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USUHS14
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Quinine
- Group: Arylaminoalcohol
- Use: oral for uncomplicated, iv for complicated
- Mechanism of action: inhibits heme polymerization and toxic heme concentrations kill the parasite
- Adverse effects: Prolonged QT; hypoglycemia; thrombocytopenia; cinchonism; 'blackwater fever'
- Pharmacokinetics: metabolized by CYP450
- Resistance in SE Asia
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Quinidine
- Group: Arylaminoalcohol
- Use: oral for uncomplicated, iv for complicated
- Mechanism of action: inhibits heme polymerization and toxic heme concentrations kill the parasite
- Adverse effects:
- Prolonged QT; hypoglycemia; thrombocytopenia; cinchonism; 'blackwater fever'
- Pharmacokinetics: metabolized by CYP450; inhibits CYP2D6
- Resistance in SE Asia
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Mefloquine
- Group: Arylaminoalcohol
- Use: oral only; prophylaxis or treatment of uncomplicated malaria
- Mechanism of action: inhibits heme polymerization and toxic heme concentrations kill the parasite
- Adverse effects: cardiotoxicity; sleep disturbances; neuro-psych concerns (not given to pilots)
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Chloroquine
- Group: 4-aminoquinolines
- Uses: prophylaxis; kills blood stage parasites
- Mechanism: inhibits heme polymerization and toxic heme concentrations kill the parasite
- Adverse effects: mild GI disturbance; retinal damage at high/prolonged doses; seizures; nerve type deafness
- Pharmacokinetics: prodrug; rapidly & completely absorbed; long elimination half life; better tolerated than quinine
- P. falciparum is resistant
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Primaquine
- Group: 8-aminoquinolines
- Use: hypnozoites in liver; terminal prophylaxis
- Mechanism: unknown
- Adverse effects: contraindicated in G6PD deficiency, pregnancy, and young children
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Doxycycline
- Group: Antibiotics
- Uses: blood stage Tx; prophylaxis of MDR malaria; always used in combination
- Mechanism: inhibits protein synthesis
- Adverse effects: interfere with bone an tooth development - contraindicated in pregnancy and young children; esophageal ulcers
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Atovaquone
- Uses: (in combination with Proguanil) uncomplicated MDR P. falciparum; prophylaxis
- Mechanism: inhibits mitochondrial electron transport at cytochrome bc1 complex
- Adverse effects: nausea, vomiting, abdominal pain
- Pharmacokinetics: oral absorption inc. by food; not metabolized
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Proguanil
- Uses: (in combination with atovaquone) uncomplicated MDR P. falciparum; prophylaxis
- Mechanism: DHFR inhibitor
- Adverse effects: granulocytopenia and aplastic anemia
- Pharmacokinetics: Oral absorption inc. by food; metabolized by CYP2D19 (10% of caucasians and 25-30% of Africans are poor metabolizers)
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