Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. Chapter 97 Antiprotozoal Drugs I: Antimalarial Agents

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.2 Antiprotozoal Drugs I: Antimalarial Agents  Except for TB, malaria kills more people than any other infectious disease  300 million afflicted each year; over 1 million die  75% of deaths are children in sub-Saharan Africa  Malaria – parasitic disease caused by protozoa of genus Plasmodium  Plasmodium vivax and Plasmodium falciparum

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.3 Fig Life cycle of the malaria parasite.

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.4 Antiprotozoal Drugs I: Antimalarial Agents  Life cycle  Types  Vivax malaria and falciparum malaria  Objectives  Treatment of acute attack  Prevention of relapse  Prophylaxis

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.5 Vivax Malaria  Caused by P. vivax  Most common form of malaria  Relatively mild and self-limiting  Drug resistance is relatively uncommon  Symptoms can be treated with medication  After 26 days merozoites emerge from hepatocytes and attack erythrocytes  Symptoms peak and decline every 48 hours  Cyclic reinfection and cell lysis

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.6 Falciparum Malaria  Caused by P. falciparum  Less common than vivax malaria  Much more severe than vivax malaria  Without treatment, 10% of victims die  Many strains are drug-resistant  Symptoms appear at irregular intervals  Can destroy up to 60% of circulating RBCs

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.7 Antimalarial Therapy  Erythrocytic forms are killed relatively easily  Exoerythrocytic forms are much harder to kill  Sporozoites do not respond to drugs at all  Three objectives of treatment  Treatment of acute attack  Prevention of relapse  Prophylaxis

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.8 Antimalarial Drugs  Chloroquine (Aralen)  Primaquine  Quinine  Mefloquine (Lariam)  Quinidine gluconate  Atovaquone/proguanil  Pyrimethamine/sulfadoxine  Artemisin derivatives: artemether and artesunate

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.9 Antimalarial Drug Selection  Largely based on two factors  Goal of treatment  Drug resistance of the causative strain

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.10

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.11 Chloroquine (Aralen)  Drug of choice in many forms of malaria  High activity against erythrocytic forms  Not active against exoerythrocytic forms  Doses required for prophylaxis are low  High doses for treatment are taken only briefly

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.12 Chloroquine (Aralen)  Adverse effects  Gastrointestinal effects  Visual disturbances  Hepatotoxicity Use with caution in patients with liver disease Use with caution in patients with liver disease  Pruritus  Headache

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.13 Quinine  Active against erythrocytic forms of malaria  IV route combined with doxycycline, tetracycline, or clindamycin treatment of choice for severe malaria  Adverse effects  Cinchonism  Hemolytic anemia  Pregnancy category X

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.14 Primaquine  Used for hepatic forms of malaria  Drug of choice for preventing relapse of vivax malaria  Adverse effects  Hemolysis – deficiency of glucose-6-phosphate dehydrogenase (G-6-PD) in red blood cells  Populations affected – black and dark-skinned individuals Iranians, Sephardic Jews, Greeks, Sardinians Iranians, Sephardic Jews, Greeks, Sardinians