Term
| What are the two main pathways of arachindonate metabolism? |
|
Definition
| COX pathway and lipoxygenase pathway |
|
|
Term
| Prostaglandins are produced via which pathway? |
|
Definition
|
|
Term
| leukotrienes are produced via which pathway? |
|
Definition
|
|
Term
| Where does the anti-platelet effect of NSAIDs come from? |
|
Definition
| inhibition of COX-1 and production of thromboxane |
|
|
Term
| Why is there vascular and renal toxicity with COX-2 selective inhibitors? |
|
Definition
| COX-2 is blocked in vascular cells, decreasing prostaglandin production, COX-2 is constitutively active in kidney |
|
|
Term
| Is COX-1 constitutive or induced? Where is it found? |
|
Definition
| constitutive, GI system, platelets, kidneys |
|
|
Term
| NSAIDs are acidic or basic? |
|
Definition
|
|
Term
| What liver enzymes metabolize most NSAIDs? |
|
Definition
|
|
Term
| How are most NSAIDs excreted? |
|
Definition
| renal, after enterohepatic circulation |
|
|
Term
| Are NSAIDs mostly free or protein bound in blood? |
|
Definition
| protein bound, mostly albumin |
|
|
Term
| NSAIDs with short half lives remain in the synovial fluid for how long? |
|
Definition
| longer than expected based on the half life |
|
|
Term
| What are the downsides to selective COX-2 inhibitors, in general? |
|
Definition
| may increase edema and hypertension, may increase cardiovascular risks |
|
|
Term
| NSAID toxicity effects which major organ systems? |
|
Definition
|
|
Term
| Long term use of NSAIDs has which effect on a type of cancer? |
|
Definition
| decrease colon cancer risk |
|
|
Term
| NSAIDs: adverse effects to the CNS? |
|
Definition
| headache, tinnitus, dizziness |
|
|
Term
| NSAIDs: adverse effects to the CV system? |
|
Definition
| fluid retention HTN, edema, CHF |
|
|
Term
| NSAIDs: adverse effects to the GI system? |
|
Definition
| abd pain, dysplasia, n/v, ulcers, bleeding |
|
|
Term
| NSAIDs: adverse effects to blood cells? |
|
Definition
| thrombocytopenia, neutropenia, aplastic anemia |
|
|
Term
| NSAIDs: adverse effects to the liver? |
|
Definition
| abnormal LFTs, liver failure |
|
|
Term
| NSAIDs: adverse effects to the respiratory system? |
|
Definition
|
|
Term
| NSAIDs: adverse effects to the skin? |
|
Definition
|
|
Term
| NSAIDs: adverse effects to the kidneys? |
|
Definition
| insufficiency, renal failure, hyperkalemia, proteinuria |
|
|
Term
| Aspirin: after dosing, how long until it reaches peak level in blood? |
|
Definition
|
|
Term
| Aspirin: hydrolyzed to ______ and ____ by ______ |
|
Definition
| acetic acid and salicylate by esterases |
|
|
Term
| Aspirin: how to increase excretion in urine? |
|
Definition
|
|
Term
|
Definition
| irreversibly inhibits platelet COX |
|
|
Term
| Aspirin: how long do anti-platelet effects last? |
|
Definition
|
|
Term
| Aspirin: decreases incidence of... |
|
Definition
| decreases incidence of TIA, ACS after CABG, colon cancer |
|
|
Term
| Aspirin: common adverse effects? |
|
Definition
|
|
Term
| Aspirin: contraindications? |
|
Definition
|
|
Term
| Nonacetylated salicylates: describe effectiveness |
|
Definition
| effective anti-inflammatory, less effective as analgesic compared to aspirin |
|
|
Term
| Nonacetylated salicylates: MOA compared to aspirin? |
|
Definition
|
|
Term
| Nonacetylated salicylates: compared to aspirin, these are better for pts with which problems? Why? |
|
Definition
| asthma, bleeding disorders, less COX inhibition and no effect on platelets |
|
|
Term
|
Definition
| selective COX-2 inhibitors |
|
|
Term
| Celecoxib: decreased frequency of which adverse effect? |
|
Definition
|
|
Term
| Celecoxib: adverse effect on skin? why? |
|
Definition
| rashes, it's a sulfonamide |
|
|
Term
| Celecoxib: may rarely interact with what drug? Why? |
|
Definition
| warfarin, CYP2C9 metabolism |
|
|
Term
| Meloxicam: MOA? Adverse effects? |
|
Definition
| "prefers" COX-2, lower incidence of GI problems compared to aspirin, no platelet effect |
|
|
Term
| Meloxicam: type of chemical? |
|
Definition
|
|
Term
| Name the drug! Nonselective COX inhibitor, phenylacetic acid derivative, decreased incidence of GI problems, can have renal toxicity, can increase aminotransferase levels. Has ophthalmic uses, topical application, rectal suppository for pre-OR analgesia |
|
Definition
|
|
Term
| Name the drug! Nonselective COX inhibitor, glucuronide metabolite, enterohepatically circulated, used for cancer pain with bone mets, dental surgery, oral lesions. Should decrease dose for pts with renal problems |
|
Definition
|
|
Term
| Name the drug! Nonselective COX inhibitor, racemic, acetic acid derivative, has no chiral inversion in the body |
|
Definition
|
|
Term
| Name the drug! Nonselective COX inhibitor, propionic acid derivative, affects TNFa and NO synthesis, hepatic metabolism, enterohepatic circulation, used for inhibition of intra-op miosis, ENT surgery, and as losenge. Rare adverse effects: cogwheel rigidity, ataxia, tremor, myoclonus |
|
Definition
|
|
Term
| Name the drug! Nonselective COX inhibitor, derivative of phenylpropionic acid, lower doses - analgesic but not anti-inflammatory. Used for closing PDA (less effect on urine output and fluid retention than indomethacin), topical cream, gel for dental pain. Contra: nasal polyps, andioedema, bronchospastic rxn to ASA. Adverse: aseptic meningitis, fluid retention, antagonizes anti-platelet effect of ASA, may decease inflammatory total inflammatory effect when taken together |
|
Definition
|
|
Term
| Guess the drug! Indole derivative, nonselective COX inhibitor, may also inh phospholipase A and C, reduce neutrophil migration, and decrease T cell and B cell proliferation. |
|
Definition
|
|
Term
| Which medication was particularly popular for gout and ankylosing spondylitis, PDA closure, ophthalmically for conjunctival inflammation and traumatic corneal abrasion, oral rinse for gingivitis, postlaminectomy injection, and in clinical trials for numerous other inflammatory conditions? |
|
Definition
|
|
Term
| What side effects and adverse reactions occur with indomethacin at higher doses? |
|
Definition
| GI effects including pancreatitis, headache, dizziness, confusion, depression, rarely psychosis with hallucinations, serious hematologic reactions like thrombocytopenia and aplastic anemia, also renal papillary necrosis. |
|
|
Term
| Which med prolongs indomethacin's half-life by inhibiting both renal and biliary clearance? |
|
Definition
|
|
Term
| Name the drug: propionic acid derivative, inhibits COX (nonsel) and lipoxygenase, levels elevated with concurrent administration of probenecid, not superior to other NSAIDs in terms of clinical efficacy, major adverse effects on GI and CNS |
|
Definition
|
|
Term
| Name the drug! NSAID promoted for systemic use mainly as an analgesic, has been used to replace morphine in mild-mod post-surg pain, may decrease opioid requirement when used together, ophthalmic prep available, renal toxicity may be more common with chronic use |
|
Definition
|
|
Term
| Name the drug! Only nonacid NSAID, converted to active acetic acid derivative in the body, once daily dosing (half-life > 24hrs), no enterohepatic circ, renal disease doubles half-life, may be less damaging to stomach, higher doses often needed and it is expensive, has caused pseudoporphyria and photosensitivity |
|
Definition
|
|
Term
| Name the drug! Naphthylpropionic acid derivative, single enantiomer, free fraction higher in women, available in slow release, oral suspension, OTC, topical and ophthalmic. Double incidence of upper GI bleeding compared to ibuprofen, rare cases of allergic pneumonitis, leukocytoclastic vasculitis, pseudoporphyria |
|
Definition
|
|
Term
| Name the drug! Proprionic acid derivative NSAID, very long half life (50-60hrs), no enterohepatic circ, mildly uricosuric (useful in gout) |
|
Definition
|
|
Term
| Name the drug! An oxicam, nonsel COX inh, at high concentrations inhibits PMN leukocyte migration, decreases oxygen radical production, inhibits lymphocyte function, long half-life, once daily dosing, high doses -> increased ulcers, bleeding, as much as 9 times higher than other NSAIDs |
|
Definition
|
|
Term
| Name the drug! Sulfoxide prodrug, metabolized to active sulfide metabolite, enterohepatic cycling, 12-16hr duration, suppresses familial intestinal polyposis, may inh colon, breast, prostate CA. Adverse- Stevens-Johnson epidermal necrolysis syndrome, thrombocytopenia, agranulocytosis, nephrotic syndrome, may elevate serum aminotransferases, sometimes assoc with cholestatic liver damage which stops if drug is DCed |
|
Definition
|
|
Term
| Name the drug! Nonsel COX inh with short half-life, not often used, ineffective for gout, may rarely cause thrombocytopenic purpura |
|
Definition
|
|
Term
| Which NSAID is less effective than the others for ankylosing spondylitis? |
|
Definition
|
|
Term
| For patients which renal insufficiency, what type of NSAID may be best? |
|
Definition
| nonacetylated salicylates |
|
|
Term
| Which NSAIDs are assoc with more LFT abnormalities? |
|
Definition
|
|
Term
| Which NSAID is probably safest for pts at high risk for GI bleeding, but may have higher risk of CV toxicity? |
|
Definition
|
|
Term
| DMARDs are ____-acting, compared to NSAIDs |
|
Definition
|
|
Term
| Atabacept: MOA? Dosing? Indications? Adverse effects? |
|
Definition
| Costimulation modulator that inhibits activation of T cells by binding to CD80 and 86 on APC and blocking them from binding CD28, IV infusion in 3 biweekly doses then monthly, mod-severe rheumatoid arthritis, slightly increased risk of infection (esp URIs), not recommended with TNFa antagonists, infusion and hypersensitivity rxns, possible increase in lymphomas |
|
|
Term
| Azathioprine: MOA and pharmacodynamics? |
|
Definition
| Acts thru metabolite 6-thioguanine, suppresses inosinic acid synthesis, B and T cell function, Ig production, and IL-2 section. Metabolism is bimodal (fast and slow metabolizers), production of active drug is dependent on TPMT enzyme, low levels -> high risk of myelosuppression if dosage is not adjusted |
|
|
Term
| Azathioprine: Indications and adverse effects? |
|
Definition
| rheumatoid arthritis, psoriatic arthritis, reactive arthritis, polymyositis, SLE and Bahnet's disease. Bone marrow suppression, GI disturbances, some increase in infection risk, lymphomas may be increased, rarely- fever, rash, hepatotoxicity signal acute allergic rxn |
|
|
Term
| Name the drug! Used mainly in malaria and rheumatic diseases, mechanism is unclear, proposed: suppression of T-lymphocyte responses, decreased WBC chemotaxis, stabilization of lysosomal enzymes, inhibition of DNA and RNA syn, trapping of free radicals |
|
Definition
| chloroquine and hydroxychloroquine |
|
|
Term
| Antimalarials - names? Protein bound? Tissue bound? Deaminated where? Blood elimination half lives up to how many days? |
|
Definition
| chloroquine and hydroxychloroquine,50% protein, bound, extensively tissue bound esp in melanin-containing tissues like the eyes, deaminated in liver, up to 45d |
|
|
Term
| Are antimalarials effective for rheumatoid arthritis? |
|
Definition
| they are approved for this use but not considered very effective DMARDs, often used for skin symptoms, serositis and joint pain of SLE, also for Sjogren's syndrome |
|
|
Term
| What adverse effects occur with antimalarials? Safe in pregnancy? |
|
Definition
| ocular toxicity at high doses, dyspepsia, N/V, abd pain, rashes, nightmares, relatively safe in pregnancy |
|
|
Term
| Name the drug! Major active metabolite - phosphoramide mustard, cross-links DNA to prevent cell replication, suppresses T and B cell function, active against RA when given orally (not IV), used regularly for SLE, vasculitis, Wegener's, etc. |
|
Definition
|
|
Term
| Name the drug! Regulates gene transcription, inhibits IL-1 and IL-2 recep production and inhibits mac-T cell interaction and T cell responsiveness, also affects T-cell-dependent B cell function, absorption is incomplete and somewhat erratic, improved by microemulsion formulation, grapefruit juice increases bioavailability, improved for RA and slows bony erosions, may be useful for other syndromes, significant nephrotoxicity, increased by interactions with diltiazem, potassium-sparing diuretics, other drugs inhibiting CYP3A, other tox includes HTN, hyperkalemia, hepatotoxicity, gingival hyperplasia, hirsutism |
|
Definition
|
|
Term
| Name the drug! Rapid conversion to metabolite A77-1726, inhibits dihydroorotate dehydrogenase, decrease ribonucleotide syn, arrest cells in G1, inhibits T cell prolif, production of autoantibodies by B cells, enterhepatic circ, cholestyramine can enhance excretion, effective for RA, diarrhea in 25%, elevation of LFTs, mild alopecia, weight gain, increased BP, rarely leukopenia and thrombocytopenia, contraindicated in pregnancy |
|
Definition
|
|
Term
| What is the DMARD of first choice for RA pts? |
|
Definition
|
|
Term
| Name the drug! Low dose: inhibits aminoimidazolecarboxamide ribonucleotide (AICAR) transformylase and thymidylate synthase, with secondary effects on PMN chemotaxis |
|
Definition
|
|
Term
| Does methotrexate have any effect on dihydrofolate reductase? |
|
Definition
| yes, affects lymphocyte and mac function, but this is not the principle MOA |
|
|
Term
| Methotrexate: pharmacokinetics? |
|
Definition
| 70% absorbed PO, metabolized to less active form, polyglutamated in cells and stays there for long time, concentration increased in presence of hydroxychloroquine, excreted principally in urine and some in bile |
|
|
Term
| What are the most common toxicities for methotrexate? |
|
Definition
| nausea and mucosal ulcers, dose-related hepatotoxicity, rare hypersensitivity lung reaction, GI and LFT problems can be reduced with leucovorin or folic acid, contraindicated in pregnancy |
|
|
Term
| What is MMF? What is the MOA? |
|
Definition
| mycophenolate mofetil, converted to active mycophenolic acid, inhibits cytosine monophosphate dehydrogenase, secondary - inhibits T cell lympho prolif, downstream -> interferes with leukocyte adhesion to endothelial cells (thru E-selectin, P-selectin and ICAM-1) |
|
|
Term
| What are the indications for MMF? |
|
Definition
| renal disease due to SLE, may be useful in vasculitis and wegener's, no good data to support use in RA |
|
|
Term
| Rituximab: MOA? Indications? |
|
Definition
| monoclonal Ab that targets CD20 B lymphos, thru cell and complement-mediated cytotoxicity and stimulation of apoptosis, RA refractory to anti-TNF agents, acute RA with methotrexate |
|
|
Term
| Why would you give glucocorticoids before Rituximab infusion? |
|
Definition
| to decrease incidence and severity of infusion rxns |
|
|
Term
| Rituximab: indications? Adverse effects? |
|
Definition
| mod-severe RA in combo with methotrexate in pts with inadequate response to TNFa antagonists, 30% pts develop rash with first treatment, Igs may decrease --> infection |
|
|
Term
| name the drug! metabolized to sulfapyradine and 5-aminosalicylic acid, sulfapyridine probably most active in treating RA, decreases IgA and IgM RF, suppresses T cell rsps, inhibits B cell prolif, inhibits release of inflammatory CKs |
|
Definition
|
|
Term
| Intestinal bacteria reduce sulfasalazine to which compounds? |
|
Definition
| sulfapyridine (absorbed) and 5-aminosalicylic acid (unabsorbed) |
|
|
Term
| What are the indications and adverse effects for sulfasalazine? |
|
Definition
| RA, juvenile arthritis, ankkylosing spondylitis, 30% pts dc drug due to tox, N/V, headahce, rash, rare hemolytic anemia and methemoglobinemia, neutropenia, thrombocytopenia very rare, pulmonary toxicity, drug-induced lupus is rare, reversible infertility in men |
|
|
Term
| What are Adalimumab, infliximab and etanercept? |
|
Definition
|
|
Term
| Name the drug! Fully human IgG1 anti-TNF monoclonal Ab, given SQ every other week usually, clearance decreased with methotrexate, indicated for RA, ankylosing spondylitis, psoriatic arthritis, juvenile arthritis, Chrohn's, etc, Adverse- bacterial infection, Mac-dependent infection, should be screened for Tb, low incidence of new dsDNA Abs, rare leukopenias and vasculitis |
|
Definition
|
|
Term
| Name the drug! Chimeric IgG1 monoclonal Ab, binds to soluble and possibly membrane-bound TNFa, given by IV infusion, with methotrexate decreases production of Abs against the drug, used in RA, AS, PA, CD, etc. Rec. to use with methotrexate but can be combined with other DMARDs, adverse- increased bacterial infections, URIs, screen for TB, rare demyelinating syndromes, rare leukopenia, vasculitis, hep B, etc. Positive ANA incidence increased. Infusion site rxns in some, assoc with anti-Abs, use of antihistamines helps |
|
Definition
|
|
Term
| Name the drug! Recombinant fusion protein consisting of two soluble TNF p75 receptor moieties linked to Fc portion of human IgG1, binds TNFa molecules and also inhibits lymphotoxin-a, given SQ, for tx of RA, JA, PA, AS, monotherapy or with methotrexate. Adverse - bacterial infections, esp soft tissue and septic arthritis, screen for TB, opportunistic inf rarely, may have pos ANA, injection site rxns |
|
Definition
|
|
Term
| Does combo of azathioprine, auranofin or sulfasalazine plus methotrexate result in additional benefit over methotrexate alone?> |
|
Definition
|
|
Term
| Which types of drugs have been used in 60-70% of RA pts, have prompt and dramatic effects, and are capable of slowing the appearance of new bone erosions? |
|
Definition
|
|
Term
| Which is an important drug for mild-mod pain when anti-inflammatory effect is not necessary? |
|
Definition
|
|
Term
| What is the prodrug that is metabolized to acetaminophen, is more toxic and has no rational indications? |
|
Definition
|
|
Term
| Acetaminophen: MOA? Absorption is related to what? Bound/unbound? Metabolism? Indications? Adverse effects? |
|
Definition
| Weak COX-1 and COX-2 inhibitor in peripheral tissues, no sig anti-inflam effects, absorption related to gastric emptying, slightly bound, partially metab by hepatic microsomal enzymes to acetaminophen sulfate and glucuronide, minor but highly active metabolite N-acetyl-p-benzoquinone is toxic to liver and kidney, toxic dose or liver disease increases half life, useful in mild-mod pain like HA, myalgia, etc, does not antag uricosuric agents, mild increase in hepatic enzymes may occur at therapeutic doses, larger dose- dizzy, excitement, disorientation, 15g can be fatal, doses over 4-6g/d not recommended, early symptoms hepatic damage include N/V/D and abd pain, overdosage - give aceteylcysteine, rare - hemolytic anemia and methemoglobinemia |
|
|
Term
| What are the first-line drugs for acute goat? |
|
Definition
|
|
Term
|
Definition
| binds intracellular tubulin, prevents polymerization into microtubules, inhibiting leukocyte migration and phagocytosis, also inhibits formation of Leukotriene B4 |
|
|
Term
| Indication for colchicine? |
|
Definition
| prophylaxis of recurrent episodes of gouty arthritis, acute Mediterranean fever, mild beneficial effect in sarcoid arthritis and hepatic cirrhosis, caution with IV use because of bone marrow toxicity |
|
|
Term
| Colchicine: Adverse effects? |
|
Definition
| diarrhea, N/V, abd pain, hepatic necrosis, renal failure, DIC, seizures have been reported. Rarely - hair loss and bone marrow depression, peripheral neuritis, myopathy, death. Acute intox after OD - burning throat pain, bloody diarrhea, shock, hematuria, oliguria, fatal ascending CNS depression |
|
|
Term
| What is the effect of NSAIDs for gout? Why isn't aspirin used? |
|
Definition
| inhibits PG synthase, also inhibit urate crystal phagocytosis, ASA not used because of renal retention of uric acid at low doses |
|
|
Term
| oxaprozin lowers serum ___ ___, although should not be pts with... |
|
Definition
| uric acid, uric acid stones because it increases excretion in the urine |
|
|
Term
| What are the uricosuric agents? |
|
Definition
| probenecid, sulfinpyrazone |
|
|
Term
| uricosuric drugs are what type of chemical, and act where in the kidney? |
|
Definition
| organic acids, anion transport sites of the renal tubule |
|
|
Term
| Sulfinpyrazone is a metabolite of an analog of... |
|
Definition
|
|
Term
| Is probenecid absorbed from renal tubules? Is sulfinpyrazone? |
|
Definition
| yes, completely. it is rapidly excreted by kidneys but duration is almost as long |
|
|
Term
| The secretion of ____ _____s is reduced by uricosuric agents. |
|
Definition
|
|
Term
| Uricosuric therapy should start how long after an acute attack? |
|
Definition
|
|
Term
| Adverse effects of uricosuric agents? |
|
Definition
| GI irritation, moreso with sulfinpyrazone, rash, nephrotic syndrome (probenecid) aplastic anemia |
|
|
Term
| What is the standard of care therapy for gout in the intercritical period? What is its MOA? |
|
Definition
| allopurinol, inhibits xanthine oxidase |
|
|
Term
| What happens to the purine ribonucleotides that are not incorporated into nucleic acids? |
|
Definition
| they are converted to xanthine or hypoxanthine and oxidized to uric acid |
|
|
Term
| Which drug is used for gout, but also as an antiprotozoal agent, and to prevent massive uricosuria following tx of blood dyscrasias? |
|
Definition
|
|
Term
| Allopurinol: adverse effects? Interactions/cautions? |
|
Definition
| GI intolerance - N/V/D, peripheral neuritis, necrotizing vasculitis, depression of BM elements, rarely aplastic anemia, hepatotoxicity and interstitial nephritis, allergic rash - pruritic maculopapular lesions, isolated cases exfoliative dermatitis, very rare cases of cataracts. Must reduce dosage of mercaptopurines when also taking allopurinol, it may increase effect of cyclophosphamide, inhibits metabolism of probenecid and oral anticoags, may increase hepatic iron |
|
|
Term
| What should be given WITH allopurinol during first weeks of therapy? |
|
Definition
|
|
Term
| What is the first nonpurine inhibitor of xanthine oxidase? |
|
Definition
|
|
