antibiotics Flashcards
what are the seven categories of antibiotics?
1 - antimetabolites (sulfonamides)
2 - inhibitors of cell wall synthesis (B-lactams, glycopeptides)
3 - agents that alter membrane permeability (polymyxins, polyenes)
4 - inhibitors of protein synthesis (aminoglycosides, macrolides, tetracycline, chloramphenicol)
5 - inhibitors of DNA replication (quinolone)
6 - inhibitors of RNA replication (rifampin)
7 - miscellaneous antibiotics
what is an antimetabolite?
interferes with synthesis of function of a substance involved in normal cell metabolism
mechanism of sulfonamides?
- broad spectrum
- penetrate sensitive bacteria and inhibit production of folic acid through competitive inhibition
why is folic acid important for cell metabolism?
bacterial DNA synthesis -
Is the action of sulfonamides reversible?
yes - bacteriostatic
name the three antimetabolites we are responsible for.
1 - sulfonamides
2 - trimethoprim
3 - isoniazid
trimethoprim action
- synergistic with sulfonamides
- inhibits enzyme that converts dihydrofolate to tetrahydrofolate
- used with sulfonamides (sulfamethoxazole) for UTIs
isoniazid action
- narrow spectrum (M. tuberculosis)
- interferes with mycolic acid synthesis (mycobacteria)
- bactericidal
- inhibits enzyme InhA - fatty acid elongation
- penetrates human cell wall to kill intracellular bacteria
name seven antibiotics that are inhibitors of cell wall synthesis
1 - penicillin 2- cephalosporins 3 - beta-lactam rings but not penicillin 4 - beta-lactamase inhibitors 5 - glycopeptides 6 - cycloserine 7 - bacitracin
why such a large difference in sensitivity between animal cells and bacteria with penicillin?
animal cells don’t have a cell wall.
what is a lactam?
an anhydride link that forms a ring structure in part of a molecule - strained and easily hydrolyzed
how does penicillin kill cells?
- B-lactam antibiotic
- bind to and inactivate penicillin binding proteins (PBPs) - which are responsible for terminal stages of cell wall reshaping during growth and division
how can you prevent or slow the lethal action of penicillin?
deprive bacteria of nutrients essential for growth. bacteria must be able to divide once or twice.
how can penicillin be hydrolyzed?
1 - acidity of the stomach
2 - penicillinases in bacteria
penicillin G is sensitive to:
acid hydrolysis and penicillinase
penicillin V is sensitive to:
penicillinase only
ampicillin is sensitive to:
penicillinase only
pencillin G is effective against:
- many gram-positive, sensitive cocci
- some gram-negative cocci (meningitis)
- spirochete (treponema pallidum - syphilis)
shortcomings of penicillin G
- no oral formulation because acid labile
- penicillinase sensitivity
- ## potential allergic response
what are some semi-synthetic penicillins and how are they used?
- oxacillin, nafcillin
- used against bacteria that produce penicillinase
penicillins that are sensitive to penicillinase and are limited spectrum include:
- penicillin G - acid labile
- penicillin V - relatively acid stable
- Penicillin VK - higher solubility
penicillins sensitive to penicillinase that are broader spectrum
- ampicillin - acid stable
- amoxicillin - acid stable
penicillins sensitive to penicillinase that are extended spectrum (more bacilli, less G+ cocci)
- tricarcillin - b-lactam effective against pseudomonas aeruginosa
- piperacillin - most active against G- bacilli
penicillins resistant to penicillinase
- methicillin - acid labile
- naficillin, dicloxacillin, oxacillin - newer, more potent, acid resistant (oral available)
What does MRSA stand for?
methicillin resistant staphylococcus aureus
penicillin structure
- 4 membered b-lactam ring
- thiazolidine ring
- CWSI - cephalosporin structure
- 4 membered b-lactam ring
- dihydrothiazine ring
- CWSI - cephalosporin characteristics
- also bactericidal (cell wall inhibitor)
- broad spectrum against G+ and some G- bacilli
- GREATER acid stability than penicillin
- resistant to some penicillinases
first gen cephalosporins and effectiveness
- cefazolin, cephalexin, cefaclor, cephalothin
- G+ cocci, some G- bacilli, NOT pseudomonas aeruginosa
second gen cephalosporins and effectiveness
- cefuroxime, cefamandole, cefonocid, cefotetan, cefoxitin
- less effective against G+, more against G- enterics, still NO P. aeruginosa
third gen cephalosporins and effectiveness
- ceftriaxone, ceftazidime, cefotaxime, cefoperazone
- broader G- spectrum
- ceftazidime - gets P. aeruginosa
- ceftriaxone - penetrates CNS
CWSI - B-lactam ring antibiotics that are not penicillin include:
- monobactams (aztreonam) - G- and P. aeruginosa
- carbapenems (imipenem) - broadest spectrum and most resistant to most b-lactamases
CWSI - 3 B-lactamase inhibitors
1 - clavulanic acid - (augmentin - with amoxicillin)
2 - sulbactam (unasyn - with ampicillin)
3 - tazobactam (zosyn - with piperacillin)
CWSI - glycopeptides - 2 important drugs
1 - vancomycin
2- teicoplanin
vancomycin characteristics
- restricted to G+ organisms
- binds R-D-Ala-D-Ala which blocks peptidoglycan precursor transfer
- somewhat toxic but used when other drugs are contraindicated
- ONLY drug available for multiply resistant enterococcus (MRE) and MRSA
teicoplanin characteristics
- chemically similar to vancomycin
- greater lipophilicity - excellent tissue and intracellular phagocytic penetration
- NO oral formulation, very expensive
- not approved by FDA yet
CWSI - cycloserine
- secondary TB drug
- toxic
CWSI - bacitracin
- restricted to G+
- toxic, topical only
- found in Neosporin with polymyxin B or neomycin
antibiotics that affect membrane permeability contrast to b-lactams
- cell growth not required for activity
antibiotics that affect membrane permeability - examples
1 - polymyxins B and E: effective against G- enteric rods
2 -
