Gout is a metabolic disorder caused by elevated levels of uric acid in the blood (hyperuricemia). Uric acid crystallizes and deposits in joints, causing sudden and severe attacks of arthritis. Gout can be primary, due to overproduction of uric acid, or secondary, due to other conditions that reduce excretion or increase production of uric acid. Treatment involves medications to reduce uric acid levels such as allopurinol and probenecid, as well as lifestyle changes like a low-purine diet and increased fluid intake. Nonsteroidal anti-inflammatory drugs and corticosteroids are used to treat acute gout attacks and bring down joint inflammation.

1. B Y
S R O T A D A W N .
1 S T Y E A R
M . P H A R M ( P H A R M A C O L O G Y )
GOUT & ITS
TREATMENT

2. INTRODUCTION
‘Gout’ is a metabolic disorder characterized by
hyperuricemia .
Hyperuricemia is a condition when blood SERUM URIC ACID LEVEL
gets increased.
Uric acid is the end product of

3. NORMAL PLASMA URIC ACID CONCENTRATIONS
In men 3-7 mg/dl
In women 2-6mg/dl
Daily excretion of uric acid is about 500 – 700 mg.
The prevalence of gout is about 3 per 1,000 persons .
mostly affecting males & post-menopausal women however
, are as susceptible as man for this disease.

4. Gout is a metabolic disease associated with over production of
uric acid. Biologically it is synthesized during purine metabolism,
Uric acid has
1. Low water solubility.
2 . Especially in low pH
When blood levels are high ,it precipitates and deposit as
sodium urate crystals on joints, kidneys and
subcutaneous tissue( tophy )

5. Gout: pathophysiology
Food intake Cell breakdown
Purines
Uric acid
HYPERURICAEMIA
Kidney Soft tissue of
the joints
Other tissue
Ear
Overproduction Under excretion

8. • FACTORS INFLUENCING GOUT FORMATION:
1. HIGH LIVING
2. OVER EATING
3. ALCOHOL CONSUMPTION
4. LEAD POISONING

9. Gout is of two types –
1. Primary gout
2. Secondary gout
1. Primary gout :
it is an inborn error of metabolism of purine due
to over production of uric acid. This is mostly related to
increased synthesis of purine nucleotides.
2. Secondary gout :
secondary hyperuricemia is due to various
disease causing increased synthesis or decreased
excretion of uric acid.

10. DISORDERS OF PURINE METABOLISM (URIC ACID SYNTHESIS PATHWAY)

12. The important metabolic defects are associated with primary gout
formation :
 ENZYMES DIRECTLY INVOLVED IN PURINE SYNTHESIS:
1. PRPP SYNTHATASE :
In normal circumstances , PRPP
synthetase is under feed back control mechanism by purine nucleotides
(ADP and GDP ).This leads to the increased production of purines .
2. PRPP glutamylamidotransferase :
The lack of feedback control of
this enzyme by purine nucleotides also leads to their elevated synthesis .
3. HGPRT deficiency :
This is an enzyme of purine
Salvage pathway , and its defects causes lesch – Nyhan
syndrome.

13. Lesch – Nyhan syndrome.
This disorder occurs with increased synthesis of purine
nucleotides by 2 fold mechanism
Decrease utilization of
Purine nucleotides (
hypoxanthine & guanine)
The defect in salvage
pathway, leads to
IMP & GMP

14.  ENZYMES INDIRECTLY INVOLVED IN PURINE SYNTHESIS:
4 . GLUCOSE 6 – PHOSPHATASE DEFFICIENCY :
In von Gierke’s
disease, glucose 6-phosphate can not be converted to glucose due to
the deficiency of glucose 6- phosphatase. This leads to increased
utilization of glucose 6- phosphate by HMP shunt ,resulting in
elevated levels of ribose 5- phosphate and PRPP and ultimately leads
to purine overproduction.
5.ELIVATION OF GLUTATHIONE REDUCTASE :
Increase glutathione reductase
generates more NADP+ which is utilized by HMP shunt. This leads to
elevated levels of ribose 5- phosphate and PRPP and ultimately leads
to purine overproduction.

15. PATHWAY OF FORMATION OF GOUT:
1.Precipitation of uric acid crystals on synovial fluid
2. Inflammatory response, chomotactic factors produced
3.Granulocyte migration into the joint, they phagocytose urate crystals and release
a glycoprotein which aggregates the inflammation by
4.Increasing lactic acid production from inflammatory cells

16. PATHWAY OF FORMATION OF GOUT:
5.local PH reduced
2. more uric acid crystals precipitates in the affected joint .
3. Release lysozomal enzymes which causes joint destruction.

17. How is Gout Cured?
 No cure
 Gout can be controlled
 Diet – eating low purine foods, drinking water
 Drugs – Allopurinal lowers uric acid production

18. Therapy for Acute Gouty Arthritis
 Colchicine
 Oral
 IV
 Nonsteroidal Anti-inflammatory Agents
 Corticosteroids
 Intra-articular
 IM (ACTH)

19. Colchicine :
BIOLOGICAL SOURCE : Colchicum autumnale
 neither analgesic nor anti – inflammatory
 but suppress the gouty inflammation
 does not inhibit the synthesis of uric acid
 does not promote the excretion of uric acid
 thus has no effect on blood uric acid levels
Colchicine inhibits release of the glycoprotein and their by inhibit the
following pathway.
TOXICITY: Dose related.
ADR: 1. Nausea ,vomiting, watery or bloody diarrhoea and abdominal
cramps.
2.overdose leads to kidney damage.
3.Chronic therapy with colchichine is not recommended because it
causes aplastic anaemia,agranulocytosis,myopathy and loss of hair.

20. Nonsteroidal Anti-inflammatory Agents :
Strong NSAID s used :
indomethacine ,
naproxen ,
piroxicam,
diclofenac,
etoricoxib
 strong anti-inflammatory action
 naproxen and piroxicam inhibits chemotactic migration of
leucocytes into the inflamed joint.
 they are not recommended for long term therapy

21. Corticosteroids :
 intraarticular injection of a soluble steroid suppresses
symptoms of acute gout.
 they are very effective and produce nearly as rapid a response
as colchicine
 but are reserved for the patients of renal failure history of
peptic ulcer bleed in whom NSAID s are contraindicated.
 Inhibit PGE2 and LTB4
 Stabilize lysosomal membranes

22. Therapy for Acute Gouty Arthritis
When pain and stiffness persist in a joint between attacks, gout has
become chronic .
Other features are :
1.Hyperuricaemia
2. tophy
3. urate stones in the kidney
Two types of drugs are used in this type of chronic gout:
 uricosuric drugs :
1 . PROBENECID
2 . SULFINPYRAZONE
 uric acid synthesis inhibitors :
ALLOPURINOL

28. Probenecid/Sulfinpyrazone
 No analgesic/anti-inflammatory activity.
 Inhibits uric acid reabsorption.
 Plenty of water /fluids should be given with
probenecid to avoid urate crystallization in urinary
tract
 Increase uric acid excretion in urine.
 Uses: Chronic gout and hyperuricemia
 Adverse effects: Hypersensitivity

29. Allopurinol
 No analgesic/anti-inflammatory activity.
 Reduces plasma, tissue and urine concentration
of uric acid.
 Reverses of deposition of urate crystals and
inhibits urate stone formation.

30. Drugs used in chronic gout (antihyperuricemic
drugs) : sites of action
Purines
Hypoxanthine
Xanthine
Uric acid
Xanthine
oxidase
Xanthine
oxidase
PROBENECID
SULPFINPYRAZON
E
-
OXYPURINOL
-
-
Overproducers:
Allopurinol
Underexcretors:
Probenecid
Sulfinpyrazome
ALLOPURINOL
-

31. Allopurinol
 Uses:
 Chronic gout
 Tophi
 Nephropathy
 Secondary gout
 Cancer radio/chemotherapy
(coadministered with
azathioprine/
mercaptopurine)

32. Allopurinol
 Drug interactions:
 Azathioprine, mercaptopurin
e
(inhibits degradation)
 Probenecid(complex
interaction)
 Warfarin,theophyline(inhibit
metabolism)
 Ampicillin(skin rashes)
Xanthine oxidase
Azathioprine
Mercaptopurine
Inactive metabolites
Allopurinol
-
• Adverse effects:
– Hypersensitivity