Which of the following chelating agent is the degradation product of Penicillin?
Penicillamine- It is obtained as a degradation product of penicillin. It was found to have a strong copper chelating propey and was used in 1956 for Wilson's disease. It selectively chelates Cu, Hg, Pb, and Zn. The d-isomer is used therapeutically because the 1-isomer and the racemate produce optic neuritis and are more toxic. It is adequately absorbed after oral administration, little metabolized in the body and excreted in urine and feces. Uses 1. Wilson's disease (Hepatolenticular degeneration): This is due to a genetic deficiency of ceruloplasmin, a protein which normally binds and disposes of Cu from the body. In its absence, the plasma concentration of free Cu is high which gets deposited in the liver, substantia nigra, basal ganglia of brain, and causes local degeneration. Life long therapy is needed to prevent progression of the disease. Dose: 0.5-1 g daily in divided doses 1 hour before or 2 hour after meals to avoid chelation of dietary metals. 2. Copper/mercury poisoning: 1-1.5 g/day is given for a few days. It is the drug of choice for Cu poisoning and alternative drug to dimercaprol/ succimer for Hg poisoning. 3. Chronic lead poisoning: It may be used as an adjuvant to CaNa2EDTA, but succimer is preferred. 4. Cystinuria and cystine stones: It promotes the excretion of cysteine and prevents its precipitation in the urinary tract because penicillamine- cysteine complex is more soluble than dicysteine (cystine). 5. Scleroderma: Penicillamine benefits by increasing soluble collagen. It was used as a disease-modifying drug in rheumatoid ahritis but has been replaced now by safer drugs Adverse effects Sho-term administration (as metal chelator) of penicillamine does not cause much problem. Various cutaneous reactions, itching and febrile episodes may occur. However, long-term use produces pronounced toxicity. Dermatological, renal, hematological and collagen reaction saw. ESSENTIALS of medical PHARMACOLOGY SIXTH EDITION-KD TRIPATHI Page: 867
EDTA
Dimercaprol
Penicillamine
Desferioxamine
Other topics and Adverse effects