Antimalarial medications

Malaria Lifecycle - Parasite's Progress

• Human Host (Asexual Cycle)

  • Exo-erythrocytic (Liver) Stage: Mosquito injects sporozoites → travel to liver → mature into schizonts → rupture, releasing merozoites.
  • Erythrocytic (Blood) Stage: Merozoites invade RBCs → mature into trophozoites → ring forms → schizonts → rupture RBCs, causing clinical symptoms.
  • Some parasites differentiate into gametocytes.

• Mosquito Host (Sexual Cycle)

  • Mosquito ingests gametocytes from human blood → mature into gametes → fertilization → oocyst forms → ruptures, releasing sporozoites.

⭐ Hypnozoites: P. vivax and P. ovale can form dormant liver stages called hypnozoites, which can reactivate months to years later, causing relapses. This is a key target for specific antimalarial drugs.

Blood Schizonticides - The Acute Attackers

• Targets the erythrocytic stage of malaria, which is responsible for clinical symptoms. The primary use is for treating acute attacks.

• Chloroquine

  • MOA: Blocks the detoxification of heme into hemozoin by inhibiting heme polymerase. The resulting accumulation of free heme is toxic to the parasite.
  • Use: Effective only against sensitive species; widespread resistance exists due to a membrane pump that decreases drug accumulation.

• Artemisinins (Artesunate, Artemether)

  • MOA: Metabolized in the parasite's food vacuole, generating free radicals that cause damage.
  • Use: First-line for severe P. falciparum. Very rapid onset. Always used in combination (ACT) to prevent resistance.

• Quinine & Quinidine

  • MOA: Interferes with heme polymerization.
  • Use: For severe malaria and chloroquine-resistant strains.
  • Toxicity: Cinchonism (tinnitus, headache, dizziness), hypoglycemia. 📌 Quinine causes QT prolongation.

• Mefloquine

  • Use: Prophylaxis and treatment of chloroquine-resistant malaria.
  • Toxicity: ⚠️ Can cause serious neuropsychiatric side effects.

⭐ G6PD Deficiency: Quinine and other oxidant drugs can trigger severe hemolytic anemia in patients with G6PD deficiency. Screening is crucial.

Tissue Schizonticides & Prophylaxis - Liver Stage & Prevention

• Primary Goal: Eradicate dormant liver hypnozoites of P. vivax & P. ovale (radical cure) to prevent relapse. Also for primary prophylaxis against all species.

• Key Agents:

  • Primaquine & Tafenoquine:
    • Active against hepatic stages (hypnozoites).
    • Added to a blood schizonticide for radical cure of P. vivax/ovale.
    • 📌 Primaquine Prevents Ping-pong relapses.
    • ⚠️ Must screen for G6PD deficiency before use; risk of severe intravascular hemolysis.
  • Atovaquone-Proguanil (Malarone):
    • Excellent for prophylaxis in chloroquine-resistant areas.
    • Disrupts parasite mitochondrial electron transport.

⭐ G6PD screening is mandatory before giving primaquine or tafenoquine. These drugs generate reactive oxygen species that overwhelm the antioxidant capacity of G6PD-deficient red blood cells, causing severe hemolysis.

High‑Yield Points - ⚡ Biggest Takeaways

• Chloroquine blocks heme polymerase but faces widespread resistance.
• Primaquine is essential for eradicating dormant hypnozoites (P. vivax/ovale); screen for G6PD deficiency to prevent hemolysis.
• Mefloquine prophylaxis is effective but carries a risk of neuropsychiatric side effects.
• Artemisinins are first-line for severe P. falciparum malaria, often used in Artemisinin-based Combination Therapy (ACT).
• Atovaquone-proguanil targets the electron transport chain and folate synthesis.
• Quinine/Quinidine can cause cinchonism and hypoglycemia.