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Snapshot
  • A 25-year-old medical student is about to embark on an international rotation in Ethiopia. Given that malaria is endemic in that area, she presents to the travel clinic for required vaccination as well as chemoprophylaxis of malaria. Upon further investigating on the CDC website, she discovers that malarial strains in Ethiopia are resistant to chloroquine. As she is already on doxycycline for the treatment of acne, her travel clinic physician informs her that there is no need for additional chemoprophylaxis.
Introduction
  • Drugs
    • chloroquine
    • hydroxychloroquine
    • quinidine
    • quinine
    • artemether/lumefantrine
    • atovaquone/proguanil
    • artesunate
    • mefloquine
    • primaquine
    • doxycycline
  • Clinical use
    • malaria
      • treatment
      • prophylaxis
    • P. falciparum and, increasingly, P. vivax may be resistant to chloroquine, hydroxychloroquine, and mefloquine
Anti-Malarial Medications
Drug Mechanism of Action
Adverse Effects
Indications

Chloroquine

  • Blocks heme polymerase, which causes heme accumulation 
  • Heme is toxic to plasmodia
  • Retinopathy
  • Pruritus
  • Gastrointestinal upset
  • Myopathy
  • All plasmodial species
    • however, there is increasing resistance to P. falciparum and, recently, P. vivax
Hydroxychloroquine
  • Unknown, but impairs neutrophils and chemotaxis and may interfere with lysosomal degradation of hemoglobin
  • Retinopathy
  • Bleaching of hair
  • Gastrointestinal upset
  • All plasmodial species
    • however, there is increasing resistance to P. falciparum 
Quinidine
  • A class IA antiarrhythmic drug
  • Diarrhea
  • QTc prolongation
  • Palpitations
  • Life-threatening/severe malaria due to P. falciparum
    • drug is discontinued in the US
Quinine
  • Disrupts plasmodial DNA transcription and replication
  • Hemolytic anemia in G6PD deficiency
  • Gastrointestinal upset
  • Flushing
  • Chloroquine-resistant P. falciparum and P. vivax
Artemether/lumefantrine
  • Inhibits nucleic acid and protein synthesis
  • Gastrointestinal upset
  • Headache
  • QTc prolongation
  • Chloroquine-resistant P. falciparum and P. vivax
Atovaquone/proguanil
  • Unknown, may interfere with cell membrane permeability and cause paralysis in the helminth
  • Gastrointestinal upset
  • Dizziness
  • P. falciparum
  • Babesia (used with azithromycin)
  • Chemoprophylaxis
Artesunate
  • Inhibits arachidonic acid metabolism, making the helminth more susceptible to the host's innate immune system
  • Hemolytic crisis in patients with G6PD deficiency
    • test for G6PD deficiency prior to starting
  • First-line for life-threatening malaria due to P. falciparum
Mefloquine
  • Inhibits oogenesis and spermatogenesis
  • Central nervous system toxicity: dizziness, hallucinations, altered mental status
  • Gastrointestinal upset
  • P. falciparum
  • Also has increasing resistance
Primaquine
  • Interferes with electron transport chain in plasmodial mitochonrdia
  • Gastrointestinal upset
  • Hemolytic crisis in patients with G6PD deficiency
    • test for G6PD deficiency prior to starting
  • Adjuvant for P. vivax/ovale to eradicate hypnozoites
  • Chemoprophylaxis
Doxycycline
  • Inhibits 30S ribosomal subunit
  • Gastrointestinal upset
  • Esophagitis
  • Photosensitivity
  • Chemoprophylaxis
  • Adjuvant therapy with chloroquine, quinine, or primaquine
 
 

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