MCB Lecture 51 Antimicrobial Agents Flashcards
Why do we make semi-synthetic drugs?
Change the spectrum, kinetics and toxicity
Differentiate between antibiotics, chemo therapeutic agents and semi-synthetic drugs
Antibiotic: naturally occuring
Chemotheraputic agent: man made
Semi-synthetic: naturally occuring, but has been altered
What are the ways that we can classify antimicrobial drugs? (3)
Source
Mode of action
Pharmological class
What are the two effects that antimicrobial agents can have on bacterial growth?
Bactericidal
Bacteria static
What are tetracyclines?
These are antimicrobial agents that have four rings in the structure
What is the structure of Beta-lactams?
Square, pentagon, N, S, O
What are some of the types of antibiotics that are examples of the beta-lactam class?
Penicillins
Cephalosporins
How were beta lactam semi-synthetic drugs developed?
Start from the naturally occuring one, then modify it to change the toxicity, spectrum etc.
Describe the development of the different penicillins
Penicillin G, very low toxicity, no good against GNR, must be injected.
Penicillin V, can now be taken orally
Ampicillin, now effective against GNR
Methicillin, effective against golden staff, but toxic
Flucloxacillin, less toxic than methicillin
Carbenicillin, effective against Pseudomonas
Which type of penicillin is the first to be effective against pseudomonas?
Carbenicillin
What is the difference between Methicillin and Flucloxacillin?
Flucloxacillin is less toxic than methicillin
Why was ampicillin important?
It was now effective against GNR
Describe the differences between Penicillin G and Penicillin V
Penicillin V can now be taken orally
What is meant by selective toxicity
This means that it only targets elements of the bacteria
Who discovered Penicillin?
Fleming and Florey
What are some of the different features that antimicrobial agents target?
Cell wall Protein synthesis (ribosomes) Cell membrane Nucleic acid Folic acid
Describe broadly how antimicrobial agents target the cell wall
Block the building of the peptidoglycan, so the cell has an influx of water, so the cell lyses
Describe the synthesis of the prokaryotic cell wall
- The subunit precursors are made inside the cell
2. Moved to the outside of the cell and linked together
Which enzymes catalyse the connections between the peptidoglycan subunits?
Transpeptidases
What are two classes of drug that target the cell wall
Beta lactams (Penicillin) and Glycopeptides (vancomycin)
Describe the action of vancomycin
Binds to the D-alas on the peptide chains of the peptidoglycan subunits. Now, the blocks can’t be connected
Describe how bacteria may become resistant to vancomycin
They replace one of the D-ala with a sugar so that vancomycin can not bind
Enerococci do this
What are penicillin binding proteins?
These are normal proteins found in bacteria that are required for connection of peptidoglycan synthesis
They are also known as transpeptidases
How does penicillin work?
It binds to transpeptidases, rendering it inactive
Describe how bacteria may become resistant to penicillin (2)
- Altered penicillin binding proteins
2. Beta-lactamase breaks down penicillin
Describe broadly how antimicrobial agents target protein synthesis
Which agents do this?
Aminoglycosides
They bind to the 30S of ribosomes and mess up the reading frame so that abnormal proteins are made
Describe the action of amino glycosides
- Bind to 30S subunit
- Mess up the reading frame
- Misense or nonsense mutation: abnormal protein made
- Abnormal protein is associated into important structures in the bacteria
Describe how bacteria may become resistant to Aminoglycosides
- Change the 30S so that the Aminoglycoside can not bind
2. Bacteria modify the Aminoglycoside so that it can not get in
What is important about metronidazole?
It is selectively toxic to bacteria, because it requires reductase enzymes (only found in bacteria) to be activated
Describe the two genetic bases for antibiotic resistance
Innate: the resistance is part of the naturally occuring bacteria
Eg. G- bacterial cell wall is resistant due to impermeability
Acquired: mutation, or plasmid
Describe the problem that multi resistance plasmids present
One we apply one antimicrobial agent to these bacteria, every single other resistance on the plasmid is selected for, so we get multi resistant bacteria
Give an exams of a glycopeptide.
What does it do?
Vncomycin
It blocks cell wall formation
What do tetracyclines do?
They interfere with the recognition phase of protein synthesis
What does chloramphenicol do?
It interferes with peptidyl transfer in translation
What are some examples of aminoglycosides?
Gentamicin
Tobramycin
Amikacin
