NSAIDS

Question 1

NSAID Outline

Answer 1

Reduce inflammation, fever and pain, inhibiting cells ability to produce prostaglandins

Question 2

Prostaglandins Outline

Answer 2

Lipid compounds derived from arachadonic acid, act locally as hormones (short half life, act on/close to production site). Produced in nearly all tissues. Each has distinct physiological roles

Question 3

Arachidonic Acid Outline

Answer 3

20 C unsaturated fatty acid in phospholipid membrane of cells. Derived from essential fatty acid (linoleic acid/omega 6). So availability is indirectly influenced by diet. Precursor of arachadonic acid and leukotrienes

Question 4

How is Prostaglandin releases from the bi-lipid membrane in cells

Answer 4

Cleaved off of glycerol backbone (is 2nd branch) by phospholipase A2, when there’s an intracellular Ca^2+ spike. This de-esterfies it, releasing it allowing it to travel through hydrophobic channels into cytosol

Question 5

How does Arachadonic acid get converted to prostaglandins

Answer 5

Arachidonic acid is converted to neutral prostaglandin H arachonidate by cyclooxygenase (COX) (folds backbone in half). Tissue specific isomerases then convert the neutral prostaglandin to a precise one to help tissue function.

Question 6

Cyclooxygenase (COX) Outline

Answer 6

Ubiquitously (all cells) expressed enzyme. 2 types: COX1 (GIT) and COX 2 (aka prostaglandin synthase)

Question 7

PG nomenclature

Answer 7

Letter = shape of cyclical region. Subscript number = number of double C bonds

Question 8

PGs function

Answer 8

Act paracrine/autocrine on cells, with an array of different functions: to maintain homesostasis

Question 9

TXA2 and PGI2 effects on platelet agg

Answer 9

Platelet agg motivates platelet agg, PGI2 inhibits. Balance eachother

Question 10

TXA2 and PGI2 effects on blood vessels

Answer 10

TXA2 = vasodilation, PGI2 = vasoconstriction. Balance eachother

Question 11

Aspirin (Acetyl Salicylic Acid) Outline

Answer 11

Irreversibly acetates serine at COX binding site. Preventing arachadonic acid binding. This action is permanent in all COX enzymes in body at time of aspirin admin. Half life = 4 hours as thet’s as long as it takes for new COX enzymes to form. Not used much anymore: as too many gastric side effects

Question 12

Low doses of aspirin effects

Answer 12

Inhibits platelet generation of thromboxane A2, results antithrombotic activity

Question 13

High doses of aspirin effects

Answer 13

Effective as anti-inflammatory agents

Question 14

Why can’t platelets replenish COX and effects

Answer 14

Platelets are anucleate (can’t regenerate COX). Have effects on clotting mechanisms

Question 15

Ibuprofen (Nurofen) Outline

Answer 15

Short acting, binds competitive (reversible) to COX active (can compete with aspirin). Treats minor pain, fever and inflammation

Question 16

Diclofenac Outline

Answer 16

Short acting, competitive reversible. Middle of spectrum for COX1 and COX2 affinity (not to COX2). Topical or oral

Question 17

Celecoxib Outline

Answer 17

Long acting, reversible and competitive antagonist. Selective for COX2. Risk of cardiovascular complications

Question 18

Paracetamol (Acetaminophen) Outline

Answer 18

Controversial NSAIDs (no anti-inflammatory action), more effective on COX on CNS. Low therapeutic index