non sterodial anti inflammatory drugs

Question 1

descibe the Arachidonic Acid Cascade & Eicosanoids

Answer 1

Arachidonic Acid in the celle membrane become the Eicosanoids by the phospholipase A2 and they are converted into lipoxygenesas and cyclooxygenase

a lot of the cyclooxygenase are the prostanoids, it is a pathway molecule

Question 2

Describe the sythesis of prostanoids

Answer 2

Arachidonic Acid is converted into pgg2 BY COX 1 OR COX2 by process of cyclooxygenase and then into PGH2 by COX1 OR COX2 by process of peroxidase

the PGH2 is converted to other molecules which are major active prostanoids
- TXA2
-PGE2
-PGF2A
-PGI2
-PGD2

Question 3

What is COX 1

Answer 3

Constitutive in most cells
Homeostasis / Housekeeping

Question 4

What is COX 2

Answer 4

Inducible by IL-1β and TNF-α
Constitutive in kidney, female
reproductive tract, CNS

Question 5

what happens when u inhibit COX1 AND COX2

Answer 5

side effects not eleborated by prof

Question 6

where are the prostanoid receptor located - prostacylcin

Answer 6

endothelum, platelets

Question 7

where are the prostanoid receptor located - thromboxane A2

Answer 7

platelets, vascular smooeth muscle cells

Question 8

where are the prostanoid receptor located - prostaglandin D2

Answer 8

mast cellls, lympocytes

Question 9

where are the prostanoid receptor located - prostaglandin e2

Answer 9

brain,vascular smooeth muscle cells

Question 10

where are the prostanoid receptor located - prostaglandin f2

Answer 10

yterus, airway, vascular smooeth muscle cells

Question 11

relaxant type Prostanoid Receptors

Answer 11

IP
EP2
EP4
DP1

Question 12

Contracitle type Prostanoid Receptors

Answer 12

TP
FP
EP

Question 13

Inhibitory Type Prostanoid Receptors

Answer 13

EP3

Question 14

List the biological finctions of Prostacyclin

Answer 14

Vasodilation, inhibit platelet aggregation

Question 15

List the biological finctions of classical prostaglandins

Answer 15

vascular permeability and pain

Question 16

List the biological finctions of thromboxane

Answer 16

vacosonstriction and induce platelet aggregation

Question 17

Biological Roles of Prostanoids(PGI2)

Answer 17

Vasodilatation
Inhibition of platelet aggregation
Renin release
Natriuresis

Question 18

Biological Roles of Prostanoids(PGD2)

Answer 18

Vasodilatation
Inhibition of platelet aggregation
Bronchoconstriction

Question 19

Biological Roles of Prostanoids(PGE2)

Answer 19

Vasodilatation
Inhibition of gastric acid secretion
Promotion of gastric cytoprotection
Bronchodilation / bronchoconstriction

Question 20

Biological Roles of Prostanoids(PGF2A)

Answer 20

Vasoconstriction
Bronchoconstriction
Uterine contraction

Question 21

Biological Roles of Prostanoids(TXA2)

Answer 21

Vasoconstriction
Promotion of platelet aggregation
Bronchoconstriction

Question 22

Aspirin machanism

Answer 22

Aspirin inhibits cyclooxygenase (COX-1/2) and
blocks prostanoids production
it is the only NSAID that binds irreversible by
forming covalent bonds with serine residue

Question 23

What is the Traditional NSAIDs
Act by Inhibition of Cyclooxygenase (COX-1/2)

Answer 23

Anti-inflammatory :: Analgesic :: Antipyretic

Question 24

How does Aspirin differ from other NSAID

Answer 24

Only Aspirin Irreversibly Acetylates COX by
forming covalent bonds with serine residue

other NSAID: Reversible Steric hindrance blocking
the hydrophobic tunnel via hydrogen
bonding

Question 25

5 imporatnt NSAID and their half lives

Answer 25

Aspirin(2h)
iduprofen 2h
naproxen 15
paracetamol 2
celecoxib 10

Question 26

How does the NSAID function as Anti-inflammatory Drugs

Answer 26

XTraditional NSAIDs block:
 Vasodilatation, which contributes to
redness, heating and edema
 Increased vascular permeability,
which contributes to swelling
 Pain associated with inflammation

Question 27

NSAIDs As Analgesic

Answer 27

PGE2 sensitization of peripheral nociceptive fibres
by blocking cox1/2, reduce the pain transmission
 NSAIDs block sensitization, but not direct nociceptive activation, may
explain why NSAIDs have an “Analgesic Ceiling”.– means only can suppress mild pain and if too high, cannot supress
 NSAIDs also have additional analgesic action in the CNS

Question 28

NSAIDs As Antipyretic

Answer 28

when there is Infection, tissue damage, inflammation, Neutrophils release Cytokines (IL-1β, TNF-α),
NSAID block COX1/2
so PGE2 at hypothalamus will not cause Fever
NSAIDs do not alter normal body temperature.
Body’s “thermostat” reset

Question 29

what is NSAID Use Beyond Inflammation

Answer 29

Aspirin As Anti-platelet Drug
effectve as a blood thinner and prevent heart attack and stroke

under normal condition, the blood fluid and there is TXA2 promotes platelet aggregation,
leading to stroke and heart attack. and PGI2 inhibits platelet
aggregation.

thus when aspirin binds irrevicisbke to COX , TXA2 more than PGI2, it result in blood thinning

Question 30

list the Adverse Effects of Traditional NSAIDs

Answer 30

 GI Tract: N&V, gastric upset, and gastric ulceration, mainly due to COX-1 inhibition: ↓ PGE2
 Pseudo-allergic reaction: skin rash, nasal congestion, anaphylactic shock
 Bleeding due to blood thinning by aspirin
 All non-aspirin NSAIDs have increased risks of heart attack/stroke
 Aspirin-linked Reye’s Syndrome in children with viral infection
 Aspirin-induced asthma in susceptible asthmatics, associated with viral
URTI
 Kidney: acute renal failure, hypernatremia, H2O retention, edema,
hyperkalemia, ↓ glomerular filtration rate (GFR)
 Pregnancy toxicity: 1st trimester (risk of miscarriage) and 3rd trimester
(premature closure of ductus arteriosus)
 High dose: Dizziness, deafness, tinnitus

Question 31

what does lipoxygenases do ?

Answer 31

mediator for astma, certain subjects take aspirin and develop asthma

Question 32

COX-2 Selective Inhibitor

Answer 32

Coxibs
celecoxibs
safer for the gi tract

Question 33

Limitations of Coxibs

Answer 33

Expectation of complete GI tract sparing with COX-2 selective inhibitors
not realised
Renal toxicity due to constitutive expression of both COX-1 & COX-2 in
the kidney.
Note that all NSAIDs are COX-2 inhibitors:
contraindicated in third trimester of pregnancy causing premature
closure of ductus arteriosus (fetal lung bypass) - patent ductus
arteriosus requires PGE2 production
**Relative increase in TXA2 favours platelet aggregation, which may
increase risk of thrombosis (heart attack and stroke).
COX-2 inhibitors impair wound healing and hence may exacerbate
ulcers - healing requires COX-2 and PGE2.

Question 34

paracetamol

Answer 34

CNS-selective COX (may be COX-3) inhibitor Anti-pyretic Action, do not have much inflammatory effect, painkiller and lowers fever,

relatively safe

liver converts into p aminophenol
then into AM404 which is a agonist endogenous receptor

analgesic actions

Question 35

advantages of Paracetamol

Answer 35

Good analgesic
 Potent antipyretic
 Spares the GI tract
 Side-effects few and uncommon
 Few drug-drug interactions
 Relatively safe for pediatric use

Question 36

Disadvantages of paracetamol

Answer 36

 Weak anti-inflammatory
 Toxic doses cause N&V, and
hepatotoxicity by overdose or chronic
alcohol use/abuse
 Allergic skin reactions sometimes
occur