Antibiotics Flashcards
1
Q
What is selective toxicity?
A
- Differences in structure and metabolic pathways between host and pathogens
- Want to harm the microorganisms, not the host
- Can be difficult for viruses as they live intraceullularly and fungi and parasites because they are eukaryotic, so similar to host
2
Q
Why do we have to study the therapeutic margin?
A
- Want to be able to reach the minimum inhibitory concentration of a drug
- But dont want to use too much drug that it is toxic
- Toxic drugs such as aminoglycosides have a very narrow therapeutic margin
3
Q
What is microbial antagonism?
A
- Maintain flora so there is competition between flora
- Limits the growth of competitors and pathogens
- Loss of normal gut flora allows bacterial or pathogen overgrowth
- e.g. Clostridium difficile is normal flora for 3% of pop - overgrowth leads to pseudomembraneous colitis of colon
4
Q
What are the 3 ways we classify antibiotics?
A
- Type of activity
- Structure
- Target site for activity
5
Q
What is the difference between bacteriacidal and bacteriostatic?
A
- Cidal - kill bacteria; used when the host defence mechanisms are impaired; required in endocarditis/kidney infection
- Static - inhibits bacteria; used when the host defence mechanisms are intact; used in many infectious diseases
6
Q
Broad vs narrow spectrum antibiotics
A
- Broad works against a wide range of bacteria - effective against many types (Cefotaxime)
- Narrow - works against a narrow range of bacteria -effective against very few types (Penicillin G)
7
Q
What are the differences between 1st - 3rd generation cephalosporins?
A
- 1st - bad against gram -ve, good against strep pneumoniae and gram +ve
- 2nd - moderate against all 3
- 3rd - good against gram -ve and strep pneumoniae, bad against gram +ve
8
Q
Draw the structure of a beta lactam ring
A
BE ABLE TO IDENTIFY IT
9
Q
What are the different targets for current antibiotics?
A
- Cell wall synthesis (Penicillin, Vancomycin, cycloserine, cephalosporins)
- Folic acid metabolism (sulphonamides, trimethoprim)
- Cell membrane (Polymyxins)
- DNA gyrase (Quinolones)
- DNA-directed RNA polymerase (Rifampin)
- 50S inhibitors (erythromycin, chloramphenicol, clindamycin)
- 30S inhibitors (Tetracyclin, Doxycyclin, Streptomycin, Gentamicin)
10
Q
Gram positive vs gram negative
A
- gram positive has lots of peptidoglycan outside of the plasma membrane
- gram negative has a very impermeable outer membrane; has porins that allow things to go in and to pump out waste
11
Q
How do Cell wall inhibitors work?
A
- Break down cell wall
- Peptidoglycan bridges form between different proteins in the cell wall
- Penicillins can stop them from forming these bridges by inhibitig the transcarboxypeptidases that cause the cross-linking
- Cycloserine prevents the build up of the monomers and dimers before the formation of the long bridges
- Bacitracin blocks a specific lipid transporter - means that it cannot transport the monomers across the membrane where they would be polymerised
- Vancomycin binds to the terminal D-ala-D-ala resides, blocking the glycosidic polymerisation and the peptide crosslinking
12
Q
How do beta-lactams work in Gram -ve bacteria?
A
- Gram -ve bacteria have a porin in their outer membrane, then the peptidoglycan cell wall, then the cytoplasmic membrane
- There is a PBP (penicillin binding protein) sitting in the cytoplasmic membrane
- These are enzymes that do the crosslinking of peptidoglycans
- Beta lactam goes through the porin and binds to the PBP to stop it working - can no longer make peptidoglycan chains, disrupting the structure and activating autolytic enzymes causing it to die
13
Q
How do folic acid synthesis inhibitors work?
A
- Antifolates inhibit cell division, DNA/RNA synthesis and repair and protein synthesis
- sulphonamides inhibit the enzyme that converts PABA into dihydropteroic acid (precursor to folic acid)
- This only affects the bacteria as human can get folic acid from the diet
- Could also use trimethoprim to inhibit the conversion of dihydrofolic acid -> tetrahydrofolic acid
- work in synergy
14
Q
Give 3 ways we can treat bacterial infections
A
Antibiotics
Surgery - drain abscess
Immunological (rare) - antitoxin in tetanus
15
Q
When do we use antibiotics?
A
- treating bacterial infecitons
- prophylaxis - preventing infection, peri-operative cover, people with increased susceptibility
16
Q
What routes of administration can we give them?
A
- Orally
- Serious infections - IV for rapid delivery and high blood concentration. Maybe intramuscular
- Topical
17
Q
How do we determine the correct dose?
A
- Depends on age, weight, renal and liver function
- Depends on severity of infection
- Also depends on antibiotic properties - need to give conc higher than MIC
18
Q
Why may we use antibiotic combinations?
A
- before an organism is identified in life threatening infections
- Polymicrobial infections
- Less toxic doses of an individual drug
- Synergy (penicillin and gentamicin or sulphonamides and trimethoprim)
- reduce antibiotic resistance
19
Q
What parameters would make you decide on a specific antibiotic?
A
- Distribution in body relative to bacteria distribution
- Spectrum of activity (cidal or static)
- Toxicity
- Excretion
- Patient age
- Route of administration
- Clinical condition
- Type of bacteria
- Sensitivity of bacteria
- Cost
20
Q
What are the 3 stages of antibiotic therapy?
A
- 1 - unstable, dunno pathogen or site = empirical, parental, broad spectrum
- 2 - stabilising pathogen/site infected; rationalise therapy, narrow spectrum, parental or oral
- 3 - stable, oral
21
Q
Why might antibiotic therapy fail?
A
- Drug - innapropriate drug, dose, route of administration, poor penetration, increased excretion
- Host - immunocompromised host, retained infected body (catheter), poor circulation or damaged tissue, unusual site for pathogen
- Bacteria - natural or acquired resistance, dual infections, biofilms, dormant bacteria
- Lab - errors or equivocal tests
