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• Malaria – it is a widespread infection in humans. Caused by the plasmodium protozoan and transmitted by the female anopheles mosquito.

  Plasmodium falciparum – the deadliest and able to infect RBC leading to profound anemia due to the higher parasite buildup on the RBC. This leads to RBC clumping.
• Antimalarial drug targets – tissue schizonticides – targets parasites in liver cells

  Blod schizonticides – first line drugs for treatment.

  Gametcytocides – sexual precursor cells

  Sporontocides – drugs acting on sporozoites.
• Ideal antimalarial drug – cheap, fast mechanism of action, very safe, potent, oral bioavailability and target exoerthyrocytic activity.
• Quinine – it is an alkaloid which is a 4 – quinoline methanol. The significant side effects – gives myocardial depression, vasodilation and hemolytic anemia.
• The 4-aminoquinolines and derivatives – developed from prototype quinine.
• 8 – aminoquinolines – it is gametocidal and it is often given with chloroquine to remove all malaria stages. Short term usage to avoid toxicity and resistance.

  Primaquine is the drug that was marketed.
• 8 – aminoquinoline Mechanism of action – interferes with the cell redox system. This leads to oxidative stress then cell death.
• 4 aminoquinoline

  
• Tafenoquine is an 8-aminoquinoline.

  To provide a longer acting less toxic version of primaquine. Highly effective in preventing relapse of malaria.
• Artemisinins – it is used as a template for synthetic derivatives.

  It is active in resistant and cerebral malaria

  They all have reactive endoperoxide moiety.
• Artemisinin through reduction forms an active metabolite. This can be either esters or ethers. The esters are water soluble. The ethers are oil soluble.
• Malarial treatment – ACT – artemether and lumefantrine.

  Artesunate and amodiaquine/mefloquine

  Dihydroartemisinin and piperaquine

  Artesunate and sulfadoxine
• Lumefantrine – used in combination with artemether. It acts over a longer period to remove all the parasites compared to artemether that is quick in action.
• Atovaquone – inhibits the electron transport chain in the mitochondria. It impairs pyrimidine synthesis and is synergistic with proguanil. It is also a lipophilic hydroxynaphthoquinone
• Doxycycline – the presence of an apicoplast allows some antibiotics to be effective in malaria.

  It is slow acting and it is a tetracycline.

  It inhibits prokaryote like RNA.

  It is used in prophylaxis.
• One needs new therapies due to the the resistance of drugs.