Antibiotics Flashcards
How widespread is the use of antibiotics?
They are the most widely used and most misused drugs (20-50% questionable use).
In hospitals - 30% of drug budget goes to antibiotics.
~25% of patients have received antibiotics within the previous 24h.
In ITU, 50% of patients are on antibiotics.
50 million prescriptions for antibiotics are written per year.
80% of human use is in the community, rather than the hospital:
- 50% - respiratory infections
- 15% - urinary tract infections
Describe antibiotics.
They are the natural products of fungi and bacteria (soil dwellers).
There is natural antagonism and selective advantages between microorganisms, as they competitively produce substances that kill or inhibit the growth of other microorganisms for survival.
Most antibiotics are derived from natural products by fermentation, then modified chemically. This is done to increase their pharmacological properties and antimicrobial effect.
Some antibiotics, however, are totally synthetic (e.g. sulphonamides)
List some principles of selective toxicity of antibiotics as therapeutic agents.
It is based on the differences in structure and metabolic pathways between host and pathogen.
It harms the microorganisms, not the host.
We want the target to be in the microbe, not the host (if possible).
Selective toxicity is difficult for viruses (intracellular), fungi and parasites because they’re intracellular organisms.
We need to understand that there is variation between microbes, strains within the same species.
Describe the therapeutic margin.
We need to make sure that the dose is high enough to kill off the infection you’re trying to treat without producing too much toxicity.
The dose between the therapeutic/active dose and the toxic dose is called the therapeutic margin.
What is the MIC?
The MIC (minimum inhibitory concentration) is the concentration at which you have to give a drug in order or it to be effective microbiologically.
What is microbial antagonism?
Microbial antagonism is the concept of one microorganism producing a substance that inhibits the growth of another.
This maintains flora, as they have complex interactions between themselves that maintain them at a certain level.
They limit the growth of competitors and flora.
Describe what can happen due to loss of flora as a result of antibiotic use.
Sometimes, antibiotics can come about and mess up the balance of bacteria in your gut. They can also affect your skin flora, and flora in other parts of your body.
Sometimes, it can lead to disease.
If you take too much clindamycin, broad-spectrum lactams or fluoroquinolones for example, you can cause a condition called Pseudomembranous Colitis. It is caused by the overgrowth of a bacteria called Clostridium difficile (which is normally 3% of the normal flora).
It is very easily transmittable, as it creates spores that live everywhere (e.g. diarrhoea), and can spread through aerosolization.
Explain how antibiotics interact with the immune system.
Antibiotics don’t work alone.
The antibiotics in an immune competent patient rely partly on the immune system to clear the infection.
What are the three classifications of antibiotics?
They are classified by:
- type of activity
- structure
- target site for activity
Compare bactericidal antibiotics vs. bacteriostatic.
BACTERICIDAL:
- kill bacteria
- used when the host defense mechanisms are impaired
- required in endocarditis, kidney infection
BACTERIOSTATIC:
- inhibit bacteria
- used when the host defense mechanisms are intact
- used in many infectious diseases
- example: tetracyclin
How can antibiotics be categorised according to spectrum of activity?
Broad Spectrum Antibiotics:
- effective against many types
- example: Cefotaxime
Narrow Spectrum Antibiotics:
- effective against very few types
- example: Penicillin G
Describe cephalosporins.
Cephalosporins are essentially ‘modified penicillin’.
This illustrates the idea that, as we modify the antibiotics, they change up their efficacy against different microorganisms. It is a balance.
We now use different generation cephalosporins to treat different microorganisms, based on their efficacy.
Describe the implications of the β-lactam ring.
Both penicillins and cephalosporins have retained this β-lactam ring in their molecular structure.
It is the active component of the chemical compound.
This is important when talking about resistance because some organisms have acquired enzymes called β-lactamases that degrade that β-lactam structure.
Once it has been destroyed, the antibiotics have no antimicrobial properties whatsoever.
There are many bacterial targets for selective toxicity.
List some of them.
- infolding of the plasma membrane
- capsule
- cell wall
- DNA coiled into nucleoid
- basal body
- ribosomes
- cytoplasm
- plasma membrane
- pili
- cytoplasmic inclusion
Describe the different kinds of antibiotics based on their cellular targets.
CELL WALL SYNTHESIS: These bacteria inhibit bacterial cell wall synthesis. If it cant make it’s cell wall, it will die and be cleared.
PROTEIN SYNTHESIS INHIBITORS: The drugs bind to the ribosome in different places, and are thus categorised differently. Both eukaryotes and prokaryotes have ribosome, but they are different in structure. This means that antibiotics can inhibit bacterial ribosomes within necessarily inhibiting eukaryotic ribosomes, so the drugs are essentially quite safe.
DNA AND RNA PROCESSING: These are key antibiotics that inhibit either the way that the bacteria replicates its DNA, or makes its mRNA.
DNA Gyrase is a type of isomerase; they are the coiling and uncoiling enzymes when the genome is trying to replicate itself. DNA Gyrase is unique to bacteria.
Rifampin is the key drug in treating TB. Rifampin targets the enzyme that makes mRNA (DNA-dependant RNA Polymerase).
FOLIC ACID METABOLISM: These inhibit folic acid metabolism.
Humans cannot synthesise folic acid; we can only get it form our diet.
Using both of the drugs gives us a synergetic, broad range, which is bactericidal.
These 4 are the key modes of action.
Others include:
CELL MEMBRANE: Bacterial membrane is very similar to eukaryotic membranes so the drugs targeting the cell wall are very toxic.
GENERATE FREE RADICALS: Free radicals will damage many components of the cell, mainly DNA, but they can also damage membranes, lipids, enzymes involved in metabolism, etc.
