Antibacterial drugs Flashcards
Narrow spectrum vs broad spectrum antibiotics
Narrow: An antimicrobial effective against a limited number of bacterial genera
Broad: An antimicrobial effective against a large number of bacterial genera
What are the ideal anti-bacterial properties
- Selectivity
- Bactericidal
- Slow emergence of resistance
- Narrow spectrum of activity (broad spectrum = resistance concerns)
What are the targets/processes within bacteria that antibiotics work against?
- Cell wall synthesis: peptidoglycan cell wall is the target: unique to bacteria
- Enzymes involved with metabolism
- Protein synthesis (inhibition of transcription and translation)
- Nucleic acid synthesis, DNA and mRNA
2 classifications of antibiotics? Give examples of each
- Beta-lactams: penicillin, amoxycillin. Cephalosporins (cefradine)
- Glycopeptides: vancomycin - only active against GRAM POSITIVE organisms due to its size, it cannot cross the cell membrane of G-neg cells
Mechanism of beta-lactams and glycopeptides
Beta lactams: Inhibit enzyme penicillin-binding-proteins which are required for transpeptidation (linkage). Causing the bacterial cell wall to be improperly made, allowing water into the cell causing it to burst (cytolyisis)
Glycopeptides: Bind to cell wall subunit and blocks new linkages (vancomycin)
Mechanism of fosfomycin & spectrum
PEP analogue
Inhibits enzyme MurA that is required for synthesis of NAM (N-acetyl muramic acid), an essential component of bacterial cell wall
BROAD SPECTRUM
Mechanism of quinolones
Inhibit DNA replication
- Gyrases, topoisomerases
- Ciprofloxacin
Mechanism of rifamycins
Blocks mRNA synthesis
Mechanism of metabolite analogues & give examples
Inhibit synthesis of nucleic acid precursors (ATCG) in bacteria
- Sulfonamides: bacteriostatic. Inhibit synthesis of purines and pyrimidines, competitive inhibitor with PABA for enzyme
E.g SULFAMETHOXAZOLE - Trimethoprim: structural analog of folic acid
Inhibits enzyme involved in processing dihydrofolic acid to the final building blocks of purines and pyrimidines
Action of polymyxins
- Act like a detergent on the membrane, to affect cytoplasmic membrane function
- Mainly TOPICAL usage (systemic administration leads to neurotoxicity and nephrotoxicity)
What is the minimum inhibitory concentration?
Minimum concentration of the antibacterial agent (in a given culture medium) below which bacterial growth is not inhibited
- used to classify resistance
3 mechanisms for how a bacterium becomes resistant to an antibiotic
- Modifying the antibiotic target
- If the target is changed sufficiently, the antibiotic may not work - Limiting the access of the antibiotic to the target
- Easier way - Enzymatic inactivation of antibiotic:
- If the antibiotic makes it in, there may be an enzyme which cleaves it before it reaches its target
How does resistance to beta-lactams occur?
- The bacteria acquire the enzyme beta lactamase, this will cleave the beta-lactam antibiotic and will render the bacterium resistant
- Alter the PBP so that the beta-lactam cannot interact with it
How is resistance to an antibiotic acquired?
- Horizontal gene transfer: acquisition of genes that mediate resistance, such as the gene that encodes beta-lactamase. These genes can be found on plasmids that can be passed on to other species of bacteria by conjugation
- Mutations: mutations in native genes or regulatory elements such as a promotor which enhances transcription of the DNA, is changed via mutations to enhance the transcription of more efflux pumps
How can antibiotic resistance be helped?
- Education on antibiotic use
- Extending life of existing antibiotics: such as inhibiting the resistance enzyme (beta-lactamase) with a drug
- Good practices in clinic established to reduce spread: prevent overuse, misuse and abuse. - Optimise therapy for individual patients
- Reduce infection risk from catheters, instruments and cannulae etc
- Reduce reservoirs of infection
- High standards of hygiene in clinical practice - Facilitated by surveillance e.g global AMR surveillance system (GLASS)
