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DRUG RESISTENCE: CHLOROQUINE

DRUG RESISTENCE: CHLOROQUINE. BY: STEPHANIE RASMUSSEN & JESSICA HERNANDEZ. Drug Resistance. the ability for a parasite to survive/multiply even when a drug has been administered and absorbed in doses that are within the limits of tolerance Most commonly seen in P. falciparum.

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DRUG RESISTENCE: CHLOROQUINE

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  1. DRUG RESISTENCE: CHLOROQUINE BY: STEPHANIE RASMUSSEN & JESSICA HERNANDEZ

  2. Drug Resistance the ability for a parasite to survive/multiply even when a drug has been administered and absorbed in doses that are within the limits of tolerance Most commonly seen in P. falciparum

  3. Characteristics Associated with Drug Resistance • Longer half-life • Longer time for the drug’s activity to be reduced by half • Point mutation causing resistance • Poor compliance • High number of people using the drug • Drug pressure

  4. Degrees of Drug Resistance Developed by WHO Studies the parasitemia over the course of 28 days Smears on days 2, 7, and 28 determine the degree of resistance Results are graphed and gaged from Sensitive, RI, RII, RIII

  5. Degrees of Drug Resistance • Sensitive • Reduces to 25% of the pre-treatment level on Day 2 and doesn’t return • RI Delayed Recrudescence • Reduces to <25% but reappears in 2-4 weeks • RI Early Recrudescence • Same as RI Delayed Recrudescence except the parasites reappear faster

  6. Degrees of Drug Resistance • RII Resistance • By Day 2, asexual parasites have reduced, but not fully done by Day 7, parasites continue to live • RIII Resistance • Minimal reduction to an increase of asexual parasites by Day 2

  7. Chloroquine

  8. Discovery of Chloroquine Discovered in 1934 by Hans Andersag at Bayer I.G. Farbenindustrie A.G. laboratories in Eberfeld, Germany 1st name was resochin Established as a safe and effective antimalarial by British/U.S. scientists in 1946

  9. Chloroquine • The drug of choice • Inexpensive • Effective against all of the Plasmodium species that affect humans • Children and pregnant women can use it

  10. How Chloroquine Works Targets the digestive vacuole of the parasite Interferes with the elimination of toxic heme CQ prevents the polymerization of toxic heme to nontoxic hemozoin by binding to the hemozoin Heme = iron containing part of hemoglobin

  11. Chloroquine Drug Resistance • Chloroquine was used for over 20 years • Save millions of lives • The overuse of chloroquineresulted in drug pressure • Drug pressure results in genetic mutations which lead to chloroquine resistant parasites • Resistant parasites expel chloroquine from their food vacuole 40-50 times faster than sensitive parasites

  12. Resistance arose from 2 foci

  13. Spread of Resistance • Chloroquine resistance spread in 3 ways: • Spread in a growing number of locations and regions • Number of resistant strains has increased • Degree of resistance has intensified • RI parasites have become RII or RIII parasites

  14. Effects of Chloroquine Resistance • Resistance has created many problems • Eliminated the use of the most widely used drug • Public health implications • People treated with chloroquine will not get better if they are infected with chloroquine resistant parasites

  15. What happens now? Different drugs must be used in chloroquine’s place Sulfadoxine-pyrimethamine Mefloquine Artemisinin-based combination therapy

  16. Thank you for listening!

  17. Works Cited Arrow, Kenneth Joseph et al. Saving Lives, Buying Time: Economics of Malaria Drugs in an Age of Resistance. 2004. Web. 3 April 2012. http://books.google.com/books?id=lGXjCX8cdfQC&pg=PT444&lpg=PT444&dq=how+many+lives +did+chloroquine+sa&source=bl&ots=WLjrOkWJaj&sig=7iMPUvv28J7iRh0herFs3x-2O0Y&hl=en&sa=X&ei=EjmGT_rzA- zYiAKBuNTFDw&ved=0CCIQ6AEwAA#v=onepage&q=how%20many%20lives%20did %20chloroquine%20save%3F&f=false “Drug Resistance.”n.p., n.d. Web. 30 March 2012. http://www.malariasite.com/malaria/drugResistance.htm “The History of Malaria, an Ancient Disease.” n.p., n.d. Web. 30 March 2012. http://www.cdc.gov/malaria/about/ history/ Image of the 2 foci associated with chloroquineresistance. http://www.jci.org/articles/view/38307/figure/5 “Malaria and Drug Resistance.” n.p., n.d. Web. 3 April 2012. http://anthro.binghamton.edu/BiomedWebsite/malaria.shtml Trape, Jean-François. “The Public Health Impact of Chloroquine Resistance in Africa.” The American Society of Tropical Medicine and Hygiene, 2001. Web. 3 April 2012. http://www.ajtmh.org/content/64/1_suppl/12.full.pdf Wiser, Mark F. “Mechanisms of Drug Action and Resistance(Focus on Antimalarials)” n.p., n.d. Web. 3 April 2012. http:// www.tulane.edu/~wiser/protozoology/notes/drugs.html

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