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
Plasmodium Vivax
- Most common
- Can produce hypnozoites that can lead to recurrent infections
Plasmodium Ovale
- Uncommon
- Can produce hypnozoites that can lead to recurrent infections
Plasmodium Malarie
- Less common
- More persistent
Sporozoite
Infective stage
- Malaria parasite is transmitted to humans through mosquito bite
Merozoite
Released from infected hepatocytes into blood stream
Trophozoite
Early stage of malaria parasite development within RBCs during erythrocytic phase
Schizont
Mature stage of malaria parasite in RBCs
Hypnozoite
Dormant liver stage parasite
- Associated with Vivax and Ovale infections
Gametocyte
Some merozoites develop into sexual forms called gametocytes
