Antibacterial Drugs Flashcards
Name the key benefit and downside of antibiotics
+ allow for more invasive procedures
- bacteria can become resistant after time
What is the difference between gram-positive and gram-negative bacteria?
Gram-negative:
- lipid outer layer, 2 periplasms, small peptidoglycan layer
gram-positive
- thicc peptidoglycan layer, periplasm, membrane
Name comes from biological assay, peptidoglycan gives a stronger result therefore thicker peptidoglycan wall -> gram pos
What is the difference between bacteriostatic and bactericidal drugs?
static:
requires immunocompetent host
non-life threatening
for uncomplicated infections
cidal:
deep-seated infection
life-threatening
Define MIC and MBC and how they are calculated?
Minimal inhibitory concentration and minimal bactericidal concentration
Calculated with Dilution test:
-serial dilution of antimicrobial drug
- incubate on plate
- last conc to not have any growth = MBC
- last conc to not show visible growth = MIC
What is a broad spectrum antibiotic (as opposed to a narrow spectrum antibiotic)
Treats many types of bacteria, not specific
What are the 3 types of antimicrobial therapy?
- Definitive Drug therapy: antibiotics prescribed based on Organism identity and susceptibility
- Empiric therapy: “this other person had the same thing and reacted well to this”
- prophylactic therapy: use of antimicrobial agent to prevent infection
How do Penicillin and Aminoglycoside synergize when given as an antibiotic treatment?
Aminoglycoside is a protein synthesis inhibitor, but it can’t reach the ribosomes because of the cell wall
Penicillin inhibits the cell wall but doesn’t do anything else
What are the 5 major mechanisms of bacterial resistance?
Decreased entry enhanced efflux Bypass pathway Altered target site Enzymatic Degradation
True/False? We only have a few antibiotic drugs because we don’t need that many
False, bacteria become resistant and don’t respond to them anymore
True/False? A resistant bacterium can transmit antibacterial resistance to another bacterium
True
Which of the gram types of bacteria is easier to treat and why?
Gram-positive, because its cell membrane is much simpler and doesn’t contain many enzymes that could interfere with antibiotics
How is the periplasm of bacterial cell walls formed?
3 thick steps
1) peptidoglycan units (made up of MurNAc and GlcNAc, which each have L-Lysine and D-alanine residues) are phosphorylated by Bactoprenol IN CYTOPLASM
2) Bactoprenol flips the peptidoglycan unit into the periplasm and pops off (to repeat the process)
3) Penicillin-Binding protein (PBP) polymerizes the peptidoglycan units and crosslinks their L-lys and D-ala residues together
What do all beta lactams have in common?
square carbonyl-N ring
What is a beta-lactamase and what is its problem?
They open the beta-lactam ring making them ineffective
What is NDM-1?
Gene that confers resistance to all beta-lactam antibiotics in Canada
What is the poster child for glycopeptides?
Vancomycin
How do beta-lactams function?
They bind PBP and inhibit the crosslinking of peptidoglycan units
How do glycopeptides function?
They bind to the amino acids of the peptidoglycan unit and prevent more amino acids from being added as well as preventing cross-linking
How does Bacitracin work?
By inhibiting the shuttle pump from hydrolysing phosphate bonds, it can’t incorporate peptidoglycan units into periplasm
How do lipopeptides such as colistin (polymyxin) and daptomycin work?
Disrupts the CYTOPLASMIC MEMBRANE and punches a hole, K+ spills out and causes cell death
Effective against gram- bacteria, but toxic (used as last resort)
What class of drugs are D-Cycloserine and Fosfomycin and what are their respective mechanisms of action?
Intracellular inhibitors
Fosfomycin: mimics PEP and inhibits conversion of glcNAc to MurNAc
D-cycloserine: mimics D-alanine and prevents synthesis of D-alanine from L-alanine
How do aminoglycosides function?
They diffuse through porins in the outer membrane of gram- bacteria, then through active transport of the inner cytoplasmic membrane
Bind to ribosomal 30S subunit
What is the cause for the postantibiotic effect of aminoglycosides?
Irreversible binding to 30S ribosome
Intracellular drug accumulation persists after plasma levels decline
What do tetracyclines bind to?
30S ribosomal subunit
What are all protein synthesis inhibitors susceptible to?
Decreased influx/increased efflux
Change in 30S/50S
Which 3 enzymes degrade aminoglycosides (among others)?
N-acetyltransferases (AACs)
O-adenylyltransferases (ANTs)
O-phosphotransferases (APHs)
Is it possible to overcome bacterial resistance? How or how not?
Yes, with library screening to identify new/unexpected synergies
eg loperamide potentiates minocycline
What do topoisomerase inhibitors do?
Cause supercoiling of bacterial DNA during cell division
Name the 4 antimycobacterial drugs included in the First-line cocktail for tuberculosis
Rifampicin
Isoniazid
Pyrazinamide
Ethambutol
What does Isoniazid do?
Inhibits synthesis of Mycolic acid
*Part of TB first line cocktail
What does Pyrazinamide do?
Inhibits synthesis of Mycolic acid
*Part of TB first line cocktail
What does Ethambutol do?
Inhibits synthesis of Arabinogalactan
*Part of TB first line cocktail
Name 4 Beta-lactam cell wall synthesis inhibitors
Penicillins
Cephalosporins
Carbapenems
Monobactams
Name the type of non-beta lactam cell wall synthesis inhibitor we learned in class and its example
Glycopeptides (vancomycin)
Name the class of cell membrane disruptors learned in class
Lipopeptides
How does Rifampicin work?
Inhibits DNA-dependent RNA polymerase
*Part of TB first line cocktail
