SACCM 158: Nonsteroidal Antiinflammatory Drugs Flashcards
(21 cards)
Name 9 relative contraindications for NSAID administration
- History of GI disease
- NSAID intolerance
- renal disease
- hepatic disease
- anemia
- coagullopathy
- hypovolemia or dehydration
- hypotension
- hypoproteinemia
What are the functions of constitutive prostaglandins?
- gastroprotection via secretion of gastric mucus and bicarbonate production
- renal perfusion under hypotensive conditions
- vascular hemostasis via thromboxane and prostacyclin production
What are the functions of induced prostaglandins?
- production of inflammatory mediators (endotoxins, cytokines)
- production of growth factors resposible for sensitizing peripheral nociception
Where is COX-3 located?
cerebral cortex
How does COX-3 inhibition cause analgesia?
COX-3 inhibition PGE2 synthesis –> COX-3 located in the cerebral cortex –> central mechanism of analgesia
How are NSAIDs metabolized and excreted?
- metabolized via cytochrome P450 enzymes –> either glucoronidation or oxidation
- excretion via the biliary route or urine
Why are NSAIDs of the phenolic compoud group contraindicated in cats?
require glucoronidation for metabolism –> cats have deficient glucuronidation –> acetaminophen contraindicated and carprofen used with caution (slow elimination and longer half-life)
What is the washout period between two different NSAIDs?
- unknown
- anecdotal: 2-3 days is acceptable
Fill in the blanks
PGH2 - prostaglandin H2
HPETE –> leukotriene production
Explain how NSAIDs cause GI complications
COX-1 inhibition
* decreased local blood flow
* suppression of bicarbonate secretion
* suppression of mucous production
COX-2 inhibitio
* suppresses healing once damage has occured
some NSAIDS (e.g., aspirion) –> cause direct damage to GI mucosa
lower GI damage –> related to prolonged and repeated exposure from enterohepatic recirculation
PLUS (not in this chapter) –> “trapping” theory = NSAIDs diffuse across gastric mucosal epithelial cell membranes into the cytoplasm, where pH is neutral. In neutral pH, NSAIDs are converted into the re-ionized and relatively lipophobic form. Therefore NSAIDs are trapped and accumulate within cells, leading to the cellular injury
Why can concurrent PPI administration with NSAIDs cause increased risk of lower GI signs?
PPI-induced alternations of the intestinal microbiome
Explain how the COX payhways are involved in renal protection
maintenance of renal perfusion and autoregulation
PGE2/PGI2 - promote vasodilation and inhibition of Na+ reabsorption
TXA2 - modulates renin productin and vasoconstriction
How do COX-1 and COX-2 affect hemostasis?
COX-1 –> TXA2 production –> platelet aggregation and vasoconstriction
COX-2 –> prostacyclin –> anticoagulant and vasodilation
How long do aspirin’s antithrombotic properties last?
binds to COX irreversibly –> lasts for whole platelet life-span, i.e., 9-11 days
What breed is predisposed to the idiosynchratic hepatic injuries from NSAIDs?
more likely to develop in Labrador Retrievers
Where is the arachidonic acid pathway does Grapiprant work?
EP4 prostaglandin receptor antagonist
What is the proposed mechanisms for analgesia by acetaminophen?
inhibits PGE2 synthesis in the central nervous system related to COX-3 activity (subform of COX-1)
What are the adverse events associated with acetaminophene toxicosis in dogs and cats
hepatotoxicity (more common in dogs)
methemoglobinemia (more common in cats) –> oxidative injury ot RBCs with anemia, Heinz body formation
cats deficient in glucuronidation –> more sensitive to acetaminophen toxicity
What are the clinical signs of methemoglobinemia?
- cyanosis
- facial edema
- prolapsed conjunctival membranes
- brown blood and urine
- tachypnea
- dyspnea
What is the treatment for methemoglobinemia?
supportive care:
* fluid therapy
* NAC
* ascorbic acid
What is the proposed mechanism of action of Metamizole?
- COX-3 inhibition
- potential: activation of opioid and cannabinoid systems
