S2 Eicosanoids & NSAIDS Flashcards
Cloprostenol
Estrumate brand
PGF2-alpha derivative
Functions
1. Lysis of corpus lutetium = synchronize
2. Increase uterine contractions = expel pus or abortion
Similar to Dinoprost (Lutalyse)
Dinoprost
Lutalyse brand PGF2-alpha derivative Functions 1. Lysis of corpus lutetium= synchronize 2. Increase uterine contractions = expel pus or abortion Similar to Cloprostenol (Estrumate)
Travoprost
Travatan brand PGF2-alpha derivative Functions 1. drainage of intraocular fluid = glaucoma Similar to Lantanoprost (Xalatan)
Lantanoprost
Xalatan PGF2-alpha derivative Functions 1. drainage of intraocular fluid = glaucoma Similar to Travoprost (Travatan)
Tepoxalin
NSAID
Dual COX-1,2 & 5-LOX inhibitor
Less gastropathy
Osteoarthritis in dogs
Acetaminophen
Tylenol brand
NO anti-inflammatory activity
Very narrow safe dose range in cats
Risk for acute liver failure
Aspirin
NSAID Irreversible inhibition of COX enzymes Poor absorption in ruminants & rapid metabolism Cats = poor glucuronidation = toxicity High doses = hyperthermia
Carprofen
NSAID Rimadel brand Dogs (cats) Cattle (outside US) COX-2 > COX-1 a. Blood clotting normal b. Reduced ulcer risk
Deracoxib
NSAID
Dogs
COX-2 > COX-1
Loss of specificity at high doses
Etodolac
NSAID
Flunixin meglumine
NSAID
Standard treatment for cattle & other food animals
Non-selective COX inhibitor
Meloxicam
NSAID
COX-2 > COX-1 only at low doses
Small animal use
Esp. cats
Phenylbutazone
NSAID Dogs and horses Non-selective COX inhibitor Not good for food animals = causes anemia in humans Chondro-destructive effects
Lipoxygenase enzyme (LOX)
Inhibited by some NSAIDS
Involved in synthesis of Leukotrienes & Lipoxins
Cyclooxygenase enzyme (COX)
Inhibits by NSAIDS
Involved in synthesis of Prostanoids
COX-1 characteristics
COX-1
- Constitutive expression
- Three protective effects
a. GI mucosal protection
b. Hemostasis (platelet function)
c. Maintains blood flow in hypoperfused kidney
Misoprostil
Cytotec brand
PGE derivative
Cytoprotection
Used to treat GI ulcers
Adverse effects of Prostaglandins: PGE and PGF2-alpha
- GI upset
a. Vomiting
b. Diarrhea
c. Cramps (colic) - Smooth muscle contraction
a. Uterine & GI contractions
b. Bronchoconstriction
c. Hypertension
* ** These drugs can be absorbed through skin = human pregnancy risk
Adverse effects of NSAIDS
- Gastropathy
- Blood clotting alterations
- Nephropathy
- Hepatotoxicity
- Reproductive system
- Other species specific toxicities
PK/PD of NSAIDS
Weak acids High plasma protein binding = low Vd Accumulate in alkaline cytoplasms Excretion in bile BUT salicylates in urine
Other positive effects of NSAIDS
- Inhibition of NF-kappaB (transc. factor) = reduced pro-inflam. gene transcription
- Reduce/neutralize free radicals
- Reduce neutrophil adherence and activation
COX-2 characteristics
COX-2
- Induced expression
- Three main effects
a. Inflammation
b. Pain
c. Fever
