EXAM 3 Prostanoids and Anti-Inflammatory Drugs Flashcards
what are the 3 major classes of anti-inflammatory drugs?
- nonsteroidal anti-inflammatory drugs (NSAIDs)
- glycocorticoids
- DMARDs (disease modifying anti-rheumatic drugs)
what is the mechanism of NSAIDs?
inhibit cyclooxygenase enzymes
what is the mechanism of glucocorticoids?
inhibit phospholipase A2 (PLA2)
what are the two types of DMARDs?
- traditional (non-biologic) DMARDs
- biologic DMARDs
what are eicosanoids?
- oxygenation products of poly-unsaturated long chain fatty acids
- G-coupled proteins
eicosanoids act in ___ and/or ___ fashions
autocrine and/or paracrine
what are prostanoids?
subclassification of eicosanoids
which 3 drugs are prostanoids?
- prostaglandins
- thromboxanes
- prostacyclins
prostanoids have major biological effects on what 5 things?
- smooth muscle
- platelets and blood cells
- nerve terminals
- endocrine organs
- adipose tissue
which drugs do not inhibit platelet aggregation or cause GI upset/ulceration?
COX-2 selective inhibitors
what are 3 common NSAIDs?
aspirin, ibuprofen, and naproxen
aspirin is also known as ___
acetylsalicylic acid
the following are contraindications for which drug?
avoid in patients with NSAID allergies, renal insufficiency, gout, hemophilia or other bleeding disorders, taking blood thinners, ACE inhibitors, methotrexate or oral hypoglycemic drugs, within 10 days of surgery, or near term pregnancy
avoid in children with viral-induced illness (Reye syndrome)
aspirin
___ is antipyretic and algesic (600-1000mg/day) and anti-inflammatory (3.2-4g/day)
aspirin
describe aspirins inhibition of COX enzymes
nonselective COX-1 and COX-2 inhibition
___ is the only NSAID to inhibit both COXs in an irreversible manner
aspirin (ASA)
___ is valued primarily for its antiplatelet aggregation effects at either 81mg/day or 325mg every other day
aspirin (ASA)
ibuprofen is an NSAID derivative of ___
propionic acid
___ is antipyretic and analgesic (doses <2400mg/day) and anti-inflammatory (doses >2400mg/day)
ibuprofen
if taken together, ibuprofen interferes with the ___ effect of low-dose aspirin, rendering aspirin less effective for ___ and ___
- antiplatelet
- MI and stroke prevention
___ is an NSAID with similar pharmacological profile as other NSAIDs but is available in slow-release formulation
naproxen
aka aleve
what are the main adverse effects common to all NSAIDs?
CNS, cardiovascular, GI, hematologic, hepatic, pulmonary, skin, renal, reye syndrome
describe adverse effects on the GI common to all NSAIDs
abdominal pain, dysplasia, nausea, vomiting, ulcers, or bleeding
describe reye syndrome that is an adverse effect common to all NSAIDs
rapidly progressive encephalopathy which occurs after recovery from viral infections
common in children taking salicylates after viral-induced illness
celexocib (celebrex) is a ___ inhibitor
COX-2 selective
celecoxib (celebrex) has ___, ___, and ___ effects that are similar to aspirin
analgesic, antipyretic, and anti-inflammatory
celecoxib (celebrex) has no effect on ___
platelet aggregation
___ is 10-20x more selective for COX-2 than COX-1. what is the significance?
- celecoxib (celebrex)
- significantly fewer GI adverse effects, no cardiorotective effects, and increase risk of edema, hypertension, myocardial infarction, and stroke
acetaminophen is known as a ___ pain reliever
non-aspirin
___ relieves fever, headaches, and other mild-moderate aches and pain
acetominophen
is acetominophen anti-inflammatory?
no
therefore it is NOT an NSAID
___ can be used as an alternative to NSAIDs in patients that have allergies, stomach ulcers, bleeding problems, or are taking prescription “blood thinners” like warfarin
acetominophen
the following are adverse effects of which drug?
rash, chest pain, bone marrow suppression
should be avoided in patients with liver disease or insufficiency due to alcoholism
acetaminophen
acetaminophen overdose results in ___
hepatotoxicity over days/weeks → liver failure → death
___ are steroid hormones
glucocorticoids
what is the mechanism of glucocorticoids?
prevents conversion of membrane phospholipids to arachidonic acid by inhibiting the phospholipase A2 enzyme
glucocorticoids decrease ___
inflammation
what are the 3 short- to medium-acting glucocorticoids?
hydrocortisone, cortisone, perdnisone
what is the long-acting glucocorticoid?
dexamethasone
___ is a synthetic short- to medium-acting glucocorticoid effective as an immunosuppressant drug once converted via hepatic metabolism to its active metabolite, ___
- prednisone
- prednisolone
what is the mechanism of action of prednisone?
blocks phospholipase A2, thus shuts down immune responses
___ are NSAIDs and GCs (glucocorticoids), which primarily alleviate the symptoms of rheumatoid arthritis only
non-biolic DMARDs (small molecules)
how can DMARDs suppress the progression of rheumatoid arthritis?
through their actions against the underlying immunological abnormalities
what are 2 important non-biologic DMARDs?
methotrexate and azathioprine
___ is the first line DMARD for rheumatoid arthritis
methotrexate
what is the mechanism of methotrexate?
inhibits transformylase and thymidylate synthetase enzymes
the following are the clinical uses for which drug?
rheumatoid arthritis, juvenile chronic arthritis, psoriasis, systemic lupus erythromatosis, and vasculitis
methotrexate
which drug has the following adverse effects?
nausea and mucosal ulcers most common; leukopenia, anemia, GI ulcers, alopecia, stomatitis, hepatotoxicity, and lung damage
methotrexate
the risk of serious, life-threatening adverse effects is increased if ___ is taken with NSAIDs such as aspirin, naproxen, or other salicylates
methotrexate (DMARD)
methotrexate is contraindicated in ___
pregnancy
the following mechanism describes what drug?
prodrug that acts through its main metabolite, 6-thioguanine, to strongly suppress DNA synthesis and production of rapidly proliferating cells like B-cell and T-cell function, immunoglobulin production, and IL-2 secretion
azathioprine (imuran), a DMARD
which drug has the following clinical uses?
approved for rheumatoid arthritis, kidney transplant rejection prophylaxis, crohn’s disease, SLE, and scleroderma
azathioprine (imuran), a DMARD
the following are adverse effects of which drug?
bone marrow suppression, GI upset, inreased risk of infection, increased risk of lymphomas in humans, rare allergic reactions
azathioprine (imuran), a DMARD
what are biologic DMARDs?
- large molecules
- proteins produced by recombinant DNA technology
- T-cell modulators
- TNF-alpha blocking agents
what is the mechanism of abatacept (orencia)?
acts as a fusion protein to prevent activation of T-cells
the following are clinical uses of which drug?
FDA approved for the treatment of rheumatoid arthritis in patients who have failed or are inadequately responding to anti-TNF-alpha therapy
abatacept (orencia)
the following are adverse effects of which drug?
increased risk of lymphomas, infections, congestive heart failure, demyelinating disease, a lupus-like syndrome, induction of auto-antibodies, and infection site reactions
abatacept (orencia)
what is the monthly cost of abatacept (orencia)?
$3500-$3800 (like other biological drugs of its class)
what is the mechanism of adalimumab (humira)?
it is a biologic DMARD that prevents ligand from binding to TNF-alpha receptor
which drug has the follwoing clinical uses?
rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriasis, and refractory asthma
adalimumab (humira)
the following adverse effects describe what drug?
increased risk of lymphomas, infections (especially reactivation of latent tuberculosis), congestive heart failure, demyelinating disease, a lupus-like syndrome, induction of auto-antibodies, and infection site reactions
adalimumab (humira)
