Pharm - Antibiotics and antifungals Flashcards
Describe gram + bacteria
Thick peptidoglycan cell wall e.g. s. aureus
Describe gram - bacteria
Outer membrane with LPS e.g. e coli
Describe mycolic bacteria
Outer mycolic acid layer
All bacteria have a
Cell wall and membrane
Explain nucleic acid synthesis in prokaryotes
- PABA —- (DHOp synthase) —-> DHOp
- DHOp —> DHF
- DHF — (DHF Reductase) –> THF. THF important in DNA synthesis
Explain DNA replication in prokaryotes
DNA Gyrase (aka topoisomerase) —> releases tension from DNA molecule by unwinding
Explain RNA synthesis in prokaryotes
RNA Polymerase —> produces RNA from DNA template, differ from eukaryotic RNA polymerase
Name and describe 2 antibiotics that interfere with nucleic acid synthesis
- Sulphonamides - inhibit DHOp synthase
2. Trimethoprim - inhibits DHF reductase
Name a antibiotic that inhibits DNA gyrase and topoisomerase 4 (i.e. inhibits DNA replication)
Fluoroquinolone (eg Ciprofloxacin)
Name an antibiotic that interferes with RNA synthesis
Rifamycins (e.g. rifampicin) —> inhibits bacterial RNA polymerase
Name 4 antibiotic types that inhibit protein synthesis/translation by ribosomes
- Aminoglycosides
- Chloramphenicol
- Macrolides (e.g. erythromycin)
- Tetracyclines
Describe bacterial cell wall synthesis
- Pentapeptide formed on NAM
- NAG associates with NAM —> forms proteoglycan
- PG moved across membrane by bactoprenol into periplasm
- PG incorporated into cell wall when transpeptidase cross-links PG pentane-tides
Which bacterial wall inhibitor antibiotics inhibit PG synthesis?
Glycopeptides (e.g. vancomycin) –> bind pentapeptide —> prevent PG synthesis
Which bacterial wall inhibitor antibiotics inhibit PG transport
Bacitracin —> inhibits bactoprenol regeneration –> prevents PG transport
Which bacterial wall inhibitor antibiotics prevent PG incorporation into cell wall
Beta-lactams —> bind covalently to transpeptidase —> inhibit PG incorporation into cell wall
e.g. carbapenems, cephalosporins, penicillin
Which bacterial wall inhibitors affect cell wall stability
- Lipopeptide (e.g. daptomycin) –> disrupt gram + cell walls
- Polymyxins - binds LPS and disrupts gram - membranes
What are the causes of AB resistance
- Unnecessary prescription
- Livestock farming
- Lack of regulation
- Lack of development
What are the 5 resistance mechanisms
- Destruction enzymes breakdown antibiotics
- Additional targets (e.g. different DHF reductase made)
- Enzyme alteration (e.g. mutations in DNA gyrase)
- Hyperproduction (e.g. of DHF reductase)
- Drug permeation - reduce drug influx, increase drug efflux systems
What are the destruction enzymes that bacteria can make
Beta-lactamases hydrolyse the C-N bond of B-lactam ring of antibiotic
(1. Penicillins G and V originally used for gram + infections)
2. Flucloxacillin and temocillin are B-lactamase resistant –> can enter cell wall
3. Amoxicillin has broad spectrum activity —> but it is not beta-lactamase resistant (gram - activity, also coadministered with clavulanic acid to confer beta-lactamase resistance)
How may bacteria use additional targets as a resistance mechanism
- Bacteria make separate, alternative target which is unaffected by drug
e. g. e coli makes a different DHF reductase –> giving it resistance to trimethoprim
How may bacteria alter their target enzymes as a resistance mechanism
Enzyme is still effective but the drug is ineffective on it
e.g. s aureus develops mutation in ParC region of topoisomerase4, giving it resistance to quinolones
How may bacteria hyper produce their target/enzyme as a resistance mechanism
e.g. e coli produce additional DHF reductases –> makes trimethoprim less effective
How may bacteria reduce drug permeation as a means of drug resistance?
Reducing aquaporins and increasing efflux systems e.g. gram -ve
Fungal infections can be classified by the tissues/organs affected. Elaborate
- Superficial - outermost skin layers
- Dermatophyte - skin/hair/nails
- Subcutaneous - innermost skin layers
- Systemic (mostly resp tract)
What are the 2 most common anti-fungal drugs?
- Azoles - e.g. fluconazole
2. Polyenes - amphotericin
How do azoles work
Inhibit CYP450-dependent enzymes involved in membrane ergosterol synthesis
e.g. fluconazole for candidiasis and systemic infections
How do polyenes work
Interact with cell membrane sterols —> forming membrane channels/pores —> bursts
e.g. amphotericin (4) —> systemic infections (but has bad SE)s
Summarise the intracellular targets of antibiotics and drugs used
- Nucleic acids - sulphonamides (DHOp), trimethoprim (DHFR)
- DNA gyrase - fluoroquinolone e.g. ciprofloxacin
- RNA polymerase - rifampicin
- Bacterial ribosomes - macrocodes (aminoglycosides, tetracyclines)
Summarise the cell membrane targets of antibiotics and drugs used
- PG synthesis - vancomycin inhibits pentapeptide
- PG incorporation - carbapenems, cephalosporins and penicillins inhibit transpeptidase
- Membrane stability - lipopeptides and polymyxins
