Gout

Pharmacotherapeutics of Gout

1. Gout Dr. V. S. Swathi Assistant Professor

2. Definition Gout is most common inflammatory disease caused by deposition of mono sodium urate crystals in joints and tissues following chronic Hyperurecemia

3. Epidemiology In the world, prevalence of gout ranges from 0.1%-10% In India, prevalence of gout is 0.12%

4. Types Based on progression of disease Asymptomatic Hyperurecemia In this, patients will not show any symptoms Uric acid levels in the synovial fluid increases Patients are treated by non pharmacological management (life style changes) Acute Gout Uric acid crystals deposited and cause inflammation and intense pain Pain subside within 3-10 days It is triggered by stress, alcohol, drugs, and cold weather   Interval Gout It is the stage between attacks of acute gout In this stage, deposition of urate crystals occurs continuously

5. Chronic tophaceous Gout It is severe condition Permanent damage occurs in joints and kidneys Patients develops tophi in joints and fingers Pseudo Gout Here symptoms are similar to Gout Crystals which are deposited in joints are calcium pyrophosphate

6. Based on Causes Primary Gout- It is not a consequence of acquired disorder Secondary Gout- It is a consequence of specific disorder and specific use of drugs

7. Risk factors Family history Genitical defects in Enzymes (HPRT) Etiology Renal disease Obesity Gender-Men are having more risk than women Dyslipidemia Glucose Intolerance Hypertension Diet Alcohol consumption Medications

8. Etiology Primary Gout Rare enzyme deficiencies Hypoxanthine –Guanine phosphoribosyl transferase deficiency (HPRT) Phosphoribosyl pyrophosphate synthetase superactivity Ribose -5-Phospahe AMPdeaminase deficiency

9. Secondary Gout Increased uric acid production Chronic haemolytic anemias Secondary polycythemia Severe exfoliative psoriasis Gaucher’s disease Cytotoxic drugs Glucose-6-Phosphate deficiency High purine diet

10. Decreased uric acid excretion Renal failure Alcohol Down’s Syndrome Myxedema Lead poisoning Beryllium poisoning Drugs like: Aspirin Ciclosporin Cytotoxic drugs Diuretics Ethambutol Levodopa Pyrizinamide Ribavirin Interferon Teriparatide

11. Pathogenesis

12. Clinical Presentation In the joints of lower limbs like big toe, ankles, knees, arms Pain Swelling Redness Warmth Shiny overlying skin Anorexia Nausea Change in mood Pruritis Tophi

13. Complications Secondary infections Chronic renal failure Severe degenerative arthritis Uric acid nephropathy Nerve/ Spinal cord impingement Joint damage Joint deformity Loss of mobility Osteoporosis

14. Diagnosis Medical history Medication history Family history Clinical presentation Physical examination Lab tests (Elevated ESR, WBC) Synovial fluid exam Polarised light microscopy

15. Diagnostic criteria According to American college of Rheumatology Presence of characteristic urate crystals in the joint fluid/ Presence of tophi which contain urate crystals by chemicals or polarised light microscopy/ Presence of six or more of the following: Asymptomatic swelling with in a joint on radiography Attack of mono articular arthritis Culture of joint fluid negative for microbes during attack of joint inflammation Development of maximal inflammation with in one day Hyperurecemia Joint redness More than one attack of acute arthritis Pain/ redness in the first metatarsophalangeal joint Subcortical cyst without erosions on radiography Suspected tophi Unilateral attack involving first metatarsophalangeal joint Unilateral attack involving tarsal joint

16. Non Pharmacological Treatment Avoid purine rich food like meat, sea foods, and sweet soft drinks Avoid alcohol consumption Exercise in interval attacks Rest in acute attacks Avoid medications which decrease uric acid excretion Topical ice application Patient counselling Hydration Surgery Tophi removal Joint fusion Joint replacement

17. Treatment Algorithm Acute attack Rest for 1-3 days and Topical ice application Review medication and life style Resolve pain with NSAIDs/ Colchicine / Corticosteroid Chronic attack Uricostatic agents- Allopurinol / Febuxostat Uricosuric agents-Probenacid/ Sulfinpyrazone Uricolytic agents- Rasburicase / PEG- Uricase

18. Drugs used in treatment of Gout Drug Category Mode of Action Dose Adverse Effects Diclofenac NSAID Inhibit COX enzyme and release of Prostaglandins 100mg-OD-PO Abdominal Cramps Constipation Diarrhea Dyspepsia Edema Prednisolone Corticosteroid Inhibit inflammation by suppressing migration of PMNs and stabilizing lysosomes at cellular level 30mg-OD-PO for 5 days and slowly discontinue the drug by tappering Acne Diabetes Hypertension Edema Weight gain Methyl Prednisolone Corticosteroid Inhibit inflammation by suppressing migration of PMNs and stabilizing lysosomes at cellular level 80mg-OD-IA Acne Diabetes Hypertension Edema Weight gain

19. Allopurinol Xanthine Oxidase Inhibitor Inhibit uric acid production 100-900mg/day-PO Rash Fever Nephrotoxicity Hepatotoxicity Vasculitis Febuxostat Xanthine Oxidase Inhibitor Inhibit uric acid production 80-120mg/day-PO Respiratory infection Diarrhea Headache Hepatotoxicity Arthralgia Probenacid Uricosuric agent Increases uric acid excretion 0.5-2g/day-PO Head ache Loss of Appetite Anemia Renal calculi Leukopenia Sulfinpyrazone Uricosuric agent Increases uric acid excretion 200-800mg/day-PO Unusual bleeding Hepatotoxicity Nephrotoxicity GI ulceration Fluid retention

20. Rasburicase Uricolytic agent It coverts insoluble uric acid in to soluble allontoin 0.2mg/kg for 5-7 days Fever Rash Diarrhea Head ache Hypersensitivity Colchicine Uricosuric agent It prevents activation, degranulation and migration of neutrophils and increases uric acid excretion 1-1.8mg-OD-PO GI disturbances Bone marrow suppression Neuropathy Myopathy Hepatotoxicity Anakinra Immunomodulator Inhibits Interleukin actions by binding to IL-1 receptor 100mg/day-SC Injection site reactions Arthralgia Pyrexia Nasopharyngitis Neutropenia

21. Resources https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322774/ https://www.sciencedirect.com/science/article/pii/S0041134518302343?via%3Dihub https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254413/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196879/