1. Poisoning PWM OLLY INDRAJANI 2014

2. ACETAMINOPHEN

3. Introduction Recommended dose, (every 4-6 hours) : – Adults = 650 – 1000 mg (max. 4 gr) – Children = 10 – 15 mg / kgBW (max. 75 mg/kgBW) Absorbed rapidly. Peak plasma concentration = ± 1 hour; complete absorption = ± 4 hours. Absorbed  inhibits PGE2 synthesis by -direct COX-2 inhibition or - inhibition of membrane-associated PG synthase  antipyretic, analgesia.

4. Pathophysiology A. After ingestion of therapeutic amounts, predominant metabolism is via glucuronidation and sulfation. The small amount of N-acetyl-p-benzoquinoneimine (NAPQI) generated is metabolized by adequate glutathione stores to a nontoxic compound.

5. Pathophysiology B. After ingestion of large amounts, glucuronidation and sulfation are saturated, and an increased amount of NAPQI is generated. Metabolism of NAPQI to a nontoxic compound soon depletes glutathione stores, leaving excess NAPQI to bind to intracellular proteins, causing cell death. APAP = N-acetyl-p-aminophenol (acetaminophen).

7. Clinical Features Source : Rosen’s Emergency Medicine – Concepts & Clinical Practice,7 th ed., 2010

8. Diagnosis A toxic exposure to acetaminophen is suggested when an adult ingests : (1) >10 grams or 200 mg/kg as a single ingestion, (2) >10 grams or 200 mg/kg over a 24-hour period, or (3) >6 grams or 150 mg/kg per 24-hour period for at least 2 consecutive days.

9. Management Acetylcysteine Dosing Regimens

10. Management Limiting GI absorption : consider early gastric emptying in cases of recent, life-threatening congestions. N-Acetylcysteine (NAC) : delay of administration of NAC > 6-8 hrs after ingestion  ↑ risk of hepatotoxicity.

11. Management Treatment guidelines for acetaminophen (APAP)ingestion.

12. ASPIRIN & SALICYLATES

13. Pharmacokinetics Absorbed from the GIT within 30’ (2/3 in 1 hrs); peak levels = 2-4 hrs. Intestinal wall, liver, RBCs : aspirin hydrolyzed  free salicylic acid  reversibly binds to albumin. Liver : conjugated w/ glucuronic acid & glycine. Renal excretion : free salicylate & its conjugates.

14. Patophysiology Acid-base disturbances & metabolic effects. Stimulates the medullary respiratory center & ↑ the sensitivity of the respiratory center to pH & pCO2  hyperventilation  metabolic acidosis. Toxicity : interference w/ aerobic metabolism  uncoupling of oxidative phosphorylation. Inhibition of Krebs cycle  ↑ production of pyruvic acid & conversion to lactic acid. ↑ lipid metabolism  ↑ production of ketone bodies.

15. Patophysiology Tissue glycolysis  hypoglycemia. Hepatic gluconeogenesis & release of adrenaline  hyperglycemia. Inefficiency of anaerobic metabolism  less energy used to create ATP  energy is released as heat  hyperthermia. pH ↓  more salicylate particles become un- ionized  cross the cell membrane & BBB  ↑ movement of salicylate into the tissues & CNS.

16. Patophysiology Fluid & Electrolyte Abnormalities. ↓ renal blood flow / direct nephrotoxicity  acute non-olyguric renal failure. Induce secretion of inappropriate ADH  affect renal function. Potassium loss : (1) vomiting, secondary to stimulation of the medullary chemoreceptor trigger zone;

17. Patophysiology (2) increased renal excretion of sodium, bicarbonate, and potassium as a compensatory response to the respiratory alkalosis; (3) salicylate-induced increased permeability of the renal tubules with further loss of potassium; (4) intracellular accumulation of sodium and water; and (5) inhibition of the active transport system, secondary to uncoupling of oxidative phosphorylation.

18. Patophysiology ↑ pulmonary vascular permeability  Noncardiogenic Pulmonary Edema.

19. Clinical Features

20. Management Source : Rosen’s Emergency Medicine – Concepts & Clinical Practice,7 th ed., 2010

21. METHANOL

22. INTRODUCTION Colorless, volatile, slightly sweet-tasting alcohol. Methanol intoxication in the US (2006) : 73% unintentional, 8% moderate-major complications, 8 fatalities.

23. PATOPHYSIOLOGY

24. CLINICAL FEATURES Early symptoms : depressed mental status, confusion Non-specific : weakness, dizziness, headache, anorexia, nausea, vomiting, abdominal pain Severe : coma, seizure Visual disturbances : “snow field” vision Minimal lethal dose = 50 - 100 mL

25. TREATMENT Ethanol Fomepizole HD Folic acid

26. TREATMENT American Academy of Clinical Toxicology recommends ethanol / fomepizole  criteria: – Plasma methanol concentration > 20 mg/dL, – Recent hx of methanol ingestion with serum osmolal gap > 10 mOsm/L, or – Strong clinical suspicion of methanol poisoning with at least 2 of the following : Arterial pH < 7,3; serum, HCO3- < 20 mEq/L, osmolal gap > 20 mOsm/L.

27. ETHANOL

28. INTRODUCTION Rapidly absorbed Peak blood levels ± 30’ - 60’ after ingestion Eliminated via hepatic metabolism

29. PATHOPHYSIOLOGY

30. CLINICAL EFFECTS Behavioral CNS depression Respiratory depresssion, coma. Nausea, vomiting Peripheral vasodilatation

31. MANAGEMENT Activated charcoal IV glucose Thiamine

32. ORGANOPHOSPHATES POISONING

33. INTRODUCTION Insecticides Commonly used  parathion Accidental exposure at home, recently sprayed / fogged areas using pesticide applicators, agriculture, industry, homicides, suicides.

34. Include : – diazinon, – acephate, – malathion, – parathion, and – chlorpyrifos Organophosphates

35. PATHOPHYSIOLOGY Inhibits the enzyme cholinesterase  excess acetylcholine accumulation at the myoneural junctions & synapses. Excess acetylcholine initially excites  paralyzes neurotransmission at the motor endplate & stimulates nicotinic & muscarinic effects.

36. CLINICAL FEATURES

37. MANAGEMENT

38. COCAINE

39. INTRODUCTION Natural alkaloidal extract of Erythroxylum coca leaves (South America). 1 st used therapeutically in 1884 for ophthalmologIc procedures. The 2008 National Household Survey on Drug Abuse (US) : – 5.3 million Americans had used cocaine within the past year  during 2008 : ± 700,000 new cocaine users. – 1/3 of drug-related ED visits  related to cocaine use.

40. PHARMACOLOGY

41. PHARMACOKINETICS

42. CLINICAL FEATURES Sympathomimetics : Hypertension Hyperthermia Tachycardia Mydriasis Diaphoresis

43. MANAGEMENT

44. COCAINE WITHDRAWL Irritability Paranoid ideation Delayed depression Symptoms of withdrawal : – strongest  during the first 48 hours. – milder symptoms  can last up to 2 weeks.

45. THANK YOU