This document discusses drugs used to treat gout, which is caused by excess uric acid in the blood. It describes: 1) Drugs for acute gout that reduce inflammation like colchicine and NSAIDs or inhibit neutrophil migration. 2) Drugs for chronic gout that inhibit uric acid synthesis like allopurinol or increase excretion like probenecid. 3) The mechanisms of several anti-gout drugs including how NSAIDs inhibit prostaglandin synthesis and allopurinol inhibits xanthine oxidase to reduce uric acid production.

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Anti-gout Drugs
♦ LEARNING OBJECTIVES ♦
After completing this chapter, reader should be able to:
• Describe the drugs that can be used in gout disease.
14.1 INTRODUCTION
• Gout is a common and complex form of arthritis that can affect anyone. It's
characterized by sudden, severe attacks of pain, swelling, redness and tenderness in
the joints, often the joint at the base of the big toe.
• It is metabolic disorders characterized by hyperuricemia. Purine metabolized to uric
acid by xanthine oxidase. In gout patients either increased in uric acid production or
unable to excrete uric acid normally.
• So excess of uric acid in blood, this uric acid combine with sodium and forms sodium
ureate, which accumulates in typical sites like kidney, cartilage, joints and ears.
• Uric acid is the final product of the metabolism of endogenous and exogenous
purine in man. An excess of uric acid, measured in the plasma as sodium urate,
constitutes hyperuricaemia.
• This excess may be caused by an overproduction or under excretion of urate. It is
influenced by genetic and environmental factors and may be classified as primary
(mainly idiopathic) or secondary.
• An increase in urate production may be caused by excessive dietary purine intake,
certain cancers or their treatment, or, more rarely, enzyme defects of purine
metabolism.
• Reduced urate excretion may be caused by renal disease, hypertension, or the intake
of certain drugs such as thiazide diuretics. Other factors contributing to
hyperuricaemia include hyperlipidaemia, obesity, alcohol consumption, and lead
exposure.
• Gout is a form of inflammatory arthritis that develops in some people who have high
levels of uric acid in the blood.
• The acid can form needle-like crystals in a joint and cause sudden, severe episodes
of pain, tenderness, redness, warmth and swelling.
• Gout is caused initially by an excess of uric acid in the blood, or hyperuricemia.
• Uric acid is produced in the body during the breakdown of purines - chemical
compounds that are found in high amounts in certain foods such as meat, poultry,
and seafood.

2. Pharmacology - II 14.2 Anti-gout Drugs
14.2 CLASSIFICATIONS OF DRUGS USE IN THE TREATMENT OF GOUT
Drugs which acts in Acute Gout:
• Drugs which inhibits neutrophils migration in joint: Colchicines.
• Drugs which inhibits inflammation and pain: NSAIDS, Prednisolone.
Drugs used in Chronic Gout:
• Drugs which inhibits uric acid synthesis: Allopurinol, Febuxostat.
• Drugs which increase uric acid excretion: Probencid, Sulphinpyrazone,
Benzhromarone.
Nucleic acid
Degradation
Purine
Allopurinol inhibits Xanthenes oxidase
Inhibits uric acid synthesis
Anti-gout action
Therapeutic Uses:
• Anti gout drugs in chronic and acute gout.
• Secondary hyperuricemia.
ADR:
• Hypersensitivity reaction, Skin rashes, Arthralgia, pain, Fever, hepatitis, GIT distress,
Nausea, Peripheral neuritis, Cataract formation.
Probencid:
• Increased uric acid excretion by inhibiting its active reabsorption from renal tubules.
Result increased uric acid excretion. Uricosuric effect.
Therapeutic Uses:
• Chronic gout.
• Hyperuricemia.
ADR:
• Git distress, Allergic dermatitis, dyspepsia, nephritic syndrome.
Sulfinpyrazone:
• Increased uric acid excretion by inhibiting its active reabsorption from renal tubules.
Result increased uric acid excretion. Uricosuric effect.
Therapeutic Uses:
• Chronic gout
• Hyperuricemia
ADR:
• GIT disturbance, Nausea, Vomiting, hyperuricemia.

3. Pharmacology - II 14.3 Anti-gout Drugs
Prednisolone:
MOA:
• Inhibits gene transcription of COX2, cytokines, interleukins, as a result produce relief
from inflammation.
• Increase release and synthesis of annexin-1, which is potent anti-inflammatory to
cells hence produce anti-inflammatory actions.
• Symptomatic pain relief.
• Inhibition of chemotactic migration of leucocytes.
ADR:
• Prolonged use leads to toxic effect.
Therapeutic Uses:
• Acute gout.
• Hyperuricemia.
NSAIDS:
MOA:
• NSAIDs reduce inflammation and pain but it does not have any effect on disease
progression.
Cyclooxygenase (COX)
COX 1 COX 2
Phospholipids
Phospholipase A2
Arachidonic acid
Aspirin
COX-1 COX-2
(Celecoxib, Rofecoxib Inhibition)
PGG2
PGH2
PGI2 PGH2 PGE , PGF , PGD
2 2 2
a
• Inhibits pain sensation-Analgesic action.
• Reduced capillary permeability, decreased tissue edema-Anti inflammatory action.
• These release Prostaglandins which are responsible for inflammation, pain etc.

4. Pharmacology - II 14.4 Anti-gout Drugs
• COX inhibitors cause inhibition of COX enzyme and inhibits conversion of
arachidonic acid into PGG2 later PGG2 to PGH 2, PGI2, PGE2, PGF2α and PGD2. So
inhibits pain sensation-Analgesic action, decreased tissue edema-Anti inflammatory
action.
• Symptomatic pain relief
• Inhibition of chemotactic migration of leucocytes.
• Inhibits crystal urate formation.
Therapeutic Uses:
• Acute gout
• Hyperuricemia
Adverse Effects:
• Nausea, Vomiting, Constipation, Diarrhea, Dizziness, Edema, Kidney failure, Ulcers.
Colchicines:
• Drugs which inhibits neutrophils migration in joint. Inhibition of chemotactic
migration of leucocytes.
• Relief from gout.
Therapeutic Uses:
• Acute gout.
• Hyperuricemia.
ADR:
• GIT disturbance, Nausea, Vomiting, hyperuricemia.
QUESTIONS
• Discuss the pharmacology of anti-gout drugs.
• MoA of drugs used as anti-gout drug.