Drug Therapy Of Gout/fibromyalgia/osteoarthritis

Front 1

relation of gout with hyperuricemia

Back 1

gout is always preceeded by hyperuricemia, but hyperuricemia does not always lead to gout

Front 2

transient attacks of gout initiated by?

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crystallization of urates in and around joints

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podagra

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gout of greater toe/ most common joint affected

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tophi

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lg aggregates of urate crystals and the surrounding inflammatory response

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Lesch-Nyhan syndrome

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x-linked recessive d/o affecting only males in which HGPRT(required for salvage pathway) is totally absent

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four stages of gout

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1. asymptomatic hyperuricemia
2. acute gouty arthritis
3. intercritical gout
4. chronic tophaceous gout

Front 7

renal manifestations of gout

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-HTN
-renal colic(uric acid nephrolithiasis in 10-25%
-chronic gouty nephropathy(20% die of renal failure)

Front 8

MOA of allopurinol and febuxostat

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block synthesis of uric acid and xanthine oxidase inhibitor

Front 9

MOA of probenecid

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increase uric acid excretion with a uricosuric agent

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indications for pegloticase

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chronic gout refractory to conventional therapy

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colchicine

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blocks entry of leukocytes into affected joints with microtubule disrupting agent--used to limit inflammation

Front 12

tx of pain and inflammation of gout

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-NSAIDs are effective @ inflammatory doses
-steroids can be given orally or by interarticular injection

Front 13

ASA and gout

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contraindicated since salicylate competitively inhibits the active tubular secretion of urate, causing net urate retention

Front 14

Acid urine promotes urate crystallization, therefore tx by?

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intaining an alkaline urine with liberal fluid intake and sodium bicarbonate; continue until serum uric acid normalizes and tophi disappear

Front 15

MOA of uricosuric agents

Back 15

block active reabsorption(normally 80% reabsorbed) and enhance urinary uric acid excretion

Front 16

Probenecid (uricosuric agent)
MOA

Back 16

-inhibits tubular reabsorption of urate, increases excretion and decreases serum levels

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what is meant by probenecid causing "mobilization"

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retards urate depostion and promotes reabsorption of urate deposits

Front 18

Probenecid dosing

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-initiate with small doses to avoid dumping large amts of urate into urine and possible stone formation
-maintain adequate hydration and alkalinize the urine

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Probenecid is indicated for tx of gout in pts who have no hx of?

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nephrolithiasis

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DI of probenecid

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-anionic form may competitively inhibit the active tubular secretion of other organic acids
-beneficial interaction with beta lactams

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probenecid pt info

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-avoid ASA
-may take with food or antacid for GI upset
-drink 6-8 full glasses per day to prevent ddevelopment of kidney stones
-must take continuouslyfor therapeutic effect

Front 22

allopurinol

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xanthine oxidase inhibitor--decrease production of uric acid without affecting synthesis of vital purines

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oxipurinol

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active metabolite of allopurinol

Front 24

allopurinol warnings/ADR

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--allergic skin rash/severe hypersensitivity rxn
--avoid in acute gout attacks due to mobilization/can give maintenance doses of colchicine prophylactically
-fluid intake >/=2L required to prevent acid urine

Front 25

allopurinol pt info

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-take with food or milk
-drink 10-12glasses of fluid q day
-avoid agents which acidify the urine

Front 26

Febuxostat

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selective nonpurine xanthine oxidase inhibitor

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indication for febuxostat

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chronic management of hyperuricemia in gout pts

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Febuxostat
1. DI
2. ADR

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1.DI with meds metabolized by XO
2. gout flares at beginning of tx, use prophylactic therapy of NSAIDs or colchicine

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Pegloticase

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recombinant polyethylene glycol(PEG)-modified mammalian uricase(urate oxidase)
-XO inhibitor

Front 30

Pegloticase MOA

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oxidation of uric acid to allantoin (water soluble purine metabolite)resulting in lower serum uric acid levels

Front 31

Peloticase indications

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chronic gout refractory to conventional therapy in adults

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Pegloticase Boxed Warning

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for infusion-related and anaphylactic rxns;
-premedicate with antihistamines and corticosteroids
-prophylactic NSAIDs or colchicine starting 1 wk prior to 1st infusion an dcontinue 6 mo to prevent gout flares

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contraindication of Pegloticase

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G6PD deficiency=> increases hemolysis and methemoglobinemia

Front 34

Cochicine MOA

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binds to tubulin preventing polymerization--inhibition of leukocyte migration, decreased phagocytosis and diminished inflammatory response to deposited crystals, and blocks cell division by binding to mitotic spindles

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Colchicine FDA safety concerns

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--cases of fatal toxicity at therapeutic doses with other meds
-substantiallly lower dose as effective , but fewer ADR

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Colchicine warnings

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-do not give P-glycoprotein(Pgp) inhibitors or strong 3A4 inhibitors to pts with renal or hepatic impairment who are on colchicine

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Colchicine indications

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used for relief of acute gout attacks and for regular prophylactic use between attacks
-often effective in aborting an attack if taken at first sign of discomfort

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Colchicine ADR

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severe GI effects: N/V/D and abdominal pain
-diarrhea most common and dose limiting effect
-can tx diarrhea with opiates

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tx of osteoarthritis is _______

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empiric and should be directed at symptom relief

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acetominophen for tx of osteoarthritis

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-effective/recommended as initial therapy at max adult doses
-max daily dose: <4g/d

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NSAIDs in tx of osteoarthritis

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-used if any inflammatory component is present or if pain relief from acetominophen is inadequate

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Antidepressants in tx of fibromyalgia

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-dual mechanism antidepressants block reuptake of both NE and 5HT

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Antidepressants approved for use in fibromyalgia

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-duloxetine(Cymbalta)
-milnacipran(Savella)

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pregabalin(Lyrica) in tx of fibromyalgia

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-anticonvulsant
-1st FDA approved drug for fibromyalgia