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62 Cards in this Set
- Front
- Back
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diazepam
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along with other benzos, they activate GABA-A which has a relaxing effect usefull as a spasmolytic; side effect is sedation
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Baclofen
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spasmolytic; active GABA-B agonist, acts presynaptically by opening K+ channels and closing Ca++ channels which inhibits NT release; produces less sedation than the benzos; analgesic effect may be due to Substance P inhibition
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Gabapentin
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structural analog of GABA which has NO action on A or B receptors; instead it blocks Ca++ channels; is a spasmolytic as well as an anti-epileptic so esp useful in MS spacicity
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glycine
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good spasmolytic
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tizantidine
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similar to clonadine but spasmolytic effects not due to a2 agonism; increases pre and posynaptic inhibition and exhibits analgesic effect; adverse effects are sedation, hypotension and dry mouth
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riluzone
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glutamate release blocker with spasmolytic effect; only used in ALS
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cyclobenazprine (include mech, use and 2 side effects)
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relieve local muscle spasms from tissue trauma or muscle strain; sedation and hallucination may occur; effects may be due to blockage of 5HT projections terminating on dorsal horn neurons
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dantrolene (include 2 side effects)
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spasmolytic; blocks Ca release from SR by binding to ryanodine receptor; inhibits skeletal muscle contraction; adverse effects are muscle weakness and sedation; used for malignant hyperthermia
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botulinum toxin
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blocks release of Ach, local injection provides 1-2 months of relied for cerebral palsy patients
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mechanism of NSAID analgesic action
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act locally to block pain; do this by blocking the synthesis (not binding) of PGs which induce pain
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mechanism of NSAID antipyretic action
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block action of pyrogens and IL-1 in the hypothalamus
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why is low dose aspirin safe?
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600 mg, low doses can be rapidly conjugated into inactive forms by the liver and readily excreted in the urine
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why is aspirin toxic at high doses
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the salicylate-metabolizing enzymes get saturated and the kidney has limited ability to excrete unchanged salicylate
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is aspirin a prodrug
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no, although it gets metabolized and its metabolite, salicylate is also active, aspirin before metabolization is 50% more potent
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cyclooxygenase inhibition
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occurs irreversibly by aspirin and reversibly by other NSAIDs
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acute toxicity of salicylate
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caused by 10-30 g/day; saturation of salicylate metabolizing enzymes in the liver and limited ability for kidney to secrete salicylate lead to elevation in salicylate plasma levles to a toxic dose; causes metabolic acidosis, respiratory alkylosis
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metabolic acidosis related to acute salicylate toxicity
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caused by uncoupling of oxidative phosphorylation which causes an increase in heat production and metabolic rate; compensitory mechs include increased O2 consumtion which increases CO2 production and increased glucose utilization; this causes a metabolic/lactic acidosis
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respiratory alkylosis related to acute salicylate toxicity
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due to the metabolic acidosis, ventilation is stimulated due to increased CO2 production; this inhibits CO2 transport by RBC, high levels of CO2 stimulate the medulla which causes hyperventilatio; this results in respiratory alkylosis and compensitory increased excretion of bicarb and K+ (causes hypokalemia)
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therapy for acute salicylate toxicity
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sodium bicarb to increase salicylate excretion by urine alkalyzation (increases the amount of unionized drug which destroys the gradient that would normally cause reabsorption of salicylate so now the equation favors excretion) and to correct metabolic acidosis; also give K+ to correct hypokalemia due to respiratory alkylosis (give in separate IVs or they will precipitate); also glucose to protect the brain
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best NSAID to give a pregnant woman or child with flu or chicken poxs
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acetaminophen because there is no risk of Reye's syndrome
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activity of acetaminphen
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analgesic and antipyretic but no anti-inflammatory; does not produce the side effects of aspirin and NSAIDs (like gastric irritation)
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OD of acetaminophen
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5% of acetomenofin is metabolized to quinoneimine by Cyt P450 which is toxic; at high doses, there is saturation of the normal liver enzymes and so there is an increase in quinoneimine produced which can cause hepatic necrosis which is delyed 3-5 days; quinomeinmine also depletes glutathione
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antidote for acetaminophen OD
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N-acetylcysteine which serves as a precursor for glutathione
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Celecoxib
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selective Cox2 inhibitor; very low gastric irritation (because it doesn't effect COX-1) and disturbance in platelet function; prothrombotic (increased risk of MI ir stroke); causes sulfa allergy; used in OA, RA, acute pain, dysmenorrhea
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indomethacin
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most potent inhibitor of COX; used primarily to treat acute attacks of gout (short term); also in OA, halting of labor and patent ductus arteriosus; limited use in RA because long term can have toxic effects
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sulindac
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prodrug activated to sulfide in the liver; because the prodrug does not inhibit COX, it has low gastric irritation; low kidney toxicity because the inactive form is excreted so it is useful for patients with renal complications; sulindac undergoes enterohepatic recirculation
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profens
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low gastric complications, do not displace methotrexate, warfarin and sulfonylureas from albumin
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anti-inflammatory doses of aspirin
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4-6 g/day, half life is extremely high due to saturation of liver enzymes to metabolize salicylate; now plasma levels are only influenced by kidney excretion
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unique aspects of aspirin (1 action, 1 use and 3 side effects)
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irreversible inactivator of cyclooxygenase; used to prevent coronary artery thrombosis (inhibits platelet aggregation); comliance problem due to gastric irritation; risk of Reyes syndrome in children with the flu or chicken pox; displaces drugs from albumin
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anti-inflammatory mechanism of NSAIDs
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acts on leukocytes and lymphocytes; dose required is 10x higher than analgesic and antipyretic dose; common mechanism is the inhibition of the cyclooxyegenase pathway
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COX-1
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widely distributed and constitively expressed; does housekeeping functions such as gastric cytoprotection and platelet aggregation
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COX-2
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expressed consititively in some tissues (brain, kidney, repro organs); but is usually low in most tissues unless induced in response to local inflammatory conditions
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nonselective NSAIDs on platelet function
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inhibit platelet aggregation and increase bleeding time by reducing the synthesis of thromboxane; NSAID therapy (esp aspirin) must be avoided between surgery
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cox-2 selective inhibitors and platelet function
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are actually prothrombiotic and also decrease synthesis of prostacyclin; would be contraindicated in patients in post-op setting
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aspirin prophylaxis
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used for pts about 50 yo with 1 or more risk factors (which includes RA and other autoimmune disorders)
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mechanisms of gastric ulceration and bleeding when taking NSAIDs
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is due to COX-1 inhibiton; they accumulate in the stomach mucosa and can cause irritation that can cause tissue damage; also decreases the production of cytoprotective PGs which promote secretion of mucus and bicarb; also inhibit platelets (increases bleeding)
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hypersensitivty reactions of NSAIDs
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caused by COX-1 inhibition; can cause bronchoconstriction and anaphylactic shock in patients with asthma or nasal polyps; can use acetaminohen or glucocorticoids instead
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alteration in renal function with NSAIDs
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due to COX-2 inhibition; decrease renal blood flow in pts with CHF or hepatic cirrhosis; causes retantion of salt and water (enhance ADH)
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effect of NSAIDs on reproductive organs
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due to COX-2 inhibition; causes a decrease in ovulation via a delay in follicular rupture; can induce reversible infertility; also cause prolongation of gestation (contraindicated in pregnancy)
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CNS disturbances of NSAIDs
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tinnitus, decreased hearing, vertigo
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NSAID drug interactions
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most NSAIDs bind firmly to plasma proteins (albumin) and displace other drugs like warfarin and methotrexate (this causes their plasma levels to increase, can be toxic)
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Naproxen
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profen; low side effects; 20 times more potent than aspirin at inhibiting COX; potent inhibitor of leukocyte migration (treats inflammation)
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glucocorticoids
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most potent and rapid acting anti-inflammatory agents which also have immunosupressive effects; intra-articular injection for local reflief or oral use in advanced age; induce expression of lipocortins which decrease the amount of AA released but don't directly inhibit COX or LIPOXY pathways; cause dramatic decrease in the # of circulating leukocytes and inhibits their return to circulation; have lots of side effects
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methotrexate mechanism
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is converted to polyglutamate once it enters cells to prevent it leaving; PG inhibits AICAR which is involved in purine synthesis; this acuases an increase in adenosine which inhibits the production of cytokines and other inflammation mediators
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adverse effects of methotrexate
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is generally well tolerated but can frequently cause GI disturbances, mild alopecia and myelosupression (can be decreased by folate ingestion); less common ones include liver cirhossis and pneumonitis
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leflunomide mechanism
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is rapidly converted to M1 metabolite which inhibits dihydroorotate dehydrogenase which is a pyramidine enzyme (activated lymphocytes require 8-fold increase in pyramidines)
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side effects of leflunomide
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diarrhea, elevation of liver enzymes, teratogenic
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hydroxychloroquinine mechanism and side effects
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unclear; interferes with lysosomes and inhibits DNA and RNA synthesis; causes ocular damage but is safe in pregnancy
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sulfasalazine
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RA prodrug (disease modifying); is broken down by gastric bacteria into 2 compounds, 1 with anti-inflammatory function and one with antibacterial action
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adverse effects of sulfasalazine
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toxicity is high in slow acetylators; sulfa drug reactions; safe in pregnancy
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mech of TNFa inhibitors
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bind to TNF and prevent it from associating with cell-surface receptors; block inflammatory cascade and prevent tissue distruction
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side effects of TNF-a inhibitors
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serious infections inclduing sepsis; TB; demyelinating disorders; drug-induced lupus
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2 TNF-a inhibitors
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etanercept (nonneutralizing ab) and infliximab (neutralizing ab)
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side effects of glucocorticoids
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peptic ulceration, osteoporosis, susceptibility to infection and cataracts
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NSAIDs and gout
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at anti-inflammatory doses, non-aspirin NSAIDs inhibit lipoxygenase in addition to cyclooxygenase and the inhibition of lipoxygenase (LT and other chemotactic factors) is more important in gout
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aspirin and gout (3)
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is not used since it inhibits tubular secretion of uric acid and increases gouty attacks; also doesn't inhibit lipoxygenase; finally, it inhibits uricosuric action
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cochicine
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prevents the production of crystal induced chemotactic factor; limited use in acute attack; used more for phophylactic therapy at low dose
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uricosuric drugs
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probenecid (and sulfinpyrazone (also anti-platelet effect); use in patient who has had multiple gouty attacks but who isn't an overproducer
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mechanism of uricosuric drugs (also, what other things must you do to prevent side effects from these drugs)
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increase renal excretion of uric acid by decreasing active reabsorption of uric acid in the glomeruli, compete with uric acid for the organic-acid transporter; must maintain high urine volume and pH to prevent uric acid stone formatio
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allopurinol
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long half life; decreases uric acid synthesis by inhibiting xanthine oxidase; due to the hypersensitivity reactions, it is preffered only when uricosuric drugs are contraindicated
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contraindications of uricosuric
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uric acid overproducer, renal stones, renal insufficiency
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interaction between uricosurics and allopurinol
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uricosurics increase the excretion of allopurinol by preventing its tubular reabsorption; allopurinol decreases P450 which increases the 1/2 life of uricosuric agents
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