Salicylate Toxicity

Question 1

Is salicylic acid (ASA) a weak/strong acid/base?

Answer 1

Weak acid.

Question 2

Pathways by which salicylic acid is eliminated/metabolized:

Answer 2

1. Conjugated w/ glycine = salicyluric acid.
2. Conjugated w/ glucuronide = phenolic glucuronide.
3. Conjugated w/ glucuronide = acylgluronide.
4. Oxidized = gentisic acid.
5. Unchanged in urine = pH dependant.

Question 3

Toxic dose of ASA in adults & children; chronic toxicity dose:

Answer 3

Adults: 10-30 grams
Children: 3 grams
Chronic: > 100 mg/kg/day for 2 or more days

Question 4

Therapeutic and Toxic range for serum salicylate concentrations:

Answer 4

Therapeutic: 0.7 - 2.2 mmol/L
Toxic: > 2.9 - 3.6 mmol/L (display signs of toxicity)

Question 5

Acute signs of salicylate toxicity include:

Answer 5

Hyperpnea, tachypnea, elevated temp, N/V, tinnitus, hypovolemia (sweating, dehydration, vomiting), CNS effects (agitiation, confusion, delirium, seizures), bleeding/bruising, hypoglycemia, noncardiogenic pulmonary edema, acid-base disturbances.

Question 6

Chronic signs of salicylate toxicity include:

Answer 6

Similar to acute, but slower onset & less severe.

Question 7

Explain the mechanism of salicylate toxicity.

Answer 7

1. Respiratory Alkalosis: direct stimulation of respiratory centres in brain produces hyperventilation, causing an early fall in CO2, which increases pH levels.
2. a. Salicylates are wear acids: impairs renal hemodynamics, leading to an accumulation of inorganic acids
   b. Salicylates interferes w/ Krebs cycles which limits ATP production
   c. Salicylates uncouple oxidative phosphorylation (accumulation of pyretic and lactic acids)
   d. Salicylate induced fatty acid metabolism generates ketone bodies.