Antimicrobials, Antifungal and Antibiotics Flashcards
What are antibiotics effective on?
bacteria
What are the two ways in which antibiotics work on bacteria?
Bactericidal (killing bacteria)
Bacteriostatic (inhibiting/ arresting growth of bacteria)
* bacteriostatic antibiotics allow the immune system to act as well
Where can antibiotics act on the cell (these are why they do not effect the human cells and just the bacteria)?
- the cell wall
- inhibiting DNA biosynthesis
- inhibiting RNA
What allows us to classify bacteria in to catergories?
- gram negative (pink)
- gram positive (purple)
What are the difference between bacteria that is gram positive compared to gram negative bacteria.
positive - the cell wall has thick peptidoglycan layer
negative - has a thin peptidoglycan layer. It has an outer membrane
What antibiotics act on the peptidoglycan layer?
penicillins
cephalosporins
carbapenems
vancomycin
Penicillins, cephalosporins, carbapenems and vancomycin all act on the peptidoglycan layer on bacteria. Why is vancomycin different.
- it does not have the structural component of the beta lactam ring.
- has a different mode of action
What are b-lactam antibiotics effective on?
- against growing and dividing cells
Are B-lactam antibiotics bactericidal or bacteriostatic?
- bactericidal
How do resistant bacterial species act on B-lactam antibiotics
secrete enzyme (B-lactamase) which inactivates antibiotics by breaking down their B-lactam layer
How do B-lactam antibiotics act?
- Inhibit the enzyme involved in the transpeptidase cross-linking reaction
- interfere with linking the individual chains together
- disrupt the peptidoglycan layer
- leading to autolysis
What are penicillin effective against?
- very effective against gram positive
What are the problems with penicillin’s ?
- some allergy reactions
- aminopenicillins better tolerated
What are cephalosporins effective against?
1st generation - gram positive
2nd generation - anaerobes
3rd generations - gram negative
4th generations - pseudomonas
What are carbapenems effective against?
- broad spectrum
- generally effective aginst all accept : MRSA and VRE
What are the problems with carbapenems ?
can only be administered by IV
What are the problems with vancomycin?
allergy reactions
How does vancomycin act?
- still acts on the peptidoglycan layer
- but precludes peptidyl bridges
What is vancomycin effective against?
- MRSA
How is vancomycin administered?
IV
How is penicillin administered?
orally
other antibiotics target the RNA synthesis. What does this mean?
- They are more universal as all bacteria have the same mechanism of RNA synthesis.
- mostly basteriostatic, associated with greater toxicity
What are examples of antibiotics which bind to and inhibit protein components of the 30s subunit?
- tetracycline
- aminoglycosides (gentamycin, streptomycin)
What are examples of antibiotics which bind to and inhibit protein components of the 50s subunit?
- macrolides (erythromycin)
- chloramphenicol
What is the different between the RNA of bacteria and human cells?
human cells are bigger
What type of antibiotics inhibit DNA biosynthesis?
fluroquinolones
What are examples of fluroquinolones which inhibit DNA biosynthesis?
all end in floxacin
Which enzyme does floroquinolones inhibit?
DNA gyrase which is important to unwind DNA
What are fluroquinolones effective against?
gram negative
- broad spectrum
Rifampicin is used to treat what?
TB
How does rifampicin act?
inhibits bacterial but not human RNA polymerases
What is one way in which we can indirectly target nucleic acids biosynthesis?
- by blocking biosynthesis of folic acid (by PABA)
- because we can not synthesis folic, we get it from our food
What are examples of antibiotics that block folic acid biosynthesis?
sulphonamide
trimethoprim
co-trimoxazole ( a mixture of both)
How do antibiotics become resistant?
- decreased accumulation of the drug
- reduced permeability of the drug
- enzymatic inactivation of the drug (B-lactamase)
- (mother to daughter or sideways to other species)
Fungal diseases are know as mycoses. What are examples of superficial or systemic mycoses?
superficial - scalp - skin - oral cavity - vagina Systemic - affects internal organs (kidney, lungs, brain)
Fungal cells are what type of cell?
eukaryotes
- opportunistic pathogens
What puts patients at higher risk of developing fungal infections?
- impaired immune system HIV/AIDs organ transplant if on long-term broad spectrum antibiotics premature birth cancer hospitalisation in ICU - menstrual cycle in women (vaginitis/thrush caused by C. albicans)
What are the differences between fungal and human cells?
- plasma membrane (Contain ergosterol in fungi)
- cell wall (no cell wall in human cells)
- Nucleus (DNA/RNA synthesis)
How do echinocandins such as caspofungin and micafungi work?
- inhibit B1,3 glucan synthesis
- these drugs are fungicidal
Antifungals that act on ergosterol do to things what are these?
- kill existing cells by binding to ergosterol in their plasma membranes
- inhibit new cells by inhibiting ergosterol biosynthesis (Fungistatic)
What do polyene antifungals do?
- bind to ergosterol and form pores in plasma membrane
- causing leakage of cell constitutes
What is the complication of prolonged use of polyene antifungals?
associated with severe side effects such as kidney failure
*because of the similarity between ergosterol and cholesterol
What are the main examples of polyene antifungals?
- amphotericin B
- nystatin
Nystatin is a polyene antifungal what is it used to treat?
- creams and lotion
- treat oral or GI fungal infections
What is the polyene antifungal amphotericin B used to treat ?
only severe fungal infections due to its serious side effects such as kidney failure
How do azoles act?
- inhibit the enzymes lanosterol demethylase
- so block ergosterol biosynthesis and stops growth (fungistatic)
There are two types of azoles what are they?
- imidazoles (miconazole, clotrimazole and ketoconazole)
- triazoles ( fluconazole, voriconazole and itraconazole)
What is the difference between imidazoles and triazoles?
- imidazoles have two nitrate rings
- triazoles have 3 nitrate rings - more potent
How do flucytosines work?
- inhibit fungal DNA and RNA synthesis
What are examples of allyamines?
- terbinafine (Lamisil)
- amorolfine (curanail, loceryl, locetar)
What are allyamines used to treat?
- nail infections
What are normally combined with flucytosines?
azoles
What are flucytosines associated with ?
- high levels of resistance
How are resistance to antifungal drugs caused?
- decreased accumulation of the drug (reduce permeability to drug)
- inactivation of the drug
- mutations in the drug targeting encoding genes
- biofilm formation
What are the high incidences of intrinsically resistance of antifungals?
azoles to candida species
