Malaria Flashcards

1
Q

Quinoline and Related Compounds

A

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

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2
Q

Quinine

A

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)

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3
Q

Quinidine

A

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)

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4
Q

Chloroquine

A

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

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5
Q

Mefloquine

A

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

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6
Q

Primaquine

A

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)

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7
Q

Tafenoquine

A

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

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8
Q

PyraMAX

A

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

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9
Q

RIAMET

A

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

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10
Q

Sulfonamides

A

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

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11
Q

Proguanil

A

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

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12
Q

Atovaquone

A

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)

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13
Q

Tetracycline

A

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

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14
Q

Doxycycline

A

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

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15
Q

Plasmodium Falciparum

A

Deadliest
- Causes most severe form of malaria
- One of the most common

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16
Q

Plasmodium Vivax

A
  • Most common
  • Can produce hypnozoites that can lead to recurrent infections
17
Q

Plasmodium Ovale

A
  • Uncommon
  • Can produce hypnozoites that can lead to recurrent infections
18
Q

Plasmodium Malarie

A
  • Less common
  • More persistent
19
Q

Sporozoite

A

Infective stage
- Malaria parasite is transmitted to humans through mosquito bite

20
Q

Merozoite

A

Released from infected hepatocytes into blood stream

21
Q

Trophozoite

A

Early stage of malaria parasite development within RBCs during erythrocytic phase

22
Q

Schizont

A

Mature stage of malaria parasite in RBCs

23
Q

Hypnozoite

A

Dormant liver stage parasite
- Associated with Vivax and Ovale infections

24
Q

Gametocyte

A

Some merozoites develop into sexual forms called gametocytes