NSAIDs Flashcards
1
Q
NSAIDs
A
- Non-Steroidal Anti-Inflammatory Drugs
- decrease pain, fever, inflammation
- inhibit production of prostaglandins from arachidonic acid by the cyclooxygenase (COX) enzymes
2
Q
COX-1
A
- constitutive prostaglandins
- housekeeping
- protective effect on gastric mucosa
- platelet function
- renal blood flow
- some inducible inflammatory role
3
Q
COX-2
A
- inducible prostaglandins
- pain
- inflammation
- fever
-
some constitutive “housekeeping” role
- kidney, brain, uterus
- healing gastric ulcers
- species differences
4
Q
non-selective NSAIDs
A
- block both COX-1 and COX-2
5
Q
selective NSAIDs
A
- only block COX-2
6
Q
COX-1: COX-2 ratios
A
- [IC50] of each isoform
- ratio > 1 = preference for COX-2 (selective)
- carprofen 1.75, meloxicam 12.27
7
Q
contraindications for NSAIDs
A
due to COX-1 effects
- renal disease (low BP->first organ affected is kidney)
- liver disease
- GI disease
- mast cell tumor
- risk of bleeding or low BP in sx
- on corticosteroids
- Cushingoid
8
Q
renal blood flow and NSAIDs
A
- PGs maintain RBF during periods of hypotension (COX-1 > COX-2)
- important during general anesthesia and sx
- pre-operative use of NSAIDs (selective)
- IV fluid support
- BP monitoring and support
9
Q
NSAIDs and platelet function
A
- COX-1 –> PGG & PGH –> thromboxane
- thromboxane allows platelets to aggregate
- COX-1 inhibition causes decreased thromboxane synthesis in the platelet
- most NSAIDs inhibit COX by competitive inhibition when drug is removed
- effect on platelet function is 48-72 hours
- selective (COX-2) inhibition- little effect
10
Q
aspirin and platelet function
A
- aspirin acetylates COX-1 enzyme irreversibly
- platelets are unable to synthesize more COX (no nucleus)
- effect lasts the life of platelets (10 days)
- no sx for 7-10 days!
11
Q
perioperative use of NSAIDs
A
- nonselective NSAIDs-not recommended
- COX-2 selective NSAIDs
- rimadyl and meloxicam (injectable)
- no documented effects on renal function or platelet function
- pre-operatively for preemptive analgesia
- administer 30-60 minutes prior to recovery (time to take out PGs)
12
Q
gastric mucosal protection
A
- increase mucus secretion
- increase bicarbonate secretion
- increase epithelial cell renewal
- increase mucosal BF
- decrease acid secretion
- prostaglandins, nitric oxice, autonomic nervous system
13
Q
gastric mucosal protection and NSAIDs
A
- block COX-1 and subsequently prostaglandins and PGE
- PGE: most important in protecting gastric mucosa
14
Q
mechanisms of NSAID-induced gastritis
A
- inhibition of COX
- decreased production of PGE
- concurrent administration of misoprostol (synthetic PGE) decreases severity of NSAID gastropathy with non-selective NSAIDs
-
decrease in gastric mucosal BF
- increase in neutrophil adherence to vascular endothelium
- leukotrienes cause chemotaxis for neutrophils and other inflammatory cells, vasoconstriction and increased vascular permeabilityd
15
Q
NSAID elimination
A
- metabolized by liver
- glucuronidation or oxidative enzymes
- glucuronidation most common
- depends on NSAID
- metabolites exreted in bile or urine
16
Q
corticosteroids
A
- do not inhibit prostaglandin synthesis
- therefore they:
- are not analgesics
- do not inhibit platelet function
- do cause GI dysfunction, but by a different mechanism than NSAIDs
17
Q
corticosteroids and gastric mucosal protection
A
block:
- increased mucus secretion
- increased bicarbonate secretion
- increased epithelial cell renewal
- increased mucosal BF
- decreased acid secretion
18
Q
COX-1 and COX/LOX inhibitors
A
- COX/LOX mechanism addresses some of the GI side effects of COX inhibition but does not address renal blood flow or platelet function
- COX/LOX inhibitors are non-selective
- effects of COX-1 inhibition are not known
- use with caution for perioperative use or with renal disease
19
Q
cats and NSAIDs
A
- reduced glucuronidation of drugs in cats
- prolonged elimination half-lives
- many NSAIDs
- some NSAIDs (meloxicam) are cleared by oxidative enzymes in cats
- more sensitive to renal effects of NSAIDs
- species differences
- COX-2 may have a more constitutive role in kidney in cats
20
Q
acetaminophen and cats
A
- contraindicated
- decreased glucuronidation -> metabolism by alternate pathways
- toxic metabolite
- N-acetyl-p-benzoquinone
- methemoglobinemia
- Heinz body anemia
- detoxified by glutathione
- antedote = acetylcysteine
- glutathione precursor
21
Q
aspirin
A
- relief of mild to moderate pain associated with musculoskeletal inflammation or osteoarthritis
- rapidly absorbed in stomach/SI after oral admin
- high first pass effect in liver to yield salicylic acid (main metabolite)
- aspirin mainly inhibits COX-1, salicylic acid has more balanced COX-1/2 activity
- widely distributed in tissues and fluids and crosses placental barrier
- salicylate highly protein bound
- metabolism and elimination via hepatic conjugation w/ glucoronic acid, followed by renal excretion
- adverse effects: mucosal erosion and ulceration in dogs, vomiting and melena at ghigher doses
- aspirin OD -> salicylate poisoning: severe acid/base abnormalities, hemorrhages, seizures, coma, death
22
Q
ketoprofen
A
- acute pain (up to 5 days) in dogs and cats
- horses: pain and inflammation with osteoarthritis or visceral pain (colic)
- potent inhbitor of COX and bradykinin, may inhibit some lipooxygenase pathways
- rapidly absorbed after oral administration
- half life of 2-3 hrs in cats and dogs
- metabolized in liver to inactive metabolites that are eliminated by renal excretion
- adverse effects: GI upset and similar NSAID effects
23
Q
flunixin meglumine
A
- non-selective COX inhibitor
- treatment of visceral pain (equine colic)
- may have anti-endotoxic activity
- rapidly absorbed following PO or IM administration
- elimination half- life is short (2-3 hrs)
- primarily renal excretion
- adverse effects: GI ulceration and erosion
- has been used to treat mastitis and pulmonary emphysema in cattle (not approved)
24
Q
phenylbutazone
A
- primarily COX-1?
- tx of laminitis in horses
- plasma half-life is 5-6 hr in horses/dogs and >30 hrs in cattle
- absorbs to hay when given PO, may reduce GI absorption and bioavailability
- metabolized by liver to active and inactive metabolites
- excreted in urine
- low therapeutic index
- adverse effects: GI effects and depression, ulcers
25
Q
carprofen
A
- manage pain and inflammation associated with osteoarthritis and acute pain associated with soft-tissue and orthopedic sx in dogs
- half-life is ~ 8 hrs, highly protein bound
- elimination via hepatic biotransformation, excretion of metabolites in feces and urine
- greater selectivity for COX-2 but considered weak COX inhibitor
- adverse effects: GI signs (V, D, GI ulceration), idiosyncratic hepatopathies
26
Q
meloxicam
A
- potent inhibitor of prostaglandin synthesis
- tx of acute and chronic inflammation associated with musculoskeletal dz, mgmt of postoperative pain
- COX-2 selective
- highly protein bound
- long half life
- safer for GI than non-selective
27
Q
deracoxib
A
- control of postoperative pain and inflammation associated with orthopedic sx for up to 7 days
- control of pain and inflammation associated with osteoarthritis
- inhibits COX-2 mediated PGE-2 production
- elimination half-life is 3 hrs in dogs
28
Q
firocoxib
A
- control pain and inflammation associated with osteoarthritis
- control of postop pain and inflammation associated with soft-tissue and orthopedic sx in dogs
- rapidly absorbed after PO administration
- eliminated by hepatic metabolism and fecal excretion
- more selective for COX-2
- highly protein bound
- greater GI safety
29
Q
piroxicam
A
- selective COX-2 inhibitor
- extensive enterohepatic recycling in dogs resulting in prolonged plasma half-life
- GI ulceration and bleeding, renal papillary necrosis in dogs
30
Q
robenacoxib
A
- COX-2 inhibitor
- osteopedic post-op pain, osteoarthritis
- use for no more than 3 days
- liver metabolism
31
Q
tepoxalin
A
- non-selective COX and LOX inhibitor
- rapidly absorbed
- short plasma half-life, but has active metabolite
- highly protein bound
- adverse effects: GI
