S2 Eicosanoids & NSAIDS

Question 1

Cloprostenol

Answer 1

Estrumate brand
PGF2-alpha derivative
Functions
1. Lysis of corpus lutetium = synchronize
2. Increase uterine contractions = expel pus or abortion
Similar to Dinoprost (Lutalyse)

Question 2

Dinoprost

Answer 2

Lutalyse brand
PGF2-alpha derivative
Functions
1. Lysis of corpus lutetium= synchronize
2. Increase uterine contractions = expel pus or abortion
Similar to Cloprostenol (Estrumate)

Question 3

Travoprost

Answer 3

Travatan brand
PGF2-alpha derivative
Functions
1. drainage of intraocular fluid = glaucoma
Similar to Lantanoprost (Xalatan)

Question 4

Lantanoprost

Answer 4

Xalatan
PGF2-alpha derivative
Functions
1. drainage of intraocular fluid = glaucoma
Similar to Travoprost (Travatan)

Question 5

Tepoxalin

Answer 5

NSAID
Dual COX-1,2 & 5-LOX inhibitor
Less gastropathy
Osteoarthritis in dogs

Question 6

Acetaminophen

Answer 6

Tylenol brand
NO anti-inflammatory activity
Very narrow safe dose range in cats
Risk for acute liver failure

Question 7

Aspirin

Answer 7

NSAID
Irreversible inhibition of COX enzymes
Poor absorption in ruminants & rapid metabolism
Cats = poor glucuronidation = toxicity
High doses = hyperthermia

Question 8

Carprofen

Answer 8

NSAID
Rimadel brand
Dogs (cats)
Cattle (outside US)
COX-2 > COX-1
a. Blood clotting normal
b. Reduced ulcer risk

Question 9

Deracoxib

Answer 9

NSAID
Dogs
COX-2 > COX-1
Loss of specificity at high doses

Question 10

Etodolac

Answer 10

NSAID

Question 11

Flunixin meglumine

Answer 11

NSAID
Standard treatment for cattle & other food animals
Non-selective COX inhibitor

Question 12

Meloxicam

Answer 12

NSAID
COX-2 > COX-1 only at low doses
Small animal use
Esp. cats

Question 13

Phenylbutazone

Answer 13

NSAID
Dogs and horses
Non-selective COX inhibitor 
Not good for food animals = causes anemia in humans
Chondro-destructive effects

Question 14

Lipoxygenase enzyme (LOX)

Answer 14

Inhibited by some NSAIDS

Involved in synthesis of Leukotrienes & Lipoxins

Question 15

Cyclooxygenase enzyme (COX)

Answer 15

Inhibits by NSAIDS

Involved in synthesis of Prostanoids

Question 16

COX-1 characteristics

Answer 16

COX-1

1. Constitutive expression
2. Three protective effects
   a. GI mucosal protection
   b. Hemostasis (platelet function)
   c. Maintains blood flow in hypoperfused kidney

Question 17

Misoprostil

Answer 17

Cytotec brand
PGE derivative
Cytoprotection
Used to treat GI ulcers

Question 18

Adverse effects of Prostaglandins: PGE and PGF2-alpha

Answer 18

1. GI upset
   a. Vomiting
   b. Diarrhea
   c. Cramps (colic)
2. Smooth muscle contraction
   a. Uterine & GI contractions
   b. Bronchoconstriction
   c. Hypertension
   * ** These drugs can be absorbed through skin = human pregnancy risk

Question 19

Adverse effects of NSAIDS

Answer 19

1. Gastropathy
2. Blood clotting alterations
3. Nephropathy
4. Hepatotoxicity
5. Reproductive system
6. Other species specific toxicities

Question 20

PK/PD of NSAIDS

Answer 20

Weak acids
High plasma protein binding = low Vd
Accumulate in alkaline cytoplasms
Excretion in bile
BUT salicylates in urine

Question 21

Other positive effects of NSAIDS

Answer 21

1. Inhibition of NF-kappaB (transc. factor) = reduced pro-inflam. gene transcription
2. Reduce/neutralize free radicals
3. Reduce neutrophil adherence and activation

Question 22

COX-2 characteristics

Answer 22

COX-2

1. Induced expression
2. Three main effects
   a. Inflammation
   b. Pain
   c. Fever