Antibiotics and Anti-fungals Flashcards
What are the membrane properties of gram positive bacteria and give an example of one
Prominent peptidoglycan cell wall
E.g. Staphylococcus Aureus
What are the membrane properties of gram negative bacteria and give an example of one
Outer membrane with lipopolysaccharide
E.g. Escherichia Coli
What are the membrane properties of mycolic bacteria and give an example of one
Outer mycolic acid layer
E.g. Mycobacterium Tuberculosis
Describe the process of nucleic acid synthesis in bacteria
- Paraaminobenzoate (PABA) converted to Dihydropteroate (DHOp) via DHOp synthase
- DHOp converted to dihydrofolate (DHF)
- DHF converted to tetrahydrofolate (THF) by DHF reductase
- THF used in DNA synthesis
Describe the process of DNA replication in prokaryotes
Occurs using DNA gyrase
Topoisomerase - releases tension
Describe RNA synthesis in prokaryotes
RNA polymerase
Produces RNA from DNA template
Differ from eukaryotic RNA polymerase
Describe protein synthesis in prokaryotes
Ribosomes
Produce protein from RNA templates
Differ from eukaryotic ribosomes
Give two drugs that target nucleic acid synthesis in prokaryotes and state the action in which they target
Sulphonamides inhibit DHOp synthase
Trimethoprim inhibits DHF reductase
Give examples of drugs that target DNA replication and RNA synthesis in prokaryotes and state the action in which they target
Fluoroquinolones (e.g. Ciprofloxacin) inhibit DNA gyrase + topoisomerase IV
The rifamycins (e.g. Rifampicin) inhibits bacterial RNA polymerase
Give examples of drugs that target protein synthesis in prokaryotes
Macrolides (e.g. Erythromycin)
Aminoglycosides
Chloramphenicol
Tetracyclines
Explain the process of bacterial wall synthesis
- A pentapeptide is created on N-acetyl muramic acid (NAM)
- N-acetyl glucosamine (NAG) associates with NAM forming Peptidoglycan (PtG)
- PtG is transported across the membrane by bactoprenol
- PtG is incorporated into the cell wall when transpeptidase enzyme cross-links PtG pentapeptides
Give examples of drugs that might target Peptidoglycan synthesis
Glycopeptides (e.g. Vancomycin) bind to the pentapeptide preventing PtG synthesis
Give examples of drugs that might target peptidoglycan transportation
Bacitracin inhibits bactoprenol regeneration preventing PtG transportation
Give examples of drugs that might target peptidoglycan incorporation
beta-lactams bind covalently to transpeptidase inhibiting PtG incorporation into cell wall
Give examples of beta lactams
Carbapenems
Cephalosporins
Penicillins
Give examples of drugs that might target cell membrane stability and explain how they work
Lipopeptide - (e.g. daptomycin) disrupt Gram +ve cell membrane
Polymyxins - binds to LPS and disrupts Gram -ve cell membrane
What are the causes of antibiotic resistance
Unnecessary prescription
Livestock farming
Lack of regulation
Lack of development
What are the types of resistance
Destruction enzymes Additional target Alteration of target Alteration in drug permeation Hyperproduction
Explain of how resistance arises from destruction enzymes
beta-lactamases in the cell membrane hydrolyse C-N bond of the beta-lactam ring
Give examples of drugs that bacteria may be resistant against due to production of destruction enzymes
Penicillins G + V - Gram +ve
Flucloxacillin + Temocillin - beta-lactamase resistant
Amoxicillin - Broad spectrum
Gram -ve activity
Co-administered with Clavulanic acid - resistant
Explain the resistance mechanism of Additional targets and give an example
Bacteria produce another target that is unaffected by the drug
Example
E Coli produce different DHF reductase enzyme making them resistant to trimethoprim
Explain the resistance mechanism of alteration in target enzymes and give an example
Alteration to the enzyme targeted by the drug. Enzyme still effective but drug now ineffective
Example
S Aureus - Mutations in the ParC region of topoisomerase IV confers resistance to quinolones
Explain the resistance mechanism of alteration in drug permeation and give an example
Reductions in aquaporins and increased efflux systems
Examples
Primarily of importance in gram –ve bacteria
Explain the resistance mechanism of hyper production and give an example
Bacteria significantly increase levels of DHF reductase
Example
E Coli produce additional DHF reductase enzymes making trimethoprim less effective
Give the classifications of fungal infections
in terms of tissue/organs:
Superficial - Outermost layers of skin
Dermatophyte - Skin, hair or nails
Subcutaneous - Innermost skin layers
Systemic - Primarily respiratory tract
How many anti-fungal drugs are licensed in the UK and what are the two most common categories
15 anti-fungal drugs licensed in the UK
Two most common categories:
Azoles: Fluconazole
Polyenes: Amphotericin
What is the mechanism of azoles
Inhibit cytochrome P450-dependent enzymes involved in membrane sterol synthesis
What is the mechanism of polyenes
Interact with cell membrane sterols forming membrane channels
What are azoles used for
Fluconazole (oral) - candidiasis and systemic infections
What are polyenes used for
Amphotericin (I-V) - systemic infections
