Exam #01c (NSAIDs) Flashcards
What is the main biochemical mediator of sensitization of nociceptors?
prostaglandins
Explain the MOA of NSAIDs
Pain is felt when damaged tissue releases biochemical mediators which stimulate nerve endings.
NSAIDs inhibit the formation of these biochemical mediators by inhibiting cyclooxygenase
What are the (4) main indications for NSAIDs?
- pain
- fever
- antiplatelet
- inflammation (not APAP)
What (4) advantages does APAP have over ASA in terms of AEs?
- less GI upset
- no antiplatelet effect
- does not effect uric acid levels
- OK in children with viral infections
What is the major AE associated with APAP? Is it reversible? How is it treated?
Causes severe hepatotoxicity via toxic metabolic intermediates
Irreversible
Can be treated with Mucomyst (Acetylcysteine)
True or False - APAP is an appropriate NSAID to treat a child with a viral infection, fever, and general inflammation?
False! - APAP is appropriate to treat everything EXCEPT inflammation
Based on your current knowledge of blood thinners and APAP, APAP would not cause any interference with drugs like Warfarin?
True - APAP has no antiplatelet effect seen with other NSAIDs
Under normal dosing, how is APAP metabolized?
How does APAP metabolism change if given high doses and what potential adverse effects can this cause?
APAP metabolized via phase II conjugation
With high doses, APAP is metabolized by CYP450 enzymes producing a toxic metabolite that can become covalently attached to the liver cells causing IRREVERSIBLE liver damage
Where do NSAIDs and other COX-inhibitors interfere in the prostaglandin biosynthesis pathway?
NSAIDs and COX inhibitors reversibly inhibit cyclooxygenase from converting Arachidonic acid to PGG2 (prostaglandin precursor for many other mediators)
Which prostaglandin agonist drug is given to patients that chronically take NSAIDs. What is its MOA?
Misoprostol
MOA: Misoprostol is a prostaglandin E2 agonist that, after binding, activates the Gi protein, inhibiting adenylate cyclase activity, which decreases [cAMP], and reduces gastric acid secretion
What is the main difference between ASA and other NSAIDs with regards to COX inhibition?
ASA COX inhibition is IRREVERSIBLE b/c it acetylates the COX enzyme
What are the main AEs associated with NSAIDs? What AE is worse with ASA compared with all other NSAIDs?
- GI bleeding - from antiplatelet effects
- Renal problems - esp taking chronically - prostaglandins affect renal perfusion)
- CV effects - higher incidence of stroke, MI
GI bleeding, ulcer occurs more often with ASA than any other NSAID
Although acetylsalicylic acid (ASA, Aspirin) can be used for pain, inflammation, and fever, what is it primarily used for today?
Use primarily in low doses for inhibition of platelet aggregation
What is the concern with giving ASA to children with a viral infection?
Child could develop Reyes syndrome - vomiting and encephalopathy
Tinnitus, vertigo, decreased hearing, hyperventilation (hyperpnea) are symptoms of salicylism caused by what NSAID?
ASA
True or False - ASA is a highly protein bound drug and therefore can displace other highly protein bound drugs, increasing their effects?
True
Which arylalkanoic acid NSAID comes as a suppository and injection (and PO)?
Indomethacin
Which arylalkanoic acid NSAID comes as optical, topical gel, and in combo with Misoprostol (and PO)?
Diclofenac
Which arylalkanoic acid NSAID comes as optical and injection (and PO)?
Ketorolac
What is the Blob-blob theory?
There are 3 sites on COX important for binding and inhibition. They are:
- Acid center (usually 1-2 C’s from a flat surface binds to a cationic site on the COX enzyme)
- Flat hydrophobic area (usually an aromatic ring)
- A second hydrophobic portion (binds to trough area on COX)
True or False - the conformation which NSAIDs assume is important for activity with respect to COX binding?
True
Which enantiomer is usually the active form of propionic acid derivative NSAIDs?
(S)-(+) enantiomer
True or False - when a racemic mixture of propionic acid derivative NSAIDs are administered, a portion of the R is converted to S? Which 2 enzymes are responsible for this action?
True
fatty acyl-CoA synthetase AND epimerase
Name (3) non-biologic DMARDs?
- Methotrexate
- Hydroxychloroquin
- Leflunomide
What are the (4) MOA of biological DMARDs?
- TNF inhibitors
- T-cell activation inhibitors
- IL receptor antagonists
- monoclonal antibodies that destroy B-cells (Rituximab)
What (2) drugs are indicated for an acute gout attack?
- Colchicine
2. Indomethacin
What (4) drugs are used as gout prophylaxis?
- probenicid
- sulfinpyrazole
- allopurinol
- febuxostat
What is MOA of allopurinol and febuxostat?
inhibits xanthine oxidase
