Antimicrobial Medications (Part I) Supplemental instruction Designed by Pyeongsug Kim ©2010 Fall 2010 For Dr. Wright’s Bio 7/27 Class Picture from

Antimicrobials- what are they? What is meant by the term chemotherapeutic? What distinguishes antibiotics from other antimicrobials? According to your text, what four microbes produce most of the antibiotics? We talked about generations of drugs, using penicillin as the prime example. Why has it been modified (i.e., what advantages or uses do the new-generation drugs have versus the “original” ones?) What do we mean by: Selective toxicity Therapeutic index Broad-spectrum or narrow-spectrum. Why are broad spectrum antibiotics often prescribed first? What problem might this cause? (I’m giving the answer away but…why IS killing the normal flora a problem?) What are some of the adverse effects of antimicrobials? (think how this ties in with the above questions) We talked about some of the specific antibacterial mechanisms. Be able to distinguish one from the other and give examples of antibacterials that act this way Inhibition of cell wall synthesis Inhibition of protein synthesis Inhibition of nucleic acid synthesis Inhibition of metabolic pathways Damaging cell membranes There are some antimicrobials that are prescribed specifically to treat tuberculosis. What are the features of the bacterium that are targeted? What is the difference between the MBC and MIC (and what is the difference between bactericidal and bacteriostatic)? Antimicrobial resistance: How do bacteria acquire it? What are some examples? What do we mean by vertical acquisition of resistance? Horizontal? Why is this a problem? How can we reduce the spread of antimicrobial resistance? Give examples of drugs that are antiviral, antifungal and antiprotozoan/helminthic. Why is it more difficult to develop safe versions of these drugs than it has been to develop antibacterial drugs?

_______________ - treats disease with chemicals. - drugs that killed the microbe but not the patient.Antimicrobials Chemicals that inhibits the growth of or kills microorganisms. eg. Antibiotics, synthesized drugs. Chemotherapeutics Picture from Designed by Pyeongsug Kim, ©2010

_______________ - A compound naturally produced by mold or bacteria that inhibits the growth of or kills other microorganisms. - -Come from microbes that normally reside in the soil. - -Antimicrobial drugs. Antibiotics Picture from Designed by Pyeongsug Kim, ©2010

_________________ organisms that produce antibiotics.Mold(fungi), bacteria Penicillin ~ fungi; used to treat S.aureus infection penicillin G Cephalosporium ~ fungi Streptomyces ~ bacteria; from soil.; Streptomycin Bacillus ~ bacteria Microbes produce most of the antibiotics Designed by Pyeongsug Kim, ©2010

________________ - lowest dose toxic to the patient - High therapeutic index (less/more) toxic to patient. Penicillin G ~ interferes with bacterial cell wall synthesis. - Low therapeutic index Should monitor the blood to check the toxic level. topical applications eg. 1 st –aid antibiotic skin ointments. ________________ - greater harm to microbes than the patients. - interfering with biological structure and biochemical process of microbes.  shoud NOT be in human cell. Selective toxicity Therapeutic index Designed by Pyeongsug Kim, © Features of antimicrobials

________________ -Affect a wide range of bacteria -When need immediate antimicrobial therapy acute-life-threatening disease -No time to culture and identify the disease-causing agent. -But, disrupt the normal flora ________________ -Affect a narrow range of bacteria Identification -Identification of the pathogen -Less disruption to the normal flora Broad-spectrum Narrow-spectrum Picture from Designed by Pyeongsug Kim, ©2010

Adverse effects of antimicrobials Allergic ReactionsAllergic Reactions -hypersensitivities eg. Penicillin ~ rash or anaphylactic shock Toxic effectsToxic effects -at high concentrations eg. Aminoglycosides ~ damage kidneys chloramphenicol ~ aplastic anemia -Usually toxic antimicrobial in topcal(skin) Suppression of the normal floraSuppression of the normal flora -Broad-spectrum antibiotics(orally) eg. C.diffcile Designed by Pyeongsug Kim, ©2010

Antibacterial mechanisms -We, human, have eukaryotic cells. -Target for selective toxicity :Target different things in bacterial cells from eukaryotic cells. Medications usually target….. Inhibit cell wall synthesis Peptidoglycan – Gram positive bacteria Chitin- Fungi 70S ribisomes (30S & 50S subunit) - Prokaryotes - inhibit protein synthesis Metabolic pathway(folic acid) Enzymes for nucleic acid synthesis Cell membrane Designed by Pyeongsug Kim, ©2010

Inhibitors of cell-wall synthesis -Peptidogican cell wall Only in bacteria (high/low) therapeutic index Penicillins, Cephalosporins Enzyme inhibitors (  -lactam rings) Prevent formation of peptidoglycan (vancomycin) Interfere with precursor transport (bacitracin) So, which microbes are the most sensitive to these drugs? Gram positive : purple in gram stain Designed by Pyeongsug Kim, ©2010

Picture from Dr. Wright’s Bio27 class slide Designed by Pyeongsug Kim, © Inhibit prokaryotic protein synthesis -70S ribisomes bind 30S or 50S subunit) -Toxic mitochondria of Eukaryoties have 70S ribosomes. -Aminoglycosides- kidney damage, deafness Neomycin can’t be taken internally Tetracyclines can discolor teeth in children Chloramphenicol- aplastic anemia

- Inhibitors of enzymes required nucleic synthesis Fluoroquinolones ~ inhibit topoisomerases Both in Gram positive & negative  However, acquired resistance Rifamycins ~ inhibit polymerase Many Gram positive & some Gram negative Mycobacterium (tuberculosis) ~ Gram negative  However, develop resistance rapidly Picture from Designed by Pyeongsug Kim, © Inhibit nucleic acid synthesis

*human get folate from dietary Inhibit metabolic pathways - the pathways lack in human. - The synthesis of folic acid trimethoprim, sulfanolamides (sulfa drugs) - The nucleic acid synthesis  by inhibiting the coenzymes Picture from Designed by Pyeongsug Kim, ©2010

Damage cell membranes Polymixin B first-aid skin ointments limited in Topical use ~ since bind to eukaryotic cell membrane lead to leakage cellular content alters cell membrane Gram-negative cell Bacteriocidal Daptomycin Gram-positive cell Bacteriocidal HOWEVER, NOT for Gram-negative cell  cannot penerate outer membrane of gram– cell. Designed by Pyeongsug Kim, ©2009 Picture from

Designed by Pyeongsug Kim, ©2009 Picture from Dr. Wright’s Bio27 class slide Designed by Pyeongsug Kim, ©2009 Picture from Dr. Wright’s Bio27 class slide

Antituberculosis - Mycobacterium slow growth; waxy coat; intracellular - -1 st line Target cell wall less toxic; more effective combination drugs  to prevent the development of resistant mutants - - 2nd line When 1 st line drugs do not work. more toxic; less effective Designed by Pyeongsug Kim, ©2009 Picture from