Chronic therapy of gout

							Chronic therapy of gout

Uricosurics
These are substances which promote uric acid excretion. Uric acid enters the urine by:
(i) filtration; (ii) active transport into the proximal renal tubule. Part of the uric acid in
the urine is reabsorbed into the body by a second active transport carrier system in the
proximal tubule. Both carrier systems are competitively blocked bv uricosurics and
high concentrations of aspirin and many anti-infiammatories.

This means that although no active elimination is occurring, uric acid is still lost by
means of filtration into the urine, and no active re-uptake into the body is occurring to
counteract this. (Low doses of aspirin block only the smaller active elimination
transport system, leaving the greater active re-uptake to predominate and increase the
body's uric acid levels.)

Probenecid, sulfinpyrazone and benzobromarone are used as uricosurics. Other agents
such as oxyphenbutazone. whilst effective, are too toxic to be used for this purpose.
The uricosurics can aggravate the symptoms of gout in the initial stages of treatment
when pain-causing crystal deposits are being mobilized from the joints.

The urine should be alkalinized during uricosuric therapy, because the uric acid entering
the urine may crystallize out in acidic urine, causing kidney damage. Uricosurics are
contra-indicated in patients who are known to have existing kidney damage.

Inhibition of uric acid synthesis

Allopurinol (Zyloprim) competes with hypoxanthine and xanthine for the xanthine
oxidase enzyme which converts these substrates to uric acid. Allopurinol is itself
converted to a metabolite which also inhibits xanthine oxidase, further preventing the
formation of uric acid. During antineoplastic therapy, gout may be precipitated by
increased cell destruction with the release of high concentrations of purines.

If allopurinol is used together with 6-mercaptopurine (Purl-nethol). exaggerated
therapeutic and toxic effects of the antineoplastic agent are seen, because it is also
inactivated by xanthine oxidase which is now being inhibited by the allopurinol.
Allopurinol is generally free of serious side-effects.

Skin rashes and other hypersensitivity reactions occur. Allopurinol can aggravate the
symptoms of gout in the initial stages of treatment. Headache, GIT disturbances and
blood abnormalities have been reported.