LEISHMANICIDAL DRUGS

The parasite exists in two forms: a flagellated form, found in a sand fly (the insect vector) that feeds on warm-blooded animals, and a non-flagellated form, which occurs in the bitten mammalian host. In the latter, the parasite is taken up by the mononuclear phagocyte system where it remains alive and viable.

 There are several clinical types of leishmaniasis: A simple skin infection that may heal spontaneously A mucocutaneous form in which there may be large ulcers of the mucous membranes A visceral form (kala azar) where the parasite spreads through the bloodstream and causes hepatomegaly and splenomegaly, anaemia and intermittent fever.
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 All three forms of leishmaniasis are treated with stibogluconate sodium (antimony sodium gluconate-pentavalent antimony) amphotericin B is used as alternative for visceral form

sodium stibogluconate
The mechanism of action is not clear These compounds are reduced to the more toxic Sb3+ species that kill amastigotes within the phagolysosomes of macrophages. The drugs interfer with the trypanothione redox system and/or Inhibit phosphofructokinase

 Irritant to the intestinal mucosa therefore are administered by IM or slow IV injection. Peak blood concentrations occur in 2 hours. Found in high concentrations in the liver and spleen. Rapidly excreted in the urine, with up to one-half of the administered dose excreted in 24 hours.

Side effects
Nausea, vomiting, abdominal pain; muscle pain, joint stiffness, and less commonly cardiac or hepatic toxicity; rarely anaphylaxis 20 mg/Kg/day given iv or im in a single dose for 28 consecutive days. Therapy should be repeated using the same dose for another 40 to 60 days in patients with relapse or incomplete response. C/I: significant renal impairment, breast-feeding.
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Pentamidine Isethionate
Is useful for the treatment of antimony-resistant leishmania infections Is effective for the treatment of T. brucei gambiense sleeping sickness but not T. brucei rhodesiense or T. cruzi infections 3 to 4 mg/kg i.m daily or every other day for up to 15 doses

Side effects
Reversible nephrotoxicity, acute hypotension, pancrititis, hypoglycemia, cardiac arrhythmias, and sterile abscesses at the injection sites. Caution: Risk of severe hypotension following administration (establish baseline blood pressure and administer with the patient lying down; monitor blood pressure at regular intervals, until treatment concluded); Hepatic and renal impairment
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TRYPANOSOMICIDAL DRUGS
There are three main species of trypanosome that cause disease in humans Trypanosoma gambiense and T. rhodesiense, which cause sleeping sickness in Africa, and T. cruzi, which causes Chagas' disease in America

suramin
is given by slow intravenous injection The drug binds firmly to plasma proteins is relatively toxic, particularly in a malnourished patient, the main toxic effect being in the kidney. Other include optic atrophy, adrenal insufficiency, skin rashes, haemolytic anaemia and agranulocytosis. A small proportion of individuals have an immediate idiosyncratic reaction to suramin injection-nausea, vomiting, shock, seizures, and

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Nifurtimox
Effective for American trypanosomiasis undergo activation by partial reduction to nitro radical anions The generated nitro anion radicals then form covalent attachments to macromolecules leading to cellular damage that kills the parasites is well absorbed after oral administration, with peak plasma levels observed after about 3.5 hours
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 less than 0.5% of the dose is excreted in urine. The elimination half-life is only about 3 hours. undergoes rapid biotransformation Side effects Peripheral neuropathy and GI symptoms are especially common after prolonged treatment hypersensitivity reactions such as dermatitis, fever, pulmonary infiltrates, and anaphylaxis will occur

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