Antibiotics

Question 1

Describe the origin of antibiotics?

Answer 1

• 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

Question 2

Describe how antibiotics are formed?

Answer 2

• 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

Question 3

State the 2 key principles of antibiotics as therapeutic agents? (PART 1)

Answer 3

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

Question 4

State the 2 key principles of antibiotics as therapeutic agents? (PART 2)

Answer 4

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

Question 5

Describe the effect of microbial antagonism?

Answer 5

• MA - Inhibition of one bacterial organism by another (flora)
• Maintains flora - complex interactions
• Competition between flora -> Limits growth of competitors and PATHOGENS

Question 6

What can loss of flora lead to?

Answer 6

• Bacterial/pathogen overgrowth -> AB associated colitis (clindamycin, broad-spectrum lactams, fluoroquinolones) - pseudomembranous colitis -> Ulcerations (IF), severe diarrhea, serious hospital cross-infection risks

Question 7

What factors determine bacterial clearance and what occur if the patient is immunosuppressed?

Answer 7

• Antibiotic + immunity - Bacterial clearance
• If individual is immunosuppressed -> use different dosage or combination of antibiotics as immunity is compromised

Question 8

What 3 categories can antibiotics be classified by?

Answer 8

• Type of activity
• Molecular structure
• Target site for activity

Question 9

State the 2 ways the type of activity can be classified for antibiotics?

Answer 9

1. Bactericidal vs bacteriostatic
2. Spectrum of activity -> broad vs narrow spectrum antibiotics

Question 10

State the bactericidal vs bacteriostatic activity classification with 3 features for each one?

Answer 10

• 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

Question 11

Describe the spectrum of activity classification for antibioitos stating an example for each one?

Answer 11

• Broad Spectrum Antibiotics: Effective against many types Example: Cefotaxime
• Narrow Spectrum Antibiotics: Effective against very few types Example: Penicillin G

Question 12

State the 5 types of pencillins (type of beta-lactam)?

Answer 12

• 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)

Question 13

Describe the difference between basic and anti-staphylocooccal pencillins stating examples? (PART 1)

Answer 13

• 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

Question 14

Describe the difference between basic and anti-staphylocooccal pencillins stating examples? (PART 2)

Answer 14

• Anti-staphylococcal penicillins
• e.g. flucloxacillin
• Narrow spectrum, G+ves, beta-lactamase resistant, less potent than PenG
• Not MRSA

Question 15

Describe the difference in terms of adminsteration and type of gram bacteria Pen G and Pen y affects?

Answer 15

1. 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
2. pen phenoxymethlypenicillin
   a. oral (more acid stable than penG)
   b. less active against G-ves, but same activity against G+ves as PenG

Question 16

Describe and state an example for broader spectrum, anti-pseudomonal P and beta-lactam inhibitior combinations?

Answer 16

• 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

Question 17

Describe how molecular structure can be used to classify antibiotics and explain using beta-lactams as an example? VD

Answer 17

• Molecular structure = Antibiotics are structural mimics of natural substrates for bacterial enzymes
• Example= beta-lactams - categoried by:
• 1. Pencillins
• 2. Cephalosporins
• These both have a beta-lactam ring - active structure which goes against bacteria
• Check diagram, need to know what that structure is

Question 18

Describe the different bacterial targets for antibiotics stating examples of drugs (6)? (PART 1)

Answer 18

1. Cell wall synthesis
2. Folic acid metabolism: Thmethoprim, Sulfonamides
3. Cell membrane: Colistin, Cyclic polypeptides
4. Protein Synthesis: a. 50s inhibitor: Erythromycin, Chloramphenicol. b. 30s inhibitor: Tetracycline, Gentamicin, Doxycycline

Question 19

Describe the different bacterial targets for antibiotics stating examples of drugs (6)? (PART 2)

Answer 19

5. DNA and RNA processing: Quinolones -> targets DNA gyrase, Rifampin - Blocks transcription
6. Anaerobic infection/free radical generators: Metronidazole -> Release free radicals, Nitrofurantoin

Question 20

Describe the difference between gram -ve and gram + ve bacteria?

Answer 20

• 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.

Question 21

Describe bacterial cell wall synthesis outlining the process?

Answer 21

VD

Question 22

Describe the mechanism of action of beta-lactams in gram -ve bacteria?

Answer 22

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

Question 23

Can beta-lactams act against mycoplasma pneumonia?

Answer 23

• No as MP doesn’t have peptidoglycans
• Use a protein synthesis inhibitor instead e.g. erythmyocin

Question 24

Describe how folic acid synthesis inhibtors work statign examples of drugs?

Answer 24

VD

Question 25

State examples of drugs with brief action involved in protein synthesis inhibitors :

Answer 25

• 30s ribosome binding -> streptomycin (binding), genatmicin (translocation), tetracycline (competition)
• 50s ribosome binding -> chloramphenicol (blocks formation) + erythromycin/fusidic acid (blocks translocation)

Question 26

When do we use antibiotics and state an example of an inappropriate use?

Answer 26

• 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

Question 27

Describe the different routes of adminsteration?

Answer 27

• 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

Question 28

What will the dose of antibacterial MIC depend on?

Answer 28

• 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

Question 29

Draw the Antibiotic serum concentration v time of area under the inhibitory curve

Answer 29

VD

Question 30

What two factors does the pharmacodynamic properties of antibiotics describe killing activity?

Answer 30

1. Time-dependence
2. Conc.-dependence

Question 31

State 5 reasons with examples as to why antibiotic combinations would be used?

Answer 31

• 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