Wilson’s disease, treatment

Figure 7.30 (A) D-Penicillamine used for Wilson s disease treatment. (B) Copper-histidine...

Wilson s disease is a copper storage disorder that is apparently due to an inherited lesion in the copper excretion mechanism. One in 200-400 persons is a carrier of the disease. Diagnosis may be made by measuring serum ceruloplasmin levels. Whereas normal serum ceruloplasmin is 200-400 mg/L, in Wilson s disease patients it is well below 200 mg/L. Liver copper in these patients (determined by biopsy) is more than 250 /xg/g, whereas normal individuals show a value of only 20-45 /xg/g. Liver function deterioration is the most prominent symptom of Wilson s disease. Treatment includes chelation therapy with penicillamine. 

In a 25-year-old woman with Wilson s disease, treatment with penicillamine (1.5 g/day) was first followed by the development of hirsutism, mainly of the face (255). After she started to use an oral contraceptive, her breasts enlarged rapidly and she experienced cyclic mastodynia in addition, gingival hyperplasia developed. All symptoms improved on withdrawal of penicillamine, but additional mammoplasty was needed. 

Vitamins their coenzymatic functions Vomiting caused by antineoplastic agents Wilson s disease treatment of Wound infection and sepsis in surgical patients treatment of... 

Calcium carbonate Calcium hydroxide Calcium monocarbonate Whiting will bind bile Cholestyramine Wilson s disease treatment Triethylenetetramine windbreakers... 

Penicillamine has also been used in cystinuria and for the treatment of rheumatoid arthritis. Discovery of its chelating properties led to its use in patients with Wilson s disease (hepatolenticular degeneration) and heavy-metal intoxications. Penicillamine is administered by mouth and should be taken on an empty stomach [4],... 

Treatment. Since the 1950s, the treatment of Wilson s disease has relied on chelating agents [25]. Early attempts to use BAL or EDTA for this purpose were unsuccessful, but penicillamine, triethylene tetramine dihydrochloride (trientine), and tetrathiomolybdate, all in combination with a low-copper diet, have proved to be effective, and result in the urinary excretion of large amounts of copper. The use of penicillamine is complicated by the fact that it may induce a transient worsening of neurologic function due to rapid mobilization of copper, and also has other side-effects, such as the development of nephrosis. Tetrathiomolybdate is an effective alternative with fewer side-effects [26]. In cases in which the dose was rapidly escalated, however, bone marrow suppression or liver function abnormalities have been described. 

The amino acid histidine is used for the treatment of copper overload in Wilson s disease and forms a strong 1 2 complex (Fig. 27) (553). Copper-histidine therapy is also an efficient treatment for copper deficiency in Menkes disease (554). 

Lupus erythematosus Certain patients will develop a positive antinuclear antibody (ANA) test and some may show a lupus erythematosus-like syndrome similar to other drug-induced lupus, but it is not associated with hypocomplementemia and may be present without nephropathy. A positive ANA test does not mandate drug discontinuance however, a lupus erythematosus-like syndrome may develop later. Sensitivity reactions Once instituted for Wilson s disease or cystinuria, continue treatment with penicillamine on a daily basis. Interruptions for even a few days have been followed by sensitivity reactions after reinstitution of therapy. 

Penicillamine (Cuprimine) can be used to treat acute, severe rheumatoid arthritis, producing reductions in joint pain, edema, and stiffness. The response to penicillamine is usually delayed (4-12 weeks), and remissions can last several months after withdrawal of treatment. Radiographic evidence of this drug s efficacy is limited thus, penicillamine is seldom used to treat rheumatoid arthritis. The mechanism of action of penicillamine is unknown, but some evidence suggests that it may involve the inhibition of angiogenesis, synovial fibroblast proliferation, or transcriptional activation. Because penicillamine can chelate copper and promote its excretion, it is used to treat Wilson s disease (hepatolenticular degeneration) and has also been used in mercury and lead intoxication. 

Brewer GJ Zinc acetate for the treatment of Wilson s disease. Expert Opin Pharmacother 2001 2 1473. [PMID 11585025]... 

Schilsky ML Diagnosis and treatment of Wilson s disease. Pediatr Transplant 2002 6 15. [PMID 11906637]... 

Penicillamine is used chiefly for treatment of poisoning with copper or to prevent copper accumulation, as in Wilson s disease (hepatolenticular degeneration). It is also used occasionally in the treatment of severe rheumatoid arthritis (see Chapter 36). Its ability to increase urinary excretion of lead and mercury had occasioned its use in outpatient treatment for intoxication with these metals, but succimer, with its stronger metal-mobilizing capacity and lower adverse-effect profile, has generally replaced penicillamine for these purposes. 

In the area of rheumatology, the importance of using optically pure drugs is well illustrated by penicillamine o-penicillamine has been used for many years in treatment of Wilson s disease and cystinuria and is now widely used in rheumatoid arthritis. It is well established now that this drug, which is chiral, should only be given in the pure d (or S) form, because the toxicity of the l (or R), or the dl (RS) racemic forms, is much greater. This fact was found by trial and error, with some earlier patients on DL-penicillamine experiencing severe adverse side reactions such as optic neuritis. Now only the pure d form is available for prescription (see also 62.2.3.4).61... 

A woman with Wilson s disease treated with penicillamine developed severe hirsutism (257). After treatment with oral contraceptives, her breasts enlarged rapidly, and she had cyclic mastodynia. Around the same time she also developed gingival hyperplasia. 

Excessive levels of essential metal ions can be undesirable and chelation therapy may be needed for adequate control to be achieved. The treatment of patients suffering from Wilson s disease (hepatolenticular degeneration in which there is intracellular deposition of copper in the liver and brain, accompanied by a deficiency of the copper-containing protein, caeruloplasmin) is an example45. ... 

Walshe JM (1982) Treatment of Wilson s disease with trientine (triethylene tetramine) dihydrochloride. Lancet, 319 643-647... 

Copper in plasma can be estimated following twenty-fold dilution with 0.1 normal HC1. Although few metals cause interference when using flame AAS [31] standards containing 6/xgCu per 100 ml should be made up in the plasma or mine equivalent [32]. Only very small amounts of copper are excreted in the urine of normal subjects and specimens are best aspirated undiluted. However, in Wilson s disease and especially during treatment urine copper may be high and appropriate dilution will be needed. 

D-Penicillamine 26 (Figure 2.8) has for long time been used for the treatment of Wilson s disease, a metabolic disorder in which absorbed copper is deposited mainly in the liver and in the brain. Long-term application of this compound leads to suppression of rheumatoid arthritis, which now is its main therapeutic use [3],... 

Mo04] with H2S or sulfiding reagents in basic solutions. These salts are interesting because of their roles in Cu-Mo antagonism in ruminants, and their potential as treatments for Wilson s disease. Several alkylammonium salts of [MoS4] have been reported, which has facilitated the study of the nonaqueous chemistry of this dianion. 

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