This document provides an overview of gout, a metabolic disease characterized by high blood uric acid levels that can cause painful inflammation in joints. It discusses the production and excretion of uric acid, the pathophysiology of gout, diagnosis methods including blood tests and joint fluid aspiration, and treatment approaches for acute and chronic gout including medications that inhibit uric acid synthesis or increase excretion such as allopurinol, febuxostat, and lesinurad. The mode of action and pharmacokinetics of select medications are also summarized along with references for additional information.

1. RAEBARELI
Prepared by :-
Gulam Navi Azad
MS Pharma 1st year
August 31,2018
Pharmacology & Toxicology
National Institution Pharmaceutical Education & Research
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2. CONTENTS
Introduction
Fate of Uric acid
Pathophysiology of Gout
Diagnosis
Treatment
References
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3. INTRODUCTION
 Metabolic disease
 High blood uric acid
 Monosodium urate stones in joints, kidney&
some soft tissues
 Its inflammatory disease
 Normal value of uric acid (2-6 mg/dl)
 Symptoms
1. Joints Pain
2. Swelling in the joints
3. Stiffness
4. Physical deformities
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4. RNA DNA
purine
hypoxanthine
xanthine
uric acid (low water soluble)
PRODUCTION OF
URIC ACID
PRPP
Xanthine oxidase
Xanthine oxidase
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URATE
EXCRETION
 HOAT 3 ( human renal organic anion transporter)
1. HUAT1
2. HUAT2
3. URAT1

5. 5
Fig :- Uric acid crystals ( source of Gout DR. G.Callie
& DR. Michael B)
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GOUT
PRIMARY
GOUT
SECONDARY
GOUT
TYPES OF GOUT

6. 6
PATHOPHYSIOLOGY OF GOUT
Fig:- 94 etiology of &pathogenesis of hyperuricemia of gout Robert T. Keenan& Michael h.Pillinger
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7. 7
DIAGNOSIS
JOINT FLUIDS
ASPIRATION
BLOOD TEST (SERUM
URIC ACID LEVELS)
X -RAYS
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8. TREATMENT OF GOUT
Acute gout
1. NSAIDS
2. Colchicine
3. Corticosteroids
Chronic gout
1. Inhibition of uric acid synthesis
Allopurinol
Febuxostate
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9. 2. Increase the uric acid excretion
 Probencid
 Sulphinpyrazole
o IL 1bita inhibitors
o Anakinra
o Rilonacept
o Canakinumab
New treatment for gout
1. Pegloticase
2. Losartan ( URAT1 & GLUT9)
3. Fenofibrate ( URAT1)
4. Lesinurad
5. Ulodesine (under trial 3 phase)
6. Levotofisopam (under trial 2 phase)
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10. MODE OF ACTION
 Allopurinol
 Xanthine oxidase inhibitor
 Metabolism: liver (80% oxipurinol, 10% allopurinol)
 Elimination half-life: 2 h (oxipurinol 18-30 h)
 Febuxostat
 Potent than allopurinol
 Elimination half-life: ~5-8 hour
 Pregnancy category: US: C)
 Metabolism: via CYP1A2, 2C8, 2C9, UGT1A1
 Lesinurad (200mg)
 USFDA approval on 22 Dec 2015
 URAT 1 transporter inhibitors
 Combination with allopurinol
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Purine catabolism
Hypoxanthine
Xanthine Xanthine Oxidase
uric acid Allopurinol

11. REFERENCES11
1. Saag KG, Mikuls TR, Abbott J. The Epidemiology of Gout and Calcium Pyrophosphate Dihydrate
Deposition Disease in: Wortmann RL ed. Crystalinduced arthropathies: gout, pseudogoutand apatite-
associated syndromes. Taylor and Francis 2006; 7-36.
2. Aromdee E, Michet C, Crowson C, O’FallonM, Gabriel S. Epidemiology of gout: isthe incidence
rising? J Rheumatol 2002;29:2403–2406.
3. Wallace KL, Riedel AA, Joseph-Ridge N,Wortmann R. Increasing prevalence of goutand
hyperuricemia over 10 years amongolder adults in a managed care population.J Rheumatol 2004;
31:1582–7.
4. Choi HK, Mount DB, Reginato AM.Pathogenesis of gout. Ann Intern Med 2005; 143:499.
5. Becker MA, Jolly M. Clinical gout andthe pathogenesis of hyperuricemia. In.Koopman W.J., Moreland
L.W., ed. Arthritisand Allied Conditions: A Textbook of Rheumatology, (ed. 15) Lippincott Williamsand
Wilkins Philadelphia, PA2005: 2303-39.
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