Penicillamine

Penicillamine (3,3-dimethylcysteine) is a trifunctional amino acid containing carboxyl, amino and sulfhydryl groups, an analogue of the natural amino acid cysteine. Due to the asymmetrically located carbon atom, penicillamine can exist as D- and L-isomers. Penicillamine obtained by controlled hydrolysis of penicillin exists only in the form of a D-isomer, which is currently used in clinical practice.

[1], [2], [3], [4], [5], [6], [7]

Indications for use and dosing

At the beginning of treatment, the drug is recommended to be prescribed once a day at a dose of 125-250 mg 1-2 hours before breakfast, and with a fractional dose, a second dose of penicillamine should be taken 2-3 hours before dinner. This is due to the fact that food significantly reduces the absorption and bioavailability of the drug.

Penicillamine is prescribed after meals only if the intake before meals causes the development of symptoms of gastrointestinal lesions.

After 8 weeks, the dose of the drug is increased by 125-250 mg / day. It is believed that 8 weeks is the optimal time to evaluate the clinical effectiveness of penicillamine treatment. An increase in the dose of 125 mg / day is indicated with the appearance of nausea, vomiting, loss of appetite and other signs of toxicosis. In the event that the daily dose of penicillamine reaches 1 g, it is divided into two doses. During the treatment should be used not a fixed dose of the drug, but try to select the optimal dosage depending on the clinical effectiveness.

When treating penicillamine, it is recommended to prescribe vitamin B6 (pyridoxine) in a dose of 50-100 mg / day and multivitamin supplements, especially when eating disorders of patients. Although clinical signs of pyridoxine deficiency are noted extremely rarely, there is a description of the observations of patients with peripheral neuropathy, which could only be stopped by the administration of pyridoxine.

In the process of treatment, careful monitoring of patients, including clinical examination, blood testing (including platelet count), and urine in the first few months of treatment every 2 weeks is necessary. And then at least once a month.

General characteristics

Being a water-soluble substance, penicillamine is well adsorbed on the upper gastrointestinal tract, excreted in the urine in the form of oxidized metabolites. Has the ability to stay in the tissues for a long time after the cessation of treatment.

The mechanism of action of penicillamine

The mechanism of action of penicillamine in rheumatic diseases is not fully understood. However, the drug is used in inflammatory rheumatic diseases, since in the treatment of patients in vitro it provides various immunological and anti-inflammatory effects

1. Water-insoluble active sulfhydryl groups of D-penicillamine are capable of eliciting chelation of heavy metals, including copper, zinc, total, mercury, and participate in the reaction of sulfhydryl disulfide exchange. It is suggested that this mechanism determines the ability of D-penicillamine to lower the copper content in hepatolenticular degeneration (Wilson).
2. The interaction of D-penicillamine with aldehyde groups of collagen leads to a violation of the cross-linking of collagen molecules and an increase in the content of water-soluble collagen.
3. Interchain exchange of sulfhydryl (SH) groups of the D-penicillamine molecule and disulfide bonds leads to the formation of the RF IgM polymer molecules, individual subunits of which are lined with SS bridges.

The anti-inflammatory effects of penicillamine are due to:

• selective inhibition of the activity of CD4 T-lymphocytes (T-helpers); suppression of the synthesis of gamma-interferons and IL-2 CD4 T-lymphocytes;
• suppression of RF synthesis, formation of CEC and dissociation of RF-containing immune complexes;
• antiproliferative effect on fibroblasts.

Side effects of penicillamine

Against the background of penicillamine treatment, it is possible to develop various side effects.

Frequent non-severe (do not require drug withdrawal):

• a decrease in taste sensitivity;
• dermatitis;
• stomatitis;
• nausea;
• loss of appetite.

Frequent heavy (require discontinuation of treatment):

• thrombocytopenia;
• leukopenia; proteinuria / nephrotic syndrome.

Rare heavy:

• aplastic anemia;
• autoimmune syndromes (myasthenia, pemphigus, systemic lupus erythematosus, Goodpasture's syndrome, polymyositis, dry Sjogren's syndrome).

The main factor limiting the use of penicillium in rheumatology, frequent side effects. Some of them have a dose-dependent nature, they can be quenched with short-term interruption of treatment or a decrease in the dose of the drug. Other side effects are associated with idiosyncrasy and do not depend on the dose. Most side effects of penicillamine develop in the first 18 months of treatment, fewer side effects occur during other periods of treatment.

Clinical efficacy of penicillamine

Penicillamine is used in the treatment of active rheumatoid arthritis, including various systemic manifestations (vasculitis, Felty syndrome, amyloidosis, rheumatoid lung disease); palindromic rheumatism; some forms of juvenile arthritis as a reserve drug.

The use of the drug is also effective in diffuse scleroderma.

The drug is not effective in AC.

[8], [9], [10], [11], [12], [13], [14],