Antibacterial Agents Flashcards
How do polymyxins work?
They bind to Lipid A on LPS and disrupt the membrane causing leakage of cytoplasmic contents.
Only work in gram negative bacteria (as LPS only in gram neg)
How do B-lactams work?
- Bind to PBPs (transpeptidases) and prevent X-linking
- Mimic d-ala-d-ala residues on peptide side chain
- Stimulate autolysins -> break down cell wall
How do Glycopeptides work?
e.g Vancomycin, Teicoplanin
- Binds terminal d-ala-d-ala on peptide side chain. Prevents transglycosylase enzyme from adding PG monomer onto the glycan chain
- Prevents X-linking (by steric hinderance)
Not effective against gram-negative bacteria as they are too large to fit through the pores in the outer membrane
How does cycloserine work?
Inhibits cell wall synthesis
How does Bacitracin work?
Inhibits cell wall synthesis
What is polyfax?
Polymyxin B & Bacitracin
Used topically for skin & eye gram negative infections & prevention of wound infection
How do lipopeptides work?
e.g Daptomycin
They cause rapid depolarisation of the membrane which inhibits ATP synthesis (leading to loss of function)
Only active against gram positive
They are used for skin & soft tissue infections and also endocarditis
How do sulphonamides work?
They are metabolic inhibitors of nucleic acid synthesis
They inhibit Dihydropterate synthetase (which converts para aminobenzoic acid to dihydropteroic acid)
How does Trimethoprim work?
It is a metabolic inhibitor of nucleic acid synthesis
It inhibits Dihydrofolate reductase (which converts dihydrofolic acid to tetrahydrofolic acid -> purines and pyrimidines)
What is trimethoprim normally used for?
Gram negative UTIs (Not pseudomonas)
What is the combination product of Trimethoprim and Sulphamethoxazole (Sulphonamide) called?
Co-trimoxazole
Which drug can lead to stevens-johnson syndrome?
Co-trimoxazole (combination of Trimethoprim and Sulphamethoxazole)
How do Fluroquinolones work?
e.g Ciprofloxacin, Levofloxacin, Moxifloxacin etc
They are inhibitors of DNA replication
They inhibit DNA gyrase and type IV topisomerase
Can chelate so should be given on an empty stomach
What is the main problem with using Ciprofloxacin?
It is very broad spectrum and so has a high risk of C. diff!
What can Ciprofloxacin (fluroquinolone) be used for?
It is active against both gram positive and gram negative but PARTICULARLY gram negative
Also active against INTRACELLULAR pathogens
Limited use against streptococci and enterococci
How do Rifamycins work?
e.g. Rifampicin
They are inhibitors of RNA polymerase
Bactericidal
Normally used for treatment of TB, prophylaxis of meningitis, infections involving prosthetic material
What are the main side effects of Rifampicin?
- Hepatotoxicity
- Increased metabolism of other drugs
- Orange-red colour of secretions!
How do nitroimidazoles work?
e.g. Metronidazole
They inhibit nucleic acid synthesis by disrupting the DNA
Can be used to treat C.diff
How do Aminoglycosides work?
e.g. Gentamicin (Amikacin, Tobramycin, Steptomycin)
They mostly bind to the 30s subunit
Decrease assembly of initiation complex & binding of tRNA to A site
Some bind the 50s subunit
Decrease assembly of initiation complex
What is Gentamicin (an aminoglycoside) normally used for?
Serious infections from AEROBIC bacteria
Active against many G-ves
Active against some G+ves
What are the main side effects of aminoglycosides?
Nephrotoxicity and Ototoxicity
How do Oxazolidinones work?
e.g. Linezolid
Binds the 23S rRNA in 50S subunit
Decreases assembly of the initiation complex
Active against gram positive bacteria
How do Tetracyclines work?
e.g. Doxycycline (Minocycline, Tigecycline)
Binds to the 30S ribosomal subunit
Decreases tRNA binding to A site
What are the main side effects associated with Tetracyclines?
Staining in teeth
Phototoxic reactions
Can lead to superinfections (candida albicans, proteus, pseudomonas)
How do Macrolides/Ketolides work?
e. g. Erythromycin, Clarithromycin, (Azithromycin)
e. g. of ketolide is Telithromycin (more potent macrolide designed to overcome resistance)
Bind to the 50S subunit
Decreases translocation and release of tRNA
How do Lincosamides work?
e.g. Clindamycin
Bind to the 23s portion of the 50s subunit
What are lincosamides normally used for?
IV, IM or Oral treatment of Stapylococcal bone & joint infections, respiratory infections, peritonitis, septicaemia etc
How does Fusidic acid work?
It binds to the EF-G-Ribosome complex
Decreases translocation of tRNA
Narrow spectrum antiobiotic
What is Fusidic acid normally used for?
Staphylococcal skin infections
How does Chloramphenicol work?
It binds to the 50S subunit
Prevents peptide bond formation
Broad spectrum antibiotic
Normally used for the treatment of eye infections
What is the most important side effect of Chloramphenicol?
Aplastic anaemia
Rare but fatal, bone marrow cells die.
Normal haemopoetic cells absent. Space now filled with adipose tissue
Which antibiotics give a long post effect?
- Benzylpenicillin
- Aminoglycosides
