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Year 4 - Toxicology > 5 - Salicylates > Flashcards

5 - Salicylates Flashcards

1
Q

Describe absorption of salicylates

A

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

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2
Q

When do salicylates reach peak levels?

A
  • 30 minutes (within 1 h)

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

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3
Q

What factors of salicylates affect absorption?

A
  • Formulations (effervescent b/c bubbles increase absorption in stomach, EC)
  • Pylorospasm (if drug is trapped in stomach longer, absorption is decreased)
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4
Q

Describe normal distribution of salicylates. What happens in overdose?

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

- Protein binding = 90% (decreases in OD)

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5
Q

Elimination of salicylates

A
  • First-order kinetics
  • Liver metabolism
  • Renal elimination = 2.5% (dependent upon urine pH)
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6
Q

Normal half-life of salicylates and overdose t1/2

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

- t1/2 = 18 – 36 h in OD

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7
Q

Therapeutic salicylate doses for adults

A

325-650 mg 4-6 times/day

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8
Q

Therapeutic salicylate doses for children

A

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

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9
Q

Toxic doses for acute ingestion of salicylates

A
  • 150-200 mg/kg = mild intoxication
  • 300-500 mg/kg = severe intoxication
  • > 500 mg/kg = potentially lethal
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10
Q

Dangerous serum levels of salicylates

A
  • > 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
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11
Q

What effect do salicylates have on respiratory centre?

A
  • Stimulation, so cause:
    • Hyperventilation
    • Respiratory alkalosis
    • Dehydration
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12
Q

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

A
  • Cerebral and pulmonary edema
  • Platelet function
  • GI effects (hemorrhagic gastritis)
  • Renal effects (tubular damage, proteinuria)
  • Hepatic effects (salicylate-induced hepatitis)
  • Ototoxicity (tinnitus, hearing loss)
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13
Q

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

A

Replacement of 2-3 mEq/L of plasma bicarbonate

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14
Q

Intracellular effects of salicylate toxicity

A
  • 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
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15
Q

Symptoms of acute salicylate toxicity

A
  • Vomiting
  • Hyperpnea
  • Tinnitus
  • Lethargy
  • Mixed respiratory alkalosis and metabolic acidosis
  • Progresses to coma, seizures, hypoglycemia, hyperthermia, cerebral and pulmonary edema
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16
Q

What is considered chronic salicylate toxicity?

A

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

17
Q

Symptoms of chronic salicylate toxicity

A
  • Hearing loss & tinnitus
  • N/V (may be absent)
  • Dyspnea, hyperventilation
  • Hyperthermia
  • Neurologic manifestations (confusion, agitation, seizures, coma)
  • Cerebral and pulmonary edema (more common)
18
Q

Management of salicylate toxicity

A
  • Emergency management
  • Lab tests (salicylates, ABG, electrolytes)
  • Monitoring
19
Q

Intervention options for salicylate toxicity

A
  • Gastric emptying
  • Activated charcoal, MDAC
  • Sodium bicarbonate
  • Urinary alkalinization
  • Hemodialysis, hemoperfusion
  • CVVHF (continuous venovenous hemofiltration)
20
Q

Describe the process of activated charcoal for salicylate toxicity

A
  • 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
21
Q

Describe the process of sodium bicarbonate for salicylate toxicity

A
  • 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)
22
Q

How can elimination of salicylates be enhanced?

A

Predominantly in the plasma, so easily removed w/ hemodialysis

23
Q

Indications for use of hemodialysis for salicylate toxicity

A
  • 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)
24
Q

What effect does hemodialysis have on salicylate toxicity?

A
  • Salicylate removal

- Correction of acid-base and fluid abnormalities

Year 4 - Toxicology (22 decks)

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