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52 Cards in this Set
- Front
- Back
define inflamation
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1) a normal protective response to tissue injury caused by physical trauma, noxious chemicals or micrologic agents
2) the body's effort to inactivate or destroy invading organisms, remove irritants ans set the stage for tissue repair |
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What happens in inflamation?
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1) blood vessels dialate
2) increase vascular permeability 3) increased leukocyte accumulation |
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mediators of inflamation
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1) histamine
2) kinins 3) neuropeptides 4) cytokines 5) eicosanoids (arachadonic acid metabolites) |
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prostoglandins
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1) unsaturated FA derivitaves
2) produced in minute quantities in all tissues 3) act locally on tissue where they are produced 4) rapidly metabolize into their inactive metabolite at their site of action 5) Do NOT circulate in blood in significant quantities |
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therapudic indications for NSAID's
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1) inflamation
--erythema, edema, hyperalgesia ***prostoglandins and other cell mediators ***autoimmunity (RA) ***infectious agents, ischemia, physical injury 2) Pain --sensitization of pain fibers by prostoglandins 3) Fever --pyrogenic stimulus release cytokines, increase prostoglandins in the hypothalmus, increase temp, and decrease heat loss |
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Overview of NSAID's
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1) differing antipyretic, analgesic, and anti-inlamatory activity
2) inhibits COX but not lipoxygenase enzymes 3) COX 1 is constituitive ---platelets, kidneys, and GI tract 4) COX 2 is inducible and associated with inflamation --less gastric damage caused by COX-2 than is with COX-1 inhibitors |
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side effect of COX-1 inhibition
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inability to form stomach protecting prostoglandins
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Pharmicokinetics of aspirin
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1) AKA acetylsalicylic acid (ASA)
2) absorbed in the stomach and the duodenum 3) low gastric pH keeps most ASA in the non ionized form, which enhances absorption 4) rapid absorption leads to high concentration in gastric mucosal cells resulting in irritation of mucosal lining 5) buffering (gastric pH >3.5) can decrease irritationby slowing the absorption rate |
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phase metabolism of aspirin
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hydrolyzed by esterase in the tissue and blood --> acetic acid + salicylate
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phase 2 metabolism of aspiin
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1) conjugated with glycine (liver)
--water soluble conjugate is excreted in the urine (kidneys) |
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peak plasma level for aspirin occurs in ______(time)
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15 min
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peak plasma level for sallicylateoccurs in ______(time)
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1-2 hours
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serum half life of salocylates =
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low dose =3-5 hours
high doses = 15 hours |
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MOA for aspirin and salicylate
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1) aspirin = irreversible COX inhibitor
2) Salycilate = reversible COX inhibitor -----decreases prostoglandin synthesis |
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effect of decreasing prostoglandin synthesis
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1) antiinflamatory
--PG mediates inflamatory events 2) analgesic --PG thought to sensitize nerve endings to bradykinin, histimine, and other chemical mediators 3) Antipiuretic --PG increases set-point in the hypothalmus periphreal vasodilation and sweating |
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thromboxane is a product of
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COX-1
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fx of thromboxane
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increase platelet aggregation
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Prostoglandin is a product of
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COX-2 (from endothelial cells, and inflamatory cells)
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Fx of prostoglandins (dealing with platelet aggregation)
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decrease platelet aggregation
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aspirin at low doses_________
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<80 mg / day can irreversibly inhibit TXA2 production in platelets w/o affecting prostoglandin production in the endothelial cells
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adverse effect of aspirin and other salycilates
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1) GI
--epigastric destress, nausea, vomiting, and microscopic GI bleeding 2) blood --prolonged bleeding time --no ASA for 1 week prior to surgery 3) respiration --toxic doses can cause respiratory depression, respiratory and metabolic acidosis ***warning sign = tinnitus |
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Misoprostol
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PFE1 analog, reduces NSAID induced ulcers
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Tx for aspirin overdose
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1) Gastric lavage
2) I.V. sodiumbicarbonate --alkalinize the urine promotes excretion (by trapping salycilates in the ionized form) |
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Non selective COX inhibitors
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reversible
analgesic anti-inflamatory antipyretic |
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examples of non selective COX inhibitors
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Ibprofen
indomethacin ketoprofen ketorolac naproxen piroxicam |
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t1/2 of non selective COX inhibitors
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Ibprofen (2h)
indomethacin (5h) ketoprofen (2h) ketorolac (4-10h) naproxen (14h) piroxicam (57h) |
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selective inhibitors for COX-2
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1) Celecoxib
2) rofecoxib (no longer on the market) 3) Valdecoxib (No longer on the market) |
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Pharmicokinetics of Celoxib
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1) easily absorbed (peaks in 3 hours)
2) metabolized in the liver by cytochrome P450 3) excreted in feces and urine 4) once daily dosage (half life = 11 hours) |
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Adverse effect of celecoxib
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1) abdominal pain, dyspepsia, and diarrhea
2) GI ulcers double that of the plecebo, but 1/3 of that taking IB profen, and 1/5 that of people taking neproxen 3) kidney toxicity 4) P450 interactions are likely |
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acetaminophen
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1) tissue specific COX inhibitor
2) antipyretic and analgesic --inhibits COX-3 in the CNS 3) NOT antiinflamatory --minimal effect on COX in the periphery (inhibited by peroxides at the site of inflamation) 4) Metabolized in the liver 5) excreted in the urine |
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Methotrexate
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immunosuppresant
--inhibits aminoimidazolecarboxamide (AICAR), transformylase, and thymidylate synthetase |
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chlorambucil
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cross links DNA
--inhibits cell replication |
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Cyclophosphamide
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cross links DNA
--inhibits cell replication |
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cyclosporine
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Inhibits IL-1 and IL-2 receptor production
--dysrupts T cell mediated response |
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TNF-alpha blocking agents
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1) adalimumab
2) Infliximab 3) Etanercept 4) Leflunomide |
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function of adalimumab & Infliximab
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anti-TNF-alpha mAB
--inhibits macrophage and T cell function |
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function of entanercept
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recombinant fusion protein
--TNF-alpha Rc IgG which binds to TNF alpha |
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function of Leflunomide
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1) inhibits rhibonucleoside synthesis
--inhibits T cell proliferation |
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define gout
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1)metabolic disorder with high serum levels of UA (deposited in the jonts and cartilidge)
2) many people have hyperuricemia w/o gout 3) urate crystals initiate inflamation |
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risk factors for gout
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1) primary
--inherited abnormality in UA metabolism 2) secondary --obesity --high alcohol intake --high BP --abnormal kidney function --drugs (thiazides and chronic low dose aspirin) |
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DX of gout
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1) usually affects only 1 joint at a time
2) arthrocentesis - remove fluid from the joint and inspect for crystals 3) X-ray may shoe crystals deposits and bone damage |
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Prophylactic tx of gout
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1) limit alcohol
2) drink pleanty of water 3) avoid foods rich in purines (shellfish, organ meats) 4) reduce weight |
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drugs used to tx gout
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1) colchicine
2) probenecid 3) sulfinpyrazone 4)Allopurinol 5) NSAID's |
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colchicine
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1) plant alkyloid
2) used for acute attacks of gout --also prophylactically |
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MOA of colchicine
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prevents polymerization of tubulin in microtubules
--inhibition of leukocyte migration into affected area 2) inhibits synthesis and release of leukotrienes |
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MOA of Probenecid &Sulfinpyrazone
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1. Increases the excretion of uric acid by inhibiting the reabsorption of uric acid in the proximal tubule
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pharmicokinetics and metabolism of Probenecid & Sulfinpyrazone
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1. Completely absorbed in gut
2. peak plasma concentration 2-4 h 3. Half-life is dose-dependent (5-8 h) 4. 85-95% bound to plasma binding proteins |
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MOA of Allopurinol
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Inhibitor of xanthine oxidase
---Purine analog (hypoxanthine isomer) this reduces the production of uric acid |
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allopurinol is metabolized to _________
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1) alloxanthine which retains capacity to inhibits XO
--this explains the the long duration of action |
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__________NSAIDs are usually given first in acute gout attack
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1) non-salicylate NSAIDs
---Due to toxicity of colchicine, |
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which NSAID's are most effec in tx gout
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b. Propionic acid derivatives most effective
--Ibuprofen --Naproxen --Ketoprofen |
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can you use aspirin to tx gout?
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c. DO NOT USE ASPIRIN for gout
--It results in UA retention |