2017B Question 12

Describe the clinical effects of non-steroidal anti-inflammatory drugs including mechanisms through which they exert these effects.

Examiner Report

83.3 % of candidates achieved a pass in this question.

NSAIDs are a class of medications commonly used by both our patients and us, as anaesthetists, in the peri-operative period.

In order to achieve a pass in this question, candidates were required to mention that NSAIDs act via the inhibition of cyclo-oxygenase (COX) enzymes resulting in a reduction in prostaglandin synthesis. Marks were awarded for mentioning that there are different isoforms on the COX enzyme, which have different physiological roles and that most of the therapeutic effects of NSAIDs result from blockade of the COX2 isoform. It was expected that the candidate would then discuss some of the multitude of therapeutic and side effects of NSAIDs, and indicate the mechanism for the effect. Most candidates were able to do this adequately, as indicated by the high pass mark. To pass, the drug class must have been mentioned. It was not adequate to just talk about prostaglandin function.

More comprehensive answers included details regarding which isoenzyme needed to be blocked to produce the beneficial or adverse effect. Those who mentioned the specific prostaglandin involved also gained points for this. Merely stating the mechanism of the effect as “reduced prostaglandin synthesis” scored minimal points, as the mechanism by which these drugs produce their effects has been well elucidated.

Many candidates did not mention the anti-inflammatory effect of NSAIDs, despite this effect being featured in the name of the drug class. Overall there was a better understanding of the mechanism of the side effects produced by NSAIDs compared with the therapeutic benefits. Many people overstated the renal effects of the drug class in normal individuals. There was confusion regarding the isoenzymes and prostaglandins involved in platelet and vasculature function and the consequent clinical effects of NSAIDs.

Model Answer


  • Classification and examples
  • Arachidonic acid pathway
  • Prostaglandin receptors
  • The big 3 effects
  • Organ system effects
  • COX-2 selective

NSAID Classification

Class Details
Non-selective irreversible - Salicylates: Aspirin
Non-selective reversible

- Propioinic acids (e.g. Ibuprofen, naproxen)

- Phenylacetic acid derivative (e.g. Diclofenac)

- Indoles (e.g. Indomethacin)

- Enolic acid derivatives (e.g. Meloxicam)

- (many others)

COX-2 selective

- Celecoxib

- Parecoxib (pro-drug for valdecoxib)

- Rofecoxib (no longer in use)

Arachidonic Acid Pathway

Prostaglandin Receptors

Type Details
G protein coupled receptor subtypes

- Gs: ↑ cAMP

- Gi: ↓ cAMP

- Gq: ↑ IP3 → ↑ ICF [Ca2+], ↑ DAG

Prostaglandin receptor subtypes

- PGD2: Gs, Gi

- PGE2: Gq, Gs

- PGF2α: Gq

- PGI2: Gi

- TXA2: Gq, Gs

The Big Three

Effect Details
Anti-pyretic - ↓ PGE2 in hypothalamus

- ↓ PG (especially E2) production at inflamed tissue

- ↓ Nociceptive receptor activation and expression

- ↓ Hyperalgaesia and allodynia


- ↓ PG (especially E2) production by inflamed tissues

- ↓ Vasodilatation, ↓ capillary leak, ↓ oedema, ↓ WBC chemotaxis

- ↓ Healing: Bone (post fracture), pleura (post pleurodesis)

Organ Systems

System Details

- ↓ PGI2 → Vasoconstriction, ↑ platelet aggregation → Thrombosis e.g. AMI
(especially COX-2 inhibitors; rofecoxib withdrawn for this reason)

- ↓ TXA2 → Vasodilatation, ↓ platelet aggregation → Bleeding, bruising

- Risk of systemic vasculitis


- ↓ PGD2 → Bronchodilatation

- ↓ PGE2 → Bronchoconstriction

- ↓ PGF2α → Bronchodilatation

- ↑ Shunt of arachidonic acid to leukotrienes → Bronchoconstriction

- (Overall: Bronchoconstriction, ↑ in 20% asthmatics)


- ↓ PGE2 → ↑ Parietal cell activity → ↑ HCl secretion

- Deranged LFT


- ↓ PGE2, ↓ PGI2 → ↓ Tubuloglomerular feedback, ↓ renin release

 - Risk of renal failure, hyperkalaemia

 - Important if hypovolaemic or also taking ACE inhibitor

- ↓ Ureteric contraction → Pass kidney stone (indomethacin)

- Risk interstitial nephritis


- ↓ PGE2 → Myometrial relaxation

- ↓ PGF2α → Myometrial relaxation

- ↓ PGE2 → Closure of ductus arteriosus → Asphyxia


- Displace other drugs from protein-binding sites, e.g. Warfarin on albumin

- Metabolic acidosis in overdose

COX-2 Inhibitors

Factor Details

- Selective for inflamed tissue (enzyme is inducible cf. constitutive)

- ↓ Peptic ulceration

- ↓ Bronchoconstriction

- ↓ Renal impairment (examiner 2013)

- ↓ Bleeding risk


- ↑ Thrombosis risk, AMI (rofecoxib)

- ↑ Fluid retention

- Expensive

- Sulfur allergy

- Parecoxib is a prodrug with very slow onset of effect

Last updated 2021-08-23

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