Aspirin

Chemical

Salicylate

Use

  1. Pain
  2. IHD
  3. Prevent TIA, stroke, DVT
  4. Fever

Presentation

Tablets 75 – 600mg

Dose

75mg – 100mg OD (antiplatelet)

300 – 400mg Q4h (analgesia) MAX 4g/day

Route

PO

Onset

30 mins

DoA

3 – 6hrs

NB: aspirin is a prodrug → converted to SALICYLATE (active form) in stomach

MoA

  • Irreversible inhibition of COX enzyme
  • ↓synthesis PG, prostacyclin & thromboxane
  • Inhibits COX1 > COX2
  • ∴ more affinity for platelet COX
    • Antiplatelet activity
    • Antipyretic

PD

CNS

  • Analgesia
  • Antipyretic

CVS

  • Antiplatelet
  • ↑ blood loss post op
  • Exac HF

RESP – bronchospasm in sensitive individuals

GI – ↑risk GI ulcer & bleeding

GU

  • Proteinuria
  • Haematuria
  • Renal impairment

PK

A

  • Complete because weak acid & UNIONISED in stomach/GB
  • But 70% OBA 2° 1st pass metabolism

D

  • PPB 80%
  • VD15L/kg (small)
  • Hydrolysed rapidly to salicylate by esterases 

M

  • 50% salicylic acid metabolised to salicyruvate in liver → SATURATABLE → ZERO ORDER KINETICS
  • 20% metabolised by conjugate to glucuronide → also SATURABLE
  • Due to 2 saturable metabolism pathways, NON LINEAR KINETICS
    i.e. half life varies with dose

E

  • Salicylate metabolites in urine
  • 10% unchanged → via glom filtration, active prox secretion
  • Urinary excretion is pH dependent ↑pH 5 → 8

Traps ionised salicylate from 3% → 80%!

Adverse Effects

  • Crosses placenta! + gets trapped!
  • GI ulcer/lung
  • Hepatic impairment
  • Renal papillary necrosis
  • Bronchospasm
  • Aplastic AN
  • OD = mortality 2%
    • Alkalisation of urine ↑excretion of free salicylic acid
    • Removed by HD
Contraindicated in spinal/epidural
  • Assoc w ↑periop blood loss → requires cessation
  • Last for lifespan of platelet = 10 days
    ∴ stop 5 – 10 days pre-op