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What are the generic names of the agents used to treat hyperuricemia (gout)? (3 main groups)
Uric Acid Treatment
1. Increase excretion (uricosurics)
a. probenecid/sulfinpyrazone
2. Decrease production of uric acid
a. allopurinol/febuxostat
3. Increased uric acid conversion
a. rasburicase/PEG-uricase
What are the associated symptom treatment drugs with hyperuricemia... what do they control?
pain and inflammation management
1. NSAIDs and COX-2 specific
a. ibuprofen/naproxen
b. celecoxib
NO ASPIRIN!
2. Colchicine- for prophylaxis
3. glucocorticosteroids- most potent for anti-imflammatory (block good prostoglandin, immunity)
4. Narcotics- block OP (opioid) receptors of CNS, (codeine, hydrocodone, oxycodone)
What are the uricosurics (generic names) and what is mechanism of action? When are they indicated?
- increase UA excretion (block renal reabsorption of uric acid by URAT1)

Indicated if patient can not get rid of uric acid through urine

not for acute attack

1. probenecid
2. sulfinpyrazone
1. What are the (generic names) and what is mechanism of action drugs that decrease uric acid production?
2. When are they indicated?
1. Mechanism- inhibiting xanthine oxidase (enzyme to make uric acid)
a. allopurinol
b. febuxostat
2. If patient gets rid of uric acid but produces too much
1. What are the (generic names) and what is mechanism of action drugs that increase uric acid conversion to other products?
2. When are they indicated?
1. rasburicase
2. PEG uricase
Serve as form of urate oxidase converting uric acid to more soluble allantoin, decrease uric acid
Used pediatric malignancies or hospital patients with IV access
What are the key contraindications for use of the following...
a. nsaids (ibuprofen, indomethacin, naproxen, diclofenac, ketoprofen, piroxicam) and selective cox-2 inhibitors
b. colchicine
c. corticosteroids (prednisone, prednisolone, triamcinolone, methylprednisolone)
All contraindications for GI distress
a. increased serum sodium, kidney
b. bone marrow suppression
c. HTN, immune supression, thinning of bone
The following side affects are specifically associated with what drug?
a. malaise/myopathy, sj syndrome
b. pain at injection site, rash
c. HTN, immune supression, thinning of bone
a. Xanthine oxidase inhibitors- allopurinol and febuxostat
b. urate oxidase inhibitors- rasburicas and peg-uricase
c. corticosteroids (prednisone, prednisolone, triamcinolone, methylprednisolone)
The following side affects are specifically associated with what drug?
a. kidney stones, H/A
b. increased serum sodium, kidney
c. bone marrow suppression
a. urocosurics- probenecid and sulfinpyrazone
b. nsaids (ibuprofen, indomethacin, naproxen, diclofenac, ketoprofen, piroxicam) and selective cox-2 inhibitors
c. colchicine
What are the two first line oral prophylaxis indicated drugs for gout and roles? What are generics and effects?
1. Uricosurics- long term lowering of uric acid
a. probenecid and sulfinpyrazone

2. xanthin oxidase inhibitors- long term lowering of uric acid and reduce tophi
a. allopurinol and febuxostat
What is the IV 1st line prophylaxis drug for gout and roles? Generic names?
Urate Oxidase Inhibitors- pediatric malignancy
a. rasburicase and PEG- uricase
What are 2nd line acute treatment drugs for gout? (generics) Any prophylaxis?
a. Colchicine - effective at preventing and treating gout
b. Corticosteroids- for severe acute gouty attacks
1. prednisone, prednisolone, triamcinolone, methylprednisolone
What causes overall blood uric acid level increases... What four processes does that entail?
Changes in PURINE METABOLISM
Involves
1. Dietary uptake
2. Purine degradation
3. Purine salvage pathways
4. synthesis of purine nucleotides
What big picture causes gout?
What 4 main biochemical pathways cause gout? Which is most significant for gout?
deposit of uric acid (sodium rate crystals) in joints which causes inflammatory response
Biochemical
1. Diminished Excretion of Uric Acid (most significant- underlying kidney problem)
2. High Purine Diet
3. Over production of purine nucleotides
4. Increased Nucleic acid productoin and turnover
What causes high diminished uric acid excretion?
1. Renal disease
2. High levels of KLT- ketones, lactate, triglycerides
How does a high purine diet cause gout?
more dietary proteins more get converted to base purines and uric acid
What causes overproduction of purine nucleotides (which causes gout)?
Defects in Enzymes:
1. HGPRT
2. APRT
Leads to increased PRPP levels which leads to increased uric acid production
What mental retardation syndrome is characterized by lack or huge deficit of enzyme Hypoxanthine guanine phosphoribosyl transferase (HGPRT)?

What is enzyme that makes uric acid... what breaks it down first?
Lesch Nyhan Syndrome

xanthine oxidase, urate oxidase
What causes increased nucleic acid production and turnover associated with gout?
1. Myeloproliferative diseases= more bone marrow created makes more DNA and RNA
2. Obesity- increased tissue mass= more RNA + DNA needed
What is significant about salvage pathways that relates to purine metabolism and uric acid formation?
Salvage pathways- are paths of intermediates from de novo nucleotide formation and dietary nutrients that are used to make nucleotides anywhere in the body
What makes uric acid?
Describe pathways of AMP and GMP to xanthine
Purine degredation from GMP or AMP to xanthine to uric acid

AMP
a. AMP-IMP-Iosine-Hypoxanthine-xanthine
GMP
b. GMP-guanosine-guanine-xanthine