Non-steroidal anti-inflammatory drugs in the perioperative period

Question 1

Effects of prostaglandins and TXA2

Answer 1

COX 1
- Protect renal blood flow by decreasing afferent arteriolar resistance (some COX 2)
- Enhance gastric protection by increasing mucus and HCO3 production in the stomach
- Vasoconstriction and platelet aggregation

COX 2
- Sensitisation of nociceptors via TRPV1 and Na channels in the peripheral neurones
- Stimulates the hypothalamus and causes pyrexia

Question 2

Commonly used NSAIDs and their doses

Answer 2

• Ibuprofen 200-400mg
• Naproxen 250-500mg
• Diclofenac 25-50mg
• Celecoxib 200mg
• Parecoxib 20-40mg
• Ketorolac 10-30mg

Question 3

NSAID pharmacokinetics

Answer 3

• Generally high bioavailability
• Peak plasma conc with 2-3hrs
• Acids pKa 4-5
• Extensively protein-bound
• Generally metabolised by the liver and excreted by the kidney

Question 4

Contraindications to NSAIDs

Answer 4

• Heart failure
• Inflammatory bowel disease
• GI ulceration
• CKD stage 3 and above
• Hepatic impairment (Alb <25)
• Uncontrolled HTN
• IHD, CVA
• Significant blood loss, fluid shift anticipated
• Previous bronchospasm