Arsenicals

Melarsoprol (trivalent) and tryparsamide (pentavalent) are organic compounds containing arsenic that bind to sulfhydryl groups in proteins, thereby affecting cellular structure and function. The action of arsenic is nonspe cific, and any selective toxicity achieved is related to differences in drug permeability and sulfhydryl content of the affected structure or enzyme. Melarsoprol shows some selectivity for the trypanosome enzymes phos-phopyruvate kinase and trypanothione reductase. These drugs are administered intravenously. Resistance has started to emerge among trypanosomes responsible for African trypanosomiasis.

The arsenicals are trypanocidal. Melarsoprol is highly active against all stages of trypanosomiasis, but its toxicity restricts its application to the meningoen-cephalitic phase of the disease. Their value lies in their ability to penetrate the CNS; hence, they are useful in treating meningoencephalitis caused by trypanosomes. The drugs are rapidly eliminated.

Vomiting and abdominal cramping occur but may be minimized by slow injection in the supine fasting patient. Great care should be taken to prevent painful drug extravasation into the tissue. The most frequently observed adverse reaction is encephalopathy, which develops on or about the third day of therapy and can be fatal. Other side effects include fever, rashes, proteinuria, peripheral neuropathy, and rarely, agranulocytosis. Since the overall incidence of side effects to tryparsamide is quite high, it largely has been replaced by melarsoprol in the treatment of trypanosome infestation.

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