Salicylates Toxicity Lecture 16 PDF

Salicylates Toxicity Lecture 16 Salicylate is available for ingestion as tablets, capsules, and liquids. Salicylate is also available for topical application, in creams or lotions. Salicylate ingestion continues to be a common cause of poisoning in children and adolescents. The prevalence of a...

Salicylates Toxicity Lecture 16 Salicylate is available for ingestion as tablets, capsules, and liquids. Salicylate is also available for topical application, in creams or lotions. Salicylate ingestion continues to be a common cause of poisoning in children and adolescents. The prevalence of aspirin-containing analgesic products makes these agents, found in virtually every household, common sources of The incidence of salicylate poisoning in unintentional and suicidal ingestion. children has declined because of reliance on alternative analgesics and the use of child-resistant containers. Repackaging has decreased children's accessibility to lethal amounts, and salicylate's association with Reye syndrome has 1 24 ،‫ تشرين الثاني‬24 significantly decreased its use.  Background -Hippocrates – 5th century B.C. Powder from the willow bark -Introduced 100 years ago as Antipyretic, analgesic, anti-inflammatory -Decline in use, but…may be used as Prophylactic for migraine, colon cancer and as Antiplatelet agent -OTC medications: Combined with antihistamines, caffeine. 2 24 ،‫ تشرين الثاني‬24  Source of poisoning -Aspirin overdose -Excessive topical applications -Ingestion of topical products containing salicylates (eg, Ben-Gay, salicylic acid [keratolytic], oil of wintergreen or methyl salicylate), can cause severe salicylate toxicity. -According to published sources, one teaspoon of 98% methyl salicylate contains as much as 7000 mg of salicylate, the equivalent of nearly 90 baby aspirins and more than 4 times the potentially toxic dose for a child who weighs 10 kg. -Salicylate toxicity has been reported with the topical use of salicylate- containing teething gels in infants. 3 24 ،‫ تشرين الثاني‬24 The prevalence of alternative medicines and the popularity of herbs and traditional medicine formulae are increasing in North America. Many of these medicines may contain salicylate. Therefore, consider salicylate poisoning when topical herbal medicinal oil is involved. 4 24 ،‫ تشرين الثاني‬24  Salicylate Overdose 5 24 ،‫ تشرين الثاني‬24  Mechanism of Toxicity 1- Metabolic Acidosis -Inhibition of mitochondrial respiration (prevents the formation of ATP) which leads to increase pyruvate and lactic acid= Metabolic acidosis. -Inhibits the Krebs cycle enzymes, encouraging lipid metabolism, accumulation of organic acids that leads to metabolic acidosis besides to ketogenisis. -Inhibition of amino acid metabolism leads to amino aciduria. 6 24 ،‫ تشرين الثاني‬24  Mechanism of Toxicity 2- Respiratory alkalosis -Salicylate increases the sensitivity of the respiratory center to pH and carbon dioxide partial pressure (Pco2). Majority of the effect comes from the CNS respiratory centre. -Increase in O2 consumption and CO2 production, increase heat and respiration= Respiratory alkalosis. -Hyperventilation develops early due to direct stimulation in the medulla center= Increases respiratory rate =Leads to coma and respiratory failure. 7 24 ،‫ تشرين الثاني‬24  Mechanism of Toxicity 3- Hypoglycemia -Salicylate causes secretion of insulin that result in decreased glucose levels. -local irritation of the GIT produces emesis and upper GI ulceration and bleeding. -N, V, Abdominal pain. -Dose-dependant hepatotoxicity= rare to hepatitis. 8 24 ،‫ تشرين الثاني‬24  Mechanism of Toxicity 4-Water and Electrolyte Losses -Increased the metabolic rate leads to pyrexia, Vomiting and dehydration due to fluid loss. -Compensation to respiratory alkalosis leads to Increased renal excretion of bicarbonate, sodium and K+ follow acidosis= hypokalemia. -Loss of bicarbonate decreases buffering capacity and intensifies the metabolic acidosis. 9 24 ،‫ تشرين الثاني‬24  Mechanism of Toxicity 5- Coagulation Abnormalities -Decrease in thromboxane A2 synthesis that causes in-ablility to activate platelets= Prevent platelet aggregation. -In severe cases, the liver may not be able to produce factors 2, 7, 9, and 10 (vitamin-K dependant synthesis of these factors) leads to prolonged prothrombin time. 6- Ototoxicity Vasoconstriction of auditory micro-vasculature=Tinnitus or Deafness. In most cases, reversible. 10 24 ،‫ تشرين الثاني‬24  Clinical Features A toxic dose of aspirin is 150 to 300 mg/kg. 500 mg/kg is potentially lethal. Initial manifestations (signs and symptoms) of acute salicylate: Tinnitus Impaired hearing Hyperventilation Vomiting Dehydration Hyperthermia 11 24 ،‫ تشرين الثاني‬24 Lab Diagnostic Strategies A serum salicylate concentration should be measured 6 hours or more after ingestion. A second sample should be obtained 2 hours later. If the second concentration is greater than the first, serial concentrations should be obtained to monitor continued absorption. Acid-base status can change quickly, and frequent monitoring of arterial pH is necessary to guide treatment. 12 24 ،‫ تشرين الثاني‬24  Management 1- Stabilization -Physical examination: -including vital signs (including oxygen saturation and a counted respiratory rate and reliable temperature). -Chest auscultation may provide evidence of pulmonary edema. 2- Decontamination -Multiple-dose activated charcoal (MDAC) -Gastric lavage. - WBI 13 24 ،‫ تشرين الثاني‬24 3- Enhance Elimination -Hemodialysis In acute Aspirin toxicity is indicated if patient develops: Pulmonary Odema, Vomiting & diarrhea and Hyperthermia. 4- Antidote -Urine alkalinization= Alkalinizing the urine to pH=7.5 to 8 by a constant infusion of sodium bicarbonate (NaHCO3 bolus IV). -Salicylate is renally excreted, alkaline urine traps the salicylate ion and increases excretion. 14 24 ،‫ تشرين الثاني‬24 5- Supportive care -Dehydration should be treated with intravenous fluid. -Start potassium supplementation early (in the absence of renal insufficiency) to correct hypokalemia -Hydration and electrolyte replacement= should be given cautiously because excessive fluid administration can worsen cerebral and pulmonary edema. -Intravenous fluid should contain dextrose, and the serum glucose level should be frequently monitored to prevent hypoglycemia 15 24 ،‫ تشرين الثاني‬24