Salicylates

1
Salicylates

• ?????
• 91-8-23

2
Formulations

• Aspirin(acetylsalicylic acid or ASA)and
  non-acetylated salicylates
• Mixed pharmaceutical preparations
• Over 200 contain salicylate
• Examples-Percodan, Fiorinal, Pepto-Bismol, Alka
  Seltzer, Dristan
• Methyl salicylate
• Contained in topical liniments, used in atomizers
• Examples- oil of wintergreen, Ben Gay
• Pure methyl salicylate contains 1.4 grams of
  salicylate per 1 mL and a teaspoon is potentially
  fatal to a 2 yr old

3
Pharmacokinetics

• Absorption- depends upon several factors
• Formulation
• Rapid for methyl salicylate
• 1 to 2 hrs in therapeutic dosing
• Tablet dissolution is rate- limiting step
  therefore absorption is prolonged if an enteric
  coated tablet or overdose (due to tablet
  coalescence)is ingested

4
Pharmacokinetics

• Absorption- depends upon several factors
• Peaks
• Therapeutic- serum peak in 1-2hus
• Overdose- may be prolonged(4-6 hrs or longer)due
  to delayed gastric emptying or concretion
  formation

5
Pharmacokinetics

• Distribution
• Protein
• Therapeutic aspirin is rapidly hydrolyzed into
  salicylate which is largely protein bound
• Overdose- the albumin becomes saturated thus
  increasing the free salicylate

6
Pharmacokinetics

• Distribution
• pH effects
• Salicylate is a weak acid(pKa3.0)so at
  physiologic pH(7.4)most remains ionized which
  delays distribution into tissues
• If acidosis develops(as in overdose), salicylate
  equilibrium shifts more drug into not-ionized
  form which can penetrate tissues more rapidly
• Volume of distribution
• Vd0.15 to 0.35 L/kg therapeutically and is
  increased in overdose

7
Pharmacokinetics

• Distribution
• pH effects
• Salicylate is a weak acid(pKa3.0)so at
  physiologic pH(7.4)most remains ionized which
  delays distribution into tissues
• If acidosis develops(as in overdose), salicylate
  equilibrium shifts more drug into not-ionized
  form which can penetrate tissues more rapidly
• Volume of distribution
• Vd0.15 to 0.35 L/kg therapeutically and is
  increased in overdose

8
Pharmacokinetics

• Metabolism/ Elimination
• Therapeutic
• Salicylate is hepatically conjugated with
  glucuronic acid or glycine and its elimination
  follows first order kinetics(fixed of durg
  metabolized/time)(Half-life about 2-4hrs)
• Only a small proportion of free salicylate is
  eliminated in the urine

9
Pharmacokinetics

• Metabolism/ Elimination
• Overdose
• Enzymes become saturated which changes metabolism
  into zero order kinetics(fixed amount of drug
  metabolized/ time)and elimination is prolonged
  (Apparent half-life about 15-20hrm)
• Due to this saturated hepatic metabolism, renal
  elimination of free salicylate becomes critical

10
Pathophysiology

• Metabolic
• Uncouples oxidative phosphorylation
• Inhibits dehydrogenase enzymes in Krebs cycle(at
  higher conc )
• Acid/ Base Status
• Initial respiratory alkalosis
• Metabolic acidosis develops
• Development of actual acidemia
• Dehydration and electrolyte imbalance

11
Clinical Manifestations

• Gastrointestinal
• Pulmonary
• Cardiovascular
• CNS
• Diaphoresis and hyperthemia
• Hematologic
• Renal and Hepatic
• Chronic Intoxication

12
Evaluation

• If gt150 mg/kg of aspirin ingested, refer to
  emergency department
• Ferric Chloride Test
• Urinalysis
• Arterial or Venous Blood Gas
• Serum Electrolytes
• Assessment of hydration status
• Serum Salicylate Level

13
Treatment

• Gastrointestinal Decontamination
• Fluid Resuscitation
• Airway management
• Urine Alkalinization
• Serial Serum Salicylate Levels Q2-4 hrs
• Extracorporeal Removal