Antimicrobial Drugs Chapter 10 PDF

Chapter 10: Antimicrobial Drugs  Drugs Chemicals that affect physiology in any manner Chemotherapeutic agents Drugs that act against diseases Antimicrobial agents (antimicrobials) Drugs that treat infections Natural antibiotics Drug naturally occurring in...

Chapter 10: Antimicrobial Drugs  Drugs Chemicals that affect physiology in any manner Chemotherapeutic agents Drugs that act against diseases Antimicrobial agents (antimicrobials) Drugs that treat infections Natural antibiotics Drug naturally occurring in nature Semisynthetic antimicrobials Modified version of natural antibiotic Synthetic antimicrobials Developed from a drug not found in nature Successful chemotherapy requires selective toxicity Targets enzyme/pathway critical for bacterial survival Targets enzyme/pathway not present/very divergent in humans Fewer drugs to treat eukaryotic infections Antiviral drugs limited  DNA Synthesis Metabolic Pathways Fluoroquinolones Folic Acid Synthesis RNA synthesis Sulfonamides Cell Wall Rifamycin Mycolic Acid Synthesis b lactams Izoniazid Glycopeptides Bacitracin Ribosomes 30S Aminoglycosides Tetracyclines 50S Plasma Membrane Macrolides Polymyxins Lincosamide Chloramphenicol Inhibition of Cell Wall Synthesis Inhibition of Synthesis of Bacterial Walls Most common agents prevent cross-linkage of NAM subunits Beta-lactams are most prominent in this group Transpeptidase Bacteria have weakened cell walls and eventually lyse Inhibition of Cell Wall Synthesis Inhibition of Synthesis of Bacterial Walls Semisynthetic derivatives of beta-lactams More stable in acidic environments More readily absorbed Less susceptible to deactivation More active against more types of bacteria Inhibition of Cell Wall Synthesis Inhibition of Synthesis of Bacterial Walls Vancomycin Interfere with particular bridges that link NAM subunits in many Gram-positive bacteria Inhibition of Cell Wall Synthesis Inhibition of Synthesis of Bacterial Walls Bacitracin Blocks transport of NAG and NAM from cytoplasm Isoniazid Disrupt mycolic acid formation in mycobacterial species Inhibition of Protein Synthesis Prokaryotic ribosomes are 70S (30S and 50S) Eukaryotic ribosomes are 80S (40S and 60S) Drugs can selectively target translation Mitochondria of animals and humans contain 70S ribosomes 80S 70S Can be harmful 30S Aminoglycoside Streptomycin 30S Tetracycline 50S Chloramphenicol 50S Lincosamide Disruption of Cytoplasmic Membranes Polymyxin disrupts cytoplasmic membranes of Gram- negative bacteria Toxic to human kidneys Inhibition of Metabolic Pathways Antimetabolic agents can be effective when pathogen and host metabolic processes differ Metabolic antagonists Inhibition of Nucleic Acid Synthesis Quinolones and fluoroquinolones Act against prokaryotic DNA gyrase Either “locks” topoisomerase/gyrase in place with DNA DNA replication halts Prevents enzyme from “resealing” double stranded breaks SOS response Accumulation of reactive oxygen species Spectrum of Action Number of different pathogens a drug acts against Narrow-spectrum effective against few organisms Broad-spectrum effective against many organisms May allow for secondary or superinfections to develop The Spectrum of Activity of Selected Antimicrobial Drugs *Do not need to Prokaryotes Eukaryotes Viruses know material in Gram-positive Chlamydias, the chart Mycobacteria Gram-negative bacteria bacteria rickettsias Protozoa Fungi Helminths Isoniazid Niclosamide Arildone Polymyxin Azoles Ribavirin Penicillin Praziquantel Acyclovir Streptomycin Erythromycin Tetracycline Sulfonamides Routes of Administration Measuring Effectiveness Ascertained by: MBC somewhere between 8 ug/ml and 16 ug/ml Diffusion susceptibility test Concentration of antibacterial drug (μg/ml) Minimum inhibitory concentration test (MIC) Clear Minimum bactericidal MIC tube concentration test (MBC) 8 μg/ml 16 μg/ml 25 μg/ml Bacterial colonies No colonies No colonies Drug-free media Antibiotic Resistance The Development of Resistance in Populations Some pathogens are naturally resistant Resistance by bacteria acquired in two ways: New mutations of chromosomal genes Acquisition of R plasmids via transformation, transduction, and conjugation. *Do not need to know material in the graph Mechanisms of Resistance At least six mechanisms of microbial resistance Production of an enzyme that destroys or deactivates drug b lactamase Mechanisms of Resistance At least six mechanisms of microbial resistance Expression of efflux pumps Mechanisms of Resistance At least six mechanisms of microbial resistance Changes in cell membrane/wall reduce antibiotic uptake Mechanisms of Resistance At least six mechanisms of microbial resistance Changes in structure of target Mechanisms of Resistance At least six mechanisms of microbial resistance Changes in metabolic pathways Mechanisms of Resistance At least six mechanisms of microbial resistance Biofilm formation Multiple Resistance and Cross Resistance Pathogen can acquire resistance to more than one drug Common when R plasmids exchanged Develop in hospitals and nursing homes Constant use of drugs eliminates sensitive cells Multiple-drug-resistant pathogens are resistant to at least three antimicrobial agents Cross resistance Resistance to one antimicrobial provides resistance to multiple antimicrobial Preventing Drug Resistance “Antibiotic Husbandry” Only use antibiotics when appropriate Complete full round of antibiotics Use multiple antibiotics different targets Preventing Drug Resistance “Antibiotic Husbandry” Only use antibiotics when appropriate Complete full round of antibiotics Use multiple antibiotics different targets Reduce use of antibiotics within food supply