SALICYLATE & PARACETAMOL POISONING.

MR. OLORO JOSEPH DCM, BSc. PHARM, MSc. Pharm*

Salicylate

 These are most commonly ingested as aspirin, it is rapidly metabolized to the active drug, salicylic acid. Even at therapeutic doses, salicylates cause direct uncoupling of oxidative phosphorylation and direct stimulation of the CNS, resulting in hyperventilation and respiratory alkalosis. Also because they disrupt the krebs cycle, the drug causes metabolic acidosis.

Clinical Presentation
Hyperventilation and respiratory alkalosis due to medullary stimulation. Vomiting and hyperthemia, will lead to fluid loss and dehydration. Chronic intoxication produce, ringing in the ears, nausea and dehydration.

Treatment
Include: General supportive care, Gut decontamination with activated charcoal, since the drug has low volume of distribution. Hemodialysis if Salicylate level> 100mg/dl to remove the drug from the system and restore acid-base balances. Serum is the preferred sample, although the compound can be detected in urine.

Acetaminophen
Acetaminophen is used therapeutically for its analgesic and antipyretic activity. When taken in therapeutic doses, most of the acetaminophen is metabolized to nontoxic glucuronide and sulfate metabolites. Some amount is metabolized by several Cyp450 isoenzymes and some of these P450s produce a toxic metabolite, N-acetylp-benzoquinoneimine(NAPQI).

 Some NAPQI is produced under therapeutic conditions but is rapidly removed by glutathione before significant damage is done. Excess NAPQI is produced in overdose because there is not enough glutathione to remove the metabolites.

 Acute ingestion of more than 150-200mg/kg for children and 7g for adult may be toxic. Hepatoxicity increases with the use of any drug that induces P450 production e.g. Isoniazid, ethanol, phenytoin,barbiturates and carbamazepine.

 No or mild nonspecific symptoms within 6 hours of ingestion Symptoms Nausea, vomiting, and abdominal discomfort within 1 to 12 hours after ingestion Right upper abdominal quadrant tenderness typically within 1 to 2 days

 Signs Typically no signs present within first day Jaundice, scleral icterus, bleeding within 3 to 10 days Oliguria occasionally within 2 to 7 days With severe poisoning, hepatic encephalopathy (delirium, depressed reflexes, coma) within 5 to 10 days

 Laboratory Tests Toxic serum acetaminophen concentration no earlier than 4 hours after ingestion by comparison with nomogram Elevated aspartate aminotransferase (AST), alanine aminotransferase(ALT), serum bilirubin, and hypoglycemia within 1 to 3 days Elevated serum creatinine and blood urea nitrogen (BUN) within 2 to 7 days

Treatment
General measures as required at the time. Activated charcoal should be given within the first 2hrs of ingestion. Administer acetylcysteine which acts as a glutathione substitute, binding the toxic metabolites . Best when given 8-10hrs of an exposure but may be used up to 36 hrs later.

References.
Betrum G Katzung; Basic & clinical pharmacology 11th editon. Laurence & Bennet; Clinical Pharmacology. 7th edition. Casarett and Doull's Toxicology. The Basic Science of Poisons7th edition Josep T Dipiro et al. Pharmacotherapy a pathophysiologica approach, 7th edition