gout and K disorde5r..................pptx

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1. PHARMACOLOGY I GROUP WORK GOUT AND K + DISORDER Pharma Group

2. Gout What is gout? Gout is a type of arthritis. It results from an excess of uric acid in the blood and tissues of the body, inflammatory arthritis with red, tender, hot and swollen joints Pathogenesis: Deposits of sodium urate crystals in articular (>6.8 mg/dl) , periarticular subcutaneous tissues tophus = localized deposit of monosodium urate crystals (needle shape )

3. Stages of gout Treat or not to treat? Prevent recurrent attacks Terminate The attack - Prevent complications -Lower serum uric acid Four distinct stages: a)asymptomatic hyper- uricemia ; b) acute intermittent gout; c) Intercritical stage ; d) chronic gout

4. Non-pharmacologic Therapy Lifestyle modifications Loss of weight Smoking cessation Diet control Exercise

5. Prevention of recurrent attack Inhibition of uric acid synthesis - Allopurinol - Febuxostat Uricosuric drugs - Probenacid Sulfinpyrazo ne Mammalian Uricase

6. ALLOPURINOL po Decrease the production of uric acid by inhibiting the enzyme xanthine oxidase Management of hyperuricemia associated with chemotherapy Uric acid stones or nephropathy it is metabolized by xanthine oxidase into alloxanthine which is pharmacologically active It is contra-indicated in acute gout because uric acid has inhibitory effect on release of cytokines and allopurinol may aggravate the inflammation by reducing uric acid.

7. ADRS (side effect): 1- Diarrhea, nausea, abnormal liver tests 2- Acute attacks of gout 3- Fever, rash, toxic epidermal necrolysis hepatotoxicity, marrow suppression vasculitis 4- DRESS syndrome ( D rug R eaction, E osinophilia, S ystemic S ymptoms) 5- 20% mortality rate

8. FEBUXOSTAT For hyperuricemia in patients with gout (as it reduces serum uric acid levels) Chemically distinct from allopurinol (non purine) * Can be used in patients with renal disease * Oral specific xanthine oxidase inhibitor

9. ADRS (side effect): Increases number of gout attacks during the first few months of treatment Increases level of liver enzymes Nausea, Diarrhea Numbness of arm or leg Headache

10. URICOSURIC DRUGS Blocks tubular reabsorption of uric acid & enhances urine uric acid excretion - competitive inhibitors Probenecid inhibits Urate Transporters (URAT1) in the apical membrane of the proximal tubule It also inhibits organic acid transporter(OAT)→↑plasma concentration of penicilin Sulfinpyrazol inhibits URAT1 & OAT4

11. Uricosuric drugs should not be used if v Creatinine clearance is <50ml/min. v History of nephrolithiasis (uric acid or calcium stones ) v Evidence of overproduction of uric acid (> 800 mg of uric acid in a 24-hour urine col l ection ) Probenecid Exacerbation of acute attack Risk of uric acid stone GIT upset Allergic rash Sulfinpyrazone : C an aggravate peptic ulcer disease Aspirin reduces efficacy of sulfinpyrazone enhance the action of certain anti-diabetic drugs

12. PEGLOTICASE IV Used for the treatment of chronic gout in adult patients refractory to conventional therapy Drugs Increasing Metabolism catalyzing uric acid to the water- soluble purine metabolite allantoin enzymatically convert urate to allantoin , which is more soluble and readily excreted in the urine

13. ADRS (side effect): Infusion reactions Anaphylaxis Gout flare Arthralgia ( arthra : joints, algia : pain) Muscle spasm

14. Treatment of acute gout Colchicine NSAIDs Acute gouty arthritis Corticosteroids

15. NSAIDS NSAIDs  inhibit the cyclooxygenase 2 ( COX -2 ) enzymes, which are involved in the inflammatory process and prostaglandin production . Commonly used NSAIDs during an acute gout attack include ibuprofen 800 mg three to four times daily or indomethacin 25 to 50 mg four times daily . Treatment should be discontinued when symptoms resolve They can, however, sometimes give rise gastropathy , nephropathy, liver dysfunction . They can also aggravate asthma, heart and kidney failure and raise blood pressure

16. COLCHICINE is more effective and faster acting than NSAIDs but is used rarely due to its high toxicity . It acts by inhibiting granulocyte migration into the inflamed joint It causes metaphase arrest its toxixty . Most common and dose limiting toxicity is diarrhea . It can also cause kidney damage, myopathy and bone marrow depression i t can be effective, but tends to be used less often than NSAIDs as it can make you feel very sick or give you diarrhoea

17. Steroids ( Corticoste roid ) Used when NSAIDs are contraindicated or not tolerated. such as elderly people, patients with kidney or hepatic impairment, IHD, PUD. Should be IV route to get arthritis site Side effects mild insomnia or flushing short course but weight gain, fluid retention, high blood pressure and diabetes, as well as osteoporosis and wasting of the skin and musclesl ong term . Corticosteroids such as prednisolone are different from, and should not be confused with, the anabolic steroids that are sometimes misused by athletes to build up muscle bulk and strength.

18. HYPOKALEMIA hypokalemia comes from hypo- 'under' + kalium 'potassium' + - emia 'blood condition'. serum potassium concentration < 3.5 mEq /L normal 3.5-5 Potassium plays a role in the transmission of nerve signals, muscle contractions, fluid balance, and various chemical reactions.

19. Sign and symptom weakness. feeling tired. muscle cramps. confusion. constipation. an abnormal heart rhythm (arrhythmia) – skipped heartbeats or an irregular heartbeat. tingling or numbness. increased urination.

20. Category & Clinical presentation State Serum K level Clinical presenttation mild 3-3.5 mEq /L asymptomatic moderate 2.5-3 mEq /L cramping, weakness, malaise, and myalgias severe < 2.5 mEq /L ECG changes arrhythmias

21. KCl oral administered with or after meals To reduce gastrointestinal irritation and cathartic effect ,   mild hypokalemia and minimal symptoms IV if  when the oral or enteral route is not available or will not achieve the required increase of serum potassium within a clinically acceptable time to peripheral vein over 1 hour Avoide with D5W

22. Side effet p otassium can cause  stomach  upset, nausea ,  diarrhea ,  vomiting , or intestinal gas . ACE inhibitors ARBs Potassium-sparing diureti cs)

23. Alternative therapy Potassium-sparing diuretics Spironolactone anatagonist aldotrone in the distal renal tubel can olso for HTN side effects: hyperkalemia, gynecomastia , breast tenderness, impotence

24. Diety

25. Hyperkalemia sign and symptom   heart palpitations , shortness of breath, chest pain, nausea , or vomiting. Sudden or severe hyperkalemia is a life-threatening condition.

26. Hyperkalemia Treatment & Management Calcium salts. Beta-adrenergic agonists. Antidiabetics , Insulins . Diuretics, Loop. Potassium Binders. Alkalinizing Agent

27. Reference http:// www.ukgoutsociety.org/PDFs/Final_All_about_gout_and_treatment_2014.pdf https:// en.wikipedia.org/wiki/Hypokalemia Pharmacology_Basics.pdf

28. THA PHARMA GROUP II