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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