NSAIDs & Immunosuppressants Flashcards
10 questions
NSAIDs have eicosanoid-depressing action. what are eicosanoids?
PGs and interleukins
what catalyzes the formation of PGs and thromboxane from arachidonic acid?
COX enzymes
MOA of NSAIDs?
non-selective inhibitors of COX-1 and COX-2 enzymes
all NSAIDs, except _____ irreversibly inhibit COX-1 and COX-2 by acetylation of the enzymatic active site
aspirin
what is leukotrienes usually accompanied by?
release of histamine
housekeeping enzyme that is found in the stomach
COX-1
what hormone is a major product of COX-1? what does it do?
thromboxane
platelet aggregation
why is aspirin effective at reducing cardiac events?
because it inhibits platelet COX-1
enzyme that induces the inflammatory response
COX-2
where does COX-2 work? (3)
kidney
lungs
inflammatory cells
what 2 drug types inhibit COX-2 gene expression?
NSAIDs
glucocorticoids
why can the use of NSAIDs not eliminate leukotriene synthesis?
NSAIDs do not inhibit lipoxygenases
what is required for NSAIDs to be an antiinflammatory?
large doses 600-800mg
how does pyresis occur?
pyrogens stimulate interleukin-1 release = stimulates PG in hypothalamus = increases thermo set point
what is the DOC for pyresis? what should be avoided when taking it?
acetaminophen
avoid ethanol
how does pain occur?
PGs sensitize pain fibers to stimuli
what makes acetaminophen different?
only works in the CNS
what NSAID is used to inhibit premature labor?
indomethacin
what kind of inflammation can NSAIDs work well for? (3)
osteoarthritis
RA
ankylosing spondylitis
how is aspirin converted to salicylate?
by first pass hepatic metabolism
what does it mean when large doses of aspirin exhibit non-linear kinetics?
it has an increased half life
what is a sign that aspirin dose is too high?
tinnitus
what NSAID can interfere with the antiplatelet effect of aspirin by preventing acetylation of acetylsalicylic acid?
ibuprofen
what kind of NSAIDs have little effect on platelets, thus little risk of bleeding?
nonacetylated salicylates
what’s important about nonsalicylate NSAIDs?
less GI toxicity
what are the 4 nonsalicylate NSAIDs?
diclofenac
etodolac
ibuprofen
indomethacin
which 2 nonsalicylate NSAID are relatively COX-2 selective?
diclofenac
etodolac
which 2 nonsalicylate NSAIDs have some inhibitory action against lipoxygenase? (decrease leukotriene)
diclofenac
indomethacin
ADR of diclofenac?
increased risk of MI
ADR of indomethacin? (2)
CNS (esp in elderly)
increased risk of GI ulcers
which nonsalicylate NSAID is only used for acute moderately severe pain?
indomethacin
-coxib
COX-2 inhibitors
what is the half life of celecoxib?
10 hours
what is celecoxib used for? (3)
arthritis
dysmenorrhea
post-surgical pain
ADR of celecoxib? (2)
increased risk of MI
increased risk of stroke
why do NSAIDs have a small Vd?
highly bound to plasma albumin
how are NSAIDs mostly excreted?
kidneys
what are 3 ADR specific for aspirin/salicylates? what causes them?
hypersensitivity -
rhino conjunctivitis
angioedema
urticaria
increased leukotriene synthesis
a patient presents with rhino conjunctivitis, angioedema, and urticaria after taking aspirin/salicylate. about when did the patient take it?
within the last 3 hours
why do NSAIDs cause increased BP?
allow full vasoconstriction caused by NE
how do NSAIDs cause salt/water retention? what can it lead to? (3)
decrease renal blood flow and GFR
hyperkalemia
interstitial nephritis
reversible acute kidney failure
the nephrotoxicity of celecoxib is = to _____ NSAIDs
non-selective
how do NSAIDs cause GI ulceration and bleeding?
inhibit PG who are produced by the stomach to maintain the mucosal integrity
what can be given to geriatric patients with prior history of NSAID-induced GI ulceration?
misoprostol
stable analogue of PGE1 used to treat gastric erosions and ulcerations caused by NSAIDs
misoprostol
what 2 products can be used together to prevent NSAID-induce GI ulcers but can predispose patients to C. diff?
NSAID + H2 receptor antagonist (famotidine)
OR
NSAID + proton pump inhibitor (omeprazole)
what do many physicians Rx to treat arthritis in elderly patients?
NSAID + PPI (omeprazole)
what CNS reactions can NSAIDs cause?
headache
rebound headache
dizziness
why are NSAIDs CI in pregnancy?
can cause fatal pulmonary hypertension in fetus
what is safe to use in pregnancy to treat pain?
acetaminophen
ADR of acetaminophen?
hepatotoxicity
when does toxicity from acetaminophen occur?
when glutathione is depleted
(glutathione pushes the toxic metabolite out of the system)
what is the treatment for acetaminophen overdose?
gastric lavage + IV N-acetylcysteine
how does ethanol increase the risk of acetaminophen hepatic toxicity?
ethanol increases CYP450
class of drugs that increase gene expression of lipocortin which inhibits phospholipase A2 and inhibits inflammation
corticosteroids
prednisone
prednisolone
drug class that suppresses interleukin-2 production in T lymphocytes
calcineurin inhibitors
what are the 2 calcineurin inhibitors?
cyclosporine
tacrolimus
which calcineurin inhibitor is used to prevent graft-vs-host disease?
cyclosporine
which calcineurin inhibitor is used to reduce risk of organ rejection?
tacrolimus
ADR of cyclosporine?
swelling gums
how are corticosteroids metabolized?
liver
suppress intracellular signaling pathway important for cell growth and proliferation of T lymphocytes
mTOR inhibitors
what are the 2 mTOR inhibitors?
Sirolimus
Everolimus
what is sirolimus used for?
reduce risk of organ rejection by coating coronary stents
what is everolimus used for? (2)
reduce risk of organ rejection
HER-2 negative breast cancer
blocks DNA synthesis and expansion of lymphocyte populations
IMDH inhibitors
what are the 3 IMDH inhibitors?
azathioprine
mycophenolate
leflunomide
what are the 3 uses for azathioprine and mycophenolate?
RA
Crohn’s disease
transplants
what are the 2 uses for leflunomide?
RA
HER-2 negative breast cancer
which 2 immunosuppressants can be used for HER-2 negative breast cancer?
everolimus
leflunomide
