Antimicrobials - Antibiotics, antivirals, antifungals Flashcards
What are antibiotics?
Naturally produced antimicrobial agents
What percentage of antibiotics are clinically useful?
Less than 1%
but these can be synthetically altered to increase efficacy
What kind of drugs do Beta-lactam antibiotics comprise?
Penicillins
Cephalosporins
Cephamycins
Penicillins and Cephalosporins comprise what percentage of antibiotic production?
Over 50%
What fungus produces penicillin
Penicillin chrysogenum
What is the beta-lactam method of action?
Potent inhibitors of cell wall synthesis
The transpeptidation (cross-linking) action is essential to cell wall synthesis
Transpeptidases can also bind to the beta-lactam ring (penicillin-binding proteins/PBPs)
The cell wall is still formed but with no cross links
It therefore becomes weak
Osmosis differences result in cell lysis
Describe Cephalosporins structure
6 membered dihydrothiazine ring (penicillin has 5)
Semi-synthetic
Cephalosporin method of action?
Same as penicillin
Advantage of cephalosporins over penicillins?
More resistant to beta-lactamase enzymes
Example of a Cephalosporin antibiotic?
Ceftriaxone used to treat Neisseria infections
Describe the structure of aminoglycosides
Contain amino sugars bound via glycosidic bonding to each other
Give 4 examples of aminoglycosides
Streptomycin, kanamycin, neomycin, gentamicin
How do aminoglycosides work?
Inhibit protein synthesis at the 30S subunit of the ribosome
Aminoglycosides are active against what type of bacteria?
Gram negatives
What is the frequency of use of aminoglycosides like now?
declined and superseded by semi-synthetic penicillins e.g. ampicillin, oxacillin, methacillin
First broad spectrum antibiotic class?
Tetracyclines
Basic structure of tetracyclines?
naphthecene ring system
How do tetracyclines work?
Interferes with 30S ribosome subunit function
Wide use of tetracyclines in what area of medicine?
Veterinary
What are growth factors?
Growth factors are specific substances required by microbes because they cannot synthesise them
What are growth factor analogues?
Blocker of the utilisation of growth factors
synthetic compounds
structurally similar to growth factor but cannot duplicate their function within the cell
Give an example of a sulfa drug
Sulfanilamide
What is sulfanilamide
a growth factor analogue that is an analogue of p-aminobenzoic acid (PABA); a component of folic acid
What process does sulfanilamide block?
The production of folic acid
Where do bacteria get their folic acid from? What about eukaryotes?
Bacteria produce their own
Eukaryotes get it from their diet
Name a growth factor analogue that is effective only against mycobacterium
Isoniazid
interferes with synthesis of mycolic acid
How have nucleic acid base analogues been formed?
With the addition of bromine or flourine to an existing growth factor analogue
What are quinolones? What do they do?
antibacterial compounds that interfere with DNA gyrase
Give an example of a quinolone
ciprofloxacin
What do antiviral drugs target?
Host structures, so generally are quite toxic
Name the group of most successful and commonly used antivirals
nucleoside analogues
Give an example of a nucleoside analogue antiviral drug
AZT
How do nucleoside analogue antiviral drugs work?
Block reverse transcriptase and hence production of viral DNA
Another name for nucleoside analogues?
Nucleoside reverse transcriptase inhibitors
How do nonnucleoside transcriptaste inhibitors (NNRTIs) work?
Bind directly to reverse transcriptase and inhibit reverse transcription
Name 3 classes of antiviral drug (excluding nucleoside analogues)
- Protease inhibitors
- Fusion inhibitors
- Interferons
Name 2 categories of drug that limit influenza infection successfully
Adamantanes
Neuraminidase inhibitors
How do protease inhibitor antivirals work?
inhibit the processing of large viral proteins into individual components
How do fusion inhibitors work?
prevent viruses from successfully fusing with the host cell
What are interferons and how do they work?
They are small proteins that prevent viral multiplication by stimulating antiviral proteins in uninfected cells
Why do fungi pose special problems for chemotherapy?
Because they are eukaryotic
as a result, many antifungals are topical
Name 7 things antifungal drugs can possibly target
- Membrane function
- cell wall synthesis
- ergosterol synthesis
- nucleic acid synthesis
- microtuble formation
- folate synthesis
- chitin synthesis
How do antifungal drugs target membrane function?
Polyenes can bind to ergosterol and disrupt membrane integrity
How do antifungal drugs target cell wall synthesis?
Polyoxins inhibit chitin synthesis
Echinocandins inhibit glucan synthesis
Echinocandins do this by inhibiting 1,3-beta-delta glucan synthase
What antifungal drugs target ergosterol synthesis?
Azoles and allylamines inhibit it
How do antifungal drugs target nucleic acid synthesis?
5-flourocytosine is a nucelotide analogue that inhibits nucleic acid synthesis
How do antifungal drugs target microtuble formation?
Griseofulvin disrupts microtuble aggregation during mitosis
Name a treatment for a Candida (fungal) infection
Echinocandins
Name the most successful example of computer-aided drug design for antimicrobials
Saquinavir
Binds to active site of HIV protease
What led to the discovery of platensimycin?
New methods of screening natural compounds
computer aided drug design etc.
