Aspirin
Chemical
Salicylate
Use
- Pain
- IHD
- Prevent TIA, stroke, DVT
- 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
- Assoc w ↑periop blood loss → requires cessation
- Last for lifespan of platelet = 10 days
∴ stop 5 – 10 days pre-op