Section 13 - Antiparasitic Drugs F

Click to edit Master title style Click to edit Master text styles Second level Third level Fourth level Fifth level Click to edit Master title style Click to edit Master text styles Second level Third level Fourth level Fifth level Principles of Pharmacology and Toxicology (BIOL3020) Section 13 Antiparasitic Drugs Rang et al 2006 (Chapter 49 and 50) What is a parasite @ A Malaria .  Life-Cycle of Malaria merozoites trophozoite schizont merozoites Malaria in RBC http //dpd.cdc.gov/DPDx/images/ParasiteImages/M-R/Malaria/vivax/P_vivax_trophozoite4.jpg . Antimalarial Drugs  Antimalarial Drugs  Antimalarial Drugs Pyrimethamine is a folate antagonist The drug has a higher affinity for parasite enzyme than human Resistance has occurred from a single point mutation in the DR enzyme.  Pyrimethamine dTMP Other Antimalarial Drugs Atavaquone Inhibits the parasities mitochondrial electron transport chain. Resistance is rapid Caused by a point mutation in the gene for cytochrome b. Helminths (The Worms ) Anthelminthic drugs  Anthelminthic drugs  Anthelminthic drugs Anthelmintic Drugs  Glutamate-gated Chloride Channels (from the same family as GABAA Receptors) Extracellular Intracellular Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Ivermectin Glutamate Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Neuron Inhibition Paralysis Oocyte HcGluCl gene Research on glutamate gated chloride channels in the parasitic nematode Haemonchus contortus Isolate the gene that encodes a glutamate-gated chloride channel subunit Inject into frog oocytes Let the oocyte translate the gene and produce the channel Voltage-clamp the oocyte and measure channel activation in response to drug HcGluCl is activated by glutamate and ivermectin (IVM) HcGluCl Pharmacology Activated by Ibotenate Structural analogue of glutamate Ivermectin enhances glutamate activation HcGluCl blocked by Picrotoxin Ivermectin Resistance Exact mechanism has not been determined What are some possibilities