Introduction to Antibiotics Flashcards
Categories of antibiotics based on their effects on bacteria
1. Bactericidal: kills bacteria
2. Bacteriostatic: inhibits bacterial growth (does not get rid of the bacteria)
: duration of therapy must be enough to allow cellular and humoral defense mechanisms to eradicate bacteria
Classification of antibiotics based on their spectrum
1. Broad spectrum: covers both Gram-positive & Gram-negative
2. Narrow spectrum: covers on Gram-positive
Cell Wall Inhibitors mode of action
- disrupts the integrity of the peptidoglycan layer in bacterial cell wall
- drugs all contain the beta-lactam ring
- drugs are known as beta-lactams (bacteriocidal)
Cell wall synthesis stages:
1. Cytoplasmic stage:
- synthesis of precursors (NAG, NAM)
2. Membrane stage (elongation and transfer):
- transfer of the precursors from cytosol to membrane, and incorporation into the growing peptidoglycan
3. Exctracellular stage (crosslinking):
- crosslinking of linear chains of peptidoglycans by membrane bound transpeptidases
Beta-lactam drugs and the bacteria they target
1. Penicillins: cover mostly Gram-positive, some Gram-negative
2. Cephalosporins: early drugs cover Gram-positive, later drugs cover Gram-negative
3. Monobactams (aztreonam): Gram-negative
4. Carbapenems (Imipenem): broad spectrum
How do bacteria resist mechanism to beta-lactam drugs?
- by producing penicillinase (beta-lactamases) enzyme which disrupts the beta-lactam ring found within the drug
Where is beta-lactamase found?
- found within the peptidoglycan cell wall
: in gram-positive, there are large amounts
: in gram-negative, there are small amounts (note that gram-negative bacteria have an outer membrane with porin channels)
Why do most beta-lactam drugs not work against gram-negative bacteria?
- bacteria has an outer membrane which reduces antibiotic penetration into bacteria
- the outer membrane contains porins which can be altered to resist antibiotic entry
- drugs can be pumped out of the bacteria via porins
Amoxycillin (a penicillin)- can enter gram-negative porins
The Penicillins (-cillin)
- Penicillin G (Benzyl)
- Penicillin V- stable
- Amoxycillin- stable, fast absorption, enters gram-negative porins
- Dicloxacillin- anti-ß-lactamases
- Piperacillin- used for Pseudomonas
ß-lactam drugs inhibit which stage of cell wall synthesis?
- extracellular stage (cross-linking)
- inhibits the cross-linking of peptidoglycan linear chains by transpeptidases
Vancomycin and bacitracin inhibit which stage of cell wall synthesis?
- membrane stage (elongation & transfer)
- inhibits the precursors (NAG & NAM) from cytosol to membrane for incorporation into the growing peptidoglycan cell wall
ß-lactamase inhibitors
- drugs are combined to enhance the activity of antibiotics
- Clavulanic acid + amoxicillin (Augmentin®)
- Sulbactam + ampicillin (Unasyn®)
- Tazobactam + piperacillin (Zosyn®)
- “suicide inhibitors”
Inhibitors of Protein Synthesis mode of action
- reversibly binds 30S (of prokaryotes): blocks aminoacyl t-RNA
- bacteriostatic in action
Inhibitors of cell wall synthesis: how is the target unique to bacteria and not host?
- eukaryotes do not contain a cell wall
Inhibitors of protein synthesis: how are targets unique to the bacteria and not the host?
- prokaryotic and eukaryotic ribosomes are different
: prokaryote- 70S (30S/50S)
: eukaryote- 80S (40S/60S)
- target of drug is 30S
Examples of inhibitors of protein synthesis
- Tetracycline- age sensitive, not frequently administered/advised
- Doxycycline- good for N. gonnorhea & Chlamydia
- Minocycline
- Demeclocycline
Tetracycline mode of action
- blocks amino acyl tRNA from binding to mRNA in 30S
Why is tetracycline age specific/ not recommended?
- causes tetracycline toxicity
- hypoplasia (underdevelopment), dark staining of tooth enamel
- not adminstered under 8 years old
Tetracycline Toxicity
- hypoplasia, dark stains on enamel of teeth
- GI irritation (esophageal ulcers)
- empty stomach: impaired absorption in combination with di/tri-valent cations (Ca2+, Mg2+, etc.)
- hepatotoxicity in pregnant women
- azotemia (excess nitrogen in blood- kidney damage), Fanconi Syndrome (disorder of kidney tubule function)
- vertigo (caused mainly by minocycline)
- photosensitivity
Which drug inhibits DNA replication?
Quinolones (-floxacin)
Examples of Quinolones
- Ciprofloxacin
- Levofloxacin
- Ofloxacin
- Norfloxacin
- Nalidixic acid
Quinolones mechanism of action
- blocks DNA gyrase (topoisomerase II) and topoisomerase IV
: DNA gyrase opens coiled structure of DNA, allowing unstressed segments to replicate
: also restores negative supercoils in the bacterial chromosome during and following DNA replication
Examples of Bacteriostatic Antibiotics
- Inhibitors of Protein Synthesis
: Tetracycline
: Doxycycline
: Minocycline
: Demeclocycline
Example of Bacteriocidal Antibiotics
- ß-lactam drugs
: Penicillin
: Cephelosporins
: Monobactams
: Carbapenems
