PoisoningPWM OLLY INDRAJANI

2014

ACETAMINOPHEN

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.

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.

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).

Clinical Features

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

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.

Management • Acetylcysteine Dosing Regimens

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.

Management • Treatment guidelines for acetaminophen (APAP)ingestion .

ASPIRIN & SALICYLATES

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.

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.

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.

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;

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.

Patophysiology

• ↑ pulmonary vascular permeability Noncardiogenic Pulmonary Edema .

Clinical Features

Management

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

METHANOL

INTRODUCTION

• Colorless, volatile, slightly sweet-tasting alcohol.

• Methanol intoxication in the US (2006) : 73% unintentional, 8% moderate-major complications, 8 fatalities.

PATOPHYSIOLOGY

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

TREATMENT

• Ethanol

• Fomepizole

• HD

• Folic acid

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.

ETHANOL

INTRODUCTION

• Rapidly absorbed

• Peak blood levels ± 30’ - 60’ after ingestion

• Eliminated via hepatic metabolism

PATHOPHYSIOLOGY

CLINICAL EFFECTS

• Behavioral• CNS depression• Respiratory depresssion, coma.• Nausea, vomiting• Peripheral vasodilatation

MANAGEMENT

• Activated charcoal

• IV glucose

• Thiamine

ORGANOPHOSPHATES POISONING

INTRODUCTION

• Insecticides

• Commonly used parathion

• Accidental exposure at home, recently sprayed / fogged areas using pesticide applicators, agriculture, industry, homicides, suicides.

• Include :– diazinon, – acephate, – malathion, – parathion, and – chlorpyrifos

Organophosphates

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.

CLINICAL FEATURES

MANAGEMENT

COCAINE

INTRODUCTION

• Natural alkaloidal extract of Erythroxylum coca leaves (South America).

• 1st 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.

PHARMACOLOGY

PHARMACOKINETICS

CLINICAL FEATURES

Sympathomimetics :• Hypertension• Hyperthermia• Tachycardia• Mydriasis• Diaphoresis

MANAGEMENT

COCAINE WITHDRAWL

• Irritability• Paranoid ideation• Delayed depression

• Symptoms of withdrawal : – strongest during the first 48 hours.– milder symptoms can last up to 2 weeks.

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