Antibiotics Flashcards
Describe the origin of antibiotics?
- Natural products of fungi and bacteria -> soil dwellers (found within soil)
- Have natural antagonism and selective advantage to other organisms within soil
- Kill or inhibit the growth of other microorganisms
Describe how antibiotics are formed?
- Most derived from natural products by fermentation, then modified chemically by:
- Increased pharmacological properties
- Increased antimicrobial effect
- This is done to make them better pharmacological agents
- Some are totally synthetic e.g. sulphonamides
State the 2 key principles of antibiotics as therapeutic agents? (PART 1)
Selective toxicity
- A. Due to the differences in structure and metabolic pathways between host and pathogen
- B. Harm microorganisms, not the host
- C. Target in microbe, not host (if possible)
- D. Difficult for viruses (intracellular), fungi and parasites
- E. Variation between microbes
- F. Effect on commensals
State the 2 key principles of antibiotics as therapeutic agents? (PART 2)
Therapeutic margin
- A. Active dose/MIC (dose of Al required for active effect) VS toxic effect
- MIC = Minimum inhibitory concentration - lowest concentration (in Mg/mL) of an antibiotic that inhibits the growth of a given strain of bacteria
- B. narrow TM for toxic drugs - e.g. aminoglycosides, vancomycin -> ototoxic (ear or nerve), nephrotoxic (kidney)
- C. No safe drug -> must balance between therapeutic imperative and host damage
Describe the effect of microbial antagonism?
- MA - Inhibition of one bacterial organism by another (flora)
- Maintains flora - complex interactions
- Competition between flora -> Limits growth of competitors and PATHOGENS
What can loss of flora lead to?
- Bacterial/pathogen overgrowth -> AB associated colitis (clindamycin, broad-spectrum lactams, fluoroquinolones) - pseudomembranous colitis -> Ulcerations (IF), severe diarrhea, serious hospital cross-infection risks
What factors determine bacterial clearance and what occur if the patient is immunosuppressed?
- Antibiotic + immunity - Bacterial clearance
- If individual is immunosuppressed -> use different dosage or combination of antibiotics as immunity is compromised
What 3 categories can antibiotics be classified by?
- Type of activity
- Molecular structure
- Target site for activity
State the 2 ways the type of activity can be classified for antibiotics?
- Bactericidal vs bacteriostatic
- Spectrum of activity -> broad vs narrow spectrum antibiotics
State the bactericidal vs bacteriostatic activity classification with 3 features for each one?
- Varies for drug, species and conc.
- 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
Describe the spectrum of activity classification for antibioitos stating an example for each one?
- Broad Spectrum Antibiotics: Effective against many types Example: Cefotaxime
- Narrow Spectrum Antibiotics: Effective against very few types Example: Penicillin G
State the 5 types of pencillins (type of beta-lactam)?
- Basic penicillins
- Anti-staphylococcal pencillins
- Broader spectrum P
- Anti-pseduomonoal P
- Beta-lactam/beta-lactamase inhibitor combinations
- These differe in terms of spectrum of activity (what bacteria they target)
Describe the difference between basic and anti-staphylocooccal pencillins stating examples? (PART 1)
- G = Gram
- Basic penicillins
- e.g. benzylpenicillin (PenG), penicillin V
- Active against streptococci, pneumococci, meningococci, treopnemes.
- Most strains of Staphylococcus aureus are resistant - Basic P can’t be used against
Describe the difference between basic and anti-staphylocooccal pencillins stating examples? (PART 2)
- Anti-staphylococcal penicillins
- e.g. flucloxacillin
- Narrow spectrum, G+ves, beta-lactamase resistant, less potent than PenG
- Not MRSA
Describe the difference in terms of adminsteration and type of gram bacteria Pen G and Pen y affects?
- Pen G benzylpenicillin (G= gold standard);
a. not acid stable i/v or i/m
b. good for some G-ves as well as G+ves - pen phenoxymethlypenicillin
a. oral (more acid stable than penG)
b. less active against G-ves, but same activity against G+ves as PenG
Describe and state an example for broader spectrum, anti-pseudomonal P and beta-lactam inhibitior combinations?
- BSP - Ampicillin - spectrum of activity is similar to basic pencillin - includes G-ve + enterococci
- APP -> Piperacillin -> extended spectrum beta-lactam AB -> G+ve/-ve + anaerobes
- BL/BLS inhibitor combinations -> co-amoxiclav (augmentin) -> spectrum like amoxicillin + activity against G-ve + staph aureus
- B-L combinations uses a range of pencillins together
Describe how molecular structure can be used to classify antibiotics and explain using beta-lactams as an example? VD
- Molecular structure = Antibiotics are structural mimics of natural substrates for bacterial enzymes
- Example= beta-lactams - categoried by:
- Pencillins
- Cephalosporins
- These both have a beta-lactam ring - active structure which goes against bacteria
- Check diagram, need to know what that structure is
Describe the different bacterial targets for antibiotics stating examples of drugs (6)? (PART 1)
- Cell wall synthesis
- Folic acid metabolism: Thmethoprim, Sulfonamides
- Cell membrane: Colistin, Cyclic polypeptides
- Protein Synthesis: a. 50s inhibitor: Erythromycin, Chloramphenicol. b. 30s inhibitor: Tetracycline, Gentamicin, Doxycycline
Describe the different bacterial targets for antibiotics stating examples of drugs (6)? (PART 2)
- DNA and RNA processing: Quinolones -> targets DNA gyrase, Rifampin - Blocks transcription
- Anaerobic infection/free radical generators: Metronidazole -> Release free radicals, Nitrofurantoin
Describe the difference between gram -ve and gram + ve bacteria?
- Gram-negative bacteria are surrounded by a thin peptidoglycan cell wall, which itself is surrounded by an outer membrane containing lipopolysaccharide -> Impervious barrier
- Gram-positive bacteria lack an outer membrane but are surrounded by layers of peptidoglycan many times thicker than is found in the Gram-negatives.
Describe bacterial cell wall synthesis outlining the process?
VD
Describe the mechanism of action of beta-lactams in gram -ve bacteria?
Beta-lactams targets peptidoglycans in bacteria
Process:
1. Beta-lactam binds the porin of the outer membrane
2. It passes through peptidoglycan of membrane
3. Binds to Pencillin-binding protein or transpeptidase (PBP)
4. PBP binding blocks enzymes which inhibits cross-linking of cell wall units to peptidoglycan
5. Induction of autolytic enzymes
6. Kills bacteria cell as bacterial peptidoglycan structure can’t be formed
Can beta-lactams act against mycoplasma pneumonia?
- No as MP doesn’t have peptidoglycans
- Use a protein synthesis inhibitor instead e.g. erythmyocin
Describe how folic acid synthesis inhibtors work statign examples of drugs?
VD
State examples of drugs with brief action involved in protein synthesis inhibitors :
- 30s ribosome binding -> streptomycin (binding), genatmicin (translocation), tetracycline (competition)
- 50s ribosome binding -> chloramphenicol (blocks formation) + erythromycin/fusidic acid (blocks translocation)
When do we use antibiotics and state an example of an inappropriate use?
- Treatment of bacterial infections
- Prophylaxis (Prophylactic antibiotics are antibiotics that you take to prevent infection) … below points linked to this
- Close contacts of transmissible infections - carriage rates (~80% in outbreaks) e.g. meningitis
- Prevention of infection e.g. tuberculosis
- Peri-operative cover for gut surgery
- People with susceptibility to infection
- Inappropriate use - viral sore throats - patient pressure
Describe the different routes of adminsteration?
- Community infections often treated orally by GP
- Topical - conjunctivitis, superficial skin infections, burns creams, heavy metal ointments
- Serious infections - hospitalisation - systemic treatment rapid delivery, high [blood] e.g. i/v
- Often unable to take oral - vomiting, unconscious, poor gut absorption due to trauma
- Use i/v with perivascular collapse (e.g. septicaemia)
- meningitis case i/m injection
What will the dose of antibacterial MIC depend on?
- 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)
- MIC = antibiotic conc. required in body to get clearance of infection
Draw the Antibiotic serum concentration v time of area under the inhibitory curve
VD
What two factors does the pharmacodynamic properties of antibiotics describe killing activity?
- Time-dependence
- Conc.-dependence
State 5 reasons with examples as to why antibiotic combinations would be used?
- BEFORE an organism identified in life-threatening infections e.g. endocarditis, septicaemia
- Polymicrobial infections e.g. abscess, G.I. perforation anaerobes and aerobes
- Less toxic doses of an individual drug possible
- Synergy e.g. penicillin and gentamicin Co-trimoxazole (sulphonamides + trimethoprim)
- Reduce antibiotic resistance e.g. Tuberculosis
