NSAIDs

Question 1

Which enzyme does NSAID block?

Answer 1

irreversible blocking of COX

Question 2

What are the functions of the 3 prostanoids

Answer 2

1. prostacyclin
2. prostaglandin
3. thromboxane

Question 3

4 functions of NSAID

Answer 3

1. Anti-inflammatory:
   - vasodilation–> red, heat, swelling
   - vascular permeability–> swelling
   - pain
2. Antipyretic: reduce cytokine-induced COX action, reduce prostaglandin–> inhibit thermostat reset in hypothalamus–> fever
3. Analgesic:
   - reduce prostaglandin reduce sensitisation of nerve fibres to bradykinin & leukotrienes –> reduce nociception
   - sensitisation block thus analgesic ceiling
   - addnal analgesic effect CNS
4. Anti-clotting: irreversibly blocks COX in platelets (no nuclei unable synthesise more COX enzyme) –> inhibit platelets entire lifespan –> block platelet aggregation

5. low dose as blood thinner for CVS

Question 4

What are the adverse effects of aspirin?

Answer 4

1. GI toxicity:
   - increase gastric acid secretion
   - reduce mucus, bicarbonate secretion
   - reduce mucosal blood flow
   = dyspepsia, N/V, chronic users: ulcers, hemorrhage
2. renal toxicity:
   - prostaglandin: Na+ retention in ascending limb, water retention, hypertension, peripheral edema
   - prostacyclin: reduce RAAS, hyperkalemia, acute renal failure
3. asthmatics: bronchospasm (leukotrienes overprdn –> mucus prdn + bronchoconstriction)
4. pseudoallergy: leukotrienes overprdn –> mucus prdn + bronchoconstriction + mast cell activation
5. bleeding: hemostasis failure, bruising

Question 5

Dose dependent effect of aspirin

Answer 5

1. GI
2. Tinnitus
3. renal & resp failure

increasing dose

Question 6

Which pt groups is NSAID contraindicated?

Answer 6

1. children
   - Reye’s syndrome: swelling of brain (encephalitis) & liver
   - increased risk if taken after viral
2. pregnancy (3rd trimester): premature closure of ductus arteriosus of fetus

Question 7

When is NSAID used to treat children?

Answer 7

Kawasaki syndrome (vasculitides in children)
- IVIG + 30-50mg/kg of NSAID divided into 4 doses

Question 8

3 types of NSAIDs to know

Answer 8

1. naproxen: female dysmenorrhea - long t1/2
2. diclofenac: low GI risk as short t1/2 - [ ] in synovium (arthritic NSAID)
3. indomethacin: addnal inhibition of PLA2 - CNS AR psychosis depression hallucination

Question 9

Which pt groups is NSAID contraindicated?

Answer 9

1. children
   - Reye’s syndrome: swelling of brain (encephalitis) & liver
   - increased risk if taken after viral
2. pregnancy (3rd trimester): premature closure of ductus arteriosus of fetus
3. pt w ulcer risk/ chronic ulcers (as even cox-2 selective will inhibit wound healing)
4. post surgical pt - as increase risk of thrombosis w cox-2 selective (as more overflow cox-1 hence thromboxane prdn)

Question 10

Know which NSAID Bad/Good for GIT

Answer 10

KK Uncle - Ketoprofen (worst for GIT COX-1 >> COX-2)
Please - piroxicam
Introduce - indomethacin 
A - aspirin
Nice - naproxen
Icecream - Ibuprofen

DM - diclofenac, mefenamic acid
Me - meloxicam
CP - celecoxib, parecoxib
Exciting - etoricoxib (safer for GIT - COX-2>COX-1)

Question 11

Unwanted inhibition of COX-2 w cox-2 selective nsaid

Answer 11

1. synovium
2. female repro tract- delayed follicular rupture
3. kidney - constitutive COX-1 & 2
4. CNS

Question 12

Paracetamol is also called… and is a…

Answer 12

acetaminophen… CNS selective cox-2 inhibitor

can use for paeds, safer for GIT

Question 13

Disadv for paracetamol

Answer 13

1. weak anti-inflamm
2. overdose/alcohol use: liver damage
   - as minor pathway CYP450 produce toxic metabolite removed via glutathione (inhibited by alcohol) to non-toxic metab
3. allergy