Anti-gout drugs, by Baqir Raza Naqvi..pptx

Anti-gout drugs,

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2. TOPIC ANTI GOUT DRUGS PRESENTED BY: M. BAQIR RAZA NAQVI M. Phil Pharmacology PRESENTED TO : DR. M. KHALID TIPU Department of Pharmacy Quaid.i.Azam University, I slamabad 2

3. INTRODUCTION Gout  is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot, and swollen joint . The joint at the base of the big toe is affected in about half of cases. It may also result in tophi, kidney stones, or kidney damage . There are times when symptoms get worse, known as flares, and times when there are no symptoms, known as remission. Repeated bouts of gout can lead to gouty arthritis, a worsening form of arthritis. 3

4. Gout is metabolic disease in which plasma urate concentration get increased ( hyperuricaemia ), ( Normal urate level: 1-4 mg/dl ). Uric acid is product of purine metabolism. When urate level increases in blood it gets precipitates and deposits in joints, kidney and cutaneous tissue which is called as tophy . 4

5. CAUSES: 5

6. PATHOPHYSIOLOGY: 6

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9. ANTI- GOUTS Gout medications are in two types. 1. The first type helps reduce the inflammation and pain associated with gout attacks. 2. The second type works to prevent gout complications by lowering the amount of uric acid in your blood . 9

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11. 1. Drugs used to treat gout flares; 11

12. 2. Drugs used to prevent gout complications; 12

13. Site of Action of Antigouts : 13

14. COLCHICINE Alkaloid from Colchicum autumnale / autumn crocus found as antigout in 1763 and isolated as pure form in 1820. Not having anti-inflammatory or analgesic activity but used specifically in treatment of gouty inflammation. First dated information of colchicine was available in Ebers Papyrus/Papyrus Ebers and it was written in about 1500 BC) 14

15. PROCESS OF GOUTY INFLAMATION Precipitation of urate crystals in synovial fluid Start inflammatory response By producing Chemotactic factors Migration of granulocytes in to joints Which phagocytose (engulf) urate crystals  Increases lactic acid production form inflamed cell Release glycoprotein  Decreases PH More urate crystals get precipitate and affect joint Release lysosomal enzyme Joint destruction Aggrevates / Worsen inflammatory condition 15

16. MAO of Colchicine: Precipitation of urate crystals in synovial fluid Start inflammatory response By producing Chemotactic factors Migration of granulocytes in to joints Which phagocytose (engulf) urate crystals Release glycoprotein Colchicine Bind to fibrillar protein tubulin Depolymerisation of microtubules Decreases cell motility Symptomatic relief for gout prevent 16

17. Other actions of Colchicine: Antimitotic : Binding to microtubules of mitotic spindle, results in metaphase arrest. Was tried for cancer chemotherapy But causes toxicity. Gut action : gut motility through neural mechanism . Pharmacokinetics : Absorption : Rapid orally. Distribution : Uniform. Metabolism : Liver Elemination : bile-undergoes enterohepatic circulation, Urine & faeces . 17

18. Clinical Use of Colchicine: 1 . Treatment of acute gout: Best drug to control an acute attack of gout , 1 mg orally followed by 0.25 mg 1-3 hourly till control of the attack. 2. Prophylaxis condition of gout: Colchicine 0.5-1 mg/day prevent gout attack but now a days NSAID’s are preferred. 3 . Other uses: Used in plant breeding by inducing polyploidy ( state of a cell or organism having more than two paired) in plant cells for new or improved varieties, strains and cultivars. 18

19. Adverse effects; Toxicity of Colchicine: High and dose related. At therapeutic dose: Nausea , vomiting, watery or bloody diarrhoea and abdominal cramps. Accumulation of the drug in intestine and inhibition of mitosis. In overdose: colchicine produces kidney damage, CNS depression, intestinal bleeding; death is due to muscular paralysis and respiratory failure. Chronic therapy: Not recommended because it causes aplastic anaemia , agranulocytosis , myopathy and loss of hair. 19

20. NSAIDs NSAIDs reduce both pain and inflammation. Many NSAIDs are available over the counter at low doses and at higher doses by prescription . NSAIDs commonly used for gout include: A spirin ( Bufferin ) celecoxib  (Celebrex) ibuprofen (Advil) indomethacin (Indocin) ketoprofen naproxen (Aleve) 20

21. Mechanism of action; (NSAIDs) 21

22. Cont. Produces responses slow as compared to colchicine but well tolerated so more preferred than colchicine. Naproxen, piroxicam inhibits chemotactic migration of leucocytes into the inflamed joint. But not recommended for long term management due to risk of toxicity. 22

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24. Corticosteroids Intraarticular injection of soluble steroids suppress symptoms of acute gout. Corticosteroids decrease the pain, swelling, redness and (inflammation) of gout. But Corticosteroids are used only for patients suffering from renal failure or peptic ulcer (Because NSAID’s are contraindicated). Risk of rebound of attack is observed on drug withdrawal. Example; Prednisolone 40-60 mg given once a day. 24

25. Xanthine Oxidase inhibitors This class of antigouts contain majorly two drugs. 1. Allopurinol 2. Febuxostat FEBUXOSTAT Recently approved first non-purine inhibitor of xanthine oxidase Safe in renal disease as highly metabolized to inactive metabolites in the liver 25

26. Mechanism of action; 26

27. Pharmackokinetcs ; • Absorption: Rapid orally. • Distribution : Not bound to plasma protein. • Metabolism: During chronic administration inhibit self metabolism. • Elemination : 1/3 excreted as unchanged form in urine. 27

28. Adverse effects ; Acute attacks of gouty arthritis (prophylactic treatment with NSAIDs or colchicine) GI intolerance, Peripheral neuritis ,Necrotizing vasculitis , Bone marrow depression Aplastic anemia Hepatic toxicity, Interstitial nephritis Allergic skin reactions- exfoliative dermatitis 28

29. Interactions Inhibits the metabolism of 6- mercaptopurine and azathioprine so their dosage must be reduced by 75% Prolongs t 1/2 of warfarin & probenecid (inhibits metabolism) May enhance the bone marrow toxicity of cytotoxic drugs (cyclophosphamide) Caution : Safety in children & during pregnancy has not been established 29

30. DOSE REGIMEN For acute attack ; • Absolute bed rest, • Ice packs, • Avoidance of alcohol • Tab. Colchicine 0.5 mg 3rd hrly followed by maintenance dose of 0.5 – 1 mg/day. It has significant GI toxicity and delayed onset of action. • Tab.Phenylbutazone 200mg TDS for colchicine resistant patient • Alternatively oral Prednisolone 20-40mg/day is also effective 30

31. Management of Gout (cont.) For chronic gout, Allopurinol The first choice of drug in chronic gout started with 100mg OD and gradually increased upto 300mg/day, Febuxostat It is a recently introduced nonpurine xanthain oxidase inhibitor dosage is 40-80mg/day, it has hepatotoxic side effect hence pt followed up with liver function test. 31

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33. References; katzung - basic and clinical pharmacology, 12th edition Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12th Edition www.ncbi.net LIPPENCOTS ilistrated reviews Mayoclinic.net Slideshare.net Nih.com 33

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