Paracetamol and sedative overdosage

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Paracetamol and sedative overdosage

  1. 1. PARACETAMOL & SEDATIVE OVERDOSAGE
  2. 2. OVERVIEW• Considered to be a safe and cheap analgesic/anti-pyretic• OTC• One of the most common overdosed drugs worldwide• Most common cause of acute hepatic failure in the UK & US
  3. 3. OVERVIEW• Leading indication for hepatic transplantation in patients with drug induced liver disease• Single dose of 10- 15 G can produce clinical evidence of liver injury• Fatal fulminant liver failure is usually associated with a dosage of > 25 G
  4. 4. OVERVIEW• Blood levels of > 30 micg/ml 4 hours after ingestion are predictive of severe hepatic disease• Levels < 15 micg/ ml are predictive of low risk• More risk of damage if liver is already damaged by infection (virus), alcohol or other illness
  5. 5. OVERVIEW• Available as suppositories- 120,125,325 & 650 mg• Chewtabs- 8 mg• Pedtabs - 16 mg• Regular tabs- 325 mg• Extra strong tabs- 500, 650, 1000 mg• Drops, suspension
  6. 6. OVERVIEW• Maximum permissible daily dose : 4 g• Now has been reduced to 3 g
  7. 7. CLINICAL FEATURES• Nausea, vomiting, diarrhoea, abdo minal pain, shock- first 24 to 48 hours• Once these symptoms abate, features of hepatic injury appears.• Maximum derangement & hepatic failure occurs around day 6• SGOT/PT maybe raised around 10000
  8. 8. CLINICAL FEATURES• Coma, convulsions, irritability, seizures• Renal failure• myocarditis
  9. 9. PROGNOSIS• Depends on• Quantity ingested• Timing of initiation of treatment• Pre-morbid health
  10. 10. TREATMENT• Supportive measures• Airway• Breathing circulation• Gastric lavage- oral administration of activated charcoal/ cholestyramine to prevent the absorbtion of the residual drug• Not useful if given > 3 min after ingestion
  11. 11. TREATMENT• Levels> 200 micg/ml after 4h• Or 100 micg/ml after 8 hours are indications• Administration of sulfhydril compounds( cystamine, cysteine or NAC) reduces the severity of hepatic necrosis.• They work by acting as a reservoir of – SH groups that bind to the toxic metabolytes or stimulate the synthesis/ repletion of hepatic glutathione
  12. 12. TREATMENT• Must be given within 8 hours and maybe effective upto as late as 24 to 36 hours• Dose of NAC- 140 mg/kg stat followed by 70 mg/kg Q4h for 15 to 20 doses• If evidence of hepatic failure occurs while on treatment with NAC, consider LT• Lactate levels > 3.5 mmol/L is a fair indicator of the need for LT
  13. 13. PREVENTION• Keep all medications out of reach of children• Know the correct dosage• Never mix medicines containing acetaminophen with other drugs• Remove all medications out of reach of adults if there is a past/ family history of suicide/attempt• Avoid PCM in those who consume > 3 units of alcohol/day
  14. 14. BARBITURATE OVERDOSAGE• Earliest class of hypnotic-sedatives to be developed• Marilyn Monroe & Judy Garland famous victims• Lethal dose varies according to individual tolerance (2-10 G is potentially fatal)• With other CNS depressants like alcohol,opiates or BZD, the severity of barbiturate overdosage is amplified.• Depresses CNS & respiration
  15. 15. BARBITURATE OVERDOSAGE• SIGNS & SYMPTOMS• Sluggishness, incoordination• Difficulty in thinking, slow speech• Faulty judgement, drowsiness• Shallow breathing, staggering• Apnea, hypoxia
  16. 16. BARBITURATE OVERDOSAGE• ARDS• Paranoia• Combativeness• Tachycardia, bradycardia, hypotension, Shock• Coma, death
  17. 17. BARBITURATE OVERDOSAGE• SIGNS• Hypothermia• Depressed pupillary reflex• Nystagmus• Squint• Supressed DTR
  18. 18. BARBITURATE OVERDOSAGETREATMENTSupportive care/ decontamination/Accelerate eliminationSecure airwayEndotracheal intubation- if depressed sensorium, respiratory failure, hypoxia, raised ICT O2 Venous access
  19. 19. BARBITURATE OVERDOSAGE• Naloxone 2 mg. IV to all with depressed sensorium• Measure rectal temperature- rewarming measures• Pressors- noradrenaline, dopamine, fluids• Decontamination- activated charcoal 1G/kg Q6H• Cathartics, gastric lavage
  20. 20. BARBITURATE OVERDOSAGEAlkalinise urineSodabicarb 1 meq/kg folowed by continuous infusonAdd 100- 150 meq of NaHco3 to 850 ml of D5 %Dialysis- hemofiltration preferred over HDIntravenous lipid emulsion (ILE) is emerging as an antidote
  21. 21. TRICYCLIC ANTIDEPRESSANTS• One of the most dangerous drugs• Anti-cholinergic and cardiac depressant properties(Quinidine like NA+ channel blockade)• Newer anti-depressants like sertraline, fluoxetine, fluvoxamine, citalopram, bupropion, trazodone, venlaflaxine etc. are structurally unrelated to TCAD and produce less cardiotoxicity
  22. 22. TRICYCLIC ANTIDEPRESSANTS• They can produce seizures & serotonin syndrome• S & S may occur abruptly in around 30-60 minutes• Anti-cholinergic effects- dilated pupils, tachycardia, dry mouth, flushed skin, fasciculations & reduced peristalsis
  23. 23. TRICYCLIC ANTIDEPRESSANTS• Cardiotoxicity- widens QRSc leading to ventricular arrhythmias, AV block, and hypotension• Prolonged QT – Venlaflaxine, Citalopram• Severe intoxication- coma, seizures especially Venlaflaxine & Bupropion• Hyperthermia- due to anticholinergic induced reduced sweating
  24. 24. TRICYCLIC ANTIDEPRESSANTS• Diagnosed by the combination of anticholinergic side effects & prolonged QRSc with seizures• Degree of widening of the QRSc corelates directly with the severity of intoxication rather than the drug levels• Serotonin syndrome- agitation, delirium, muscular hyperactivity, fever
  25. 25. TRICYCLIC ANTIDEPRESSANTS• TREATMENT• Observe all cases for atleast 6 hours• Admit all patients with anti-cholinergic effects or cardiotoxicity• Activated charcoal, gastric lavage• Cannot be removed by dialysis as they are highly tissue bound
  26. 26. TRICYCLIC ANTIDEPRESSANTS• SPECIFIC TREATMENT• NAHCO3 50 to 10 meq IV- alleviates the NA – channel depressing effect• Maintain pH between 7.45- 7.50• IV MG or overdrive pacing for long QT sy ndrome/Torsades de pointes• Serotonin syndrome- Benzodiazepines, cyproheptadine 4 mg P/O 3 to 4 doses
  27. 27. TRICYCLIC ANTIDEPRESSANTS• Severe hyperthermia• neuromuscular paralysis• External cooling• intubation

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