Antibact. chemotherapy Flashcards
Explain what is meant by selective toxicity?
ability for drug to kill/inhibit pathogen while reducing harm done to the host
What’s the diff. b/w broad- & narrow-spectrum antibiotics?
- Broad-: target variety (many) of pathogens
- Narrow-: target specific (few) of pathogens
What factors influence the effectiveness of antimicrobial drugs & explain?
- Ability of drug to reach site of infection: oral, topical (creams), parenteral route (injection)
- Susceptibility of pathogen to drug: how drug is transported to site
- Dosage [ ] of drug must exceed MIC @ site of infection in body: amount given, rate of uptake by body, rate of elimination from body
List & briefly describe the 4 Mechanisms of antibacterial drug action
- Inhibition of cell wall synthesis: inhibit synthesis of peptidoglycan => osmolytic lysis
- Inhibition of protein synthesis: interfere w/ translation (initiation &/or reading codons, charging tRNA, elongation on AA) => faulty proteins
- Inhibition of nucleic acid synthesis: block DNA replication/transcription (inhibiting enzymes required RNA/DNA pol, DNA helicase)
- Metabolic antagonism: molecules that make proteins dysfunctional
Briefly give the mechanism of cell wall synthesis inhibitors & give e.g. of drug
Blocks transpeptidase enzyme from cross-linking NAM & NAG during synthesis of new cell wall = weak cell wall = lysis of cell
e.g. Penicillin, Cephalosporins, Vancomycin, Telcoplanin
Briefly give the mechanism of protein synthesis inhibitors & give e.g. of drug
Aminoglycosides (AEROBICALLY)
- Tetracyclides: binds irreversibly to 30S subunit => misalignment of mRNA & tRNA (miread codons) = non-functional protein
- Chloramphenicol: binds to 50S subunit & inhibits peptidyl transferase (bacteriostatic)
- Erythromycin & Macrolides: binds to 50S & inhibits peptide chain elongation (EF2) (bacteriostatic)
Briefly give the mechanism of nucleic acid synthesis inhibitors & give e.g. of drug
- Inhibit DNA gyrase & topoisomerase II (uncoiling) ≠ DNA replication ≠ new cells (= bacteriostatic)
e. g. Quinolones
Briefly give the mechanism of metabolic antagonists & give e.g. of drug
block synthesis of folic acid ≠ produce T,A,G,C for making DNA or RNA = cell dies
e.g. Sulphonamide
What attributes would an ideal antimicrobial agent have?
- Soluble in body fluids
- Selective toxicity
- Toxicity not able to be altered
- Nonallergenic
- Stable
- Resistance not easily acquired
- Long shelf life
- Reasonable cost
How is effectiveness of antimicrobial activity expressed?
- Minimal inhibitory concentration (MIC): lowest [ ] of drug that inhibits growth of a pathogen (no growth on lowest [ ])
- Minimal lethal concentration (MLC): lowest [ ] of drug that kills pathogen (if tubes past MIC w/out growth, sub-cultured in drug free medium => no growth)
How is effectiveness of antimicrobial determined?
- Dilution susceptibility test for MIC: inoculate in broth/agar w/ diff. [drug].
- Disk diffusion test (Kirby Bauer method): disks impregnated w/ drug placed on inoculation of test microbe -> zone’s radius measured = [ ] refer to table
- E-test MIC: strips w/ different [ ] of drug ( [ ] is written on strip)
What do you do w/ therapeutic index?
used to determine selective toxicity
Equ. = toxic dose / therapeutic dose
* Must be 1< (Hi value = good to use bc no harm to host)
- Toxic dose: [ ] that’s toxic to host (=> sideffects)
- Therapeutic dose: [ ] required for clinical treatment
Where are antibiotics sourced from?
micro-o in soil (which secrete chemicals to outcompete competition w/ other micro-o)
