what u always wanted to know about hyperuricemia

1. Dr FARAZ FARISHTA
Consultant Endocrinologist
Medwin Hospital
MD Of Sparsh Endocrinology &Diabetic centers
President of Diabetes Awareness Foundation

2. Gastro-intestinal system
 Uric acid is the normal end product of the degradation
of purine* compounds.
 Major route of disposal is renal excretion .
 Humans lack the enzyme uricase to break down uric
acid into more soluble form.
 Metabolic Disorder underlying gout is Hyperuricemia
(high levels of uric acid in blood).
Uric acid & Hyperuricemia:

3. Gastro-intestinal system
• The ionized forms of uric acid, predominant in plasma,
extracellular fluid and synovial fluid.
• Approximately 98% exists as monosodium urate at pH
7.4
• Plasma is saturated with monosodium urate at a
concentration of 6.8 mg/dl.
• At higer concentrations, plasma is
therfore supersaturated, creating the potential for
urate crystal precipitation.
• 2/3 rd to 3/4 th of urate is excreted by kidneys, and most
of the remainer is eliminated through the intestines.

4. Gastro-intestinal system
Can result from:
Increased production of uric acid
Decreased excretion of uric acid
Combination of the two processes.

5. Gastro-intestinal system
• Uric acid overproduction
Accounts for 10% of hyperuricemia
Defined as 800mg of uric acid excreted
• Uric acid underexcretion
Accounts for >90% of hyperuricemia
Diminished tubular secretory rate,
increased tubular reabsorption,
diminished uric acid filtration
Classification of Hyperuricemia

10.  Meats such as beef,poultry,lamb,andpork
contain high levels of purine
 You should also avoid organ meats such as
liver and kidney .

11. Gastro-intestinal systemVarious Treatments
• NSAIDs Most commonly used.
No NSAID found to work better than others
• Colchicine
• Corticosteriods Patients who cannot tolerate NSAIDs, or failed
NSAID/colchicine therapy
• Xanthine oxidase inhibitors

12. Gastro-intestinal system
Febuxostat
• New class of Xanthine Oxidase inhibitor
• More selective than allopurinol
• Little dependence on renal excretion
• Xanthine oxidase inhibitors

13. Gastro-intestinal system
Febuxostat is a selective inhibitor of Xanthine Oxidase and is indicated for
use in the treatment of Hyperuricemia and Gout.
Xanthine oxidase generates reactive oxygen species and is an enzyme that
catalyzes the formation of uric acid.
Febuxostat received Marketing approval by the European Medicines
Agency on April 21, 2008.
Febuxostat was approved by the US FDA on February 16, 2009.
Febuxostat

14. Gastro-intestinal system
Purine nucleotides
Hypoxanthine
Xanthine
Uric acid
Xanthine
oxidase
Alimentary
excretion
Urinary excretion
Tissue deposition in
excess
Urate crystal Microtophi
Phagocytosis with
acute inflammation
and arthritis
Uricosurics
Colchicine
NSAID
Febuxostat
Mechanism of Action Febuxostat

15. Gastro-intestinal system
FEBUXOSTAT ALLOPURINOL
• Non-purine structure. •Purine analog.
• Selective Inhibitor of xanthine oxidase.
It does not inhibit other enzymes involved in
purine/ pyrimidine synthesis and metabolism.
• Inhibitor of xanthine oxidase. May inhibit
other enzymes involved in purine/pyrimidine
synthesis and metabolism.
• Both hepatic and renal elimination. Thus
can be given safely in mild to moderate
renal / hepatic patients.
• Eliminated primarily via renal excretion.
Thus can’t be given safely to renally impaired
patients.
• Requires no dose adjustment in patients
with mild to moderate renal or hepatic
impairment.
• Requires dose adjustment in patients with
renal impairment.
Febuxostat V/s Allopurinol

16. Gastro-intestinal system
FEBUXOSTAT ALLOPURINOL
The dosing is 40–mg or 80-mg tablets.
Thus, lesser Dose Dumping and lesser
dose-related toxicity (if any).
The dosing is 100-mg or 300-mg tablets.
Thus, greater Dose Dumping and
greater dose-related toxicity (if any).
Recommended starting dose is 40 mg. The minimal effective dosage is 100
mg daily.
For patients who do not achieve a serum
uric acid level of < 6mg/dl after 2 weeks,
FEBUXOSTAT
80 mg is recommended.
It is recommended the patient start with
100 mg daily and increase at weekly
intervals by 100 mg until a serum uric
acid level of < 6 mg/dl is attained.
DOSE ADVANTAGES

17. Gastro-intestinal systemFebuxostat… Role in T2DM
• Febuxostat is effective at lowering uric acid levels.
• Resulting into improved Nitric oxide production.
• Helps to decrease insulin resistance and the progression of T2DM.
• Low dose with comparable (Allopurinol) decrease in serum uric acid
level.
• A novel therapy that helps in reducing pain associated with hyperuricemia
and increases mobility.

18. Gastro-intestinal system
The superior potency for inhibition of endothelium-associated
XO is predictive of a significant role for Febuxostat. -
FreeRadicBiol Med.2011 Jul 1;51(1):179-84.
Hypertension
Uric acid/
Hyperuricemia
Endothelium
dysfunction
Linked
Nitric
oxide
Febuxostat

19. Gastro-intestinal system
• Febuxostat, by inhibiting xanthine oxidase, can decrease uric
acid production, thus decreasing the incidence of
urolithiasis.2
• 2. In a subset of patients with stage 2 to 3 CKD, febuxostat
40 and 80 mg daily were also superior in achieving the
serum urate target level in comparison to renally dose-
adjusted allopurinol (200 to 300 mg daily)1.
• 3. 80 mg febuxostat dose does not require adjustment in
CKD3
• 4. In patients with gout and preexisting mild to moderate renal
impairment, febuxostat is more effective and as safe as
allopurinol.4
• 5. In preexisting renal impairment, febuxostat is highly
effective, and as safe as allopurinol.
1-Arthritis Research & Therapy. 2009;11(4):236, 2-Clinical Medicine Insights: Therapeutics 2010:2 ,
3-Int J Nephrol Renovasc Dis. 2010; 3: 1–10. 4,5- Medpage:Pub Nov: 02, 2009

20. Gastro-intestinal system
0
20
40
60
80
APEX (6 Months) FACT (1 Year) CONFIRMS(6
Months)
Febuxostat(80 mg)
Allopurinol (300mg)
APEX study (6 months):
• 72% of patients on Febuxostat (80 mg) reached a healthy uric acid level.
• 39% of patients on Allopurinol (300 mg) reached a healthy uric acid level.
FACT study (1 year):
•74% of patients on Febuxostat (80 mg) reached a healthy uric acid level.
•36% of patients on Allopurinol (300 mg) reached a healthy uric acid level.
CONFIRMS study (6 months):
•67% of patients on Febuxostat (80 mg) reached a healthy uric acid level.
•42% of patients on Allopurinol (300 mg) reached a healthy uric acid level.
Febuxostat Vs. Allopurinol.

21. Gastro-intestinal system
• Greater proportion of Febuxostat-treated patients have
decreased size and number of tophi.
• A greater percentage of patients receiving Febuxostat versus
Allopurinol
achieved complete resolution of tophi.
• Thus, the reduction in serum uric acid level is greater with
Febuxostat and is higher when compared to Allupurinol.
• Moreover, the reoccurrence of uric acid level in blood is
significantly less with Febuxostat treatment when compared to
Allupurinol.
Observations : Febuxostat in comparision to Allopurinol …

22. Gastro-intestinal system
• Non-purine, Selective Xanthine Oxidase inhibitor.
• Powerfully lowers serum uric acid to target levels of < 6 mg/dL.
• Can be safely prescribed to patients with mild to moderate renal impairment.
• Efficacious in patients with high baseline serum uric acid levels >10mg /dl.
• Febuxostat is superior to Allopurinol in patients with mild to moderate renal
dysfunction.
• Can be safely prescribed to patients poorly controlled on Allopurinol.
• Maintains Serum Uric Acid levels <6 mg / dl even in Allopurinol intolerant patients.

24. Gastro-intestinal system