Antiprotozoal drugs

Describe the pharmacodynamic and pharmacokinetic properties of the major antimalarial drugs (chloroquine, mefloquine, quinine, primaquine, and the antifolate agents). 

Identify the major drugs used for trypanosomiasis and leishmaniasis and know their toxic effects. 

Malaria parasites have a complex life cycle that permits drug action at several points. Plasmodium species that infect humans P falciparum, P malariae, P ovale, P vivax) tire spread by the female Anopheles mosquito and, after inoculation into the human host, undergo a primary developmental stage in the liver (primary tissue phase). They then enter the blood and parasitize erythrocytes (erythrocytic phase). P falciparum and P malariae have only one cycle of liver cell invasion thereafter, multiplication is confined to erythrocytes. The other species have a dormant hepatic stage (in which they become bypnozoites) that is responsible for recurrent infections and relapses after apparent recovery of the host from the initial infection. 

The drug is rapidly absorbed when given orally, is widely distributed to tissues, and has an 

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Antiprotozoal Drugs. Table 1 New compounds registered between 1975and 1999 (with permission Trouilleretal., 2003 Lancet 359 2188-2194)... 

Antiprotozoal Drugs. Figure 1 Chemical structure of relevant antiprotozoal drugs... 

Antiprotozoal Drugs. Figure 5 Artemisinin combination therapy (ACT) Adding a 3-days artesunate course to mefloquine cleats the parasitaemia much more rapidly (A — A). The remaining parasites are exposed to higher mefloquine levels in ACT (B) compared to mefloquine monotherapy (B (with permission White, 1997 Antimicrob Agents Chemother 41 1413-1422). 

Folic Acid Vitamin B12 Antineoplastic Agents Antiprotozoal Drugs... 

K. A. Werbovetz (2002). Tubulin as an antiprotozoal drug target. Mini-Rev. Med. Chem. 2 ... 

Chapter 50 Miscellaneous Antimicrobial Agents Disinfectants, Antiseptics, Sterilants Chapter 51 Clinical Use of Antimicrobial Agents Chapter 52 Antiprotozoal Drugs... 

Metronidazole is a nitroimidazole antiprotozoal drug (see Chapter 52) that also has potent antibacterial activity against anaerobes, including bacteroides and Clostridium species. It is well absorbed after oral administration, is widely distributed in tissues, and reaches serum levels of 4-6 mcg/mL after a 250-mg oral dose. Metronidazole can also be given intravenously or by rectal suppository. The drug penetrates well into the cerebrospinal fluid and brain, reaching levels similar to those in serum. Metronidazole is metabolized in the liver and may accumulate in hepatic insufficiency. 

Basic and Clinical Pharmacology > Chapter 52. Antiprotozoal Drugs > ... 

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