Case 8- antibiotics Flashcards
Antibiotic
A medicine which inhibits the growth of or destroys bacteria
Bacteriostatic
An antibiotic which inhibits multiplication. By stopping the bacteria from growing you contain it till your immune system eventually destroys it
Bactericidal
A types of antibiotic which kills the bacteria, this is normally when the bacteria are reproducing
Antibiotic susceptibility testing
You grow a bacteria on a plate and add the antibiotic to see which kills the bacteria, This determines what antibiotic you should use for a specific pathogen
What do you look for in an antibiotic
- Selective toxicity- kills bacteria but not host
- A high LD50 vs a low MIC and/or MBC
- Favourable pharmacokinetics- reaches target site in body with effective concentration.
- Spectrum of activity- some are broad and kill a wide range of bacteria, whilst others are more narrow and only kill a few. Best to start on broad antibiotics and once you have identified the problem you go on to more narrow ones.
- Lack of side effects- it may not be tolerated if there are too many.
- Little resistance to development- The antibiotic needs to be stable
LD50
Stands for lethal dose 50, the concentration of a substance which would kill 50% of the population
MIC and MBC
MIC is the minimum inhibitory concentration and the MBC is the minimum bactericidal concentration. MIC is about inhibition, MBC is about killing. If you have a low MIC/MBC it means that you only need a low concentration of the antibiotic to stop bacterial growth, avoiding unwanted side effects
What do you need to decide before administering antibiotics?
- Is an antimicrobial agent necessary?
- Dosage and duration of dosage- You want to achieve 4 times the minimum inhibitory concentration (mic) at the site of action.
- Dose interval- don’t want to have to take it that many times a day.
- Route of administration- oral is the most usual and convenient. Parenteral can be used in hospital.
What can antibiotics target in bacteria
They inhibit cell wall synthesis, they can alter cell membranes, inhibit protein synthesis, inhibit nucleic acid synthesis and interfere with metabolic pathways.
Antibiotics- beta lactams
Penicillin, Cephalosporins and Methicillin. They inhibit cell wall synthesis by acting on the peptidoglycan in the cell wall. Later generation Beta-lactams have improved effectiveness against gram negative bacteria.
Antibiotics- inhibitors of cell wall synthesis
Include beta lactams and Vancomycin which is a glycopepetide antibiotic which is a last resort for MRSA. Inhibitors of cell wall synthesis work better against gram positive bacteria. They are bacteriocidal meaning they are effective against actively growing bacteria
Mechanism of action for antibiotics that inhibit cell wall synthesis
The peptidoglycan wall is made of a Polysaccaharide backbone with peptide crosslinks. The peptide crosslinks join with neighbouring peptide molecules and other polysaccharide molecules, this gives them mechanical strength. The peptide cross-links are formed by transpeptidases (Penicillin binding proteins). B-lactams bind to these proteins and inhibit their action. Peptide cross links are not formed, so the cell wall loses its mechanical strength. The membrane can bulge underneath the cell wall to form an emerging Spheroplast. Over time the bacteria loses its shape till it becomes spherical and is a spheroplast. It becomes vulnerable to osmotic change and undergoes cell lysis and bursts.
Beta-lactams in clinical usage
They can be broad spectrum penicillin’s i.e amoxicillin which are also effective against gram-negative bacteria. Another type is extended spectrum penicillin’s i.e. piperacillin which is also active against pseudomonads. You have reversed-spectrum penicillin’s which have a greater activity against gram negatives than gram positives
Antibiotics that inhibit protein synthesis- Chloramphenicol
Binds to the 50S portion of the ribosome and inhibits formation of a peptide bond. Causes the cell to stop growing and producing the proteins it needs
Antibiotics that inhibit protein synthesis- Erythromycin
Binds to the 50s portion of the ribosome and prevents translocation movement of the ribosome along the mRNA, this stops translation and protein formation
Antibiotics that inhibit protein synthesis- Tetracyclines
Interferes with the attachment of the tRNA to the mRNA-ribosome complex
Antibiotics that inhibit protein synthesis- Streptomycin
Changes shape of the 30s portion of the ribosome and causes the code on mRNA to be read incorrectly , a nonsense protein is formed
What types of antibiotics inhibit nucleic acid replication
Fluroquinolones
Ciprofloxacin
An antibiotic which inhibits nucleic acid replication acts by inhibiting the enzyme DNA gyrase, so the genome can not unwind. This prevents negative supercoiling of DNA which is important for normal replication or transcription. It is active against a broad range of bacteria. Resistance is beginning to emerge.
Metronidazole
A type of antibiotic that inhibits nuecleic acid formation. Prevents DNA synthesis. It is active against obligate anaerobic bacteria, oxygen is toxic to these bacteria. Metronidazole damages the electron transport proteins. It is also works against protozoa so is an antiprotozoal drug. It interacts with alcohol to give disulphiram-like reactions.
Selective toxicity
When you kill or damage the pathogen without affecting the host. You will target a substance which is present on the bacteria (70S ribosomes) and not on the host. So human cells are not damages