NSAID's

Question 1

Molecular Inflammatory Mediators (3 Major groups)

Answer 1

Kinins (bradykinin) Neuropeptides (Substance P) and Vasoactive amines (histamine, 5HT)

Arachidonic acid metabolites - Cyclooxygenase, Prostaglandin, Thromboxanes
Prostacyclin
Lipoxins and leukotrienes

Cytokines (e.g., TNF-alpha), oxygen free radicals, and proteases

Question 2

Two areas of relief of pain

Answer 2

site of injury

spinal cord

Question 3

3 main functions of NSAID’s

Targets

Answer 3

Analgesia
Anti-pyretic
Anti-inflammatory

Primary target –> COX-1, COX-2

Question 4

COX 1

Answer 4

constitutively active
widely distributed
HOUSEKEEPING FUNCTIONS

i.e. synthesis of PG in stomach mucosa

Question 5

COX 2

Answer 5

INDUCIBLE

production of INFLAMMATORY molecules

vascular endothelium - PGI-2

Renal COX-2 - essential for normal function

Question 6

What two prostaglandins are most prominent?

Answer 6

PGE-2

PGI-2

Question 7

Two major pathways from arachidonic acid

Answer 7

Lipoxygenase - leukotrienes

Cyclooxygenase - prostaglandins, prostacyclins, thromboxanes

Question 8

Two types of NSAID’s

Answer 8

COX-2 Specific

Non-specific

Question 9

Aspirin and other PG synthesis inhibitors should be avoided in what clinical scenarios?

Answer 9

Viral illness

Children - Reye’s Syndrome

Question 10

Aspirin dose dependent actions

kinetics for each

Answer 10

low dose - analgesic, anti-pyretic (first order kinetics)

high dose - anti-inflammatory (zero order kinetics)

Question 11

Aspirin has potential for drug interactions due to what characteristic?

Answer 11

bound to plasma proteins

Question 12

Acetylation of COX is _______

Answer 12

irreversible

Question 13

Anti-inflammatory and analgesic effects due to inhibition of _____

Answer 13

COX-2

Question 14

Anti-pyretic effects due to?

Answer 14

blockage of prostaglandin production in the CNS

resets temperature control at hypothalamus

fall in temp leads to dilation of superficial blood vessels

Question 15

Anti-coagulant effects due to

Answer 15

IRREVERSIBLE INHIBITION OF COX-1

decreased thromboxane A-2

Question 16

Main Adverse Effects of Aspirin

Answer 16

GI upset

GI Irritation - inhibition of protective PG’s synthesis

Platelet inhibition - prolonged bleeding time

Kidney function
Hepatitis
Hypersensitivity
TINNITUS
Reye's syndrome

Question 17

Non-selective COX inhibitors

Answer 17

Aspirin
Ibuprofen
Indomethacin
Ketorolac
Naproxen
Oxaprozin
Piroxicam
Sulindac

Question 18

COX-2 Inhibitors have ______ adverse effects

Increased incidence of _______

Answer 18

less GI adverse effects

cardiovascular thrombotic events

Question 19

COX-2 INhibitors (3)

Answer 19

Celecoxib
Etoricoxib
Meloxicam

Question 20

Acetaminophen has ______

Answer 20

NO ANTI-INFLAMMATORY PROPERTIES

Question 21

Acetaminophen safety

Answer 21

HEPATOTOXICITY at high doses

150 mg/kg liver necrosis

350 mg/kg liver failure

interactions with CYTOCHROME P450 2E1 substances

Question 22

Capsaicin MOA

Answer 22

BINDS TO VANILLOID RECEPTOR (heat activated channels on nociceptor neurons

release of substance P

PROLONGED ACTIVATION DEPLETES SUBSTANCE P

Question 23

NSAID Interactions

Answer 23

Displacement of protein binding - warfarin, phenytoin, steroids

Diuretics

Anticoagulatns

GI Effects

Question 24

Gout due to

associated with?

Answer 24

deposits of uric acid crysals in joints and cartilage

hyperuricemia

Question 25

First line treatment for acute gout

Answer 25

Indomethacin (has largely replaced colchicine)

other NSAID’s can be used

Aspirin NOT USED due to renal retention of uric acid at low dose

Question 26

Colchicine MOA

Answer 26

INHIBITS LEUKOCYTE MIGRATION AND PHAGOCYTOSIS

through inhibition of microtubule aggregation

Question 27

Xanthine Oxidase INhibitors (2)

Answer 27

Allopurinol

Febuxostat

Question 28

Uricosuric Drugs

Answer 28

Probenicid

Sulfinpyrazone