Antimalarials

Malaria is a parasitic infection caused by plasmodium that is transmitted by mosquitoes in tropical regions.  

After being bitten by a mosquito, plasmodium sporozoites infect the liver and mature into schizonts, then released as merozoites that infect red blood cells and form trophozoites, which can form schizonts or gametocytes.  Gametocytes are then taken up by other mosquitoes where fertilization occurs and new sporozoites are eventually formed in the mosquito to continue the cycle.  

Primaquine likely works as an oxidizer that damages plasmodium. Adverse effects include hemolytic anemia in glucose-6-phosphate dehydrogenase deficiency and methemoglobinemia.  Resistance can develop in all forms of malaria.

Chloroquine and quinine work by preventing polymerization of heme inside of plasmodium, which alters the pH and results in cell lysis of plasmodium and the red blood cell.  Skin discoloration, prolonged QT interval, and antibiotic resistance are all possible.

Atovaquone-proguanil is a combination medication. Atovaquone works by disrupting mitochondrial actions and proguanil inhibits dihydrofolate reductase within plasmodium.

Mefloquine works by an unknown mechanism and is used for both treatment and prophylaxis of malaria. Neuropsychiatric side effects are possible as well as cardiac reactions when combined with other malaria treatments such as quinine or quinidine.

Artemisinin is derived from the wormwood plant and works by forming free radicals after interaction with heme in plasmodium, which causes protein damage. Prolonged QT interval and hypersensitivity reactions can occur.

Pyrimethamine inhibits dihydrofolate reductase, which is important in the synthesis of DNA. Leucovorin is a medication that is used to treat the megaloblastic anemia that can develop from folate deficiency due to the drug.

Class Drugs

Primaquine

Chloroquine

Atovaquone-proguanil

Mefloquine

Quinine

Artemisinin

Pyrimethamine

Class Mechanism of Action

See individual drugs

Class Applications

Malaria

• Plasmodium falciparum

• Plasmodium vivax

• Plasmodium malariae

• Plasmodium ovale

• Drugs effect three stages of malaria

Erythrocytic form

Artemisinin

• Atovaquone/proguanil

• Chloroquine

• Quinine

• Mefloquine

• Pyrimethamine

• Gametocytic form

Primaquine

• Exoerythrocytic form

Primaquine

Class Adverse Effects

Resistance

See individual drugs

Drug Table

Drug Name	Application	Comments	Image
Primaquine		Mechanism; Likely acts as oxidizer; Adverse Effects; -Hemolytic anemia (due to oxidization action) in G6PD deficiency; -Methemoglobinemia; -Not to be used in pregnancy; Resistance; All causes of malaria can become resistant	"Prime" "Dr. Quinn Medicine Woman"
Chloroquine	Malaria; Malaria Prophylaxis	Mechanism; Prevents polymerization of heme inside plasmodium, which alters pH and results in cell lysis of plasmodium and the erythrocyte; Adverse Effects; Resistance; Discolored skin; Prolonged QT interval	"Clorox" "Dr. Quinn Medicine Woman"
Atovaquone-proguanil	Chloroquine resistant malaria; Prophylaxis and treatment	Mechanism; Atovaquone; Disrupts mitochondrial actions; Proguanil; Inhibits dihydrofolate reductase in plasmodium	"Atom" "Vacuum" "Pro" "Iguana"
Mefloquine	Multidrug resistant P. falciparum; Prophylaxis and treatment	Mechanism; Unknown, long half-life allows single dose; Adverse Effects; Some resistance present; Neuropsychiatric (hallucinations, depression, etc.); Cardiac reactions including sudden death when combined with other treatments including quinine or quinidine	"Muffler" "Dr. Quinn Medicine Woman"
Quinine	Chloroquine resistant malaria	Mechanism; Prevents polymerization of heme inside plasmodium, which alters pH and results in cell lysis of plasmodium; Adverse Effects; Cinchonism Syndrome including: tinnitus, vertigo, nausea and vomiting; Reversible Hemolytic anemia; Drug-drug interactions	"Dr. Quinn Medicine Woman" "Nine"
Artemisinin	Multi-drug resistant malaria	Mechanism; Derived from the wormwood plant; Forms free radicals after interacting with heme in the parasite, resulting in protein damage; Adverse Effects; Prolonged QT interval; Hypersensitivity, rash, angioedema	"Art" Emission"
Pyrimethamine	Treatment of toxoplasma gondii; Not generally used as a single agent for malaria due to resistance; Paired with sulfadoxine or sulfadiazine	Mechanism; Inhibits dihydrofolate reductase; Adverse Effects; Leucovorin rescue:; Leucovorin can be administered if megaloblastic anemia develops from folate deficiency in the patient; Hypersensitivity, can be severe	"Pyramid" "Meth"