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62 Cards in this Set
- Front
- Back
DMARD
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disease-modifying antirheumatic drugs
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cyclooxygenase (COX)
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enzyme at the head of the enzymatic pathway for prostaglandin synthesis
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cytotoxic drug
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interfere with essential cell processes. generally kill rapidly dividing cells; primarily for cancer & immunosuppression
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DMARDs
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modify inflammatory processes underlying rheumatoid arthritis; slow (weeks to months) onset
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NSAIDs
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inhibitors of COX. the term nonsteroidal differentiates them from steroid drugs that mediate anti-inflammatory effects through activation of glucocorticoid receptors (e.g., cortisol)
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Reye's syndrome
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rare syndrome of rapid liver degeneration and encephalitis in children treated with aspirin during a viral infection
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TNF-alpha
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Cytokine that plays a central role in inflammation
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uricosuric agent
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drug that increases the renal excretion of uric acid
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xanthine oxidase
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key enzyme in the purine metabolism pathway that ends with the production of uric acid
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Aspirin
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acetylsalicylic acid and is prototype of the salicylates.
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aspirin
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acetylsalicylic acid, is the prototypeof the salicylates
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Older nonselective NSAIDS besides aspirin
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ibuprofen, indomethacin & many more
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Celecoxib
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1st member of NSAID subgroup, the Cox-2 selective inhibitor. higher incidence of cardiovascular thrombotic events than non-selective
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COX
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enzyme that converts arachidonic acid into the endoperoxide precursors of prostaglandins, important mediators of inflammation.
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COX-1 and COX-2
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COX-1 is primarily expressed in noninflammatory cells. COX-2 is expressed in activated lymphocytes, polymorphonuclear cells & other inflammatory cells
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aspirin & nonselective NSAIDs
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inhibit both COX I and II & decrease prostaglandin and thromboxane synthesis. Release of prostaglandins necessary for homeostatic function is disrupted, as is release of prostaglandins involved in inflammation.
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Major difference between MOA of aspirin and other NSAIDs
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aspirin acetylates and thereby IRREVERSIBLY inhibits COX. Other NSAIDs are reversible. Therefore, aspirin's antiplatelet effect is longer
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NSAIDs antipyretic action
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NSAIDs suppress the prostaglandin synthesis in the CNS that is stimulated by pyrogens and thereby reduces fever
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COX inhibitors in GI
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COX inhibitors interfere with homeostatic function of prostaglandins. They reduce prostaglandin-mediated cytoprotection in the GI tract and autoregulation of renal function
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Aspirin dosages
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<300 mg/day - antiplatelet.
300-2400 mg/day: antipyretic & analgesic. 2400-4000 mg/day: anti-inflammatory effect. 1/2 life 3-5 hours at lower doses. elimination 1st order. excretion via kidney. Aspirin is readily absorbed and is hydrolyzed in blood and tissues to acetate and salicylic acid. |
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Aspirin toxicity
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gastric upset. With chronic use: gastric ulceration, upper GI bleeding & renal failure and interstitial nephritis. Increases bleeding time.
High doses: tinnitus, vertigo, hyperventilation & respiratory alkalosis Very high doses: metabolic acidosis, dehydration, hyperthermia, collapse, coma, death. |
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When prostaglandin synthesis is inhibited by aspirin, people with aspirin hypersensitivity (especially people w/nasal polyps)
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can experience asthma from increased synthesis of leukotrienes. This hypersensitivity precludes treatment with any NSAID.
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Nonselective NSAIDs (other than aspirin) toxicity
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They are also associated with significant gastrointestinal disturbance, but lower than with aspirin. Because all NSAIDs (except acetominophen) are cleared by kidney, renal disease increases toxic serum concentrations.
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Cox-2 selective inhibitors
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celecoxib, rofecoxib, valdecoxib. reduced risk of GI effects. Carry the same risk of renal damage as nonselective COX inhibitors. But increased risk of myocardial infarction and stroke. Several COX-2 inhibitors have been removed from the market.
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Acetaminophen
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only OTC non-antiinflammatory analgesic commonly available in the US.
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MOA of acetaminophen
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Unclear. Weak COX 1 and COX 2. may inhibit COX 3 in the CNS
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Per Krueger:
acetaminophen |
only has antipyretic & analgesic. not antiinflammatory. not antiplatelet
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Per Krueger:
acetaminophen SE |
hepatotoxicity
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Acetaminophen is metabolized in
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the liver.
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acetaminophen 1/2 life
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2-3 hrs in persons with normal hepatic function. Is unaffected by renal disease.
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MOA of toxicity in acetaminophen
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Oxidation to cytotoxic intermediates by phase I cytochrome P450 enzymes. This occurs if substrates for phase II conjugation reactions (acetate and glucuronide) are lacking.
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Acetaminophen overdose
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give acetylcystein. also people who regularly consume 3 or more alcoholic drinks per day are at increased risk of acetaminophen-induced hepatotoxicity.
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Disease-modifying antirheumatic drugs (DMARDS)
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aka "slow-acting antirheumatic drugs (SAARDs)" because it may take 6 weeks to 6 months for their benefits to become apparent. They slow or even reverse joint damage.
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Corticosteroids
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Intermediate rate of action between NSAIDs & DMARDs but can't use chronically & reserved for temporary control
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MOA of DMARDs
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Poorly understood. Darn
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Methotrexate
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DMARD: is cytotoxic & probably reduces the # of immune cells available to maintain inflammatory response. Many are used in treatment of cancer since cytotoxic & work on fast-replicating cells.
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DMARDs MOA
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interfere with the activity of T lymphocytes (sulfasalazine, hydroxychloroquine, cyclospirine) interfere with B lymphocytes (rituximab) or interfere with macrophages (gold compounds)
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TNA-alpha inhibitors
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infliximab, etanercept have also shown efficacy in RA.
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Anti-TNF-alpha drugs are given by
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injection
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Toxicity of DMARDs
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All disease-modifying agents can cause severe or fatal toxicities.Careful monitoring of patients is mandatory.
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Methotrexate
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initial DMARD for people with RA. Often used with TNF-alpha. Causes bone marrow suppression. Anti-cancer.
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Gout - Indomethacin
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potent NSAID inhibits inflammation of acute gouty arthritis. Reduces prostaglandin formation and the inhibition of crystal phagocytosis by macrophages
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Colchicine (in gout)
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a selective inhibitor of microtubule assembly, reduces leukocyte migration and phagocytosis. Also may reduce production of leukotriene B4 and decrease free radical formation
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Per Kruger:
Indomethacin |
NSAID used in gout
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Per Kruger:
MOA of colchicine used in gout |
Selective inhibitor of microtubule assembly
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Per Kruger:
SE of colchicine |
Kidney and liver toxicity, diarrhea.
(Per book: Overdose is often fatal) |
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Uricosuric agents
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probenecid, sulfinpyrazone are weak acids that compete with uric acid for reabsorption by the weak acid transport machanism in the proximal tubules and thereby increase uric acid excretion.
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Per Krueger:
Probenecid and sulfinpyrazone |
Agent used to treat chronic gout by increasing uric acid secretion and excretion
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Uricosuric drugs are used orally to treat
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chronic gout. No value in acute episodes
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Uricosuric drugs are sulfonamides, therefore
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may share allergenicity with other classes of sulfonamide drugs.
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Xanthine oxidase
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The enzyme that converts hypoxanthine to xanthine and xanthine to uric acid.
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Allopurinol
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treats chronic gout by decreasing uric acid production by inhibiting the production of uric acid. (a xanthine oxidase inhibitor)
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febuxostat
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a nonpurine inhibitor of xanthine oxidase that is more selective than allopurinol and alloxanthine, which inhibit other enzymes involved in purine and pyrimidine metabolism
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inhibition of xanthine oxidase
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increases the concentrations of the more soluble hypoxanthine and xanthine and decreases the concentration of the less soluble uric acid so there is less likelihood of precipitation of uric acid.
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xanthine oxidase inhibitors
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are given orally in the management of chronic gout
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Allopurinol toxicity
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GI upset, rash, rarely peripheral neuritis, vasculitis or bone marrow dysfunction including aplastic anemia.
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allopurinol drug interaction
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inhibits the metabolism of mercaptopurine and azathioprine, drugs that depend on xanthine oxidase for elimination.
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Per Krueger:
NSAID contraindicated in gout |
Aspirin
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Per Krueger:
Allopurinol treats chronic gout by decreasing uric acid production by inhibiting |
Xanthine oxidase
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Per Krueger:
Causes bone marrow suppression |
Methotrexate
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Per Krueger:
NSAID available orally, IM and ophthalmically |
Ketoralac
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Per Krueger:
NSAID that is used for acute condition, such as pre-op anesthesia and has limited duration (<5 days) of use due to nephrotoxicity |
Ketoralac
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