Poisoning

PWM 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.
 Organophosphates
• Include :
– diazinon,
– acephate,
– malathion,
– parathion, and
– chlorpyrifos
 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.
THANK YOU