Malaria Flashcards
Quinoline and Related Compounds
Malaria MOA:
- Detoxifies host’s heme by polymerization into hemozoin and uses it as a source for amino acids
MOA:
- Binds to and inhibits heme polymerase
–> Inhibits heme polymerization
- Increases generation of free radicals
- Increases Vacuole pH
- Blocks Hemoglobin proteolysis
Quinine
Anti Malaria Agent
(Cinchona Alkaloids)
Characteristics:
- Fights chloroquine-resistant P. Falciparum
- Fights erythrocytic stage of other malaria
- Gametocidal (Vivax and Malarie)
MOA:
- Binds to and inhibits heme polymerase
–> Inhibits heme polymerization
- Increases generation of free radicals
- Increases Vacuole pH
- Blocks Hemoglobin proteolysis
AE:
- Cinchonism (Tinnitus, high-tone deafness, visual disturbances, headache, nausea & vomiting, abdominal pain & diarrhea)
- Hypoglycemia (Due to Insulin Secretion)
- Cardiac dysrhythmias and Fibrillation (Acute over dosage)
Quinidine
Anti Malaria Agent
(Cinchona Alkaloids)
Characteristics:
- Fights chloroquine-resistant P. Falciparum
- Fights erythrocytic stage of other malaria
- Gametocidal (Vivax and Malarie)
MOA:
- Binds to and inhibits heme polymerase
–> Inhibits heme polymerization
- Increases generation of free radicals
- Increases Vacuole pH
- Blocks Hemoglobin proteolysis
AE:
- Cinchonism (Tinnitus, high-tone deafness, visual disturbances, headache, nausea & vomiting, abdominal pain & diarrhea)
- Hypoglycemia (Due to Insulin Secretion)
- Cardiac dysrhythmias and Fibrillation (Acute over dosage)
Chloroquine
Anti Malaria Agent
(4-aminoquinoline)
Characteristic:
- Chlorine at position 7 provides greatest antimalarial activity
- Treatment of choice
- Highly active against erythrocytic forms of Vivax, Ovale, Malariae, and sensitive Falciparum
- Active against gametocytes of Vivax, Ovale, Malariae
- Not active against gametocytes of Falciparum
- Not active against hypnozoites
MOA:
- Binds to and inhibits heme polymerase
–> Inhibits heme polymerization
- Increases generation of free radicals
- Increases Vacuole pH
- Blocks Hemoglobin proteolysis
AE:
- Hypotension
- Vasodilation
- Cardiac Arrhythmias
Mefloquine
Anti Malaria Agent
Characteristic:
- Main treatment for Chloroquine-resistant malaria cause by Falciparum and Vivax
- Highly effective on erythrocytic forms
- No activity on other stages
MOA:
- Binds to and inhibits heme polymerase
–> Inhibits heme polymerization
- Increases generation of free radicals
- Increases Vacuole pH
- Blocks Hemoglobin proteolysis
AE:
- Neuropsychiatric effects
- Severe but reversible CNS toxicity in 0.5% of patietns
–> Seizures, Confusion, Psychosis, Dysphoria, Insomnia, Vertigo
- Aberrant Atrioventricular Conduction
Primaquine
Anti Malaria Agent
Characteristics:
- Targets Hepatic, Latent Tissue Form, Gametocytes
- Combined with drugs that target erythrocytic stages
- Targets P. Vivax and P. Ovale
MOA:
- Generate reactive oxygen species that interfere with electron transport in parasite
AE:
- Acute hemolysis (In people with G6PD deficiency)
Tafenoquine
Anti Malaria Agent
Characteristics:
- Targets Hepatic, Latent Tissue Form, Gametocytes
- Combined with drugs that target erythrocytic stages
MOA:
- Generate reactive oxygen species that interfere with electron transport in parasite
AE:
- Acute hemolysis (In people with G6PD deficiency)
PK:
- Longer half life
PyraMAX
Artesunate/Pyronaridine
Characteristics:
- Works against blood stage (Trophozoite)
- Given in combination with Lumefantrine or Pyronaridine to reduce risk of resistance (Both have same MOA as Quinoline)
MOA:
- Endoperoxide bridge is critical to anti-malarial activity
- Transported to food vacuole of parasite
–> Converted into free radical by Fe2+ killing parasite
- Irreversibly inhibits calcium dependent ATPase in the ER
AE:
- Transient Heart Block
- Decrease in Blood Neutrophils
RIAMET
Artemether/Lumefantrine
(Artemisinin)
Characteristics:
- Works against blood stage (Trophozoite)
- Given in combination with Lumefantrine or Pyronaridine to reduce risk of resistance (Both have same MOA as Quinoline)
MOA:
- Endoperoxide bridge is critical to anti-malarial activity
- Transported to food vacuole of parasite
–> Converted into free radical by Fe2+ killing parasite
- Irreversibly inhibits calcium dependent ATPase in the ER
AE:
- Transient Heart Block
- Decrease in Blood Neutrophils
Sulfonamides
Uncomplicated Malaria Treatment
(Folate Acid Antagonist)
Characteristics:
Sulfadoxine + Pyrimethamine
MOA:
- Inhibits two adjacent pathways in folate biosynthetic pathway
AE:
- Increases risk of transmission to vector mosquitos through promoting gametocyte formation
Proguanil
Anti Malaria Agent
(Folate Acid Antagonist)
Characteristics
- Effects initial hepatic stage (Merozoite)
- Chemically related to pyrimethamine
- Prodrug that is converted into the active Cycloguanil
- Combined with Atovaquone
MOA:
- DHFR Inhibitor
–> Inhibits Folate Synthesis
Atovaquone
Anti Malaria Agent
(Folate Acid Antagonist)
Characteristics
- Lipophilic analog of ubiquinone
- Highly selective for active asexual blood stage (Trophozoite)
- Combined with Proguanil
MOA:
- Acts on mitochondrial cytochrome bc1 complex
–> Inhibits ETC and decreases mitochondrial membrane potential (Ubiquinone is needed for Dihydroorotate dehydrogenase activity)
Tetracycline
Anti Malaria Agent
(Antibiotics)
Characteristics:
- Slow acting toward blood stage (Merozoite)
–> Slow mode of action means these drugs are ineffective as monotherapy
–> Must be given with quinine, quinidine, or artesunate
- Short term chemoprophylaxis
- Used in chloroquine/mefloquine resistant areas
MOA:
- Inhibits protein translation in parasite plasmid
Doxycycline
Anti Malaria Agent
(Antibiotics)
Characteristics:
- Slow acting toward blood stage (Merozoite)
–> Slow mode of action means these drugs are ineffective as monotherapy
–> Must be given with quinine, quinidine, or artesunate
- Short term chemoprophylaxis
- Used in chloroquine/mefloquine resistant areas
MOA:
- Inhibits protein translation in parasite plasmid
Plasmodium Falciparum
Deadliest
- Causes most severe form of malaria
- One of the most common
