Antimicrobial Pharm Flashcards
Cell wall synthesis inhibitors
Beta-lactam
Folate synthesis inhibitors
Sulfonamides
Trimethroprim
DNA gyrase inhibitors
Fluoroquionlones
RNA polymerase inhibitors
Rifampin
Protein synthesis inhibitors
Tetracyclines
Aminoglycosides
Macrolides
Bacteriostatic
Inhibit/stop growth and reproduction of bacteria - works with your own immune system to remove microorganisms from the body
Bactericidal
Kill bacteria by interfering with a process essential for life (concentration-dependent or time-dependent)
Time-dependent
Killing effect is directly proportional to the amount of TIME the drug concentration at the site of infection is ABOVE the MIC of the organism
MIC
Lowest concentration of a drug that inhibits bacterial growth
Concentration-dependent
Bacterial kill increases with increasing levels of drug; have to avoid toxicity
Which type (static vs. cidal) should be used in patients with impaired immune defense mechanisms?
Bactericidal (required for endocarditis, meningitis, and neutropenic cancer pt)
Five principle MOAs in antimicrobial classification
- ) Inhibition of cell wall synthesis
- ) Disruption of cell membrane function
- ) Inhibition of protein synthesis
- ) Inhibition of nucleic acid synthesis
- ) Action as antimetabolites
Common target for agents that inhibit cell wall synthesis
Peptidoglycan synthesis and incorporation into bacterial cell wall
How do beta-lactam antibiotics work?
- They bind to PBPs (transpeptidase enzymes)
- PBP is unable to crosslink peptidoglycan chains
- Bacteria unable to synthesize a stable cell wall
- Weakened cell wall leads to lysis of bacteria from osmotic pressure
What is the key chemical structure found in every beta-lactam antibiotic?
Beta-lactam ring with beta-lactam bond (N-C=O)
Beta-lactamases
Bacteria can encode this enzyme that can cleave the beta-lactam bond; drug resistance
MRSA
Beta-lactam antibiotics WON’T WORK!!
-PBP is mutated in MRSA so no beta-lactam antibiotics can bind since the target site is altered
Beta-lactam antibiotics groups and characteristics
- Natural penicillins, Cephalosporins, Carbapenems, and Monobactams
- Beta-lactams are bactericidal and time-dependent killers
Penicillin groups and drugs
- Natural penicillins (penicillin G)
- Penicillinase-resistant penicillins or Antistaphylococcal penicillins (nafcillin)
- Extended-spectrum penicillins (amoxicillin)
- Antipseudomonal penicillins (ticarcillin)
Penicillin G active against…
Gram+ bac
Cephalosporins groups and drugs
First gen (cephalexin) Second gen (cefoxitin) Third gen (ceftriaxone) Fourth gen (Cefepime)
First gen mainly active against…
Gram+ cocci
With each generation of cephalosporins there is increasing…
- Activity against g- bac and less activity against g+
- Resistance to beta-lactamases
- Ability to cross BBB
Carbapenem drug
Imipenem
Monobactam drug
Aztreonam
Vancomycin action and characteristics
- Inhibits transglycosylase (prevents building block bound to phospholipid carrier from binding to growing peptidylglycan chain)
- Does not cross lipid membrane of g-
- Acquired resistance most often due to amino-acid alterations in side chain peptidoglycan building blocks (mutates binding site so Vanco can’t bind)
Bacitracin action and characteristics
- Interferes with transport of peptidoglycan precursors across cytoplasmic membrane (cell wall synthesis inhibited)
- Toxicity limits use to topical apps
- Common ingredient in non-prescription in first-aid ointments (Neosporin)
Agents that act directly on the cell membrane…
- Disrupt the integrity of the cell membrane (increase permeability leading to leakage of intracellular components)
- polymyxin and daptomycin
- Bactericidal and concentration-dependent killers
Colistin (polymyxin E)
- Binds to LPSs and phospholipids on outer cell membrane of gram-
- competitvely displaces Ca and Mg from PO4 groups of membrane lipid
- Leads to disruption of outer cell membrane, leakage of intracellular contents, bacterial death
MOA of daptomycin
- daptomycin binds to the membrane
- Ca allows many daptomycin to recruit and “poke a hole” in the membrane
- Leakage of K»depolarization»arrest of cell processes»cell death
Agents that inhibit bacterial protein synthesis….
- Translation inhibitors that target either 30S or 50S bacterial ribosome subunits
- Typically reversible inhibitors
- Generally bacteriostatic
Classes of antibiotics that inhibit bacterial protein synthesis and their drugs
- Tetracyclines (doxycycline)
- Macrolides (erythromycin)
- Aminoglycosides (gentamycin - exception to rule: AGs irreversibly inhibit protein synthesis and are generally bactericidal)
Inhibition of DNA gyrase (affect nucleic acid metabolism)
- Bacterial DNA is negatively supercoiled
- Supercoiling maintained by gyrase (topoisomerase)
- Inhibition of gyrase and type IV topoisomerase interferes with DNA replication, causes cell death
- Eukaryotic topoisomerases differ in structure
Drug that inhibits RNA polymerase
Rifampin
Drug class and drug that inhibits DNA replication
Fluoroquinolones; ciprofloxacin
Classes that target folic acid synthesis and their drugs
Sulfonamides (sulfamethoxazole) and drug: trimethoprim
Inhibition of folate synthesis
Folic acid is a cofactor needed for synthesizing the building blocks of DNA; metabolic inhibitors that target folic acid synthesis are selectively toxic to bacteria because bacteria have to synthesize a large proportion of cofactors (2-step process so you need to have both drugs to stop the pathway)
