ANTIBACTERIALS: BETA LACTAMS Flashcards
Name 6 bacterial targets for selective inhibition?
- Cell wall
- Cell membrane (different composition)
- DNA synthesis (bacteria use different enzymes used and more DNA is made)
- Transcription (different enzymes used and occurs more frequently in bacteria)
- Protein synthesis in the cytoplasm (70S not 80S ribosomes)
- (Other) metabolism (e.g. folate metabolism - essential for DNA)
Name two types of drugs that attack bacterial cell wall synthesis?
- Vancomycin
- Beta-lactams
How to determine whether a bacteria is Gram +ve or -ve, using cell well?
- Bacteria is treated with iodine, then acetone (decolourizer)
- Gram +ve bacteria - purple
- Gram -ve bacteria - colourless
- This is because +ve bacteria has more peptidoglycan
What are Norcardiform bacteria (Gram +ve or -ve) and give some examples?
- Norcardiform bacteria are Gram +ve
- Examples are mycobacteria such as M. tuberculosis
Why is it difficult to stain Nocardioform bacteria?
Peptidoglycan covalently linked to arabinogalactan, which is esterified to lipids, making it resistant to staining (also resistant to biocides and antibiotics)
Describe the structure of peptidoglycan
- Alternating NAM and NAG residues
- Branched peptide chains
- Peptide chains cross link to form peptidoglycan sheets (cross links are species dependent)
What sort of reaction forms crosslinks on peptidoglycans and what enzyme catalyzes this reaction?
- Formed by a transpeptidation reaction (nucleophillic attack
- Catalyzed by a membrane-bound transpeptidase (interact with second to last AA of peptide chain = last AA is displaced)
What is Carboxypeptidase?
- Found in the cell membrane
- Involved in cell wall synthesis
- ONLY displaces the final AA (doesn’t form cross links)
Name some beta-lactams antibiotics? (3)
- Penicillins
- Cephalosporins
- Carbapenems
What was the antibacterial broth prepared from in Flemings discovery of penicillin?
Penicillium notatum fungus (Penicillin G was the active ingredient and was purified from the broth)
What amino acid residues are Penicillin G constructed from? (3)
- Cysteine
- Valine
- Phenylalanine
What’s the mechanism of action of Beta-lactam antibiotics?
- Lactam ring binds transpeptidase/carboxypeptidase enzymes to prevent cross-linking in the cell wall
- Cell wall weakened causing cell to rupture
What five factors affect the efficacy of a Beta Lactam?
- Ability to penetrate the cell wall
- Resistance to b-lactamases
- Affinity of various Penicillin Binding Proteins (e.g. transpeptidase and carboxypeptidase)
- Resistance to stomach
- Formulation, pharmacokinetics, toxicology etc.
What are the 5 main penicillins and how susceptible are they to Beta Lactamases?
- Penicillin G (acid labile = injection) and ampicillin (acid srable = oral) - susceptible to Beta Lactamase degradation
- Amoxicillin - Resistant to class 1 Beta Lactamases
- Methicillin and Flucloxacillin - Resistant to all Beta Lactamases
What are the generations of Cephalosporins?
- 1st, 2nd and 3rd
- Generation 1 - hardly used
- Generation 2 - Gram -ve activity and orally administered
- Generation 3 - Gram -ve activity and injected