Class #12 - NSAIDS

Question 1

NSAIDS functions?

Answer 1

Anti-pain/fever/inflammation

Question 2

3 catégories + acéta

Answer 2

1. ASA
2. Traditional NSAIDS
3. COX-2 inhibitors (eg. Celecoxib)

Question 3

Salicilin found in?

Answer 3

White willow bark and meadowsweet, but gave stomach ache

Question 4

Aspirin name from? discovered by?

Answer 4

Acetyl SPIRea (plant) IN (drug) Felix Hoffman

Question 5

Discovered mechanism of action?

Answer 5

John Vane

Question 6

Precursors of PG?

Answer 6

Phospholipids (phospholipase A2)-> Arachidonic acid (COX-1/2)-> Prostaglandins

Question 7

Ara. acid substate for?

Answer 7

PG (COX), thromboxane (first PGH2, but after TXA2 by thromboxane synthase), leukotrienes (5-LOX)

Question 8

COX?

Answer 8

Cyclooxygenase, found in endoplasmic reticulum. Forms cyclopentane ring and add 2 oxygens molecules

Question 9

Parent prostaglandin?

Answer 9

PGH2

Question 10

PG receptors?

Answer 10

GPCR prostanoid receptors

Question 11

PG role?

Answer 11

1) Physio: T controle, bronchial tone, cytoprotection in stomach, GIT mobility, semen viability
2) Patho: fever, asthma, ulcers, diarrhea, inflammation, bone errosion

Question 12

NSAIDS action?

Answer 12

Blocks COX 1and 2

Question 13

Dynamics - pain receptors?

Answer 13

Nerve receptors = nociceptors

Question 14

Injured cells releases?

Answer 14

PGE2, 5-HT, Bradykinin, K+, Histamine = all stimulate nociceptors

Question 15

Dynamics - Inflammation (+definition)

Answer 15

def: Reaction of living tissues to injury, essential (redness, swelling, heat, pain).
Injured cells, chemical mediators(same as pain) dilate microcirculation + migrations of immune cells to injured site.

Question 16

Difference between PGE2/PGI2 and bradykinin, histamine, etc?

Answer 16

PG sensitize A delta nerve endings, others stimulate A deltat and C nerve endings.

Question 17

Types of chronic arthritis?

Answer 17

Osteoarthritis, rheumatoid arthritis, lupus, gout

Question 18

NSAIDS and animals

Answer 18

Given to horse and canine, but can kill cats.

Question 19

T regulating center?

Answer 19

Hypothalamus

Question 20

Physiology of fever?

Answer 20

Exopyrogens ->activation of monocytes/macrophage/T-cells ->they produce Interleukins/TNF ->Hypothalamus ->Prod. of PGE2 in brain ->Fever

Question 21

How raise T in body?

Answer 21

1. het conservation: reduce sweat, vascontriction

2. Shivering reflex, musc. contraction

Question 22

NSAIDS stop fever how?

Answer 22

Block COX-2 that produce PGE2

Question 23

NSAIDs side effects (SE)

Answer 23

GIT: Block PG prod which blocks mucus prod + attack cells, renal dysfunction, bleeding

Question 24

ASA and thrombotic effect?

Answer 24

Acetylating serine in COX-1 permanently and irreversibly, cell need to make more Enz. but plts can’t b/c they dont have a nuclei.

Question 25

Kinetics?

Answer 25

ASA converted to salicylic acid (active, binds to COX) -> conjugated by P450 in inactive metabolite. T1/2 is 3hours normally, but overdose = first order kinetics

Question 26

Reyes syndrome?

Answer 26

virus + ASA = liver and brain dammage

Question 27

Acute toxicity of ASA

Answer 27

Salicylism: Tinnitus

Question 28

Trad. NSAIDS bind.... to COX-1/2

Answer 28

Reversibly

Question 29

NSAIDS metabolism?

Answer 29

P450 and transferases

Question 30

COX 2 inhibitors why? + Eg name?

Answer 30

Channel is wider in COX2 and molecule wider. Celecoxib.

Question 31

Why increase in cardio. events with first COX2 inhibitors?

Answer 31

Rofecoxib. Normal: TXA2 (thrombotic) and PGI2 (antithrombotic) in balance, but PGI2 down because Enz. COX-2.

Question 32

Toxic metabolite aceta

Answer 32

N-Acetylbenzoquiononeimine

Question 33

Detox agent aceta

Answer 33

N-Acetylcysteine -> Glutathione-s-transferase

Question 34

EtOH bad with acéta b\c?

Answer 34

Increase P450 and deplete stock of gluthatione