Test #1 Flashcards
Uricostatic agents
- allopurinol and febuxostat
Uricosuric agents
- probenecid, salicylate, losartan
- increase the rate of excretion of uric acid
Enzymes for gout treatment
pegloticase
Anti-inflammatory agents for gout
colchicine and indomethacin
Allopurinol
Xanthine Oxidase Inhibitor
- reduces synthesis of urate
- oxypurinol is an active metabolite (long)
Effects
—prevents progression of gouty arthritis
—decrease nephropathy by decreasing stones
—increase acute gout flare
PK
—rapidly absorbed and long lasting (1/day)
—colchicine with to prevent acute flare
Adverse
—probenecid will increase clearance
—with warfarin - increase bleeding risk
—hypersensitivity
Febuxostat
- non-competitive xanthine oxidase Uses ---hyperuricemia with gout Adverse ---bad for liver, nausea
Probenecid
MoA ---inhibits transport of urate across URAT-1 Uses ---gout therapy ---combined with more fluids, bicarb, colchicine Adverse ---GI - peptic ulcer ---Salicylates will reduce efficacy ---blocks penicillin excretion High doses are uricosuric not low doses
Losartan
- moderate uricosuric agent
Pegloticase
- pegylated recombinant porcine uricase Uses ---refractory gout ---not for chronic gout Adverse ---BBW - anaphylaxis and hymolytic anemia
Colchicine
MoA
—anti-mitotic by interfering with microtubules
—prevents activation and migration of neutrophils
PK
—oral and metabolized by CYP3A4
Uses
—acute gout
—prevention while other agents are started
Adverse
—GI - stop if they continue
—Myelosuppression
Indomethacin
NSAID - inhibitor of COX 1/2 Adverse --- narrow therapeutic window --- 50% of SE ----severe frontal headache ---seizures, depression and psychosis
Hydroxychloroquine
Uses ---antimalarial drug ---anti-inflammatory agent and combined for RA PK ---oral daily Adverse ---GI and skin in short term ---retinal damage - get baseline exam ---decreases blood glucose ---don't use with psoriasis or prophyria ---hepatotoxic
Sulfasalazine
Uses ---immune suprressive for RA PK ---oral daily ---metabolized in gut and poorly absorbed Adverse ---GI and diarrhea ---skin rash ---blood dyscarsias/agranulocytosis
Methotrexate
Uses ---RA with folate replacement PK ---oral, SC ---once per week ---take 4-6 weeks for effect MoA ---anti-folate to inhibite purine synthesis ---inhibits AICAR transformylase to increase adenosine ---reduces thymidine levels (pyrimidine) Adverse ---hepatotoxicity with high doses ---teratogenic ---pulmonary toxicity ---alopecia
Leflunomide
MoA ---inhibits dihydro-orotate - inhibits pyrimidine --- inhibits T-cell proliferation Uses ---immunosuppressive agent PK ---oral daily (prodrug to teriflunomide) Adverse --- long half life causes much CYP450 inhibition ---carcinogenic and teratogenic
Minocycline
MoA ---tetracycline antibiotic ---inhibits metalloproteinases to decrease collegen degradation in RA PK ---experimental ---twice daily oral Adverse --- dizziness and hyperpigmentation
Etanercept
- anti tumor necrosis factor alpha MoA ---anti TNF alpha and stops binding to receptor PK ---SC injection weekly with methotrexate ---short duration Adverse ---headaches ---progressive multifocal leukoencephalopathy
Infliximab
MoA ---monoclonal antibody against TNF PK ---IV every 4-8 wks with methotrexate Adverse ---Cause hypotension
Adalimumab
MoA ---Anti-TNF humanized antibiody PK ---SC injection per 2 weeks ---for juvenile arthritis Adverse ---demyelination
Abatacept
MoA ---CTLA-4 analog to antagonize CD28 receptor ---T cell inhibitor PK ---SC injection weekly ---for moderate-severe RA Adverse ---serious infection risk ---infusion reaciton --- not used in those with COPD
Rituximab
MoA ---anti-CD20 monoclonal antibody ---inhibits B cells PK ---IV two weeks apart then wait 6 months ---combination with methotrexate Adverse ---infection risk is high ---progressive multifocal leukoencephalopathy
NSAIDS for Arthritis
- Naproxen is safest
- usually not sufficient for RA
Glucocorticoids for Arthritis
- prednisone mostly
- toxicity with long term use
- used in combo for RA
- bridging agent
