5 - Salicylates

Question 1

Describe absorption of salicylates

Answer 1

Very well absorbed from the stomach (due to acidic properties) and small intestine

Question 2

When do salicylates reach peak levels?

Answer 2

• 30 minutes (within 1 h)

- In overdose, peak levels = 4-6 h or longer

Question 3

What factors of salicylates affect absorption?

Answer 3

• Formulations (effervescent b/c bubbles increase absorption in stomach, EC)
• Pylorospasm (if drug is trapped in stomach longer, absorption is decreased)

Question 4

Describe normal distribution of salicylates. What happens in overdose?

Answer 4

• Vd = 0.1 – 0.3 L/kg (increases in OD)

- Protein binding = 90% (decreases in OD)

Question 5

Elimination of salicylates

Answer 5

• First-order kinetics
• Liver metabolism
• Renal elimination = 2.5% (dependent upon urine pH)

Question 6

Normal half-life of salicylates and overdose t1/2

Answer 6

• t1/2 = 2 – 4.5 h (at therapeutic doses)

- t1/2 = 18 – 36 h in OD

Question 7

Therapeutic salicylate doses for adults

Answer 7

325-650 mg 4-6 times/day

Question 8

Therapeutic salicylate doses for children

Answer 8

10-15 mg/kg 4-6 times/day

Question 9

Toxic doses for acute ingestion of salicylates

Answer 9

• 150-200 mg/kg = mild intoxication
• 300-500 mg/kg = severe intoxication
• > 500 mg/kg = potentially lethal

Question 10

Dangerous serum levels of salicylates

Answer 10

• > 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

Question 11

What effect do salicylates have on respiratory centre?

Answer 11

• Stimulation, so cause:
• • Hyperventilation
• • Respiratory alkalosis
• • Dehydration

Question 12

What effect do salicylates have on the rest of the body besides respiratory centre?

Answer 12

• Cerebral and pulmonary edema
• Platelet function
• GI effects (hemorrhagic gastritis)
• Renal effects (tubular damage, proteinuria)
• Hepatic effects (salicylate-induced hepatitis)
• Ototoxicity (tinnitus, hearing loss)

Question 13

What should be done in respiratory alkalosis associated w/ salicylate toxicity

Answer 13

Replacement of 2-3 mEq/L of plasma bicarbonate

Question 14

Intracellular effects of salicylate toxicity

Answer 14

• 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

Question 15

Symptoms of acute salicylate toxicity

Answer 15

• Vomiting
• Hyperpnea
• Tinnitus
• Lethargy
• Mixed respiratory alkalosis and metabolic acidosis
• Progresses to coma, seizures, hypoglycemia, hyperthermia, cerebral and pulmonary edema

Question 16

What is considered chronic salicylate toxicity?

Answer 16

Ingestions of > 100 mg/kg/day for 2 days or more

Question 17

Symptoms of chronic salicylate toxicity

Answer 17

• Hearing loss & tinnitus
• N/V (may be absent)
• Dyspnea, hyperventilation
• Hyperthermia
• Neurologic manifestations (confusion, agitation, seizures, coma)
• Cerebral and pulmonary edema (more common)

Question 18

Management of salicylate toxicity

Answer 18

• Emergency management
• Lab tests (salicylates, ABG, electrolytes)
• Monitoring

Question 19

Intervention options for salicylate toxicity

Answer 19

• Gastric emptying
• Activated charcoal, MDAC
• Sodium bicarbonate
• Urinary alkalinization
• Hemodialysis, hemoperfusion
• CVVHF (continuous venovenous hemofiltration)

Question 20

Describe the process of activated charcoal for salicylate toxicity

Answer 20

• 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

Question 21

Describe the process of sodium bicarbonate for salicylate toxicity

Answer 21

• 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)

Question 22

How can elimination of salicylates be enhanced?

Answer 22

Predominantly in the plasma, so easily removed w/ hemodialysis

Question 23

Indications for use of hemodialysis for salicylate toxicity

Answer 23

• 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)

Question 24

What effect does hemodialysis have on salicylate toxicity?

Answer 24

• Salicylate removal

- Correction of acid-base and fluid abnormalities