Acetaminophen Intoxication
• Acetaminophen has been the most widely used analgesic and antipyretic in the world since salicylates were known to be associated with Reye's syndrome.
• For this reason, poisoning with these drugs is frequently encountered in young children as a result of accident, and in older children for suicide purposes.
• Acetaminophen intoxication is the most important cause of acute liver failure in adolescents and adults.
pathophysiology
• Acetaminophen toxicity is caused by the reactive intermediate metabolite N-acetyl-p-benzoquinoneimine (NAPQI).
• Only 4% of NAPQI is formed at therapeutic doses and is rapidly conjugated with glutathione to form harmless mercaptopuric acid conjugates. When hepatic glutathione stores are <70%, NAPQI metabolites may combine with hepatic macromolecules and cause hepatocellular damage. The acute toxic dose of acetaminophen in children under 12 years of age is considered to be 200 mg/kg.
• Severe toxicity is rare after a single dose (even high dose) in children younger than six years of age.
• All children with a history of significant drug intake should have their plasma acetaminophen level measured, and if the normogram is in the toxic range, the child should be treated with N-acetylcysteine (NAC).
Clinical and laboratory findings
• If patients are not treated in acute high dose intake, 4 stages of clinical signs can be observed.
• Diagnosis may be difficult in the absence of a significant history or high suspicion because the early findings are nonspecific.
• In case of suspected toxic ingestion, plasma acetaminophen level should be checked 4 hours or more after ingestion.
Treatment
• In case of need for antidote treatment after high dose acute oral ingestion, treatment should be started as soon as possible, preferably 1-2 hours after ingestion.
• The antidote for acetaminophen intoxication is N-acetylcysteine.
Salicylates
• Due to the increase in the use of alternative antipyretics, the incidence of salicylate poisoning has decreased.
Pathophysiology:
• Salicylates affect many organ systems directly or indirectly by disrupting oxidativephosphosylation, inhibiting Krebs cycle enzymes and inhibiting amino acid synthesis.
• As a result, various metabolic disorders occur. The acute toxic dose of salicylates is generally considered to be >150 mg/kg.
Clinical and Laboratory Findings
• After acute salicylate poisoning, nausea, vomiting, diaphoresis and tinnitus occur due to gastric irritation.
• Salicylates cause hyperventilation and hyperpnea by stimulating the respiratory center directly.
• Increased respiratory rate results in respiratory alkalosis.
• Both potassium and sodium are excreted in the urine; however, serum potassium concentration after early exposure may be within normal limits. When enough potassium is lost from the kidneys, potassium is exchanged for hydrogen ions and the urine becomes relatively acidic. With the persistence of respiratory alkalosis, "paradoxical aciduria" occurs. As a result, dehydration and progressive metabolic acidosis occur due to the accumulation of lactic acid and other metabolic acids.
• Agitation, restlessness and confusion are common in children. Coma develops due to cerebral edema. In severe cases, pulmonary edema and hemorrhage occur. Hyperglycemia or hypoglycemia may occur, especially in young infants. Pulmonary edema and respiratory failure, cerebral edema, bleeding, severe electrolyte imbalance and death may occur due to cardiovascular collapse. (It is stated in pediatric sources that it causes hyperglycemia in the early period and hypoglycemia in the late period. It is stated in the pharmacology sources that it causes hyperglycemia (hypoglycemia in children).
Treatment
• If the patient is present immediately after acute ingestion, gastric decontamination should be done first, preferably with activated charcoal. Salicylate tablets sometimes form masses in the form of bezoars.
• Initial treatment should focus on rehydration and correction of electrolyte disturbances. If symptoms persist for a long time after acute ingestion or in some cases with chronic salicylate poisoning, large amounts of potassium and bicarbonate may be required; because the stores of these electrolytes in the body may be depleted.
• By increasing the urine pH, a larger amount of salicylate is converted into ionized form and excreted in the urine. Each unit increase in urine pH increases urinary salicylate clearance 4-fold. Urine pH should be increased to at least 7.5-8 by giving bicarbonate. Blood pH should be kept in the range of 7.45 - 7.55.
• In severe cases of salicylate intoxication, dialysis may be required both to remove salicylate and to correct electrolyte disturbances.
Tricyclic Antidepressants
pathophysiology
• These agents block the neuronal uptake (reuptake) of norepinephrine, serotonin, and dopamine in both the central and peripheral nervous systems.
• They also cause varying degrees of sedation and anticholinergic effects. Inhibition of fast sodium channels in the myocardium leads to the development of cardiac dysrhythmias and myocardial depression.
Clinical and Laboratory Findings
• The primary organ systems affected are the CNS and the cardiovascular system. CNS effects are more common in children than cardiovascular effects. Dizziness, lethargy, and coma have been reported in up to one-third of pediatric cases.
• Tachycardia is the most common cardiovascular effect. Hypotension is rare, a sign of poor prognosis, and the most common cause of death in these patients. Other cardiac findings; slowing myocardial conduction, multifocal premature ventricular contractions and ventricular tachycardia, flutter and fibrillation. In addition to widening of the QRS complex, QT prolongation, ST segment depression, right bundle branch block, and complete heart block can be seen with T wave flattening or reversal.
• Hypoventilation may be seen with respiratory arrest without symptoms. Other reported effects are hyperthermia, choreiform movements, agitation, and tics. Anticholinergic manifestations, including mydriasis, disorientation, hallucinations, urinary retention, and decreased bowel sounds, may occur.
• The patient should be closely monitored with electrocardiography (ECG) for QRS widening and QT and QTc prolongation. ECG is important as a potential toxicity indicator. ECG QRS > 100 ms and avR p wave > 3 mm are signs of toxicity.
Treatment
• To prevent and treat dysrhythmias, sodium bicarbonate should be given to keep the serum pH at 7.45-7.55.
• Sodium bicarbonate indications: QRS duration > 100 ms, ventricular dysrhythmia and hypotension.
IRON
• Iron is one of the most common causes of childhood poisoning deaths.
• The severity of exposure depends on the amount of elemental iron taken.
Clinical and Laboratory Findings
• Due to the corrosive effect, nausea, vomiting, diarrhea and abdominal pain are the main symptoms of iron poisoning and usually occur 30 minutes - 1 hour after ingestion.
• In severe poisonings, hematemesis and bloody diarrhea may develop.
• Gastrointestinal symptoms may subside after 6-12 hours; however, careful observation is required as systemic toxicity may occur (ARDS, multi-organ failure). Gastric scarring and pyloric stenosis may develop 2-4 weeks later.
• Serum iron level should be measured 4 hours after exposure.
Treatment
• Activated charcoal does not adsorb iron and should not be used.
• Deferoxamine is a specific iron chelator and an antidote for moderate to severe iron intoxication.
Cholinesterase-Inhibiting insecticides
• Commonly used insecticides are organophosphates and carbamates.
• Both are inhibitors of cholinesterase enzymes.
pathophysiology
• Both organophosphates and carbamates prevent the breakdown of acetylcholine by binding to cholinesterase enzymes and eventually cause acetylcholine to accumulate in nerve endings.
• If left untreated, organophosphates form a permanent bond with these enzymes and inactivate them.
• This situation, called aging, occurs 2-3 days after exposure. It takes weeks to months for the inactivated enzymes to regenerate. In contrast, carbamates form a temporary bond with enzymes and do not age.
Clinical and Laboratory Findings
• Clinical manifestations of organophosphate and carbamate toxicity are associated with accumulation of acetylcholine at peripheral nicotinic and muscarinic synapses and in the CNS.
• Mnemonic DUMBBELS, which is frequently used for muscarinic symptoms, diarrhea/defecation, urination, miosis, bronchore/bronchospasm, bradiacridia, emesis, lacrimation and salivation
• Nicotinic signs and symptoms are muscle weakness, fasciculations, tremors, hypoventilation, hypertension, tachycardia and dysrhythmias. CNS effects include malaise, confusion, delirium, seizures, and coma.
Treatment
• Activated charcoal can be used for gastric decontamination.
• Two antidotes are useful in poisoning with cholinesterase inhibitors: atropine and pralidoxime. Pralidoxime is not necessary in carbamate poisoning.
