Transcript Chapter 16 Cholinesterase Inhibitors

Chapter 97
Antiprotozoal Drugs I: Antimalarial
Agents
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Antiprotozoal Drugs I: Antimalarial
Agents
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Except for TB, malaria kills more people than
any other infectious disease
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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
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Plasmodium vivax and Plasmodium falciparum
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Fig. 97-1. Life cycle of the malaria parasite.
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Antiprotozoal Drugs I: Antimalarial
Agents
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Life cycle
Types
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Vivax malaria and falciparum malaria
Objectives
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Treatment of acute attack
Prevention of relapse
Prophylaxis
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Vivax Malaria
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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
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After 26 days merozoites emerge from
hepatocytes and attack erythrocytes
 Symptoms peak and decline every 48 hours
 Cyclic reinfection and cell lysis
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Falciparum Malaria
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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
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Antimalarial Therapy
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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
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Treatment of acute attack
Prevention of relapse
Prophylaxis
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Antimalarial Drugs
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Chloroquine (Aralen)
Primaquine
Quinine
Mefloquine (Lariam)
Quinidine gluconate
Atovaquone/proguanil
Pyrimethamine/sulfadoxine
Artemisin derivatives: artemether and
artesunate
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Antimalarial Drug Selection
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Largely based on two factors
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Goal of treatment
Drug resistance of the causative strain
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Chloroquine (Aralen)
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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
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Chloroquine (Aralen)
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Adverse effects
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Gastrointestinal effects
Visual disturbances
Hepatotoxicity
• Use with caution in patients with liver disease
Pruritus
Headache
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Quinine
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Active against erythrocytic forms of malaria
IV route combined with doxycycline,
tetracycline, or clindamycin treatment of
choice for severe malaria
Adverse effects
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Cinchonism
Hemolytic anemia
Pregnancy category X
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Primaquine
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Used for hepatic forms of malaria
Drug of choice for preventing relapse of vivax
malaria
Adverse effects
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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
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