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DRUG TREATMENT FOR GOUT
Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSOR DEPT. OF PHARMACOLOGYSSIMS & RC.
Pathophysiology
Uric acid is end product of purine metabolism and is excreted by the kidneys
Causes of hyperuricemia- excess alcohol, obesity Rich foods have a higher concentration of
protein Diet high in purines will not cause gout, but may
trigger an attack in a susceptible person Great toe joint most common first manifestation;
other joints may be the foot, ankle, knee, or wrist
Pathophysiology
Drugs used in gout
ACUTE GOUT Inhibit neutrophil migration into the joints-
COLCHICINE, Inhibition Of Inflammation And Pain-
NSAIDs, PREDNISOLONE, CHRONIC GOUTWhich inhibit uric acid synthesis-
ALLOPURINOL, FEBUXOSTATWhich increase uric acid excretion:
PROBENACID, SULPHINPYROZONE, BENZBROMARONE
Colchicine
Alkaloid from COLCHICUM AUTOMNALE It supresses the gouty inflammatory response and gives
relief within 24-48 hours Prevents granulocyte migration into the inflamed joint Inhibit the release of glycoproteinlactic acidrelease of
lysosomal enzymesjoint destruction Binding to intracellular protein TUBULIN and cause
depolymerization and disappearance of microtubules in granulacytes prevents migration of granulocyte drunken walk
It inhibits formation of leukotriene B4
Colchicine
INDICATIONS-prophylactic dose-0.5mg/kg-treatment of acute gout
ADVERSE EFFECTS-Diarrhoea, vomiting, abd’inal painAcute intoxication-bloody diarrhoea, hematuriaChronic- agranulacytosis, peripheral neuritisFatal ascending CNS depressionDRUG INTERACTION : Statins, Macrolides,
CyclosporineCONTRAINDICATED in dialysis pt.sCAUTIOUS USE in : renal or liver dysfunction; active
infection, age > 70
NSAIDs
INDOMETHACIN, NAPROXEN, PIROXIXCAM Inhibition of prostaglandin synthase Inhibit urate crystal phagocytosis and chemotactic
migration of leukocytes into inflamed joint ASPIRIN—uricosuric at doses >3.6g/day OXAPROZIN-lowers serum uric acid, but should be
used cautiously in uric acid stones
Corticosteroids
Reserved for refractory cases not tolerating NSAIDs and colchicine
Prednisolone 40-60mg/day Tapering dose Intra articular injection of soluble steroid
Drugs used for chronic gout
Uric acid synthesis inhibitor: ALLOPURINOL Purine anti-metabolite but not analgesic, not anti-
inflammatory Blocks conversion of hypoxanthine to uric acid by
competatively inhibiting enzyme xanthine oxidase Alloxanthine –major metabolite-is long acting-24hrs Decrease concentrtn of insoluble urates in tissues,
plasma, urine Effective in overproducers May be effective in under excretors
Uric acid synthesis inhibitor: ALLOPURINOL
It has longer duration of action-ODUses Chronic gout, gouty tophi, or nepropathyRecurrent urate stonesPatients allergic to uricosuric drugsSecondary hyperuricemia due to Ca chemotherapyKalazar- allopurinal+ sod.stibogluconate-alters purine
metabolism
Adverse effects
Oxypurinol, allopurinol metabolite, cleared by kidney and accumulates in patients with renal failure
Oxypurinol inhibits xanthine oxidase Increased oxypurinol related to risk of allopurinol
hypersensitivity syndrome GIT distress, ph. Neuritis and cataract formation
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allopurinol oxypurinol
Xanthine Oxidase
Stevens-Johnson Syndrome
Allopurinol Hypersensitivity Syndrome
Toxic Epidermal Necrolysis
Drug interaction
1. Interferes with metabolism of hep.iron stores2. It reduces metabolism of 6-mercaptopurine3. Azathioprine dose is decreased to 1/4th
4. Inhibits metabolism of oral anticoagulants and thiophylline
Febuxostat
Potent inhibitor of xanthine oxidase decreases uric acid
Treatment of chronic gout or secondary hyperuricemia
Suitable in patients intolerant to allopurinol ADR-liver dysfunction, diarrhoea,
URICOSURIC AGENTS
PROBENACID-acts by promoting the excretion of uric acid by inhibiting active reabsorption from renal tubules
Reverses most common physiologic abnormality in gout ( 90% pt.s are under excretors)
Urine excretion of uric acid increases, size of urate pool decreases and tophacious deposits of urate are reabsorbed with relief from arthritis
Not an analgesic or anti-inflammatory drug
URICOSURIC AGENTS
Uses- treatment of secondary hyperuricemia Should not be used in acute goutcan be given with
NSAIDsDrug interaction- prolong penicillin or cephalosporin
levels, inhibits biliary excretion of rifampicin, low dose aspirin blocks uricosuric action of probenacid
ADR- should be given with plenty of water and urinary alkaliniser GIT distress, dyspepsiaallergic dermatitis,higher doses- nephrotic syndrome
Sulfinpyrazone
Structurally related to phenyl butazone At sub therapeutic doses, prevents secretion of uric
acid into tubular fluid. At therapeutic doses- prevents resorption of uric
acid, increases excretion in urine If urate is high, urinary alkaliniser is added
D/I-In chronic gout- uricosuric action is additive to probenacid.
It inhibits metabolism of warfarin and sulfonylureas
BENZBROMARONE
Newer more potent uricosuric drug Used in patients allergic or refractory to probenacid
and sulfinpyrazone MOA- reversible inhibiitor of tubular reabsorption With allopurinol more effective With aspirin/ sulfinpyrazone-antagonistic action ADR- GIT distress
Pegloticase
Newest urate lowering therapy Recombinant mammalian uricase that is covalently
attached to mPEG Declines uric acid levels within 24-72hrs T1/2 - 6.4-13.8 days Urate oxidase enzyme absent in humans, converts
uric acid to allantoinADR- Infusion reaction, neprolithiasis, UTI
Interleukin-1 inhibitors
ANAKINRA, CANAKINUMAB, RILONACEPT
Drugs targeting IL-1 pathway Tried in patients refractory to traditional drugs It is fully human anti-IL1β monoclonal antibody It prevents gouty flares during urate lowering therapy It can provide rapid and sustained pain relief
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