Pentamidine

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Pentamidine (Pentam 300) binds to DNA and may inhibit kinetoplast DNA replication and function. It also may act by inhibiting dihydrofolate reductase and interfering with polyamine metabolism. An effect on organism respiration, especially at high doses, also may play a role.

Pentamidine is not well absorbed from the intestinal tract after oral administration and generally is given by intramuscular injection. The drug binds to tissues, particularly the kidney, and is slowly excreted, mostly as the unmodified drug. It does not enter the central nervous system (CNS). Its sequestration in tissues accounts for its prophylactic use in trypanosomiasis.

Pentamidine is active against Pneumocystis carinii, trypanosomes, and leishmaniasis unresponsive to pen-tavalent antimonials. It is an alternative agent for the treatment of P. carinii pneumonia. Although it is more toxic than trimethoprim-sulfamethoxazole, it has been widely used in patients with acquired immunodeficiency syndrome (AIDS), in whom P. carinii infection is common.

Pentamidine is an alternative drug for visceral leish-maniasis, especially when sodium stibogluconate has failed or is contraindicated. Pentamidine is also a reserve agent for the treatment of trypanosomiasis before the CNS is invaded. This characteristic largely restricts its use to Gambian trypanosomiasis.

Adverse reactions occur frequently. Rapid drug infusion may produce tachycardia, vomiting, shortness of breath, headache, and a fall in blood pressure. Changes in blood sugar (hypoglycemia or hyperglycemia) necessitate caution in its use, particularly in patients with diabetes mellitus. Renal function should be monitored and blood counts checked for dyscrasias.

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