GoutFamilial metabolic disease

characterized by : Acute arthritisUric acid stones in the kidneysHyperuricemia

Breakdown

of product of the

body’s purin

e (nucleic acid) metabolism.

What is the What is the treatment for gout treatment for gout

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DRUGS USED IN TEATMENT OF GOUT

Most therapeutic strategies for gout involve lowering the uric acid level below the saturation point (<6 mg/dL), thus preventing the deposition of urate crystals. This can be accomplished by: 1.interfering with uric acid synthesis with allopurinol2.increasing uric acid excretion with probenecid or sulfinpyrazone, large doses of aspirin3.inhibiting leukocyte entry into the affected joint with colchicine,4.administration of NSAIDs

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urate levels rise in the blood, but produces no symptoms

ASYMPTOMATIC STAGE

ACUTE STAGE

symptom-free intervals between gout episodes. Most people have a second attack from six months to two years, while others are symptom-free for five to 10 years.

INTERCRITICAL STAGE

CHRONIC STAGE

Non-pharmacologicTherapy

Control….

1. NSAIDs

Inhibits pain & inflammation.Inhibits urate crystal phagocytosis by

decreasing the migration of granulocytes into the inflammatory area.

( Indomethacin is commonly used & it may replace colchicine .

Aspirin in therapeutic doses is contraindicated as it compete with uric acid secretion in proximal tubule.

2. Colchicine

Basyir Bin Kamaruzaman (15)

OVERVIEW

MECHANISM OF ACTIONS

PHARMACOKINETICSPHAPHARMACOKINETICS

THERAPEUTIC USES

Adverse effectsDiarrhea is a common adverse effect. May cause nausea,vomiting ,abdominal cramps.

Chronic use may cause, alopecia, bone marrow depression, peripheral neuritis, myopathy.

Also,affect fertility

Acute intoxicationBurning throat pain.Bloody diarrhea.Shock.Hematuria.C.N.S.depression.

Contraindication & Precaution

Contraindicated in pregnancy

Should be used with caution in hepatic , renal or cardiovascular diseases.

3. Corticosteroids

Prevention of recurrent

attack

Inhibition of uric acid synthesis Allopurinol

Uricosuric drugs

- Probenacid

-Sulfinpyrazone

-Large doses of aspirin

Inhibition of uric acid synthesis

Mechanism of action

Pharmacokinetics80% absorbed after oral administration.

Metabolized to active metabolite alloxanthine.

Given once daily.Drug & its metabolite are excreted in the feces & urine.

Pharmacokinetics

Therapeutic Uses

It is drug of choice in patient with:

Chronic tophaceous deposits (reabsorption is more rapid)

High serum uric acid in patients with impaired renal functions.

uric acid stones or nephropathy.

used to prevent increased uric acid levels in patients receiving cancer chemotherapy

ALLOPURINOL(SIDE EFFECTS AND

DRUG INTERACTIONS)

Side Effects (most common)

exacerbation ofan acute attack of gout

Maculopopular skin rash

nausea, diarrhea

Side Effects (less common)

Body : fever, headache CVS : vasculitis

Thrombocytopenia Epistaxis

Drug Interactions

With oral anticoagulant:Potentiates warfarin

and dicumarol•inhibits their metabolism

in liver

With anticancer :6-mercaptopurineand azathioprine

• inhibits their metabolism (doses are reduced up to 75%

With ampicillin :Increases frequency

of skin rash

Prolongs half life ofChlorpropamide

• both compete for excretion in renal tubule

Uricosuric drugs

Probenecid  is a uricosuric drug that increases uric acid excretion in the urine

primarily used in treating gout 

Probenecid

Sulfinpyrazone

Sulfinpyrazone is a metabolite of phenylbutazone

Metabolized into an active metabolite in the liver.

Mechanism of actionUricosuric drugs ( probenecid, sulfinpyrazone, large dose of aspirin) block the active transport sites of the proximal tubules(middle segment ) the

reabsorption of uric acid is decreased.

Clinical usesShould not be started until 2-3 weeks after an acute attack.

In chronic gout when :Evidence of tophi appearsPlasma levels of uric acid are so high that may cause tissue damage

Clinical uses ( continue)Urine volume should be maintained at a high level, and urinary pH kept alkaline .

Probenecid is a general inhibitor of the tubular secretion of organic acids , so it is used to prolong action of other weak organic acids as some antibiotics e.g. penicillin.

DRUG INTERACTIONS

Probenecid prolong the action of some antibiotics as: penicillin and cephalosporins

Side effectsAcute attack of goutRisk of uric acid stoneGIT upset Allergic rash

Adverse effects ( continue)Nephrotic syndrome ( probenecid)

Aplastic anemia ( not common )

Contra-indications

History of urinary tract stone

Impaired renal functionRecent acute gouty attackAdministration of low doses of aspirin

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