NSAID 1 Flashcards
Clinical uses of NSAIDs (2)
- musculoskeletal: OA, muscle, tendon/lig., fractures
- visceral pain: abdominal( small & lg intestines), thoracic
What part of the body do centrally acting analgesics act on?
Brain
What part of the body do COX-2 inhibitors act on?
Nociceptors
Arachicdonic Acid Cascade
- 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
Function of COX 1
- homeostasis
- maintains renal funct. (PGI2), platelet funct. (Thromboxane A2), and gastric protect. (PGE2)
Function of COX 2
- inflammatory stimuli
- triggers macrophages, mast cells, neutrophils, etc.
- stims. Proinflammatory PGs & other inflammatory mediators
PGI2
- prostacyclin
- localized in vasc. Tissue, potent vasodilator, inhibits platelet coag.
TXA2
- vasoconst.
- promotes thrombus form.
PGD2
- prod. by mast cells
- recruits Th2 cells, eosin., & basoph.
- causes bronchial airway contract.
- vasodil.
PGE2
- direct vasodil. (Generally relaxes smooth m.)
- inhibits NE release
- induces fever
PGF2-alpha
Incr. in response to oxytocin elevation in uterus
COX 1 renoprotection
PGI2 & PGE2
COX 1 gastroprotection
PGE2
Purpose of the COX 1:COX 2
- compares potency (IC50) of drug towards COX isoforms
Meaning when COX 1: COX 2 is< or close to 1
Less drug needed to inhbit COX 1
More drug needed to inhibit COX 2
(Classical NSAID)
Meaning when COX 1: COX 2> 1
Less drug needed to inhibit COX 2 -or- drug is more potent towards COX2
(Preferential or selective NSAID)
Name the classical NSAIDs (5)
Aspirin
Flunixin meglumine
Phenylbutazone
Acetaminophen
Tepoxalin
List preferential NSAIDs (2)
Carprofen
Meloxicam
List the Coxibs (COX 2 selective)
Firocoxib
Robenacoxib
Deracoxib
Most common/serious side effects of NSAID use
Gastroduodenal ulcers & GI bleeding
T or F: non-specific NSAIDs cause ulcers more frequently than the specific ones
True
NSAIDs cause R dorsal colitis in which species
Horses
Are dogs or cats more prone to GI ulcers due to NSAIDs
K9
Risk factors for NSAID caused GI ulceration
- old patients
- concurrent glucocorticoid & other NSAID use
Most common cause of GI ulcer.
OD
Pathogenesis of GI adverse effects caused by NSAIDs
- direct irritation (acid)
- inhibiton of PGE2, PGI2, & TXA2 (loss of mucous secretion, bicarb. prod, mucosal epithelialization, and increased bleeding risk)
Prev. & Tx of GI issues caused by NSAIDs
- Prev: ACCURATE DOSING
- Tx: proton pump inhibitors, h2 blockers, PGE analogues
Under what conditions does Renal issues due to NSAIDs generally NOT occur?
If P is …
- healthy
- free H2O access
Which prostaglandins are important in renal blood flow?
PGE2 & PGI2
What do PGE2 and PGI2 do in the kidneys?
Ensure intramedullary renal blood flow & urine form.
Clincal presentation of analgesic nephropathy
- decre. GFR
- H2O retention
- hypertens.
Risk factors for analgesic nephropathy
- decreased blood flow to kidney
- older patients
- concurrent use of nephrotoxic/active drugs ( amino-glycoside antibiotics, diuretics, ACE inhib.)
Prev. & Tx of analgesic nephropathy
- Prev: avoid use in at risk P, adequate hydration, minimize drug interac.
Aspirin effect on platelets and endothelium
Prolonged bleeding time
Coxib effects on platelets and endothelium
Enhances thrombus prod.
What drug CANNOT be used in CATS & why?
- phenybutazone
- causes bone marrow depression
Adverse effects of NSAIDs on repro.
Prolonged gestation due to inhibition of PGF2-alpha and PGE2
Clinical uses of prostaglandins
- lyse CL
- initiate uterine contractions
2 drugs and the prostaglandins they affect that lyse CL
- Cloprostenol: PGF2-alpha
- Lutalyse: PGF2-alpha
What prostaglandin initiates uterine contractions
PGE2
