1. Dr. RAGHU PRASADA M S
MBBS,MD
ASSISTANT PROFESSOR
DEPT. OF PHARMACOLOGY
SSIMS & RC. 1

2.  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

5. ACUTE GOUT
 Inhibit neutrophil migration into the joints-
COLCHICINE,
 Inhibition Of Inflammation And Pain-NSAIDs,
PREDNISOLONE,
CHRONIC GOUT
Which inhibit uric acid synthesis-ALLOPURINOL,
FEBUXOSTAT
Which increase uric acid excretion: PROBENACID,
SULPHINPYROZONE, BENZBROMARONE

6.  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 glycoproteinlactic acidrelease
of lysosomal enzymesjoint 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

7. INDICATIONS-prophylactic dose-0.5mg/kg
-treatment of acute gout
ADVERSE EFFECTS-Diarrhoea, vomiting, abd’inal pain
Acute intoxication-bloody diarrhoea, hematuria
Chronic- agranulacytosis, peripheral neuritis
Fatal ascending CNS depression
DRUG INTERACTION : Statins, Macrolides,
Cyclosporine
CONTRAINDICATED in dialysis pt.s
CAUTIOUS USE in : renal or liver dysfunction; active
infection, age > 70

8.  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

9.  Reserved for refractory cases not tolerating NSAIDs
and colchicine
 Prednisolone 40-60mg/day
 Tapering dose
 Intra articular injection of soluble steroid

10. 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

11. It has longer duration of action-OD
Uses
Chronic gout, gouty tophi, or nepropathy
Recurrent urate stones
Patients allergic to uricosuric drugs
Secondary hyperuricemia due to Ca chemotherapy
Kalazar- allopurinal+ sod.stibogluconate-alters purine
metabolism

12.  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
12
allopurinol oxypurinol
Xanthine
Oxidase
Stevens-
Johnson
Syndrome
Allopurinol
Hypersensitivity
Syndrome
Toxic Epidermal
Necrolysis

13. 1. Interferes with metabolism of hep.iron stores
2. It reduces metabolism of 6-mercaptopurine
3. Azathioprine dose is decreased to 1/4th
4. Inhibits metabolism of oral anticoagulants and
thiophylline

14.  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,

15. 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

16. Uses- treatment of secondary hyperuricemia
 Should not be used in acute goutcan be given with
NSAIDs
Drug 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, dyspepsia
allergic dermatitis,higher doses- nephrotic syndrome

17.  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

18.  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

19.  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 allantoin
ADR- Infusion reaction, neprolithiasis, UTI

20.  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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