Læknablaðið : fylgirit - 01.07.1978, Qupperneq 94

Læknablaðið : fylgirit - 01.07.1978, Qupperneq 94
collegues (1974) have suggested that patients who develop granulocytopenia may have abnormally gold-sensitive granulocyte enzymes which catalyse the nove sjmthesis of pyrimidine nucleotids. D - Penicillamine The rationale for using D-penicillamine in rheumatoid arthritis was to dissociate rheumatoid factor. This has amply been confirmed in a number of studies, but in addition the drug has been shown to cause clinical improvement. The drug acts like gold in that it takes at least three months before its effect becomes apparent, and it produces the same amount of clinical benefit as gold. The major drawback is the drug's toxicity. The list of potential side effects is horrendous, but many can be avoided by careful monitoring. Proteinuria is common in patients receiving D-penicillamine and need not be a cause of withdrawal of the drug unless it becomes very heavy, 2 g/day or more. A nephrotic syndrome may occur with D-penicillamine and biopsy of the kidney shows both IgG and complement in the glomerular basement membrane. Recently Huskisson (1976) has published an excellent review, which should be read carefully before embarking on treating patients with rheumatoid arthritis with the drug. Immunosuppressives Cyclophosphamide and azathioprine have both been used to treat severe and progressive rheumatoid arthritis. Both have been shown to be effective, but our concern with their use is the potential danger of late neoplasia. Removal of the immunological surveillance mechanism by these drugs is fraught with danger. We would predict that tumours will start being reported in patients with benign disease treated with these compounds. We do not use these drugs at the present time. Corticosteroid Therapy It is now nearly three decades since Hench introduced cortisone in the treatment of rheumatoid arthritis, but the remarkable fact is that we have so few really "hard" facts about their use, for instance, it is still not known just how toxic they are, althcugh recent studies by ourselves have shown that they may be associated with high mortality (Brooks et al, 1975) as well as morbidity (Lee et al, 1973). Suppression of the cerebro-hypothalamo- pituitary- adrenal axis (Nuki and Downie, 1971) is probably not as serious as previously thought. Osteoporosis occurs as a generalised phenomenon and is associated with skin atrophy (McConkey et al, 1965) and a low plasma zinc concentration (Kennedy et al, 1975). The other side effects need no comment as they are well documented. It is our practice to prescribe prednisolone or prednisone in preference to other oral preparatum but not to exceed 10 mg per day. We use corticotrophin to tide patients over a severe exacerbation. Levamis ole Levamisole is a synthetic antihelmintic and has been used extensively in veterinary and human practice. The drug is rapidly absorbed when taken by mouth and has a plasma half-life of 4 hours in man. It is extensively metabolised in the liver and virtually eliminated from the body within 2 days. The metabolites are excreted mostly in the urine. Symoens and Rosenthal (1977) have summarised in an extensive review the evidence that levamisole is an immuno- therapeutic and anti-anergic drug. The evidence from studies on isolated cells, experimental animals, healthy volunteers and patients, indicated that the drug restores to normal the functions of phagocytes and T ljrmphocytes when these are depressed. The evidence, however, also indicates that these functions are not increased above normal levels by therapeutic doses. B cells do not seem to be influenced by the drug. It appears that levamisole restores a basic mechanism common to all ceUs involved and acts by altering intraceUular cycUc GMP / cycUc AMP ratios. Levamisole is effective in vitro and i n v i v o . In animals the drug does not suppress a primary invasion by virulent bacteria, viruses or tumour ceUs. It seems, however, to increase the protective 92
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