NSAIDs

Question 1

LIST of NSAID

Answer 1

NON SELECTIVE:
Aspirin, Ibuprofen, Naproxen, Diclofenac, Indomethacin

SELECTIVE:
COX 2= Celecoxib, Etoricoxib, lumiracoxib
COX 1= Flurbiprofen, Ketoprofen

Question 2

Mechanism general

Answer 2

autacoid induce pain. mediators include: eicosanoids, histamine, 5-hydroxytryptamine and nitric oxide
(Eicosanoids = prostaglandins, thromboxane A2, prostacyclin, leukotrienes) PG, TxA2 made from COX, leukotrienes made from lipoxygenase.

2 types of COX-
COX 1 - constantly made enzyme and produced prostanoid used in homeostatic regulation .
COX 2- inducible enzyme. low in normal, increased in inflammation.

prostaglandins cause pain, fever, inflammation

NSAIDs inhibit the COX enzymes and thereby reduce the production of prostaglandins, which means that NSAIDs possess anti-inflammatory (reduce inflammation), anti-pyretic (reduce body temp and fever) and analgesic (pain relieving) effects.

ASPIRIN SPECIAL AFFECT -
Most NSAID bind reversibly but aspirin is irreversible (acetylation of serine) so now platalets cant make TxA2= TxA2 reception not stimulated - phospholipase C not stimulated = IP3 not produced = Ca2+ levels dont rise = platelets remain inactive = REDUCTION IN BLOOD VOSCOSITY. = ANTIPLATLET EFFECT

Question 3

Issues

Answer 3

Nonselective NSAID can inhibit COX 1 too this is used for homeostatic regulation reducing this can cause issues like stopping the gastric acid secretion and mucus secretion, = LOADS OF GI issues like dyspepsia, ulcers, gastric discomfort, N+V.
Other issues like stopping vasodilation or bronchoconstriction when needed.

skin rashes, more severely SJS and angioedema

Renal function is reduced during NSAID treatment - PGE2 and PGI2 are normally involved with maintaining renal blood flow by dilating the renal artery. Inhibition of these PG with NSAID = blood flow through the kidney is reduced because the renal artery contracts, potentially leading to renal failure

PG cause smooth muscle relaxation in asthma this is needed so asthmatics need to be cautious of a NSAID

NSAIDs include bone marrow disturbances, liver disorders and blood dyscrasias.

Question 4

Uses

Answer 4

Mostly OTC. used for minor pains and aches but can be used for:
*Acute conditions e.g., sporting injuries, sprains and soft tissue injuries.
*Dental pain, menstrual pain, headaches and migraines
*Chronic joint disease e.g., OA, RA
*Postoperative pain.
*Severe pains e.g., bone cancer.

ASPIRIN - ANTIPLATALET

Question 5

COX 2 inhibitors issue

Answer 5

Selective COX-2 inhibitors (such as celecoxib and etoricoxib) should be effective NSAIDs with reduced side effects, as they do not inhibit COX-1, but several COX-2 inhibitors have been withdrawn from the market as their use was associated with a small increased risk of thrombotic events.

Selective COX-2 inhibitors are contraindicated in patients with established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease

During bleeding cessation (haemostasis) TxA2 will be formed more with COX2 inhibitors the PGi2 which inhibits platelets aggregation cant keep up so too much TxA2 could caused a blocked blood vessel bc of platelet plug forming too big or thrombosis may be promoted and increased risk of MI

Question 6

Common brand names

Answer 6

Ibuprofen = Nurofen, brufen, galprofen
Diclofonec = Voltarol