Antibiotics chemistry Flashcards
What is the MOA of macrolides
- Macrolides are bacteriostatic
- they bond close to p site on 50s ribosomal unit
- this blocks the passage of peptide chain into the exit tunnel
- means no amino acid can get in
- therefore no proteins can be made
What is an example of a macrolide
- Clarithromycin
- Erythromycin
What is the MOA of quinolones ad fluoroquinolone
- they stabilise DNA gyrase enzyme intermediate by ‘base stacking’ via pi-pi bonds, which stops the enzyme from working
- this stops the super coiling process after DNA gyrase has made the cut on the DNA
What is the role of DNA gyrase in bacteria
- DNA gyrase is Topoisomerase II enzyme that uses ATP hydrolysis and Mg2+ ions to
- super coil the bacteria DNA when it is not being used for replication
- in the active site of DNA gyrase there are tyrosine residues which are important for cutting the DNA
Why do Quinolones and Fluoroquinolone have a good absorption
-they are zwitterionic so have a neutral charge
What is an example of Quinolones and Fluoroquinoloes
- Ciprofloxacin
- Levofloxacin
What is the MOA of tetracycline
- Tetracyclines have planar rings with O2 (strong lewis base)
- the O2 allows it to bind to Mg2+ ions on the ribosome via metal chelation (Lewis acid- Lewis base bond)
- When the tetracycline binds, it disrupts the function of the ribosome so tRNA cannot bind
What are some of the side effects of tetracyclines
- if used in children below 12 years old it can cause yellowing of the teeth
- it can also cause photosensitivity
What is a main drug-drug or drug-food interaction with tetracyclines
-it interacts with iron, diary and antacids
because it is a metal chelator
What is an example of a Tetracycline
-Doxycycline
What is an example of a glycopeptide
Vancomycin
What is the MOA of Vancomycin
- Vancomycin caps the end of the cell wall so the bacteria cannot form the peptidoglycan cross link to strengthen its cell wall
- this means the cell wall can burst due to osmotic pressure thus releasing the bacteria’s content
What is the bacteria resistance mechanism for Vancomycin
- Bacteria switches D-alanine amino acid on the cell wall to lactic acid
- this means vancomycin cannot bind and cap it so the bacteria can still make the peptidoglycan cross link
What is the MOA of Trimethoprim
- it inhibits synthesis of essential metabolites via:
- binds to dihydrofolate reductase as a competitive inhibitor of dihydrofolic acid
- this mean dihydrofolic acid cannot be reduced to tetrahydrofolic acid
What is the MOA of Sulphanilamide
- sulphanilamide are structural analogues of PABA
- they competitively inhibit dihydropteroate synthase so folic acid cannot be produced by the bacteria
What is the MOA of metronidazole
- Metronidazole enters the cell via passive diffusion and is reduced to give radical species that are toxic to cells
- it treats anaerobic activity e.g c.diff
What is a unique side effect of Vancomycin
-Red man syndrome
What is the MOA of 𝛃-lactam
- All 𝛃-lactam have square structure which have a bond angle of 90 degrees
- C=O normally likes to be at 120 degrees bond angle because it is sp2 hybridised but in 𝛃-lactam it is as 90 degrees
- this makes it very easy to attack the 𝛃-lactam and cause it to open like a book
- the 𝛃-lactam bond to serine on the transpeptidase enzyme causing the 𝛃-lactam to open up and get stuck in the transpeptidase enzyme
- therefore peptide chain and water are blocked from entering the enzyme to be able to make the peptidoglycan cross links
- this means the bacteria bursts due to osmotic pressure
What is the MOA of gentamicin
It inhibits bacteria proteins synthesis by binding to the 30s unit of the Ribosome
Which drugs require therapeutic drug monitoring
- Gentamcin
- Vancomycin
What is an example of a 𝛃-lactam
- Penicillin
- Cephalsporin
How does bacteria form their cell wall
- they form it via a transpeptidation reaction using transpeptidase enzyme
What is the bacteria resistance mechanism against 𝛃-lactam
-Bacteria can produce 𝛃-lactamase enzymes which open up the 𝛃-lactam ring before it is able to inhibit the cell wall
What is the side effects of penicillin
- anaphylaxis
- rash
- Steven-johnson’s syndrome
