Wk18 D3 NSAIDS

Question 1

Eicosanoids made from ___. __ carbons, __ double bonds. Released from membrane by ___ (rate-limiting step __). Short ___, act on ___.

Answer 1

Arachidonic Acid
20, 4
phospholipases (PLA2 is rate limiting step)
half-life
GPCRs

Question 2

3 main pathways from arachidonic acid are…

Answer 2

Cyclooxigenase
Lipoxygenase
Epoxygenase
(Free radical-mediated oxidation)

Question 3

COX1 expressed in ___ and ___. ___ produces prostaglandins. COX2 is ___ and found in ___. They make ___ and ___. COX2 important for __, ___, ___.

Answer 3

tissues, platelets, constitutively
inducible, inflammatory cells
prostaglandins, thromboxanes
Inflammation, cancer, renal development

Question 4

PGI2 is a ___. TXA2 is a ___. They are important for ___, __, and __ protection.

Answer 4

Prostacycline
Thromboxane
GI, kidney, heart

Question 5

LTB4 is ___ for neuts and monos. ___ are important for asthma.

Answer 5

chemotactic

Cysteinyl-leukotrienes (LTC-F)

Question 6

Platelet activating factor is potent increaser of ___ and ___ mediator

Answer 6

vascular permeability

pro-inflammatory

Question 7

Glucocorticoids and NSAIDS inhibit __ expression.

Answer 7

COX

Question 8

NSAIDS 3 main action

All have all 3, except ___, which lacks effectiveness on ___.

Answer 8

Anti-inflammatory
Analgesic
Antipyretic
Acetaminophen, no anti-inflammatory

Question 9

COX1/2 have ___ homology. COX2 has a __ binding pocket and ___ pocket.

Answer 9

60%
25% larger
secondary internal

Question 10

Main NSAID side-effects include ___, typically from inhibition of ___. Effect not seen in ___. Also see effects on __.

Answer 10

GI ulcers
COX1
Acetaminophen
Renal

Question 11

Aspirin hits ___ in ___ at low doses. Therefore it limits formation of ___. It ___ COX, causing ___ inhibition. In children with viral illnesses, risk of ___.

Answer 11

COX1, platelets (they can’t make new enzyme!)
TXA2 (made in platelets)
acetylates, irreversible
Reye’s syndrome

Question 12

Ketorolac and Diclofenac are ___. K is used for ___ but not used long due to risk of ___. Diclofenac most common in ___.

Answer 12

Heteroaryl acetic acids. Postop pain. MI.

Europe

Question 13

Ibuprofen/Naproxen are ___. Trade names are __. Main difference is ___.

Answer 13

Propionic acid derivatives
Advil+Motrin/Aleve
Half-life (advil 2hr, aleve 14 hr)

Question 14

COX2 selective inhibitors are __. Clinical trials showed increased __ side effects. Maybe since COX2 major source of ___, affecting ___ balance

Answer 14

Celecoxib, Vioxx.
CV
Prostacyclin (PGI2)
thromboxane/prostacyclin balance