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 nonspecific, and any selective toxicity
achieved is related to dif-ferences 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 ex-travasation 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tryparsamide is quite high, it largely has been replaced by melarsoprol in the
treat-ment of trypanosome infestation.