1. Prepared by : Tamara Odeh Diana Jawhari Supervised by : Dr. Ola Ayesh

2. DNA Adenine Guanine Purine group Cytosine Thymine Pyrimidine group

3. Adenine&Guanine (Purines) HypoxanthineXanthineUric acid Xanthine Oxidese Xanthene Oxidase

4. Uric acid in blood Monosodium Urate Crystals deposition in joints and may be also in soft tissues Inflammatory response to the crystals Gout, Uric acid stones in kidney

6. Causes of blood uric acid Excretion Excretory defect in kidney Drugs Ex ; thiazide diuretics Production Idiopathic (mutations ) Cell turn over (chemotherapy) Consuming ethanol,types of food

7. 1)Nonpharmacological  Reduce intake of foods with high purines Exp: organ meats  Avoid alcohol  Loose Wt if obese 2)Pharmacological  Using drugs for acute & chronic gout

8. Drugs used in gout Acute NSAIDs (Indomethacin ) Corticosteroids Colchicine Chronic Xanthine oxidase inh. Allopurinol Uricosurics Ex; Probenecid Sulfonpyrazone

9.  Target : Inflammation & pain  Drugs : NSAIDs inflammatory Corticosteroids mediators Colchicine neutrophils movement to the affected area

10.  Drug of choice if there is no C/I  Exp: Indomethacin  It is as effective as colchicine but it is preferred because it has less GIT toxicity  Begin with dose (Exp: 75mg ) First 24-48hr  Then 50mg/6hr for 1day, then 50mg/8hr for 1-2days. NSAIDs

11.  S/E : headache, dizziness.  Use in caution in pt with :  Peptic ulcer  HF  Chronic kidney disease  Coronary artery disease

12.  PO dose 1mg initially, then 0.5mg/2hr  S/E of PO colchicine is GIT toxicity so IV dose is used 2mg initially, if no relief then additional 1mg/6-12hr to total dose of 4mg.  S/E of Iv colchicine: inflammation and necrosis of surrounding tissue. Colchicine Colchicine should be diluted with 20ml normal saline to minimize sclerosis of vein.

13.  C/I Of IV colchicine :  Neutropenia  Sever renal impairment  Combined renal and hepatic insufficiency Colchicine should be discontinued within 7days after Iv or PO therapy to reduce the risk of bone marrow toxicity

14.  Used for resistant cases or Pt with C/I to NSAIDs & colchicine  For multiple joint involvement: 1) Prednisone 30-60mg PO once daily for 3-5 days Corticosteroids The dose should be decreased gradually to prevent rebound attacks

15. 2) Adrenocorticotropic hormone (ASTH) gel 40-80 USP units given IM/6-8hr for2-3 days.  For limited 1-2 joint involvement ; Triamcinolone hexacetonide 20-40mg given intra-articularly.

16.  Target : Treat the cause  Drugs :  1) Colchicine  2) Uricosurics :  Probenecid Uric acid  Sulfinopyrazone excretion

17. 2) Xanthene oxidase Inh. :  Allopurinol : converted to Oxypurinol Febuxostat Allopurinol Febuxostat Inh. Xanthine oxidase Inh. Uric acid production

19.  PO 0.5mg twice daily during the first 6-12 months of uric acid lowering therapy to minimize the risk of acute attacks that may occur during initiation of this therapy. Colchicine

20.  Probenecid 250mg twice daily for 1-2weeks then 500mg twice daily for 2 weeks, then increase until control is achieved or a maximum dose of 2g/day is reached.  Sulfinpyrazone 50mg twice daily for 3-4 days then100mg twice daily,increasing the daily dose by 100mg each week up to 800mg/day. Uricosurics

21.  S/E :  GI Irritation  Rash & hypersensitivity  Precipitation of acute gouty arthritis  Stone formation

22.  C/I :  Pt allergic to these drugs.  Impaired renal function.  History of renal calculi.  Over producers of uric acid.

23.  Allopurinol is converted to oxypurinol  It has long half –life so given once daily  Po daily dose is usually 300mg  600-800mg/day may be necessary Xanthine oxidase inh.

24.  Allopurinol is DOC in Pt with :  History of urinary stones  Impaired renal function  Over producers of uric acid Before initiation of cytotoxic therapy pretreatment with allopurinol is needed to prevent acute uric acid nephropathy.

25. 1) Skin rash. 2) Leukopenia. 3) GI toxicity. 4) Increase frequency of gouty attacks with the initiation of therapy. 5) Allopurinol hypersensitivity syndrom:  Fever.  Dermatitis.  Vasculitis.  Renal & hepatic dysfunction.

27. Company : Takeda Approval Status : Approved February 2009 Treatment for : hyperuricemia

28.  Once-daily oral medication.  Available in : 40-mg and 80-mg tablets.  It is the first new treatment option for hyperuricemia in patients with gout.

29. Recommended initial dose 40 mg once daily. For patients who do not achieve a serum uric acid less than 6 mg per dL after 2 weeks with 40 mg 80 mg is recommended

30. Adenine&Guanine (Purines) HypoxanthineXanthineUric acid Xanthine Oxidese Xanthene Oxidase

31.  ULORIC was studied and evaluated in multiple clinical trials  CONFIRMS which was the largest phase 3 clinical trial shows that ULORIC 80 mg was better than ULORIC 40 mg and allopurinol 300/200 mg at achieving serum uric acid levels of less than 6.0 mg/dL

32. Uloric Allopurinol 0.60 per 100 Pt every year 0.60 per 100 Pt every year  0.74 per 100 Pt every year  0.74 per 100 Pt every year

33.  Nausea  Arthralgia  Rash  Dizziness

34.  ULORIC is contraindicated in patients being treated with :  Azathioprine  Mercaptopurine  Theophylline