Malaria and Antimalarial Agents.pptx UNIT II

This presentation provides a detailed exploration of malaria, a life-threatening disease caused by Plasmodium parasites, and the various antimalarial agents used to treat and prevent the disease. Covering key aspects like the types of malaria, transmission cycle, the role of antimalarial drugs, and emerging challenges like drug resistance, this PPT aims to provide valuable insights into the current landscape of malaria control.

It also discusses the global impact of malaria, current preventive measures, drug-resistant strains, and innovative solutions for the future, including new drug development and malaria vaccines.

Key Topics Covered:

Introduction to Malaria: Definition, symptoms, and global impact
Types of Malaria: Understanding the different Plasmodium species
Transmission Cycle: Life cycle of the malaria parasite
Antimalarial Agents: A deep dive into chloroquine, artemisinin-based combination therapies (ACTs), quinine, and newer drugs

1. By - Samruddhi S. Khonde Asst. Prof P. R. Patil Institute of Pharmacy, Talegaon (S.P.) Antimalarial Agents

2. Antimalarial Agents Malaria is a serious and sometimes fatal disease caused by parasites belonging to the genus  Plasmodium . It is transmitted to humans through the bites of infected female Anopheles mosquitoes, which serve as the primary vectors for the disease. Malaria is endemic in many tropical and subtropical regions, affecting millions of people globally and leading to significant morbidity and mortality, particularly among vulnerable populations such as children under five and pregnant women. Despite advances in treatment and prevention, malaria remains a major public health challenge, necessitating ongoing efforts in research, surveillance, and control measures to combat its spread and impact.

3. The Life Cycle of Malarial Parasites The life cycle of  Plasmodium , the causative agent of malaria, is complex and involves two hosts: the female Anopheles mosquito and humans. This cycle can be divided into several key stages: 1. Sporozoite Stage (Transmission) Infection of the Mosquito : The cycle begins when a female Anopheles mosquito bites an infected human, ingesting blood containing  Plasmodium  gametocytes (the sexual form of the parasite). Gametogenesis : Inside the mosquito's gut, the gametocytes develop into male and female gametes, which fuse to form a zygote. Oocyst Formation : The zygote develops into an oocyst, which attaches to the gut wall of the mosquito. Inside the oocyst, the parasite undergoes multiple divisions, producing thousands of sporozoites. Release of Sporozoites : After a period of development, the oocyst bursts, releasing sporozoites into the mosquito's hemolymph. These sporozoites migrate to the salivary glands of the mosquito, ready for transmission.

4. Malarial Infection

5. The Life Cycle of Malarial Parasites 2. Human Infection (Sporozoite to Liver Stage) Inoculation: When the infected mosquito bites a human, it injects sporozoites into the bloodstream through its saliva. Liver Stage (Exoerythrocytic Cycle): The sporozoites travel to the liver, where they invade liver cells (hepatocytes). Here, they undergo asexual reproduction, multiplying and developing into merozoites. This stage lasts about 7-14 days, depending on the  Plasmodium  species. 3. Erythrocytic Cycle (Merozoite Stage) Release into Bloodstream : The liver cells eventually rupture, releasing thousands of merozoites into the bloodstream. Invasion of Red Blood Cells : The merozoites invade red blood cells (RBCs), where they continue to multiply asexually. Each infected RBC can produce more merozoites, leading to the rupture of the RBC and the release of new merozoites into the bloodstream. Clinical Symptoms : This cycle of RBC invasion and rupture is responsible for the clinical symptoms of malaria, including fever, chills, and anemia. The cycle can repeat every 48 to 72 hours, depending on the  Plasmodium  species.

6. Malarial Infection

7. The Life Cycle of Malarial Parasites 4 . Gametocyte Formation Development of Gametocytes : Some of the merozoites differentiate into gametocytes (male and female forms) within the RBCs. These gametocytes are crucial for the transmission of malaria back to the mosquito. 5. Transmission Back to Mosquito Infection of the Mosquito : When another female Anopheles mosquito bites an infected human, it ingests the gametocytes along with the blood. This completes the cycle, allowing the gametocytes to develop into gametes and restart the cycle in the mosquito.

8. Antimalarial Agents

9. Species of Malarial Parasites inside RBC Plasmodium falciparum Plasmodium vivax Plasmodium malariae Plasmodium ovale

10. Antimalarial Agents

11. Antimalarial Agents

12. Quinoline Derivatives

13. Antimalarial Agents 4-Aminoquinolines Chloroquine : Mechanism of Action : Inhibits the detoxification of heme in the malaria parasite, leading to the accumulation of toxic heme. Uses : Effective against uncomplicated malaria caused by Plasmodium falciparum and Plasmodium vivax. Also used for prophylaxis in endemic areas.

14. Antimalarial Agents Quinoline Derivatives Quinine : Mechanism of Action : Interferes with the parasite's ability to digest hemoglobin. Uses : Used for severe malaria; can be administered orally or intravenously. Side Effects : Can cause cinchonism (tinnitus, headache, nausea). Mefloquine : Mechanism of Action : Similar to quinine, it disrupts the parasite's metabolism. Uses : Used for prevention and treatment, especially in chloroquine-resistant areas. Side Effects : Neuropsychiatric effects can occur; caution is advised. Mefloquine

15. Antimalarial Agents 8-Aminoquinolines Primaquine : Mechanism of Action : Generates reactive oxygen species that damage the parasite. Uses : Effective against the hypnozoite stage of Plasmodium vivax and Plasmodium ovale , preventing relapse. Primaquine

16. The mechanism of action (MOA) of cinchona alkaloids , particularly quinine and its derivatives, primarily involves the following: Inhibition of Hemozoin Formation : Quinine and other cinchona alkaloids interfere with the malaria parasite's ability to metabolize hemoglobin. They inhibit the polymerization of heme into hemozoin, leading to the accumulation of toxic free heme within the parasite. Disruption of Parasite Metabolism : By accumulating free heme, these drugs create a toxic environment for the parasite, ultimately leading to its death. Effects on Ion Channels : Some cinchona alkaloids, like quinidine, also affect ion channels in the parasite, which can disrupt its cellular functions. CINCHONA ALKALOIDS Quinoline Methanol Derivatives/Cinchona alkaloids

17. Antimalarial Agents Artemisinin and its Derivatives Artemether : Mechanism of Action : Produces free radicals that damage the parasite's proteins and membranes. Uses : Primarily used in combination therapies for severe malaria, especially in cases of resistance to other drugs. Formulation : Available in oral and injectable forms. Artesunate : Mechanism of Action : Similar to artemether, it acts rapidly against the malaria parasite. Uses : Administered intravenously for severe malaria; effective in reducing mortality. Artesunate

18. Antimalarial Agents 3. Antifolate Drugs/ Biguanides (Dihydrofolate Reductase [DHFR] Inhibitors) Pyrimethamine : Mechanism of Action : Inhibits dihydrofolate reductase, disrupting folate synthesis necessary for DNA replication. Uses : Often used in combination with sulfadoxine for treatment and prophylaxis. Note : Can cause bone marrow suppression; monitoring is required. Pyrimethamine

19. Antimalarial Agents At C-4 position, the dialkylaminoalkyl side chain has 2-5 carbon atoms between the nitrogen atoms, particularly the 4-diethylaminomethyl butyl amino side chain that is optimal for activity, as in chloroquine and quinacrine. The substitution of a hydroxyl group on one of the ethyl groups on the tertiary amine (hydroxy quinoline), reduces toxicity. Incorporation of an aromatic ring in the side chain (e.g. amodiaquine) gives a compound with reduced toxicity and activity. The tertiary amine in the side chain is important. The introduction of an unsaturated bond in the side chain was not detrimental to activity. The 7-chloro group in the quinoline nucleus is optimal, the methyl group in position 3 reduces activity, and an additional methyl group in position 8 abolishes activity. The D-isomer of chloroquine is less toxic than its L-isomer Structure Activity of Relationship Structure of Quinine

20. Thank You