NSAID 1

Question 1

Clinical uses of NSAIDs (2)

Answer 1

• musculoskeletal: OA, muscle, tendon/lig., fractures
• visceral pain: abdominal( small & lg intestines), thoracic

Question 2

What part of the body do centrally acting analgesics act on?

Answer 2

Brain

Question 3

What part of the body do COX-2 inhibitors act on?

Answer 3

Nociceptors

Question 4

Arachicdonic Acid Cascade

Answer 4

• phospholipids->arachidonic acid via phospholipase A2
• COX 1 & 2 turn arachidonic acid -> Prostaglandin G2
• Prostaglandin G2-> PGH2 via peroxidase
• PGH2 -> thromboxane A2, PGI2, PGE2, PGF2 alpha

Question 5

Function of COX 1

Answer 5

• homeostasis
• maintains renal funct. (PGI2), platelet funct. (Thromboxane A2), and gastric protect. (PGE2)

Question 6

Function of COX 2

Answer 6

• inflammatory stimuli
• triggers macrophages, mast cells, neutrophils, etc.
• stims. Proinflammatory PGs & other inflammatory mediators

Question 7

PGI2

Answer 7

• prostacyclin
• localized in vasc. Tissue, potent vasodilator, inhibits platelet coag.

Question 8

TXA2

Answer 8

• vasoconst.
• promotes thrombus form.

Question 9

PGD2

Answer 9

• prod. by mast cells
• recruits Th2 cells, eosin., & basoph.
• causes bronchial airway contract.
• vasodil.

Question 10

PGE2

Answer 10

• direct vasodil. (Generally relaxes smooth m.)
• inhibits NE release
• induces fever

Question 11

PGF2-alpha

Answer 11

Incr. in response to oxytocin elevation in uterus

Question 12

COX 1 renoprotection

Answer 12

PGI2 & PGE2

Question 13

COX 1 gastroprotection

Answer 13

PGE2

Question 14

Purpose of the COX 1:COX 2

Answer 14

• compares potency (IC50) of drug towards COX isoforms

Question 15

Meaning when COX 1: COX 2 is< or close to 1

Answer 15

Less drug needed to inhbit COX 1

More drug needed to inhibit COX 2

(Classical NSAID)

Question 16

Meaning when COX 1: COX 2> 1

Answer 16

Less drug needed to inhibit COX 2 -or- drug is more potent towards COX2

(Preferential or selective NSAID)

Question 17

Name the classical NSAIDs (5)

Answer 17

Aspirin

Flunixin meglumine

Phenylbutazone

Acetaminophen

Tepoxalin

Question 18

List preferential NSAIDs (2)

Answer 18

Carprofen

Meloxicam

Question 19

List the Coxibs (COX 2 selective)

Answer 19

Firocoxib

Robenacoxib

Deracoxib

Question 20

Most common/serious side effects of NSAID use

Answer 20

Gastroduodenal ulcers & GI bleeding

Question 21

T or F: non-specific NSAIDs cause ulcers more frequently than the specific ones

Answer 21

True

Question 22

NSAIDs cause R dorsal colitis in which species

Answer 22

Horses

Question 23

Are dogs or cats more prone to GI ulcers due to NSAIDs

Answer 23

K9

Question 24

Risk factors for NSAID caused GI ulceration

Answer 24

• old patients
• concurrent glucocorticoid & other NSAID use

Question 25

Most common cause of GI ulcer.

Answer 25

OD

Question 26

Pathogenesis of GI adverse effects caused by NSAIDs

Answer 26

- direct irritation (acid) - inhibiton of PGE2, PGI2, & TXA2 (loss of mucous secretion, bicarb. prod, mucosal epithelialization, and increased bleeding risk)

Question 27

Prev. & Tx of GI issues caused by NSAIDs

Answer 27

- Prev: ACCURATE DOSING - Tx: proton pump inhibitors, h2 blockers, PGE analogues

Question 28

Under what conditions does Renal issues due to NSAIDs generally NOT occur?

Answer 28

If P is … - healthy - free H2O access

Question 29

Which prostaglandins are important in renal blood flow?

Answer 29

PGE2 & PGI2

Question 30

What do PGE2 and PGI2 do in the kidneys?

Answer 30

Ensure intramedullary renal blood flow & urine form.

Question 31

Clincal presentation of analgesic nephropathy

Answer 31

- decre. GFR - H2O retention - hypertens.

Question 32

Risk factors for analgesic nephropathy

Answer 32

- decreased blood flow to kidney - older patients - concurrent use of nephrotoxic/active drugs ( amino-glycoside antibiotics, diuretics, ACE inhib.)

Question 33

Prev. & Tx of analgesic nephropathy

Answer 33

- Prev: avoid use in at risk P, adequate hydration, minimize drug interac.

Question 34

Aspirin effect on platelets and endothelium

Answer 34

Prolonged bleeding time

Question 35

Coxib effects on platelets and endothelium

Answer 35

Enhances thrombus prod.

Question 36

What drug CANNOT be used in CATS & why?

Answer 36

- phenybutazone - causes bone marrow depression

Question 37

Adverse effects of NSAIDs on repro.

Answer 37

Prolonged gestation due to inhibition of PGF2-alpha and PGE2

Question 38

Clinical uses of prostaglandins

Answer 38

- lyse CL - initiate uterine contractions

Question 39

2 drugs and the prostaglandins they affect that lyse CL

Answer 39

- Cloprostenol: PGF2-alpha - Lutalyse: PGF2-alpha

Question 40

What prostaglandin initiates uterine contractions

Answer 40

PGE2