Pharmacology - Discussing Anti-Malaria Drugs
Malaria, Plasmodium, and female anopheles mosquito, those three are common and today, and still on phamacology we will be looking at Anti-malaria drugs. When we say plasmodium, it is a parasite that infect the liver cells and the red blood cell with numerous species that infect, but there are five species of plasmodium that infect humans. These species are Plasmodium Falciparum, P.Vivax, P.Malariae, P.Ovale, and P.knowlesi.
While these plasmodium species infect humans, there are blood disorders/diseases that serve as protection from plasmodium. These disorders includes Thalassemia which is an inherited blood disorder, G6PD deficiency, and Sickle cell Anemia. Plasmodium life cycle starts with the female anopheles mosquito that injects its sporozoite into humans bloodstream when they take a blood meal. They go into the liver where they begin to reproduce asexually in a process known as shizogony. The evazion of the hepatocyte through the asexual reproduction will lead to the reproduction of merozoites. Merozoite is tyical in plasmodium species falciparum, malaria and knowlesi. Within one to two weeks of the merozoite production, the patient starts to feel symptoms. Also some sporozoites will become hypnozoite which is a typical situation with the specie Vivax and Ovale. Merozoite begin to invade the red blood cells where an asexual reproduction takes place again to form more merozoites which will still destroy the Red Blood Cells, and they can form gamatocytes (male and female) which will be ingested by a female anoppheles mosquite that comes to feed on blood meal. the gamatocyte in the mosquito gut fuses together to form a zygote, then an Oocyst. The Oocyst ruptures to release sporozoites which will move to the salivary gland to be injected into another person.
When treating with anti-malaria drugs or anti-plasmodium drugs, there are many cites where the drug can target. The drugs can be classified based on the stages of plasmodium they attack and the clinical indication. Anti-plasmodium drug based on stages of plasmodium can be divided into Tissue Schizonticidal anti malaria drugs, Blood Schizonticidal, and Gamatocidal anti-malaria drug. The Tissue Shizonticidal drugs act on plasmodium in the liver but not yet in the red blood cell, and they are divided into two stages. The primary tissue forms which attacks the pre erythrocytic stage with drugs that include Sulfadoxine pyrimethamine, primaquine, proguanil, and atovaquone. The latent tissue forms which attacks hypnozoites in vivax and ovale. Drugs under this stages are primaquine, and Tafenoquine. Blood Schizonticidal drugs can be grouped into rapid act with high efficacy drugs, and slow act with low efficacy drugs. Rapid act and high efficacy drugs include Chloroquine, Artemisinin, Quinine, mefloquine, Lumefantrine. Slow act with low efficacy drugs include proguanil, pyrimethamine, and clindamycin. Gamatocidal anti-malaria drugs include Artemisinin, Primaquine,Chloroquine, and Quinine.
With drug classified based on clinical indication, they can be classified into drugs for Causal prophylaxis, Suppressive prophylaxis, prevention of relapse, clinical cure, ansd transmission to mosquitoes. With Causal prophylaxis, the drugs are used to treat pre erythocytic stages in the liver and they include drugs such as Malarone and primaquine. In the Suppressive prophylaxis type of drugs, the Red blood cells have been affected by the parasite but the erythrocytic phase is suppressed. The drugs are mefloquine, Doxycycline proguanil and Chloroquine. Clinical cure drugs also supresses the erythrocytic stage of the plasmodium. The drugs for the prevention of relapse in malaria would be primaquine and this drugs kill hypnozoites forms. Also in the prevention of the plasmodium to mosquitoes, Primaquine can be used to inhibit the spread.
Let's pick the drugs one after the other based on another drug classification and derivatives. Starting with Quinolone derivatives, there are drugs such as Chloroquine, Quinine, Atovaquone, primaquine, mefloquine.
Chloroquine is a blood schizontocidal agent which is alkaline in nature. it is taken up in the food vacoules of the parasite and increasing the pH of the parasite. It inhibits the conversion of heme to hemozoin by inhibiting heme polymerase which causes damage of the plasmodium cell membrane. Side effects includes dizziness, soles and scalp, headache, diplopia, dysphagia, nausea, malaise, hypertention, pruritus of palms, and cardiac arrest.
Quinine is an alkaloid of cinchona bark which is blood shizontocidal,and gamatocidal in plasmodium parasite. it is a weak base concentrated in the food vacuoles of the plasmodium. It inhibits heme polymerase just like chloroquine, causing an increase in the cytotoxic substrate heme which will cause the damage of the cell membrane. Its side effect is dose dependent. It can cause headache, disturbed vision, nausea, if it impairs the eight cranial nerve,then it can lead to vertigo, diplopis, night blindness, photophobia, blindness, hypertension, hypoglycemia, and hemoglobinamia
Mefloquine lead to swelling in the food vacoule of the plasmodium. It form toxic complexes which is made up of Heme to damage the cell membrane of the plasmodium. It has a half-life of 2 weeks to 3 weeks, it is secreted in the bile and excreted through feces. Side effects are siezures and neuroepileptic symptoms.
Another class of anti-maleria drugs will be Artemisinin derivative, which can be used in severe malaria. It is the fastest acting anti-malaria drug and they include Artesunate, Arteether, Artemether which can be given as both oral and IV and IM. Artemisinin drugs have a short life, and it generate free radicals in the food vacoule of the plasmodium which will damage the cell lipids and protein causing cell death.
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