Antibiotics Flashcards
List the antibacterial agents.
- Cell wall inhibitors
- Protein synthesis inhibitors
- DNA synthesis inhibitors
- Anti-mycobacterial agents
- Bactericidal
- Bacteriostatic
What is antibiotic resistance?
- When bacteria develop the ability to protect themselves from drug designed to kill them.
- Methods:
1. Enzymatic degradation
2. Mutations in drug target
3. Reduced permeability
4. Xenobiotic pumps
What are cell wall inhibitors?
- Only affect bacteria and not mycoplasmas, chlamydiae or the host.
- 2 classes: b-lactams ( B lactam ring) and Glycopeptides.
What are the types of B lactams?
- Penicillins
- Cephalosporins
- Carbapenems
- Monobactams
What are the four types of penicillins?
– Standard penicillin
– Anti-staphylococcal
– Aminopenicillins
– Anti-pseudomonal penicillins
Describe the mechanism of action of cell wall inhibitors.
- B-lactams inhibit transpeptidase therefore preventing cell wall cross linking, leads to increased secretion of lipotheichoic acid which inhibits autolysin (uninhibitied autolysin leads to lysis of bacteria)
Describe the resistance of cell wall inhibitors.
- Targets produce B lactamase which hydrolyses b-lactam ring.
- Cephalosporin is resistant to B lactamase.
- Cephalosporinase is specific for cephalosporins.
What are B lactamase inhibitors?
- B lactams without any anti-microbial activity.
- Covalently bind to B lactamase but don’t inhibit cephalosporins.
- E.g Tazobactam, clavulanate.
What is combination therapy?
- B lactamase inhibitors are used in combination with b lactam antibiotics. E.g. Tazocin- piperacillin tazobactam or amoxicillin-clavulanate.
What is methicillin resistance?
- Methicillin is the principle agent for anti-staphylococcal penicillin.
- Due to gene mecA: codes for a variant penicillin binding protein (PBP 2a) with low affinity for b-lactams.
- PBP 2a takes over cell wall synthesis in the presence of methicillin.
What is vancomycin?
- Glycopolypeptide effective in MRSA.
- Only effective against Gram+ive infection.
Discuss glycopeptide resistance.
- Primarily in Enterococci (VRE).
- Cells contain VanR and VanS which detect vancomycin.
- Resistance is also due to thickening of cell wall
List the five classes of inhibitors of protein synthesis.
Bacteriostatic:
– Aminoglycosides
– Macrolides
– Tetracyclines
– Amphenicols
– Oxazolidinones
Describe the mechanism of action of protein synthesis inhibitors.
- Target prokaryotic ribosomes due to difference in size from eukaryotic ribosomes (subunits are 30s and 50s)
- All inhibit ribosome complex formation.
Describe the resistance of protein synthesis inhibitors.
- Decreased permeability: affects amino-glycosides
- Xenobiotic pump: amino-glycosides and macrocolides
- Enzymatic degradation: aminoglycosides, specific for individual antibiotic
- Target mutations: macrolides, lincosamides, streptogramin, and linezolid (rRNA mutations)
Describe the lipopetides: Daptomycin?
- A cyclic lipopeptide.
- Binds to bacterial membranes causing depolarisation resulting in an inability to synthesise proteins.
- Resistance= VRE?
*Televancin acts like vancomycin and daptomycin
List inhibitors of DNA/ nucleic acid synthesis.
- Quinolones (nalidixic acid) & fluoroquinolones (ciprofloxacin)
- Metronidazole is used for anaerobes
- Neither are used in children or during pregnancy
- Bactericidal at higher concentrations
Describe the mechanism of action of nucleic acid inhibitors.
- FQ’s inhibit DNA gyrase:
– DNA gyrase is required for DNA supercoiling - Also inhibits DNA type IV topoisomerase
- FQ’s have good oral bioavailability
- Well tolerated antibiotic but potential to cause tendonopathy and tendon rupture:
– Black box warning
Describe the resistance of nucleic acid inhibitors.
- Gram +ive resistance to first and second gen quinolones
Describe the mechanism of action of anti-mycobacterial agents.
- Rifamycins, inhibit DNA dependent RNA polymerase, used in tx of TB
- Not used as mono-therapy
- Rifampin: Can cause hepatotoxicity, fever, orange urine
List anti-mycobacterial agents.
- Rifamycins: Rifampin, rifabutin and rifapentine
