Antibiotics & Anti-fungals Flashcards
Antibiotic classes: identify the main classes of antibiotic drugs and distinguish between them in terms of mechanism of action
- Intracellular targets
- -> Nucleic acids - Sulphonamides (DHOp), Trimethoprim (DHFR)
- -> DNA gyrase - Fluoroquinolones e.g. Ciprofloxacin
- -> RNA polymerase - Rifampicin
- -> Bacterial ribosomes – - Macrolides (Aminoglycosides, Tetracyclines) - Cell membrane targets
- -> Peptidoglycan (PtG) synthesis - Vancomycin inhibits pentapeptide
- -> PtG incorporation - Carbapenems, Cephalosporins & Penicillins inhibit transpeptidase
- -> Membrane stability - Lipopeptides & Polymyxins
Antibiotic resistance: recall the mechanisms commonly used by bacteria to become resistant to drugs
Destruction enzymes - beta-lactamases
Additional target - Different DHFR enzyme
Hyper-production - More DHFR enzyme
Changes to target - Changing DNA gyrase
Alterations in permeation - Increased efflux mechanisms
Anti-fungals: differentiate between the drugs used to treat fungal infections
Azoles - Inhibit ergosterol production
Polyenes - Bind to ergosterol and create pores
describe where protein synthesis inhibitors works on in the stages of protein synthesis (their targets)
- Nucleic Acid Synthesis
- Dihydropteroate (DHOp)
- -> Sulphonamides inhibit DHOp synthase
- Tetrahydrofolate (THF)
- -> Trimethoprim inhibits DHF reductase - DNA replication
- DNA gyrase
- -> Fluoroquinolones (e.g. Ciprofloxacin) inhibit DNA gyrase & topoisomerase IV (prevents bacteria DNA fromunwiknding –> cant replicate) - RNA synthesis
–> RNA polymerase
The rifamycins (e.g. Rifampicin) inhibits bacterial RNA polymerase
(Prevents RNA production –> bacteria can no longer produce products required for their survival) - Protein synthesis
- Ribosomes
Inhibited by:
–> Aminoglycosides (e.g. Gentamicin)
–> Chloramphenicol
–> Macrolides (e.g. Erythromycin)
–> Tetracyclines
SUMMARY 1: Bacterial protein synthesis
- Folate
- -> DHoP & DHF reductase
- -> Sulphonamides & Trimethoprim
- Replication & Transcription
- -> DNA gyrase & RNA polymerase
- -> Fluoro/Quinolones & Rifampicin
- Translation
- -> 70s bacterial ribosome
- -> Macrolides
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Describe the normal process of bacterial wall synthesis
- Peptidoglycan (PtG) synthesis
- -> pentapeptide is created on N-acetyl muramic acid (NAM)
- -> N-acetyl glucosamine (NAG) associates with NAM forming PtG - PtG transportation
- -> PtG = transported across the membrane by bactoprenol - PtG incorporation
- -> PtG = incorporated into the cell wall when transpeptidase enzyme cross-links PtG pentapeptides
describe where protein synthesis inhibitors works on in the stages of bacterial wall synthesis (their targets)
- PtG synthesis
- PtG transportation
- PtG incorporation
4 Cell wall stability
- PtG synthesis
- -> Glycopeptides (e.g. Vancomycin)
- -> bind to the pentapeptide preventing PtG synthesis - PtG transportation
- -> Bacitracin
- -> inhibits bactoprenol regeneration preventing PtG transportation - PtG incorporation
–> beta-lactams
–> bind covalently to transpeptidase –> inhibiting PtG incorporation into cell wall
beta-lactams include:
- Carbapenems
- Cephalosporins
- Penicillins
4 Cell wall stability
- -> Lipopeptide - (e.g. daptomycin) disrupt Gram +ve cell membranes
- -> Polymyxins - binds to LPS & disrupts Gram -ve cell membranes
What are some causes of AB resistance
- unnecessary prescription
- livestock farming
- lack of regulation
- lack of development
Describe the mechanism of AB resistance
- production of destruction enzymes
- beta-lactamases hydrolyse C-N bond of the beta-lactam ring - additional target (pac man)
- -> bacteria produce antlers target that is unaffected by the drug
e. g E Coli produce different DHF reductase enzyme making them resistant to trimethoprim - Alterations in target enzymes (pac man)
- -> Alteration to the enzyme targeted by the drug. Enzyme still effective but drug = now ineffective
e. g S.Aureus- Mutations in the ParC region of topoisomerase IV confers resistance to quinolones - Hyperproductiom
- -> Bacteria significantly increase levels of DHF reductase
- -> e.g E Coli produce additional DHF reductase enzymes making trimethoprim less effective - Alteration in drug permeation
- -> Reductions in aquaporins & increased efflux systems
e. g gram -ve bacteria
Summary: Resistance
- Destruction enzymes
- -> Production of beta-lactamase - Additional target
- -> Different DHF reductase enzyme produced - Enzyme alteration
- -> Mutations in DNA gyrase enzyme - Hyperproduction
- -> Over-production of DHF reductase - Drug Permeation
- -> decrease drug influx, increase efflux systems
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What are the common 2 categories of anti fungals?
Two most common categories:
Azoles: Fluconazole
Polyenes: Amphotericin
How do Azoles work as anti fungals
Azoles
Inhibit cytochrome P450-dependent enzymes involved in membrane sterol synthesis
Fluconazole (oral) candidiasis & systemic infections
How do polyenes work as anti fungals
Polyenes
Interact with cell membrane sterols forming membrane channels
Amphotericin (I-V) systemic infections
