5 - Salicylates Flashcards
Describe absorption of salicylates
Very well absorbed from the stomach (due to acidic properties) and small intestine
When do salicylates reach peak levels?
- 30 minutes (within 1 h)
- In overdose, peak levels = 4-6 h or longer
What factors of salicylates affect absorption?
- Formulations (effervescent b/c bubbles increase absorption in stomach, EC)
- Pylorospasm (if drug is trapped in stomach longer, absorption is decreased)
Describe normal distribution of salicylates. What happens in overdose?
- Vd = 0.1 – 0.3 L/kg (increases in OD)
- Protein binding = 90% (decreases in OD)
Elimination of salicylates
- First-order kinetics
- Liver metabolism
- Renal elimination = 2.5% (dependent upon urine pH)
Normal half-life of salicylates and overdose t1/2
- t1/2 = 2 – 4.5 h (at therapeutic doses)
- t1/2 = 18 – 36 h in OD
Therapeutic salicylate doses for adults
325-650 mg 4-6 times/day
Therapeutic salicylate doses for children
10-15 mg/kg 4-6 times/day
Toxic doses for acute ingestion of salicylates
- 150-200 mg/kg = mild intoxication
- 300-500 mg/kg = severe intoxication
- > 500 mg/kg = potentially lethal
Dangerous serum levels of salicylates
- > 90-100 mg/dL (6.6-7.3 mmol/L) = severe toxicity in acute OD
- Chronic therapeutic values = 10-30 mg/dL
- > 60 mg/dL w/ acidosis and altered mental status is considered serious
What effect do salicylates have on respiratory centre?
- Stimulation, so cause:
- Hyperventilation
- Respiratory alkalosis
- Dehydration
What effect do salicylates have on the rest of the body besides respiratory centre?
- Cerebral and pulmonary edema
- Platelet function
- GI effects (hemorrhagic gastritis)
- Renal effects (tubular damage, proteinuria)
- Hepatic effects (salicylate-induced hepatitis)
- Ototoxicity (tinnitus, hearing loss)
What should be done in respiratory alkalosis associated w/ salicylate toxicity
Replacement of 2-3 mEq/L of plasma bicarbonate
Intracellular effects of salicylate toxicity
- Interference w/ Krebs cycle and uncoupling of oxidative phosphorylation (pyruvic and lactic acid accumulation, heat)
- Increased fatty acid metabolism (ketone accumulation)
- Metabolic acidosis
- Glucose metabolism (mobilization of glycogen stores, glycogen depletion, inhibition of gluconeogenesis) => hyper and then hypoglycemia
Symptoms of acute salicylate toxicity
- Vomiting
- Hyperpnea
- Tinnitus
- Lethargy
- Mixed respiratory alkalosis and metabolic acidosis
- Progresses to coma, seizures, hypoglycemia, hyperthermia, cerebral and pulmonary edema
What is considered chronic salicylate toxicity?
Ingestions of > 100 mg/kg/day for 2 days or more
Symptoms of chronic salicylate toxicity
- Hearing loss & tinnitus
- N/V (may be absent)
- Dyspnea, hyperventilation
- Hyperthermia
- Neurologic manifestations (confusion, agitation, seizures, coma)
- Cerebral and pulmonary edema (more common)
Management of salicylate toxicity
- Emergency management
- Lab tests (salicylates, ABG, electrolytes)
- Monitoring
Intervention options for salicylate toxicity
- Gastric emptying
- Activated charcoal, MDAC
- Sodium bicarbonate
- Urinary alkalinization
- Hemodialysis, hemoperfusion
- CVVHF (continuous venovenous hemofiltration)
Describe the process of activated charcoal for salicylate toxicity
- Very large doses (300-600 g) w/ large ingestions (30-60 g)
- 25-50 g of activated charcoal at 3 – 5 hour intervals
- Whole-bowel irrigation
Describe the process of sodium bicarbonate for salicylate toxicity
- Correction of metabolic acidemia = 0.5 – 2 mEq/kg bolus
- For salicylates OD, bring pH to 7.4 – 7.5
- Continuous titration over 4 – 8 hours to obtain urinary alkalinisation (pH 7.5 – 8)
- Monitoring
- Treat hypokalemia (30 – 40 mEq potassium/L)
How can elimination of salicylates be enhanced?
Predominantly in the plasma, so easily removed w/ hemodialysis
Indications for use of hemodialysis for salicylate toxicity
- Acute ingestion, serum levels > 100 mg/dL w/ severe acidosis or other manifestations of toxicity
- Chronic intoxication w/ serum levels > 60 mg/dL
- Renal failure
- Deterioration (CNS, acute lung injury, hepatic compromise w/ coagulopathy)
What effect does hemodialysis have on salicylate toxicity?
- Salicylate removal
- Correction of acid-base and fluid abnormalities
