Antibiotics Flashcards
Explain how we generally make antibiotics
As natural products from fungi or bacteria (usually soil dwellers) think of penicillin
- So we make them from natural products by fermentation and then modify them chemically
- Some totally are synthetic such as sulphonamides
Where, in society, is most of the antibiotic use?
80% is in the community
- but in hospitals many people are on them including around 50% of all patients in the ICU
In the community, what are the 2 main reasons for GPs prescribing antibiotics?
- Respiratory tract infections (50%)
- UTIs (15%)
Why do we have to modify these natural antibiotics in a lab usually?
- remove toxicological effects
- metabolism
- modify effects …
- generally making them into better pharmacological agents
What is a therapeutic margin?
The difference between an active dose (MIC) and the toxic effect of the drug
- so if the margin is small, it is v important to get the dose right
Name an antibiotic with a wide therapeutic margin
Penicillin
What is dysbiosis?
- The overgrowth of certain organisms
- When we give antibiotics we can cause disregulation of microbial antagonsim
- This normal microbiotia may prevent outgrowth of pathogens
Name a common cause of pseudomembranous collitis
Antibiotics causing loss of normal flora causing outbreak of clostridum difficile
What is pseudomembranous collitis?
Damaged, ulcerated, inflamed colon often caused by toxins from bacteria
- causes watery diarrhoea
Explain what bacterial clearance is
Immunity works together with the antibiotics
Name 3 ways that we can classify antibiotics
- Type of activity
- Structure
- Target site of activity
What is the difference between bacteriocidal and bacteriostatic antibiotics?
Why would we use bacteriostatic antibiotics?
As even though you are not killing it - the immune defence mechanisms clear the infections
When can we not use bacteriostatic antibiotics?
When the host immune systems are not intact
Some antibiotcs may be {?} at low dosages and {?} at high dosages
Some antibiotcs may be bacteriostatic at low dosages and bacteriocidic at high dosages
What is meant by broad spectrum vs narrow spectrum antibiotics?
How many types of bacteria the antibiotic is affective against
Is Penicillin G broad or narrow spectrum of activity?
Narrow spectrum antibiotics
Effective against very few types
Name the 2 basic penicillins
- Benzylpeniclillin (PenG)
- Penicillin V
What bacteria are basic penicillins effective against?
Active against streptococci, pneumococci, meningococci, treopnemes
Most strains of Staphylococcus aureus are resistant
What bacteria can basic penicillins NOT treat?
Staphyloccocal bacteria
Name an antistaphylococcal penicillin
Flucloxacillin
Describe the pros and cons of PenG vs PenV
Pen G
benzlypenicillin (G= gold standard);
not acid stable therefore I/v or i/m good for some G negatives as well as G positves
penV
phenoxymethlypenicillin
oral (more acid stable than penG)
less active v G negatives, but same activity y G postives as PenG
Why might we use amoxicillin or ampicillin over the basic penicillins?
Have a broader spectrum of activity as they can treat some gram negative organisms and enterococci
What might we prescribe for pseudomonal bacteria such as in cystic fibrosis?
Piperacillin
Explain what co-amoxiclav/Augmentin is
You are giving an inhibitor of a bacterial drug that would normally break down the drug + a wide spectrum drug such as amoxicillin
Why do we call penicillins and cephalosporins beta lactams?
They both have the crucial beta lactam ring
What is beta lactamase?
A bacterial enzyme that breaks down beta lactams
“Beta-lactamases, are enzymes produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins”
How do beta lactam antibiotics (Penicillins and Cephalosporins) work?
Inhibit cell wall synthesis
How do the protein synthesis inhibitor antibiotcs work?
Bind to 50s or 30s ribososmes that are only on prokaryotic cells to block protein sythesis
Name 2 common proteins synthesis inhibitor antibiotcs
- Erythromyosin
- Chloramphenicol
- Streptomycin
- Gentamicin
- Doxycyline
How do Quinolone antibiotics work?
Inhibit DNA gyrase (which is specific to bacteria as we use topoisomerase 4)
How do trimethoprim and sulfonamides work?
Inhibit folic acid synthesis (thetrahydrofolic acid)
- bacteria can synthesise folic acid but humans do not have these enzymes it so that is why it is not toxic to us
Describe the gram + vs gram - bacterial cell wall
How do cell wall synthesis inhibitors work?
Inhibit peptidoglycan-making enzymes
Gram {?} cell walls are more vulnerable to cell wall inhibitors as gram {?} bacteria have a impermeable membrane - drugs have to move across this membrane
Gram positive cell walls are more vulnerable to cell wall inhibitors as gram negative bacteria have a impermeable membrane - drugs have to move across this membrane
Are E coli and staphylococcus aureus gram + or gram -
E coli = negative
Staph Aureus = positive
What are trans-peptidases and carboxypeptidsases?
These are the enzymes that cross-link peptidoglycan and they are the enzymes that beta lactams bind to to inhibit
Why might some beta lactams be able to work on gram negative bacteria?
If the beta lactam is modified to move through the outer membrane of the cell wall
What is peptidoglycan?
Peptidoglycan or murein is a polymer consisting of sugars and amino acids that forms a mesh-like peptidoglycan layer outside the plasma membrane of most bacteria, forming the cell wall
Fully explain how the folic acid synthesis inhibitors work
How does Dapsone work?
Leprosy drug, inhibits the first enzyme in the folic acd pathway - only in bacteria
Why might we prescribe prophylactic antibiotics?
Explain what MIC is
Minimum inhibitory concentration = the minimum concentration of the antibiotic needed to clear the infection
Name some reasons as to why MIC may vary
- This will depend upon the age, weight, renal and liver function of the patient and the severity of infection
- Depend on the susceptibility of the organism
- Will also depend upon properties of the antibiotic i.e. enough to give a concentration higher than the MIC (minimum inhibitory concentration) at the site of infection
What is the difference between time-dependance and concentration-dependance antibiotics?
Some antibiotics just need a maximum dose to be achieved, others need a maintained level above the MIC (?)
