NSAIDS

Question 1

What is the role of prostanoids in inflammation

Answer 1

vasodilation/constriction, inhibit/induce platelet aggregation, vascular permeability, pain depending on which prostanoid pathway is activated

Question 2

Name 5 example of prostanoids

Answer 2

PGI2(prostacyclin), PGD2, PGE2, PGF2a, TXA2(thromboxane)

Question 3

If a person is experiencing GI tract problems, which prostanoid should he take?

Answer 3

PGE2 (inhibit gastric acid secretion, promotion of gastric cytoprotection)

Question 4

name 2 examples of prostanoids that will induce vasoconstriction

Answer 4

PGF2a and TXA2 (other 3 induce vasodilation)

Question 5

what is the clinical use of NSAIDs

Answer 5

Anti inflammatory, analgesic, antipyretic

Question 6

Explain how NSAIDs can be used as analgesic (painkiller)

Answer 6

inhibit COX1/2 thus reducing PGE2 that triggers nociceptors that signals pain. But have ceiling because it blocks sensitisation but not direct nociceptive activation

Question 7

Explain how NSAIDs as antipyretic (reduce fever)

Answer 7

NSAID inhbit COX1/2 which reduce production of PGE2, hence reducing elevated body temperature

Question 8

what is NSAID use beyond inflammation

Answer 8

Aspirin as anti-platelet drug (blockin

Question 9

what are the adverse effects of traditional NSAIDs

Answer 9

Lower PGE2: gastric ulcer + upset, pseudoallergy, aspirin: blood thinning/bleeding/reye’s syndrome, asthma. Pregnancy, renal toxicity, dizziness, deafness

Question 10

what type of drug is Naproxen and lbuprofen

Answer 10

COX 1 Selective inhibitor

Question 11

what type of drug is celecoxib

Answer 11

COX2 selective inhibitor

Question 12

when should coxib not be used

Answer 12

still harms GI tract, renal toxicity, thrombosis risk, impair wound healing, contraindication: 3rd trimester pregnancy

Question 13

what is the advantage of coxibs

Answer 13

minimize non-selective NSAID
gastrointestinal side effects since it selectively inhibits cox2 which are less constitutively active in many parts of the body (exce

Question 14

what is mechanism of action of coxibs

Answer 14

inhibit COX by reversible steric indrance blocking the hydrophobic tunnel via hydrogen bonding

Question 15

what is the mechanism of action of paracetamol

Answer 15

CNS selective COX (maybe COX3) inhibition, hence no anti inflammatory effect

Question 16

Aspirin mechanism of action

Answer 16

irreversibly acetylates COX by forming covalent bonds with serine residues, hence blocking prostanoid production

Question 17

traditional nsaid mechanism

Answer 17

inhibit COX by reversible steric hindrances by blocking hydrophobic tunnel via hydrogen bonding, blocking prostanoid production

Question 18

examples of nsaids

Answer 18

ibuprofen
aspirin
naproxen
paracetamol
celecoxib

Question 19

PGI2 function

Answer 19

Vasodilation
Inhibit platelet aggregation
Renin release (-ve feedback to increase vasoconstriction)
Natriuresis (Na+ excretion)

Question 20

Why can aspirin be used a blood thinner

Answer 20

Blocks more TXA2 than PGI2. (Platelets originally produce more TXA2 which promotes platelet aggregation. Since aspirin is a irreversible COX inhibitor and platelet is anuclear, COX cannot be regenerated in platelets, making the effect of TXA2 inhibition greater)

Question 21

Side effects of aspirin use

Answer 21

Aspirin induced asthma due to blockage in COX pathway thus increasing leukotriene production (asthma mediator)