GOUT Definition Pathogenesis Clinical Features Treatment

gout
definition
pathogenesis
clinical features
treatment

1. GOUT By : Dr. Paroma Sinha

2. GOUT Gout   is a form of inflammatory arthritis  characterized by Hyperuricemia. Most often affects middle-aged, elderly men and postmenopausal women .

3. Pathogenesis If excess uric acid is present in body, Reacts with sodium to form sodium urate, which then accumulates in soft tissues. Typical sites are the cartilage of joints and ears,kidneys The crystals irritate the cartilage, causing inflammation, swelling and acute pain. Eventually, the crystals destroy all the joint tissues. If untreated, the ends of articulating bones fuse and the joint becomes immovable

4. Factors precipitating Gout * *

5. * Common sites : heels, ankle,knees , wrists, and fingers affected

6. DIAGNOSIS I . Synovial fluid Under Polarized Light Microscopy 1ST MTP Knee joint

7. Patient

8. II. Laboratory (Blood) tests Normal uric acid level : 2-6 mg /dl. Hyperuricemia - 7.0 mg/dl (420 μmol /L ) in males 6.0 mg/dl (360 μmol /L) in females. WBC raised ESR raised

9. Differential diagnosis? Septic arthritis Gout Rheumatoid arthritis Match the following Gout Septic arthritis Rheumatoid arthritis A B C

10. Q.A patient with gout develops hypertension. The uric acid level was found to be elevated. Which of the following is not administered? A) Hydrochlorothiazide B) Atenolol C)Enalapril D) Prazosin

11. MANAGEMENT Treatment of acute attack Rest during attack Topical Ice application NSAIDS Colchicine Corticosteroid Treatment of chronic gout Uricostatic drugs Uricouric drugs Uricolytic drugs *

12. COLCHICINE

13. COLCHICINE Dose – 1 mg stat followed by 0.5 mg every 3 hours, until pain is relieved No effect in blood uric levels. S/E :- diarrhoea abdominal pain Acute intoxication leads to bloody diarrhoea, throat pain respiratory depression, Renal failure. haematuria and oliguria Chronic toxicity agranulocytosis. peripheral neuritis and myopathy.

14. NSAIDS INDOMETHACIN

15. NSAIDS Dose – Strong anti inflammatory agents. Better tolerated than colchicine so used more frequently. Drugs used : Indomethacin ,diclofenac , naproxen,piroxicam etc.,

16. Corticosteroids Dose : oral prednisolone (40-60 mg/day) stat ;for 3-5 days followed by tapering the doses over 2-3 weeks. Intra-articular injection of a soluble steroid (triamcinolone acetonid 30 mg , hydrcocotisone or prednisolone) is usually preferred . .These are very effective in suppressing - the symptoms of acute gout. These are reserved for refractory cases not tolerating NSAIDs or colchicine.

17. New drugs 1) Interleukin 1 inhibitors, canakinumab , showed moderate effectiveness for pain relief and reduction of joint swelling, A/E : back pain, headache, and increased BP. The high cost . 2) 320 mg of rilonacept 3) triamcinolone acetonide  (steroid)

18. URICOSTATIC DRUGS ALLOPURINOL

19. Allopurinol Dose - 100 mg/day, gradually increase at weekly intervals to 300 mg/day. It reduces the concentration of uric acid in tissues, plasma and urine The deposition of urate crystals in tissues (tophi) is reversed and formation of renal stones is inhibited. S/E :- Precipitate acute attack. Hypersensitivity reaction, at times, may be severe e.g., exfoliative skin rash, arthralgia, fever, lym - phadenopathy and hepatitis. GIT distress, nausea, peripheral neuritis and cata Ract formation deposition of allopurinol in lens

20. Drug interactions Allopurinol reduces the metabolism of 6 mercaptopurine, azathioprine,cyclophosphamide * It can potentiate the actions of oral anticoagulants and of theophylline by inhibiting their metabolism, It should be used with caution during pregnancy. in elderly and in children.

21. Febuxostat Dose 40-120 mg once daily. It is a recently introduced more potent more selective inhibitor of xanthine oxidase (compared to allopurinol) Does not produce hypersensitivity reaction seen with allopurinol. S/E : Liver dysfunction, diarrhoea , headache. topixostat

22. URICOURIC DRUGS Probenicid Dose: 250 mg BD orally stat then 500 mg BD after one week. MOA - Probenicid acts by promoting the excretion of uric acid by inhibiting its active reabsorption from the renal tubule. Given with plenty of water and urinary alkalinizer . S/E :- GIT distress ,allergic dermatitis, nephrotic syndrome and convulsions.

23. Drug interactions Low doses of aspirin block uricosuric action of probenecid Inhibits biliary excretion of rifampicin It inhibits urinary excretion of penicillins , cepha - losporins , methotrexate indomethacin

24. Sulfinpyrazone Dose - 100-200 mg/day oral stat. to be continued till serum uric acid levels become normal. maintenance dose - 200 mg/ day. . Adverse effects – peptic ulcer.

25. Benzbromarone Dose – 60-80 mg /day more potent uricosuric drug allergic or refractory to probenecid or sulfinpyrazone patients with renal Insufficiency where GFR is as low as 25% of the normal. Adverse effect- git distress

26. Lesinurad URAD-1 (Urad transporter-1 present in proximal tubule and is involved in uric acid absorption inhibitor.

27. URICOLYTIC DRUGS Pegloticase Dose - 4-12 mg by I.V. infusion Pegloticase is a recombinant uricase Once dosing , pegloticase decreases the levels of uric acid for up to 21 days, enabling it to be dosed every 2 weeks. Adverse effects -nausea, headache, anaemia , arthralgia, msucle regidity and nephrolithiasis .

28. MCQs

29. Q. What is the mechanism of action of colchicine? A) Inhibits synthesis of uric acid B) Promotes excretion of uric acid C) Inhibits xanthine oxidase enzyme D)Binds to tubulin and inhibits and inhibits granulocyte migration

30. Q . A) Aspirin B) Indomethacin C) Allopurinol D) Colchicine

31. Q.A middle-aged man presented to the ER with severe pain and swelling as shown in the image below. He told that he had consumed 2 bottles of beer a few hours before. Which of the following drugs is not used in the management of this patient? A. Indomethacin B. Prednisone C. Allopurinol D. Colchicine 

32. Q . A patient receiving anti-tubercular therapy has been recently diagnosed with gout. Which of the following statements is incorrect about this condition? A. The crystals are positively birefringent B. Ethambutol can precipitate gout C. More common in males D. Most commonly involves the first MTP joint

33. Q. A patient with recurrent attacks of gout was started on a therapy that inhibits the synthesis of uric acid. His symptoms were reduced after therapy. Which drug was he started on? A. Probenecid B. Colchicine C. Diclofenac D. Allopurinol

34. Q. A patient with chronic tophaceous gout was prescribed sulfinpyrazone. What is the mechanism of action of this drug? A. Inhibits formation of uric acid B Promotes excretion of uric acid C. Inhibits xanthine oxidase enzyme D. Inhibits cyclooxygenase enzyme

35. Q. A 44 year old woman presents with right knee swelling .On synovial fluid examination, showed calcium pyrophosphate crystals. What is the next best investigation? Α. ΑΝΑ B. RF C. CPK D. TSH