization of glucose hypoglycemia 3. Severe dehydration oliguria + tubular damage +proteinuria 4. therapeutic Interference of platelet aggregation prolonged PT (petechial hemorrhage) dose toxic dose Interference with Vit K utilization hypoprothrombinemia empty direct mucosal injury, bleeding & pylorospasm stomach 5. may induce pulm edema dt hypoxia guideline to toxicity use PLASMA SALICYLATE LEVEL!!! (per 100ml serum)
mild cases 45-65mg% moderate cases 65-90mg% severe cases 90-120mg% fatal case >120mg%

ACETAMINOPHEN (PCM) - analgesic (substitute aspirin in children) - interfere PG synthesis (central) antipyretic - accidental poisoning - suicidal also occurs

Absorption : - GIT within 1-4hrs Metabolism : - in liver, by cytochrome oxidase enzyme into potentially toxic intermediate metabolite (N-acetyl paraquinon eimine ( NAPQI) - NAPQI is normally inactivated by conjugation with glutathione - Toxic dose : 10 gm (140mg/kg) *children more resistant to toxicity than adults overdosage = NAPQI - glutathione is depleted toxic unconjugated metabolite binds to hepatic cells causing centrilobular hepatic necrosis (HEPATOTOXIC!)

C/P

*hepatic necrosis extends by time! Stage 1 Stage 2 1st 24 hrs 2-3 days

Stage 3 3-5 days

Stage 4 1-2

- burning in mouth, throat, abdomen - vomiting - tinnitus - tachypnea - dizziness

- metabolic acidosis - severe hyperapnea (salicylate dyspnea) + air hunger - hypoglycaemia - psychosis (delirium, hallucinations) - hypoprothrombinemia (ecchymosis of eyelid + subconj. hmrhage)

- coma - convulsion - pulmonary edema - resp failure - cyanosis - oliguria, RF - coagulopathy

(non-specific) - anorexia - N, V - diaphoresis

(hepatic affection) - right upper abd pain - hepatic tenderness - elevation of liver enzyme, bilirubin - prolongatn of PT

Dx

Inv

Rx

Cause of death 1. dehydration & shock 2. acid-base disturbance 3. pulmonary edema 4. renal failure 1. Evidence of attempting suicide 2. Hx of salicylate therapy 3. Clinically, pt with npn focal neurological manifestation +hyperventilation + sweating + acid base disorders suspect salicylate poisoning Toxicological Non Toxicological 1. Colour test (screening) 1. ABG, blood pH, acid base status - ferric chloride test violet 2. Renal Fx test 2. Plasma salicylate level (confirmatory) 3. Prothrombin level 4. Electrolyte elvel 5. CXR exclude pulm edema 6. Blood glucose 1. Care of resp & circulation (ABC) 2. Decontamination - emesis + gastric lavage up to 24hrs after ingestion - gut dialysis (delayed absorption) + cathartics 3. Elimination : alkalinization of urine (alkalinization keep salicylate in ionized non reabsorbable state) 4. Correct dehydration + hypoglycaemia IV saline & glucose electrolyte imbalance metabolic acidosis 1-2 mEq/kg sodium bicarbonate infusion hypoprothrombinemia Vit K 5. Hemodialysis, in case of - severe metabolic acidosis - high serum salicylate level (>100mg%) - altered kidney fx

( peak weeks hepatotoxicity) - hepatic death necrosis - coagulation defects - jaundice - RF - encephalopathy

Cause of death : hepatic failure

Toxicological : serum acetaminophen level (peak in 4-5hrs after ingestion) Non toxic : - Liver fx test - Renal fx test - PT (liver fx) - Blood glucose level (liver fx) General 1. ABC 2. Decontamination = emesis/lavage charcoal 3. NO elimination NAPQI is intracellular!!! Supportive liver support! - 5% dextrose IV in 1st 10 hrs - blood or fresh plasma transfusion - clotting factor, Vit K - liver transplant Specific antidote : N-acetyl cysteine = mucomyst - must be given within 8-10 hrs of ingestion - NAC taken up by hepatocyte as glutathione substitute detoxify hepatotoxic metabolites (NAPQI)