Allopurinol treatment

Elevated levels of xanthine and hypoxanthine caused by allopurinol treatment are tolerated because they remain soluble and are excreted by the kidneys. 

Allopurinol treatment alleviates the symptoms of uric acid overproduction but does not remedy the neurologic problems. 

Allopurinol is used in the treatment of hyperuricemia, which is associated with chronic gout and in cancer chemotherapy. Allopurinol has been used in renal calculi caused by the deposition of calcium oxalate and of 2,8-dihydroxy-adenine. Allopurinol treatment does cause hypersensitivity reaction, which may be fatal. 

Acute gout can be exacerbated at the beginning of allopurinol treatment unless the drug is combined with colchicine or an anti-inflammatory drug (18). 

Thiazides enhance the excretion of orotic acid, which is already increased during allopurinol treatment, but the implications for the frequency of adverse effects are not known. 

Korting FIC, Lesch R. Acute cholangitis after allopurinol treatment. Lancet 1978 1 275-276. 

In very rare cases an interference is seen if allopurinol and hypoxanthine are both present in the serum. This observation was made in patients with acute lymphoblastic leukaemia under allopurinol treatment with acutely restricted renal function (El 72, E216). 

Some investigators believe that urate may potentiate calcium stone formation, although this perception is not universally accepted. However, hyperuricosuria is common in calcium stone-forming patients, and treatment with allopurinol, thereby decreasing urate synthesis, reduces the rate of stone recurrence. Allopurinol treatment is therefore recommended for hyperuricosuric patients with calcium stone disease. The formation and management of pure urate stones are discussed in Chapter 24. 

In the absence of allopurinol, the dominant urinary purine is uric acid. During allopurinol treatment, the urinary purines include hypoxanthine, xanthine, and uric acid. Since each has its independent solubility, the concentration of uric acid in plasma is reduced and purine excretion increased, without exposing the urinary tract to an excessive load of uric acid. Despite their increased concentrations during allopurinol therapy, hypoxanthine and xanthine are efficiently excreted, and tissue deposition does not occur. There is a small risk of xanthine stones in patients with a very high urate load before allopurinol therapy this can be minimized by liberal fluid intake and urine alkalization. 

On the other hand, some diseases are associated with a very high incidence of drug-induced reactions. This seems to be the case for systemic lupus erythematosus (SLE) (Brown and Kanwar 1967) although penicillin allergy does not seem to be more frequent in such patients (Von Maur et al. 1975). Individuals with hyperuricemia on allopurinol treatment, infectious mononucleosis, or lymphatic leukemia... 

Drug-drug iuteractious Allopurinol Treatment with allopurinol, a xanthine oxidase inhibitor, shifts metabolism towards higher thioguanine concentrations, reduces aminotransferase activities, and improves disease activity scores. In 41 patients with adverse reactions to full-dose thiopurines (25 with non-hepatic reactions and 16 with hepatic reactions), a combination of allopurinol with reduced-dose thiopurine bypassed many adverse drug reactions [173 ]. Remissions were achieved in 32 patients with a median follow-up of 41 (range 0.5-400) weeks. Patients who did not respond to combination therapy tended to fail early with the same adverse reaction. 

Coe, F.L. and L. Raisen Allopurinol treatment of uric a-cid disorders in calcium stone formers Lancet January 20,... 

New information concerning the minor metabolic interactions of allopurinol was introduced by the finding of Fox al. [4] confirmed by Kelley and Beardmore [5] that allopurinol treatment results in significant excretion of orotate and orotidine in both animals and man. The demonstration that unidentified inhibitors were formed by the incubation of red cell lysates with PRPP and allopurinol and oxipurinol [6,7] and that C-orotate incorporation was inhibited... 

It is probable that it is the K values at low substrate concentration that are pertinent to the inhibition of the enz3nne in vivo, since the upper limit for orotidylate in normal rat tissues is below 1 yM and the rise that follows high dose allopurinol treatment probably does not quite reach the high Km range [10]. 

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