Antibiotics & Antifungals Flashcards
what is the main characteristic of gram +ve bacteria?
thick peptidoglycan cell wall
name a gram +ve bacteria
Staph. aureus
what is the main characteristic of gram -ve bacteria?
outer membrane with lipopolysaccharide (LPS)
smaller peptidoglycan wall
name a gram-ve bacteria
e.coli
what is the main characteristic of mycolic bacteria?
outer mycocolic acid layer
name a mycolic bacteria?
Mycobacterium tuberculosis
what are the 2 main types of target for antibiotics?
1- intracellular targets
2- extracellular targets (particularly for G+ve)
what are the intracellular targets for ABx?
1) nucleic acid synthesis
2) DNA replication
3) RNA synthesis
4) protein synthesis
what occurs in nucleic acid synthesis in bacteria?
- Dihydropterate synthase converts PABA to DHOp.
- DHOp becomes DHF
- Dihydrofolate reductase converts DHF to THF.
THF can be use for DNA synthesis
PABA–>DHOp–>DHF–>THF–>DNA synthesis
how can nucleic acid synthesis be targeted by ABx?
1) Sulphonamide inhibits DHOp synthase so no DHOp is made
2) Trimethoprim inhibits DHF reductase so no THF is made
what ABx target nucleic acid synthesis?
Sulphonamide
Trimethoprim
what occurs in DNA replication in bacteria?
DNA gyrases (topoisomerases) release the tension in DNA
how can DNA replication be targeted by ABx?
Fluoroquinolones (e.g. Ciprofloxacin)
inhibits DNA gyrase and topoisomerase IV.
what ABx targets DNA replication?
Fluoroquinolones (e.g. Ciprofloxacin)
what occurs in RNA synthesis in bacteria?
RNA polymerase produces RNA from DNA template.
Prokaryotic RNA polymerase differs to eukaryotic RNA polyermase
how can RNA synthesis be targeted by ABx?
Rifamycins (e.g. Rifampicin) inhibits bacterial RNA polymerase.
what ABx targets RNA synthesis?
Rifamycins (e.g. Rifampicin)
what occurs in protein synthesis in bacteria?
Ribosomes produce the protein from RNA templates
Prokaryotic ribosomes differ to eukaryotic ribosomes
how do prokaryotic ribosomes differ to eukaryotic ribosomes?
prokaryotic –> 70s made of 30s and 50s
eukaryotic–> 80s made of 40s and 60s
what Abx targets protein synthesis in bacteria?
1) Macrolides – e.g. Erythromycin specially for myco. tuberculosis 2) Aminoglycosides – e.g. Gentamycin 3) Chloramphenicol. 4)Tetracyclines
all inhibit prokaryotic ribosome
what are extracellular targets that be be targetted by ABx?
particularly used in gram+ve bacteria
1) peptidoglycan wall (ptg) synthesis
2) ptg transportation
3) ptg incorporation
4) cell wall stability
what occurs in Ptg wall synthesis in bacteria?
- occurs intracellularly in the cytoplasm
NAM+NAH+pentapeptide–> Ptg
which ABx is used particularly for mycobacterium tuberculosis?
erythromycin (a macrolide)
what enzyme does sulphonamide target?
DHOp synthase
PABA–> DHOp
what enzyme does trimethoprim target?
DHF reductase
how can Ptg synthesis be targeted by ABx?
Glycopeptides (e.g. vancomycin) binds to pentapeptide and prevents PtG synthesis.
what Abx targets Ptg synthesis in bacteria?
Glycopeptides (e.g. vancomycin)
what occurs in Ptg transportation in bacteria?
Bactoprenol transports the PtG across the membrane.
how can Ptg transportation be targetted?
Bacitracin inhibits Bactoprenol regeneration
bactoprenol transfers Ptg across the membrane
what ABx targets Ptg transportation?
Bacitracin
what is required for Ptg transportation to occur in bacteria?
Bactoprenol (a hydrophobic alcohol, lipid)
what occurs in Ptg incorporation into the wall in bacteria?
Transpeptidase enzyme cross-links PtGs and creates wall.
how can Ptg incorporation be targetted by Abx?
beta-lactams (e.g. Carbapenems, Cephalosporins, Penicillins)
bind covalently to Transpeptidase and inhibit its action.
what is required by bacteria for Ptg incorporation into the wall?
transpeptidase
what ABx target Ptg incorporation?
beta-lactams
e.g. Carbapenems, Cephalosporins, Penicillins
what drugs target the cell wall stability? name one for G+ve and G-ve
Lipopeptide (e.g. Daptomycin) – disrupt gram +ve walls.
Polymyxin
– binds to LPS and disrupts gram –ve membranes.
what are the causes of antibiotic resistance?
o Unnecessary prescription. o Livestock farming. o Lack of regulation – OTC in some countries. o Lack of development – no new ABs.
what are the 5 mechanism that leads to antibiotic resistance?
1) Additional targets
2) Hyperproduction
3) Alterations in target enzymes
4) Alterations in drug permeation
5) Production of destruction enzymes
how do additional targets produced by bacteria leads to ABx resistance?
- different DHF reductase enzyme produced
- another target that is then unaffected by the drug
e.g. e.coli –> trimethoprim resistance
how does hyperproduction by bacteria lead to ABx resistance?
more DHF reductase enzyme
bacteria significantly increase levels of an enzyme to overwhelm the Abx
e.g. e.coli–> trimethoprim resistance
why is hyperproduction the least effective method of a bacteria gaining Abx resistance?
this is resource expending for the bacteria
how does alteration of target enzymes by bacteria lead to ABx resistance?
alterations to enzyme to make the drug ineffective whilst the enzyme still works
e.g. S.aureus mutation in ParC region of topoisomerase IV–> quinolone resistance
how does alteration of drug permeation by bacteria lead to ABx resistance?
- reductions in AQPs
- increased efflux systems
so reduced ABx entry
Important in GRAM –VE bacteria.
what mechanism of resistance is particularly used by gram -ve bacteria?
alteration of drug permeation
how does the production of destructive enzymes by bacteria lead to ABx resistance?
name a destructive enzyme
beta-lactamases (bacterial enzymes) hydrolyse C-N bonds of the beta-lactam ring
what Abx can be used against bacteria that produce beta lactamases?
- Flucloxacillin & Temocillin.
these are beta-lactamase resistant (have a steric shield around Beta lactam ring)
- Amoxicillin (for G-ve) with clavulanic acid
which Abx is not resistant to beta lactamase?
penicillins (for G+ve)
when is amoxicillin “beta-lactamase resistant”?
resistant to beta-lactamases only when co-administered with Clavulanic acid.
what are the classifications of fungal infections?
o Superficial – outermost layer of skin. o Dermatophyte – skin, hair or nails. o Subcutaneous – innermost skin layers. o Systemic – primarily respiratory tract.
the deeper the infection, the more serious
what are the 2 main classes of drugs used for fungal infections?
azoles and polyenes
what do azoles do?
Inhibit CYP450 enzymes (CYP51p) involved in membrane Ergosterol synthesis.
name an example of an azole
Fluconazole
what do polyenes do?
Binds to Ergosterol and creates channel pores
“puncture” holes in the cell membrane so to distrupt cell homeostasis
e.g amphotercin
name an example of a polyene
Amphotericin
which infections can be treated by the azole ,fluconazole?
candidiasis
systemic infections
what infections can be treated by the polyene amphotericin?
systemic infections