Aspirin and Salicylates
Dr. Slitt
Salicylates
Aspirin and Salicylates
• One of the most widely used OTC
medications
• Analgesic and antipyretic properties have
been used for >100 years
• Used for management of CVD, dermatologic
diseases, long-term chronic inflammatory
diseases
• Acute salicylate poisoning (salicylism) is one
of the most common causes of poisoning
death in the US
• Toxic effects can be mild to moderate, but
toxicity can produce multiple system organ
failure that requires management in ICU.
• Mortality from salicylism usually occurs in
patients who are are not treated properly or
diagnosis is missed
Types of Salicylates
• Aspirin (oral and topical; alone in combination
with many other types of drugs [narcotics,
decongestants, caffeine])
• Liniments and vaporizers can high amounts of
methyl salicylates
• Oil of Wintergreen – liquid formulation that
contains 100% methyl salicylate. Quickly
absorbed in GI tract. Can cause rapid onset of
clinical salicylism.
Salicylates
Therapeutic and Toxic Doses
• Adult therapeutic dose: 650 mg every 4 hours or
1 gram every 6 hours, a total of 4 gram/day in
divided doses
• Pediatric therapeutic dose: 10 to 15 mg/kg every
4 hours not to exceed 80 mg/kg/day
• Toxic Dose: >150 mg/kg. Chronic ingestion of
100 mg/kg/day. 1 teaspoon of Oil of
Wintergreen contains 5 grams of salicylate and in
a potentially lethal dose in a child weighing less
than 10 kg (think toddler or younger).
Absorption and Distibution
• Dependent upon amount and formulation of drug
(ex. Enteric coated (hrs) vs. methyl salicylate
(min))
• Topicals can be absorbed effectively enough to be
toxic
• Overdose can be absorbed more slowly than a
therapeutic dose because it can slow gastric
emptying
• Formation of bezoars
• Once absorbed, hydrolyzed to salicylic acid (toxic
metabolite)
Salicylates – Metabolism & Elimination
• Hepatic and renal metabolism and elimination
predominate
• Therapeutic levels – main pathways are conjugation
and hydroxylation; kidneys excrete the metabolites via
glomular filtration and tubular excretion
• Toxic levels – hepatic metabolism becomes quickly
saturated, leaving renal excretion as the major route
of elimination. Salicylate is excreted as salicyluric acid
and also as gentistic acid and salicylic acid phenolic
glucuronide.
• Note – Renal dysfunction will compromise ability to
eliminate salicylate burden
Salicylates - Metabolism
Clinical Presentation – Salicylates
Overdosage
• Nausea, vomiting, abdominal discomfort,
tinnitus, diaphoresis, and hyperventilation
reported with serum levels > 30 mg/dL.
• Ototoxicity – reversible, serum concentration
20- 40 mg/dL, concentration dependent.
• Acid – base disturbances: respiratory alkalosis
and metabolic acidosis.
Salicylates – sequence of events
http://ucsdlabmed.wikidot.com/chapter-17-clinical-toxicology#toc15
Pathophysiology – Salicylates
• Complex and multifactorial
• CNS – Direct stimulatory effect of CNS medullary
respiratory center
• Muscles: Inhibits oxidative phosphorylation,
increases CO2
• Acid – Base disturbances
• Glucose
• Pulmonary Injury
• Renal
• Coagulation System
More Pathophys
Clinical Presentations
Chronic salicylism
• Concern for geriatric patients
• Need to get a salicylate level
• Symptoms
– Hyperventilation, tremor, neurological
disturbances
• Salicylate jag: restlessness and mental
aberrations; similar to alcohol intoxication
• More likely to have other complications:
– Pulmonary edema, seizures, renal failure
Treatment
• ABCs
• Supportive Care to correct
– dehydration,
– electrolyte, and acid-base derangement
– Enhance salicylate elimination/decrease body
burden
Decontamination
• Skin – wash off with soap and water
• GI – Activated charcoal (AC) is appropriate
(10:1) for a large dose within 1-2 hours. Initial
dose of 1 to 2 g/kg recommended in acute
overdose.
• Repeated doses (0.25 to 0.5 g/kg) every 4-5
hours can decrease absorption.
Antidotes
• Sodium bicarbonate!!!!!!!! Know this!!!!!
• Mechanism: Reduces the entry into tissues
and enhances renal elimination.
• Urine alkalinization (target pH of 8.0 or
higher) should be empirically initiated in
patients with signs and symptoms of salicylate
toxicity.
Urine alkalinization by sodium bicarbonate to
enhance excretion
Urine alkalinization by sodium bicarbonate to
enhance excretion
References
• Dart – Medical Toxicology, 3rd Edition
