Structure and Mode Of Action Of Antibiotics and Antifungals Flashcards
Example of Lincosamide and uses
Clindamycin - staphs and Streps commonly
Bacteroides fragilis and other anaerobes.
Used in toxic shock to block M protein which blocks SIRS.
Toxoplasmosis/ parasitic Protozoa and malaria
Action of lincosamides bacteriostatic or bacteriocidal?
Bacteriostatic
Major targets for antibacterial agents
- Inhibits cell wall synthesis (DNA)
- Interferes with DNA synthesis snd replication (nucleic acids and DNA replication)
- Inhibits protein synthesis (mRNA and ribosomes)
- Disrupts cell membrane (proteins)
Cell wall synthesis inhibitors
Beta lactams (penicillins, cephalosporins and carbapenems)
Glycopeptides e.g. Vancomycin and teicoplanin
Monobactams e.g. Aztreonam
Bacitracin
Fosfomycin
Isoniazid e.g. Mycolic acid/TB
Mode of action of ‘Lincosamides’ e.g. Clindamycin,
- interfere with the synthesis of proteins
- bind to 23s portion of 50s subunit of bacterial ribosomes and cause dissociation of RNA from the ribosome
What is a beta lactam?
Broad spectrum abx containing a beta-lactam ring.
Three examples of a beta-lactam abx
Penicillins
Cephalosporins
Carbapenems
Examples of macrolide and its uses
- Some gram positive I.e. S.pneumonia and limited gram negative i.e B. Pertussis, H. inf, some resp tract and soft tissue infections
- Effective against L. Pneumophila, mycoplasma, mycobacterium, some rickettsia and chlamydia.
- substitute for penicillin allergic
- Clarithromycin, Azithromycin and Erythromycin.
Action of macrolides (clary, ery and Azithromycin) bacteriostatic or bacteriocidal?
Bacteriostatic
Mode of action of macrolides (ery, Azithromycin, clary)?
Macrolide ring inhibits protein synthesis. - blocks peptidyl transferase from adding to growing peptide attached to tRNA to the next AA. - > inhibits ribosomal translation
Macrolides actively concentrate within leukocytes - transported to site of infection.
Example and uses of Aminoglycoside
- Active against most gram negative aerobic and facultative anaerobic bacilli.
- generally not active against MRSA, gram negative anaerobes and gram positive bacteria.
- Gentamicin, Kanamycin, Amikacin, Tobramycin.
- gentamicin can be used against GN orgs + staphs. Used for RTI, UTI, blood, bone and soft tissue infections.
Action of Aminoglycoside bacteriocidal or bacteriostatic?
Bacteriocidal
Mode of action of Aminoglycosides
Inhibit protein synthesis
‘Cell membrane effect’ - integrity of cell membrane can be lost due to Aminoglycoside exposure and transport.
What class of abx does Vancomycin belong to?
Glycopeptide
Uses of Vancomycin.
- 1st line IV for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections and MRSA meningitis.
- PO for severe C. difficile colitis
Mode of action of Vancomycin
Inhibits proper cell wall synthesis in gram positive bacteria.
Vancomycin binds to D-ALA-D-ALA of NAM NAG peptides of cell wall -> prevents cell wall synthesis of polymers of NAM & NAG -> prevents backbone polymers from cross linking with each other.
How does resistance develop to vancomycin?
Last D-ALA reissued replaced with D- lactate (loss of H binding interaction) -> vancomycin cannot bind and cell wall synthesised as normal.
Beta-lactams (penicillins, carbapenems and cephalosporins) bacteriocidal or bacteriostatic?
Rapidly bacteriocidal
Protein synthesis inhibitors
Macrolides (ery, clary and Azithromycin)
Aminoglycosides (Gent, Tobra, Amik, Kanamycin)
Tetracyclines (doxy and tetracycline)
Chloramphenicol, Rifampicin, Mupirocin, Linezolid.
Disrupters of cell membrane
Polymixins e.g colistin
Lipopeptides e.g. Daptomycin
Interfere with DNA synthesis and replication.
Sulphonamides e.g. Sulphamethoxazole
Diaminopyrimidines e.g. Trimethoprim
Quinolones e.g. Ciprofloxacin
Nitroimidazoles e.g. Metronidazole
Bacteriostatic definition.
Prevents growth and division, don’t kill
Bacteriocidal definition.
Kill bacteria
What is a monobactam, it’s uses and an example.
Abx closely related to beta-lactams but with a slightly different ring structure.
Useful in beta-lactam allergic patients.
E.g Aztreonam
Beta lactam structure of Penicillins
Beta lactam ring (4 C and 1 N) and Thiazolidine ring (4 C and 1 S)
1 modifiable residue
Beta lactam structure of Cephalosporins
Beta lactam ring (4 C and 1 N) and Dihydrothiazine ring (4 C, 1S and 1N)
2 modifiable residues
Beta lactam structure of Carbapenems
Beta lactam ring (4C and 1N) and carbapenem core (4C and 1N)
Three modifiable residues
What can be done with chemical residues on beta lactam structures?
Changed/ substituted in order to make large numbers of different abx in each sub-group.
Allows the pharmaceuticals to be changed or antibacterial spectrum to be changed.
