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Microbio L15
| Question | Answer |
|---|---|
| Antimicrobial | Kill microbe or inhibit growth Antibacterials, antivirals, antifungals, antiparasitics |
| Antibiotic | naturally occurring antimicrobial Commonly used interchangeably |
| Selective Toxicity | Antimicrobial should target something not in the host (human) Prevent severe side effects Difference between an antimicrobial and disinfectant |
| Spectrum | how many species it targets Broad: many species (G+ and G-) Narrow: a few or one species Empiric Therapy: start patient on broad as precaution, ID pathogen, then move to narrow |
| Bacteriostatic | prevent growth Rely on host immunity to clear infection Might prevent sepsis (Endotoxin) |
| Bactericidal | kill microbes |
| Antimicrobial Origins | -Some are naturally occurring Why? -Some are completely human-made Synthetic -Some modified from natural Semi synthetic Generations |
| Considerations Before Use (3) | Side effects Delivery Half-Life |
| Side effects | Trade off with symptoms from infection Common in filtering organs (nephrotoxic, hepatotoxic) Some digestive (lost of commensals) Determine dosing |
| Delivery | Differs between drugs (due to stability and site of infection) Example: Oral, parenteral, tropical Influences dosing and frequency |
| Half- Life | How long the drug remains in the system Determines dose frequency |
| Common Antibacterial Targets 5 main targets | 1. Things that mess with the cell wall 2. Things that mess with the plasma wall 3. Things that mess with the nucleic acids 4. Things that mess with protein synthesis 5. Things that mess with certain metabolic pathways, folic acid synthesis |
| Cell Wall Targeting | Many target transpeptidation |
| Transpeptidation | Cross bridge formation between peptidoglycan strands |
| Bactericidal due to | lysis Loss of pressure regulation (weak cell wall) |
| Beta-lactam family | Have special beta-lactam ring Inhibit transpeptidation Resistance is common Bacteria have beta-lactamases to cleave (cut the beta lactams in half) |
| Beta-lactams can be co-delivered with a | beta-lactamase inhibitor |
| Penicillins | Narrow spectrum G+, a few G- Later generations: Expand spectrum More beta lactamase resistance Easier delivery Minimal side effects Allergy is possible tho |
| Other Cell Wall Targeters Glycopeptides | similar action to lactams, but different structure Resistant to lactamases IV delivery |
| DNA Targeting | Target bacteria-specific replication enzymes |
| Quionolones | DNA TARGETER |
| RNA Targeting | Inhibit bacterial RNA polymerase Different than eukaryotic polymerase |
| Rifamycons | RNA TARGETER |
| Antifolate Drugs | Inhibit folate synthesis Needed for nucleic acids Humans don’t synthesize folate!! We get folate from diet |
| Sulfa drugs/ sulfonamides | Mimic PABA- intermediate compound when synthesizing folate Bacteriostatic, broad spectrum Varied delivery |
| Ribosome Targeting | Prevent protein translation Bacteria have distinct ribosomes from eukaryotes Macrolide |
| Macrolides | Broad spectrum and delivery |
| Aminoglycosides | narrow spectrum (Only G-), short half life Common in combo therapy (ex. Triple ointment) |
| Membrane targeting | Tear holes in membranes Polymyxins |
| Polymyxins | Specific to bacteria since they need LPS to bind G- spectrum Triple ointment e |
| Antivirals | Target some step of viral replication Difficult since viruses use our own machinery HIV, hepatitis, herpes, influenza, and coronavirus |
| Antifungals | Eukaryotic, so targeting difficult Target ergosterol in membrane (rather than cholesterol) Azoles, allylamines Polyenes Target cell wall |
| Antiprotozoan Drugs | Antimalarials (fight off malaria) Combo therapy common since resistance is rampant Metronidazole: used to treat wide variety of protozoa infections Target nucleic acids |
| Antihelminthic Drugs | Inhibit glucose uptake into the worm OR Paralyze the worms Good for digestive infections (tapeworm) Paralyzed worms excreted in feces |
| Whats Selective pressure to mutate | Resistance genes passed horizontally Shared amongst microbiome and commensals |
| Mechanisms of Resistance (3) | 1. Alter drug target 2. Break drug 3. Keep drug out Block entry Pump out Multi drug resistance efflux pumps |
| Antibiotic stewardship | Reduces unnecessary antibiotic use Don’t mis-prescribe Finish complete antibiotic doses Use narrow spectrum drugs when possible |
| Human activity promotes | resistance |
Created by:
liladdoyle