2021A Question 10

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

Examiner Report

66.5% of candidates achieved a pass in this question.

The first half of the question was reasonably well answered by candidates which is reflected in the high pass rate as this is where the bulk of marks where allocated. Better answers included more detail and discussed effects on a wider variety of body systems. Many candidates did not demonstrate an appreciation that the antiplatelet effects of these agents can be both a therapeutic and adverse effect depending on the clinical context. Many answers gave the impression that bronchospasm was a frequent adverse effect rather than affecting a minority of patients with asthma.

The second half of the question was frequently answered with minimal detail and many errors. The major advantages of selective COX-2 agents include decreased long-term risk of gastric erosions, minimal effect on bronchial tone and reduced anti-platelet effects. This last benefit was overlooked by around half the candidates. Few candidates demonstrated an appreciation that the selectivity of COX-2 agents is not absolute nor identical within this class.

Model Answer


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

NSAID Classification

Class Examples
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

Receptor Messenger
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 Mechanism
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 System Effects

System Effect

- ↓ 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 Mechanism

- 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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