Antibiotics

Question 1

Describe the concepts of selective toxicity in relation to antibiotics

Answer 1

• avoid damage on commensal bacteria
  (mcirobiome imbalance causes disease)
• target proteins specific to the bacteria
• differences in structure and metabolic pathways between pathogen and host
• maintains flora: limits growth and competition from pathogens
  eg: pseudomembranous colitis (overgrown c.difficile)=> megacolon
• minimum affect on host (physiological difference between bacteria and host)

Question 2

Define the biological and pharmaceutical origins of antibiotics

Answer 2

• origins of penicillin (Flemming 1928)
• mould secreted toxins which inhibited/destroyed growth of e.coli

Question 3

Define the terms: bactericidal, bacteriostatic, broad and narrow spectrum, MIC

Answer 3

bactericidal = destroys all bacteria - needed for kidney infections

bacteriostatic : bacterial inhibition, maintain host defence mechanism

broad spectrum: effective against many types

narrow spectrum: effective against few bacteria
MIC: minimum inhibitory concentration: minimum amount of antibiotic required for a inhibitory effect.

Question 4

Describe the categories of antibiotics, their modes of action, and targets, giving a named example of an antibiotic for each category

Answer 4

• β-lactams: penicillin V, PenG effective against streptococci, pneumococci, meningicocci, treopmemes

Question 5

Relate the structure of a bacterial cell to the action of different antibiotics

Answer 5

COLISTIN: attacks lipid membrane in cell membrane [can destroy commensal]

CHLORAMPHENICOL: 50-S inhibitors = inhibition of RNA synthesis in ribosomes

ERYTHROMYCIN: inhibitor of protein synthesis/ blocks peptide tRNA translocation

TETRACYCLINS: inhibition of 30-S unit in ribosomes = ❌RNA production

FIDAMOXICIN: prevents mRNA production

METRONIDAZOLE: produces free radicals inside bacteria cells

QUINOLONES: impacts DNA/RNA processing by targeting DNA gyrase and RNA polymerase

TRIMETHOPRIM & SULFANOMIDES: inhibits folic acid metabolism by ❌ production of THFA and DHFA precursors for metabolism. [👍🏼 selective toxicity)

VANCOMYCIN: prevents cell wall synthesis by interfering in D-ala crosslink and blocking access to PBP active site.

CEPHALOSPORIN / β-LACTAM: preventing cell wall synthesis (induction of autolytic enzymes)

Question 6

Explain in broad principles when antibiotics are used and how they are delivered

Answer 6

• therapeutic margin = MIC
  active dose - toxic effect
  ⬆️ toxicity = narrow MIC
• combinatory antibiotics

Question 7

What are the differences in cell wall structure between gram➕ and gram➖ bacteria?

Answer 7

GRAM+
- cell wall (allows access to b-lactam)
- pentopeptide crosslinks

GRAM -
- different peptidoglycan enzyme structures
- porin structures = impermeability defence

Question 8

briefly describe how β-lactams when modified, can prevent cell wall synthesis in gram➖ bacteria

Answer 8

1. travel through porin
2. binds to PBP (penicillin binding protein) located in cytoplasmic space
3. ❌ peptidoglycan subunit production = disruption
4. induction of autolytic enzymes = ❌disintegration of impermeable cell wall structure

Question 9

which bacteria in particular in unaffected by β-lactams and why?

Answer 9

mycoplasma
- because they do not have peptidoglycan