Antibiotics and antifungals Flashcards
What are the main classes of antibiotic drugs?
- Sulphonamides 2. Trimethoprim 3. Fluoroquinolones 4. Rifamycins 5. Macrolides 6. Glycopeptides 7. Carbapenems, cephalosporins, penicillins 8. Polymyxins 9. Lipopeptide
How do carbapenems, cephalosporins + penicillins work? WHat group of drugs are they?
Target transpeptidase enzyme involved in PtG incorporation into cell wall. The group of drugs they are is beta-lactams
How do fluoroquinolones work?
Target DNA gyrase/topoisomerase IV to inhibit DNA synthesis
What drugs are used to treat fungal infections and how do they work?
- Azoles(e.g. fluconazole) - inhibit ergosterol production (in fungal CM) 2. Polyenes(e.g. amphotericin) - bind to ergosterol and make pores in CM
How do rifamycins work?
Target RNA polymerase to inhibit RNA synthesis
What does bacitracin do
•Bacitracin inhibits bactoprenol regeneration preventing PtG transportation
What are mycobacteria?
- Gram positive w/more complex outer wall - Wall contains a PtG-arabinogalactan polymer that binds mycolic acids, pore forming proteins and a number of extractable lipids - Gives bacteria a ‘waxy’ outer layer - E.g. mycobacteria tuberculosis, mycobacteria leprae
How do polymyxins work?
Target LPS to disrupt Gm-ve CMs
How is tuberculosis treated?
- RNA-polymerase inhibitor - rifampicin 2. Mycolic acid synthesis inhibitors 3. Pyrazinamide - reduces availability of ribosomes required for protein translation
Describe structure of mycolic bacteria, and what other types of bacteria are there
Mycolic Bacteria
- Outer mycolic acid layer
- E.g. Mycobacterium Tuberculosis
other types : gram negative and positive
Mechanism of antibiotic resistance
•Desctruction enzymes(b-lactamases hydrolyse C-N bond of the b-lactam ring)
Additional target(Bacteria produce another target that is unaffected by the drug[•E Coli produce different DHF reductase enzyme making them resistant to trimethoprim])
Alterations in target enzymes(Alteration to the enzyme targeted by the drug. Enzyme still effective but drug now ineffective[•S Aureus - Mutations in the ParC region of topoisomerase IV confers resistance to quinolones])
Hyperproduction
•Bacteria significantly increase levels of DHF reductase(e.g.Coli produce additional DHF reductase enzymes making trimethoprim less effective)
Alterations in drug permeation(.Reductions in aquaporins & increased efflux systems[•Primarily of importance in gram –ve bacteria])
NOTE:
Difference between ‘Additional target’ and ‘Alterations in target enzymes’ is that in the former we still have the first enzyme working but another has been added which is unaffected by the drug; and in the latter, there is a replacement , withthe replacement being unaffected by the drug
Last
Describe process of bacteria l protein synthesis
1.Nucleic Acid Synthesis
Dihydropteroate (DHOp)
- Produced from paraaminobenzoate (PABA)
- Converted into dihydrofolate (DHF)
Tetrahydrofolate (THF)
- Produced from DHF by DHF reductase
- THF ® Important in DNA synthesis
2.DNA replication
DNA gyrase
•Topoisomerase ® releases tension
3.RNA synthesis
RNA polymerase
- Produces RNA from DNA template
- Differ from eukaryotic RNA polymerase
4.Protein synthesis
Ribosomes
- Produce protein from RNA templates
- Differ from eukaryotic ribosomes
Describe the process of bacterial cell wall synthesis
1.Peptidoglycan (PtG) synthesis
- A pentapeptide is created on N-acetyl muramic acid (NAM)
- N-acetyl glucosamine (NAG) associates with NAM forming PtG
2.PtG transportation
•PtG is transported across the membrane by bactoprenol
3.PtG incorporation
•PtG is incorporated into the cell wall when transpeptidase enzyme cross-links PtG pentapeptides
How do macrolides work?
Target ribosomes to inhibit protein synthesis
How do sulphonamides work?
Targets DHOp synthase to inhibit NA synthesis
What are the 4 main steps in prokaryotic protein synthesis? What drugs target each step?
- Nucleic acid synthesis - sulphonamides, trimethoprim 2. DNA replication - fluoroquinolones 3. RNA synthesis - rifamycins 4. Protein synthesis - macrolides
