GOUT By Prof Azza ElMedany Dr Osama Yousf
GOUT
By Prof. Azza El-Medany Dr. Osama Yousf
OBJECTIVES At the end of lectures students should : Define gout Describe outlines of treatment Describe treatment of acute gouty arthritis Describe the mechanism of action , clinical uses & side effects of drugs used in acute attacks
OBJECTIVES ( continue) Classify drugs used in chronic treatment Define each group of drugs Describe the mechanism of action, clinical uses & side effects & drug interactions for drugs used in chronic treatment
What is gout? High blood uric acid level Acute arthritis monosodium urate stone in kidney ♂>♀ Familial metabolic disease Breakdo wn of product of the body’s purine (nucleic acid) metabol
Idiopathic decrease in uric acid excretion (75%) Impaired uric acid excretion secondary to thiazide diuretics, chronic Renal failure etiology of raised uric acid level High dietary purine intake Increase uric acid production due to increased cell turn over (tumors), increase uric acid synthesis
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What is the treatment for gout ?
Clinical stages of Gout
2 • Asymptomatic Stage • Acute stage 3 • Intercritical stage 4 • Chronic stage 1
ASYMPTOMATIC STAGE urate levels rise in the blood, but produces no symptoms
ACUTE STAGE
INTERCRITICAL 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.
CHRONIC STAGE
Broad lines in treatment of gout Nonpharmacolo gic Acute gouty arthritis Chronic gout(long term treatment)
Non-pharmacologic Therapy
Control….
Acute gouty arthritis NSAIDs colchicine corticoster oid
1. NSAIDs
NSAIDs (Selective or non- selective ) Inhibit pain & inflammation. Inhibit urate crystal phagocytosis by decreasing the migration of granulocytes into the inflammatory area. They are commonly used now for treatment of acute attack or to prevent recurrent attacks with other drugs. ( Except aspirin & paracetamol)
2. Colchicine
Basyir Bin Kamaruzaman (15)
OVERVIEW A plant alkaloid A Selective drug effective only in gouty arthritis Has No analgesic effects
MECHANISM OF ACTIONS Binds to tubulin (microtubular protein ) disrupt cellular function ( migration of granulocytes to affected area Inhibits the synthesis and release of leukotrienes & TNFα Blocks cell division by binding to mitotic spindles
PHARMACOKINETI CS PHAPHARMACOKINETICS Given orally, followed by rapid absorption from the GI tract Reaches peak plasma levels within 2 hours Excreted unchanged in the faeces & urine. Should be used with caution in patients with renal impairment
THERAPEUTIC USES The anti-inflammatory activity of colchicine is specific for gout, alleviating the pain within 12 hours Colchicine is used as prophylaxis to prevent recurrent attacks in more than 80 percent of patients. Treatment for Mediterranean Fever
Adverse effects Severe diarrhea ( cause of its restriction in use ) Chronic use alopecia, bone marrow depression, peripheral neuritis, myopathy.
Acute intoxication ( large doses) Burning pain in throat Bloody diarrhea Shock Hematuria C. N. S. depression
Contraindication pregnancy Precaution in hepatic , renal problems
3. Corticosteroids
Chronic gout (long term treatment) 1 -Inhibition of uric acid synthesis 2 -Increase excretion of uric acid
Treatment of Refractory Gout Mammalian uricase enzyme
Inhibition of uric acid synthesis
Xanthine Oxidase Inhibitors
Mechanism of action
ALLOPURINOLPharmacokinetics Well absorbed orally (80% ) Metabolized in the liver to oxypurinol which is responsible for most of its urate-lowering effect Given once daily. Drug & its metabolite excreted through the kidney. Dose adjustment is needed in
Pharmacokinetics
Therapeutic Uses Treatment of primary hyperuricemia
Hyperuricemia secondary to other conditions such as :
Impaired renal functions.
uric acid stones or nephropathy.
In patients receiving cancer chemotherapy
ALLOPURINOL SIDE EFFECTS & DRUG INTERACTIONS
Side Effects (most common) exacerbation of an acute attack of gout
Maculopopular skin rash
nausea, diarrhea
Side Effects (less common) Body : fever, headache CVS : vasculitis
Thrombocytopenia Epistaxis
Drug Interactions Inhibits metabolism of oral anticoagulant: ( warfarin ) Potentiates its action
Inhibits metabolism of anticancer drugs : (6 -mercaptopurine & azathioprine ) • So , doses of anticancer • Must be reduced up to 75%
With ampicillin : Increases frequency of skin rash
Febuxostat Is a new oral non-purine xanthine oxidase (XO) inhibitor. Is structurally different from allopurinol as it lacks purine ring Selective and potent inhibitor of XO than allopurinol Well absorbed orally ( 84%), given once daily Can be given with or without food Metabolized in liver & excreted in urine & feces No dose adjustment is needed in renal impairment
Continue Suitable than allopurinol in patients with impaired renal function as no dose adjustment is required. Used for treatment of chronic hyperuricemia in gout patients Given to patients who do not tolerate allopurinol
Adverse effects Recurrent attacks of acute gout during the first few months of treatment Increase level of liver enzymes Nausea, Diarrhea Headache Numbness of arm or leg
DRUGS INCREASED EXCRETION OF URIC ACID
Uricosuric drugs
1 - Probenecid
2 - Sulfinpyrazone 3 - Large doses of aspirin ( more than 5 g )
Mechanism of action of uricosuric drugs Block the active transport sites of the proximal tubules(middle segment ) causing : reduction of Uric acid re-absorption ( uric acid excretion
Clinical uses Chronic gout
Warning Urine volume should be maintained at a high level, and urinary p. H kept alkaline.
Adverse effects Acute attack of gout Risk of uric acid stone GIT upset Allergic rash
( continue) Nephrotic syndrome ( probenecid) Aplastic anemia ( rare )
DRUG INTERACTIONS Probenecid prolong the action of some antibiotics as: penicillins
Contraindications History of urinary tract stones Impaired renal function Recent acute gout attack Administration of low doses of aspirin
Treatment of Refractory Gout Mammalian uricase enzyme
Modified mammalian uricase enzyme Pegloticase Is a modified mammalian uricase enzyme Converts uric acid to allantoin Given I. V. Infusion peak decline in uric acid level within 24 -72 hours
Continue Used for the treatment of gout in adult patients refractory to conventional therapy Adverse effects Infusion reactions Anaphylaxis Gout flare Nephrolithiasis Arthralgia, muscle spasm Headache
THANK YOU
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