Analgesia

Question 1

Where are NSAIDs absorbed?

Answer 1

Small bowel
Low vol of distribution

Question 2

What is the MOA of NSAIDs?

Answer 2

• Reversibly inhibit cyclo-oxygenase (COX) preventing production of prostaglandins & thromboxane
• Leads to anti-inflammatory effects & reduced platelet aggregation
• Antipyrexial effects due to inhibition of centrally produced prostaglandins

Question 3

What activates Thromboxane production by platelets?

Answer 3

• Adenosine
• Collagen
• Adrenaline

Question 4

What is the MOA of Aspirin?

Answer 4

Selectively inhibits platelet thromboxane production

Question 5

What are COX 1 & COX 2 responsible for?

Answer 5

1) Constitutive form, produces prostaglandins controlling renal blood flow, form gastric protection
2) Inducible form, produced in response to tissue damage, facilitates inflammatory response, produces vascular endothelium prostaglandin

Question 6

What are the effects of NSAIDs?

Answer 6

• Gastric irritation (ibuprofen lowest risk)
• Major vascular events (Diclofenac & ibuprofen)
• Asthma: More arachidonic acid converted to leukotrienes
• Impaired renal function
• Hepatotoxicity

Question 7

What is the MOA of Aspirin?

Answer 7

• Selectively inhibits platelet COX & preserves vessel wall COX
• Reduces TXA-induced VasoConstriction & platelet aggregation

Question 8

What is the metabolic mechanism in Aspirin overdose?

Answer 8

• Uncouples oxidative phosphorylation
• Inc O2 consumption & CO2 production
• Resp centres stimulated causing resp alkalosis

Question 9

How is Aspirin absorbed?

Answer 9

• Gastric absorption- mostly unionised
• Mainly albumin bound
• Rapidly hydrolysed by intestinal & hepatic esterases to salicylate
• Further hepatic metabolism to salicylic acid & glucuronide

Question 10

What is Diclofenac?

Answer 10

Phenylacetic acid derivative

Question 11

How is Diclofenac absorbed?

Answer 11

• Highly plasma bound & small vol of distribution
• Undergoes hepatic hydroxylation & conjugation to inactive metabolites

Question 12

When is phenylbutazone used?

Answer 12

• Ank Spond
• Serious haematological SE

Question 13

How is Ibuprofen absorbed?

Answer 13

• Converted from inactive R enantiomer to active S enantiomer
• Metabolised by P450

Question 14

What are contraindications for COX 2 inhibitors?

Answer 14

IHD
CVD
Heart Failure
PVD

Question 15

What is the MOA of Gabapentin? & Pregabalin

Answer 15

• Presynaptic a2d subunit of voltage gated Ca2+ channels in cortical neurones
• Gabapentin: Inc synaptic conc of GABA
• Pregabalin: No inc on GABA conc