Antimicrobial Drugs Flashcards
Paul Ehrlich
Developed concept of selective toxicity (Chemical is toxic to microorganism but NOT toxic to host)
i.e. “magic bullet”
Discovered Agent 606, Salvarsan, for treatment of STD-syphilis
Alexander Fleming (1881-1955)
Growth of Staphylococcus aureus inhibited contamination mold: Penicillium (produces penicillin)
Inhibition called antibiosis and antibiotic
Howard Florey and Ernst Chain
Performed first clinical trials for penicillin (WWII)
Chemotherepay
Use of drugs to treat a disease
Antimicrobial drugs:
Interfere with growth of microbes within a host
Antibiotic
Substance produced by a microbe that, in small amounts, kills/inhibits another microbe
Three sources of antibiotics
Naturally occurring, semi-synthetic, or synthetic
Semi synthetic antibiotics
Naturally occurring compounds taken and modified
Synthetic antibiotics
(Drugs made in the lab)
Extended spectrum of activity
(Modifying drugs to extend narrow spectrum drug to become a broader targeting drug)
Disadvantage of broad spectirum antibiotics
Kills all bacteria (encourages growth of other opportunistic pathogens)
Encourages antibiotic resistance
Mechanism of Action
Different antibiotics act on m/os in different ways
Mechanisms of resistance
Prevent entrance of drug
Drug transport into S. aureus
Pump out drug
Efflux pumps in P. aeruginosa.
Inactivation or degradation of drug
b-lactamase (Penicillinase)
Alteration of target enzyme or organelle
Penicillin binding proteins in MRSA
Alternative pathways or increased production of target metabolite
Examples of Natural occuring antibiotic sources
Bacteria
Gram (+) rods (endospore formers)
Actinomycetes- Streptomyces
Fungi
Penicillium
Ex of semi-synthetic antibiotics
Ampicillin
Amoxicillin
Synthetic antibiotic ex
Trimethoprim
Drug Resistant “Superbug”
Drug resistant organisms are a serious threat to human health
Two major superbugs
Methicillin-resistant S. aureus (MRSA)
Vancomycin-resistant enterococci
(VRE)
How is the misuse of antibiotics contributing to antibiotic resistance
Treating viral infections (common cold)
Use of expired antibiotics
Using of antibiotics in animal feed
Not completing prescribion
Using someone else’s leftover prescription
How does over use/inappropriate use of antibiotics contribute to antibiotic resistance
Hospital acquired Resistance
Agricultural Practices
Environmental Contamination
Globalization
Strategies for preventing emergence ofdruge ressistence
Use drugs only when necessary
Give drug in high concentrations
Give two or more drugs at same time
Encourage the use of vaccines (if available)
Therapeutic index
A high toxicity, with a low therapeutic dose
You want the therapeutic dose to be VERY different from toxicity dose
What drug has ideal therapeutic index
Penicillin
therapeutic index of vancomyosin
Toxicity dose very close to therapeutic dose
How many ways can m/o exhibit antibiotic resisitance
Some organisms might have one type of way that they exhibit resistance, and some might have multiple
How do antibiotics target bacteria and not body cells
Target bacteria specific features
Peptidoglycan walls
70s ribosomses etc.
Why is inhibiting cell wall synthesis an effective antibiotic technique?
Cell wall maintains shape and resists osmotic lysis, no cell wall = osmotic lysis
3 categoreis of antibiotic 1. Inhibitors of Cell Wall Synthesis
Beta-lactams
Peptide antibiotics
Actimycobacterials
What are Beta-Lactams and what do they do
Preventing cross linking of petidoglycans
Includes natural and semisyntheitc types of penicllins
2 main natural types of Beta Lactam penicillin
Penicillin G (requires injection)
Penicillin V (Can be taken orally)
Examples of bacteria that natural Beta Lactams can be used to treat
Aerobic Gram(+) bacilli and anaerobic bacteria
C. tetanus, N. gonorrhoeae, N. meningitidis, T. pallidum
What is the purpose of using semisynthetic Beta Lactams?
Extended-spectrum (wipes out more pathogens)
Penicillinase resistant
- Can take out lactamase producing organisms
Semisynthetic (extended spectrm) antibiotics used against
Infections caused by non-lactamase producing organisms:
Infections caused by Gram (-) organisms, and anaerobes
Gram (+) bacilli, H. influenzae, S. aureus, E. coli, V. Cholera, N. gonorrhoeae, N. meningitidis, Shigella sp.
Penicillinase resistant semisynthetic antibiotics used against which bacteria
S. aureus and lactamase producing organisms
Inhibiters of cell wall synthesis OTHER than penicillin
Cephalosporins
Structure similar to penicillin
Grouped according to generations of development
(always begin with cef/ceph)
Polypeptide antibiotics (vancomyosin)
Antimycobacterial antibiotics
- Effective against TB causing organisms
Ihibits bacterial action with mycolic acid
How do bacteria resist antibiotics
When Beta lactam ring is opened, it is no longer effective as an antibiotic
One way bacteria can build up antibiotic resistance is to produce an enzyme that can open up that ring
Enzyme that opens penicillin ring = penicillinase
Why are most inhibitors of protein synthesis broad spectrum
Most are broad spectrum antibiotics (protien synth is similar bw G+ and G- bacteria)
How do antibiotics inhibit protein synthesis
Binding to small or large ribosomal subunit
What kind of antibiotic ouljd be used to treat UTIs and anthrax
Inhibitors of DNA/RNA Synthesis
What type of bacteria are plasma membrane damaging antibo=iotics effective against
Effective against gram (-) such as Pseudomonas sp.
How do antibiotics that are competitive inhibitors of enzymes work
Inhibit folic acid synthesis
What would inhibiting fatty acid synthesis do to a bacteria cell?
Injure the plasma mebrane
What actions of an antibiotic would affect the bacteria cell wall syntehsis
Inhibiting synthessis of peptide crosslinks
Inhibiting mycolic acid synthesis
Inibiing liopolysaccharaide synthesis
Inhibiting vonding of N acetyl glucosamine to N acetylmuramic acid
What actions of an antibiotc interfere with cell DNA replication
Interfering with DNA polymerase
IInhibitng DNA gyrase
What action interferes with RNA synthesis?
Interfering with RNA polymerase
How does an antibiotic Interfering with protein synthesis
Interfering with 30S or 50s ribosomal subunit activity
Interfering with peptide bond formation, catalzyed by ribosome
Interfering ith ataachment of tRNA to mRNA
How would antibiotics interfering with protein synthesis in bacteria exhibit toxicity to eukaryototic host cells
These antibiotics interfere with protein synthesis within eukaryotic mitochondria
Eukaryotic mitochondria have 70S ribosomes, composed of 50S and 30S subunits, which are very similar to the ribosomes of bacterial cells
How is antbiotic ressitance spread through a population
Antibiotic resistance is readily transmitted to the next generation during binary fission.
Antibiotic-resistance genes can be passed horizontally via transduction.
Antibiotic-resistance genes can be passed from one bacterium to another by bacterial transformation.
Antibiotic-resistance genes can be passed horizontally via bacterial conjugation.
Antibiotics select for those microbes that have developed resistance, increasing their frequency in the bacterial population.
Mutations are the ultimate source of antibiotic-resistance genes.
Why do antibiotics not work against viruses?
Do not contain antibiotic targets
Which drug-resistance mechanism would most likely inactivate penicillin, a drug that targets cell wall synthesis?
Inactivation by enzymes
Which antibiotic is overcome by beta-lactamases?
Penicillin
How might efflux pumps increase antibiotic resistance in bacteria?
Resistant bacteria can have more efflux pumps, and can have less specific efflux pumps.
Bacteria that are resistant to sulfonamide have enzymes that have a greater affinity for what?
PABA
Membrane transport proteins are required for which mode(s) of antibiotic resistance?
Efflux pumps, beta-lactamases, and modification of porins all utilize membrane transport proteins.
Why would an efflux pump for penicillin located on a bacterial cell membrane not be effective at providing resistance to the drug?
Penicillin disrupts the cell wall, which is located outside of the cell membrane.
The process of acquiring antibiotic resistance by means of bacteriophage activity is called
transduction
Which mutations would not result in antibiotic resistance?
silent mutations
Why is polymyxin only used on the skin?
It can also damage living human cell membranes, but the drug is safely used on the skin, where the outer layers of cells are dead.
R-plasmids are most likely acquired via
Bacterial conjugation
Quinolones and fluoroquinolones act against what bacterial target?
DNA gyrase
Why is it difficult to find good chemotherapeutic agents against viruses?
Viruses depend on the host cell’s machinery, so it is hard to find a viral target that would leave the host cell unaffected.
One of the typical mechanism of antimicrobial peptides (AMPs) is:
Disrupting the plasma membrane
The antimicrobial drugs with the broadest spectrum of activity are
tetracyclines.
A drug that inhibits cell mitosis, such as griseofulvin, would be more effective against ________.
Fungi
One of the similarities between the semi-synthetic penicillins and natural penicillins is:
Both have β-lactam core.
why is tetracycline selectively toxic against bacteria?
The drug binds to the 30S small ribosomal subunit — eukaryotes have a 40S small subunit.
the minimal inhibitory concentration of antibiotic
ONLY growth in subculture
the minimal bactericidal concentration of antibiotic
Smallest number with NO growth
