244. Pharm, Pain III

Question 1

NSAIDs mechanism of action

Answer 1

Block COX = no conversion of Arachidonic Acid to PGs (inflammation/pyretic response)

COX1: in all tissues
COX2: inflammatory one, appears only at sites of injury/inflammation, responsible for pain (always present in CNS, kidney, uterus)

Blocking cox may activate leukotrienes - Aspirin-induced asthma

Question 2

How do PGs cause pain?

Answer 2

allodynia - soft touch causes pain (lower threshold)
hyperalgesia - amplifies pain

PNS: PG binds nociceptor = increase Na influx = depolarize membrane = lower threshold = more sensitive (allodynia)

CNS: increase substance P/Glutamate release (hyperalgesia), increase sensitivity of second order neurons, decrease release of inhibitory transmitters

Question 3

How do NSAIDs reduce perception of pain?

Answer 3

NSAIDs BLUNT PNS/CNS sensitization (anti-hyperanalgesics)

Do NOT block the pain transmission itself!

Question 4

How do NSAIDs cause GI Toxicity?

Answer 4

Stomach Cox-1 PGs needed to protect acid lumen (increase mucous thickness, decrease pH gradient, increase bicarb secretion, increase bloodflow)

NSAIDs cause: 1. direct gastric irritation (weakly acidic), 2. decreased cytoprotection in stomach - silent asx ulceration

Question 5

How to prevent NSAID-GI Toxicity

Answer 5

Enteric coating to move lesions into deuodenum only (spare stomach)

PPI’s prevent NSAID UGI Ulcer

Misoprostol: synthetic PGE1 helps increase mucus to protect GI but BIG TIME DIARRHEA

Question 6

How do PGs and NSAIDs affect the kidney?

Answer 6

PGs: made from Cox1/2 to dilate AA in hypoperfused states - affect Na/H2O balance, affect BP

NSAIDs: increase BP in treated HTN (BP elevation and interacts with diuretics in HTN ptns) - does not affect normotensives

Question 7

Hematologic effects of NSAIDs/ASA

Answer 7

Cox-1: converts arachidonic acid into TxA2 = more platelet aggregation and VC

NSAIDs: reversibly bind COX - clotting normalizes after a few half lifes

ASA: irreversible acetylates COX - takes 7-10 days to make new platelets - CARDIOPROTECTIVE

NSAIDs COX-2-i’s DONT DECREASE CLOTTING

Question 8

Celecoxib (Celebrex)

Type, SE

Answer 8

Cox-2 specific inhibitor
reduces GI ulcers (like adding PPI to NSAID)
still increases BP/risk of MI/CVA
No effect on platelets - good for surgery/no interference with ASA

Question 9

topical NSAIDS

Answer 9

Diclofenac: EXPENSIVE, gel/ointment/patch, use on superficial joints, less systemic effects

Question 10

IV NSAIDS

Answer 10

Ketorolac, Ibuprofen, Acetominophen