Non-steroidal anti-inflammatory drugs (NSAIDS)

Question 1

What is the NSAIDS classification?

Answer 1

1. Salicylic acid derivatives
2. Phenylacetic acid derivatives
3. Indolacetic acid derivatives
4. Enolic acid derivatives
5. Sulphonanilides
6. Selective COX-2 Inhibitors (COXIBS)
7. Fenamic acid derivatives
8. Others

Question 2

NSAIDS pharmacokinetics?

Answer 2

Good oral absorption, BBB/BPB penetration hence has teratogenic effects on fetus. Liver metabolism via conjugation by glycine and glucoronic acid. Removed in urine but elimination is PH dependent. In high PH more NSAIDS elimination increases and in low PH reduced elimination, reabsorption in kidney.

Question 3

NSAIDS pharmacodynamics?

Answer 3

Function to inhibit 2 forms of COX 1 and 2, decreased PG synthesis. COX responsible for “prostanoid biosynthesis”, precursor for PG. 4 actions of NSAIDS are recognised:

1. Anti-inflammatory - lack of PG means no PG mediation in inflammation.
2. Analgesic - lack of PGE2, lowered sensitisation to bradykinin, lowered sensation of pain.
3. Anti-pyretic - PGE2 elevates set point, in absence of which the set point returns to normal via heat dissipation with peripheral vasodilation/sweating.
4. Reduced platelet aggregation - Thrombolytic action due to the salycic acid sderviced (Aspirin), which irreversibly binds to thromboxane A2

Question 4

NSAID therapeutic uses

Answer 4

1. GOUT : Aspirin (high dose) inhibits tubule reabsorption of uric acid.
2. Aspirin (low dose) is used to inhibit platelet aggregation and reduce the risk of stroke and myocardial infarction (thrombus induced).
3. Treatment of conditions requiring analgesia (headache, toothache, arthralgia, myalgia).

Question 5

NSAIDS contraindication?

Answer 5

1. Pregnancy and breast-feeding. (breast milk transmission).
2. Renal and hepatic failure.
3. Aspirin given during viral infections has been associated with
   an increased incidence of “Reye’s syndrome” (fatal hepatitis with cerebral oedema).

Question 6

ADR’s of NSAIDS

Answer 6

1. GI : NSAIDs inhibit prostaglandins synthesis resulting in diminished mucus protection, and increased risk for GI ulceration and bleeding.
2. Renal : NSAIDs reduce renal blood flow, which leads to –> retention of sodium and water (Oedema) and interstitial nephritis.
3. Blood : Prolonged bleeding time (THROMBOXane A2 inhibition by salycic acid derived NSAIDS - “Aspirin”)
4. Respiratory : At therapeutic doses, aspirin increases alveolar ventilation.
   - At toxic levels aspirin cause respiratory depression, causing respiratory and metabolic acidosis.
5. Selective COX2 inhibitors (COXIBS) are associated with a higher risk of thrombotic cardiovascular events (stroke, myocardial infarction).

Question 7

NSAIDS alternative drug interactions?

Answer 7

1. NSAIDS are highly protein bound and can displace other highly protein-bound drugs, such as warfarin resulting in higher free concentrations of the other agent.
2. NSAIDs decrease the effect of diuretics and antihypertensive drugs.
3. NSAIDS + anticoagulants = increased risk of bleeding.