NSAIDS & Paracetamol

Question 0

What is an opioids used to treat?

Answer 0

Moderate to severe visceral and somatic pain

Question 1

What are NSAIDS?

Answer 1

“Non steroidal anti-inflammatory drugs” - they are used generally to treat mild to moderate somatic pain classically. They also inhibit COX1&2 (cyclooxygenase) which in turn decreases the conversion of Arachidonic acid into PGG2

Question 2

If COX is not inhibited by a NSAID what are the normal physiological functions of PGF2? And state any relevant contraindications in using a NSAID.
(PG=Prostaglandins)

Answer 2

• Uterine contraction
  Can’t use a NSAID in pregnancy as it will stop uterine contractions; however, it could be applicable if the baby is predicted to be premature as it will slow contractions and keep the baby inside the mother longer.

Question 3

If COX is not inhibited by a NSAID what are the normal physiological functions of PGE2? And state any relevant contraindications.
(PG=Prostaglandins)

Answer 3

Vasodilation and Gastric cytoprotection

Question 4

If COX is not inhibited by a NSAID what are the normal physiological functions of PGI2? And state any relevant contraindications.
(PG=Prostaglandins)

Answer 4

Vasodilation and Gastric cytoprotection and decreases platelet aggregation (prostacyclin) by decreasing TXA2

Question 5

If COX is not inhibited by a NSAID what are the normal physiological functions of TXA2? And state any relevant contraindications.
(TX= Thromboxane)

Answer 5

Platelet aggregation

Question 6

Describe the mechanism of Coxibs.

Answer 6

They are the newer and less available version of a NSAID. They act on COX2 and inhibit its activity thus causing a decrease in prostaglandins production from inducible constitutive functions of inflammation and a decrease in inflammation.

Question 7

Describe the mechanism of NSAIDS.

Answer 7

Act on COX1&2. COX1 - inhibits the homeostatic prostaglandins which decreases gastrofunction, renal function and platelet formation. COX2 - inhibits constitutive functions in inducible inflammation which decreases those prostaglandins and inflammation.

Question 8

What does COX1 do?

Answer 8

• Housekeeping enzyme
• Synthesis of housekeeping prostaglandins
• Gastric cytoprotection
• Platelet thromboxane A2
• Uterine contraction
• GIT contraction
• Vasodilation

Question 9

What does COX2 do?

Answer 9

• inducible enzyme
• induces (cytokines, growth factors and bacterial lipopolysaccharides)
• increases prostaglandins at sites of inflammation
• housekeeping function in synthesis of PGI2 and renal function

Question 10

How does COX work?

Answer 10

• it’s product is tissue dependent
• functions within the endoplasmic reticulum
• COX1 has a narrower channel (Coxibs block only COX2 while smaller NSAIDS block both 1&2)

Question 11

List the adverse drug reactions of non-selective COX inhibitors and name an example of one.

Answer 11

Eg: Aspirin
Effects as a result of PG inhibition:
- GIT problems (lesions, bleeding, ulceration etc)
- *Prolonged bleeding time
- Renal vasoconstriction (nephrotoxicity)
- *Pregnancy (prolonged gestation/bleeding)
Effects not related to PG:
- *Hypersensitivity reactions (rash/bronchospasm)
- Tinnitus (severe ringing in the ear)
- Drug interactions (anticoagulants, anti hypertensives and lithium)

Question 12

List the adverse drug reactions of selective COX2 inhibitors.

Answer 12

Effects related to PG inhibition:

• increased TXA2 by inhibiting PGI2
• renal Vasculature constriction (decreases GFR)
• *myocardial infarction & stroke

Note: 50% less chance of a serious adverse effect over a non-selective COX inhibitor

Question 13

List 2 selective COX2 inhibitors (COXIBS) and name their areas of effect/treatment.

Answer 13

• Celecoxib (arthritis)

- Etoricoxib (musculoskeletal)