Pharmacology - Antibiotics Part 1 (Exam 2) Flashcards
Who discovered the world’s first antibiotic
Alexander Fleming
3 things to know from antibiotics table
1) most antibiotics derived from a natural product
2) development is NOT continuous
3) as bacteria develop resistance, people develop new antibiotics
chemical derived from microorganisms (commonly yeasts and fungi) and used to inhibit other microorganisms (generally, a drug used for bacterial infections).
antibiotic
stop growth/reproduction with no cell killing
bacteriostatic
(STOP)
stop growth/reproduction AND cell killing
bactericidal
(KILL)
stop growth/reproduction AND cell killing/destruction
bacteriolytic
(DESTROY)
Differences between gram + and gram - bacteria
Gram +: thick peptidoglycan layer, stains purple, anaerobes found in oral cavity, no outer envelope
Gram -: thin peptidoglycan layer, stain pink, outer envelope
What factors play a role in the likelihood of a microorganism to cause an infection?
- Infectivity (ability of the bacteria to infect the host)
- # of organisms present (wash your hands)
- Immunity of host (pt. may be immunosuppressed)
Which antibiotics affect the cell wall?
Penicillins
Cephalosporins
Which antibiotics affect the plasma membrane?
Daptomycin
Which antibiotics affect DNA synthesis?
Fluoroquinolones
Which antibiotics affect metabolic pathways?
Sulfonamides
Trimethoprim
Which antibiotics affect ribosomes?
Tetracyclines (30S subunit)
Macrolides (50S subunit)
Name 5 mechanisms of action of antibiotics
1) inhibit cell wall synthesis
2) alteration in cell membrane integrity
3) inhibition of ribosomal protein synthesis
4)inhibition of nucleic acid synthesis
5)inhibition of folic acid synthesis
How does inhibition of cell wall synthesis work?
-Beta-lactam antibiotics covalently bind to active site of penicillin-binding proteins (PBP)
-These PBP remove the terminal alanine, this will allow for formation of the cross-linked peptidoglycan wall
-Binding inhibits the transpeptidase rxn and halts peptidoglycan synthesis and the cell dies
Name of rxn that halts peptidoglycan synthesis
transpeptidation
Another name for peptidoglycan
murein
Peptidoglycan is made of repeated subunits of?
N-acetylglucosamine and N-acetylmuramic acid bound by B(1,4) linkages
Peptidoglycan is cross linked via?
short peptides
Binding to the cell membrane is ____________ dependent insertion of its lipid tail
calcium
After binding to the cell membrane via calcium dependent insertion of lipid tail, what happens?
depolarization
K+ efflux
rapid cell death
Protein-making factory
ribosome
Different _________ work together to make _______ possible
proteins; life
Which drugs target the 50S prokaryotic subunit (bacterial) and 39S eukaryotic subunit (mitochondrial)?
erythromycin + chloraphenicol
Which drugs target the 30S prokaryotic subunit (bacterial) and 28S eukaryotic (mitochondrial) subunit?
tetracycline + glycylcline
Prokaryotic –> Bacterial (_____S)
It is made up of _____S and ______S subunits
70S
50S and 30S subunits
Eukaryotic –> Mitochondrial (_____S)
It is made up of ______S and ______S subunits
55S
39S and 28S
Eukaryotic –> Cytosolic/on rough ER (_____S)
It is made up of ______S and ______S subunits
80S
60S and 40S
How does inhibition of nucleic acid synthesis occur?
DNA-dependent RNA polymerase
Antibiotics inhibiting folic acid synthesis also suppress?
DNA synthesis
T/F: all microbial resistance patterns are broad
False! They’re local bc the antibiotics are based on a particular community
Name some methods for reducing bacteria resistance
-education
-improved hand washing technique
-better hospital infection control
-isolation of patients w/ highly resistant bacteria
-control of antibiotic use in hospitals
-discontinued use of antibiotics in agriculture
Mechanisms by which bacteria become resistant to drugs (6)
- Modification of target sites
- Alternate growth requirements
- Enzymatic activation
- Overproduction of target sites
- Efflux pumps
- Decrease in cell permeability
Very common mechanism of bacterial resistance
enzymatic inactivation
What enzyme hydrolyzes penicillins and cephalosporins?
B-lactamase
Which enzyme inactivates chloramphenicol, aminoglycosides, and tetracyclines?
acetyltransferases
How do bacteria alter target sites?
-ribosomal point mutations
-altering DNA gyrase & topoisomerase
-modifying penicillin-binding proteins in viridians group streptococci & pneumococci
How do bacteria alter cell wall permeability? Is this a good method?
-limiting access of antibiotic to receptor by deleting outer membrane proteins or closing membrane pore channels
Nope, low level of resistance (must be combined with another mechanism)
What is the purpose of efflux pumps?
eliminating antibiotics (already in cell) from cell interior as fast as they can enter
How many families are there of efflux transporters?
5
bacteria develop alternative metabolic growth requirements to evade destruction
auxotrophy
Requirement of a specific growth substance beyond the minimum required by the wild type/parent strain for normal metabolism and reproduction.
Give an example
auxotrophy; enterococci
This acid develops sulfonamide resistance?
Para-aminobenzoic acid
How is there overproduction of targets by B-lactamase?
resistance to B-lactam antibiotics
antibiotic no longer kills the microorganism, but it merely inhibits its growth or multiplication (growth after drug removal)
tolerance
multiplication in the presence of the antibiotic
resistance
Antibiotic resistance is characterized by a higher _______
MIC = minimum inhibitory concentration
minimum duration for killing of 99% of bacterial cells in the population versus susceptible bacteria
MDK99
What does a lower MDK99 indicate?
bacteria is susceptible
Tolerance is caused by loss of ______ activity. There is a mutation in the _____________ system controlling the bactericidal autolysin activity
autolysin; sensor-response
Resistance occurs with what kind of doses?
subtherapeutic antibiotic doses
(does not kill/inhibit the microorganism)
In resistance, _________ microorganisms are inhibited, allowing resistant ones to multiply and dominate
sensitive
In resistance, the antibiotic is considered a _________ to survival. The microorganism reacts by which 3 things?
threat
- mutation to resistance
- acquisition/transfer of resistance genes
- expression of latent resistance genes
Three mechanisms of horizontal gene transfer
- transduction
- conjugation
- transformation
Name some mobile genetic elements involved in horizontal gene transfer
naked DNA
plasmids
bacteriophages
transposons
integrons
Jumping genes
transposons
self-transfer of genetic information by plasmids or transposons to other microorganisms
conjugation
DNA from one bacterium to another by a bacteriophage intermediary
transduction
naked DNA from their environment into their genome
transformation
Name some genetic variations in bacteria
-local nucleotide changes in genome
-rearrangement of genomic sequences
Name some adverse effects of antibiotic therapy
-allergies
-resistance
-superinfection
-nephrotoxicity
-ototoxicity
-antibiotic induced photosensistivity
-prolonged QTc interval
-possible interference w/ oral contraceptives
drug deposited in the skin absorbs UV light and transfers energy to local tissue
phototoxicity
sunlight causes haptens to become complete antigen to the skin; allergic rxn is immediate or delayed
photoallergy
Antibiotics can ___________ the efficacy of oral contraceptives by __________ their clearance from the body
decrease; increase
Some anti-coagulants act through inhibition of _______________ blood coagulation proteins.
Since gut bacterial flora produce majority of vitamin K, you could further ________ vitamin K production when taking antibiotics
vitamin K-dependent; decrease
(decreased vitamin K production = increased effect of Warfarin (anticoagulant) = excessive bleeding)
T/F many antibiotics can be used during pregnancy
FALSE
Which antibiotics are ok to use during pregnancy?
Penicillin
Erythromycin
Which antibiotic is NOT ok to use during pregnancy?
Tetracycline
