Lec 1- Intro

Question 1

Classification in clinical practice

Answer 1

• Bacteria: Prokaryotic organism (No nucleus). Main groups identified by microscopic observation and staining (Gram positive and Gram negative). WIth further groups such as Spirochaetes or mycoplasmas
• Protozoa: Non-photosynthetic unicellular organisms with protoplasm differentiated into nucleus and cytoplasm (e.g. malaria)
• Fungi: Non-photosynthetic organisms that possess relatively rigid cell walls (Chitin)
• Virus: Infect other cells and requires host cell machinery to replicate

Question 2

Anti-microbial drugs

Answer 2

• Drugs used to treat infections caused by bacteria and other micro-organisms (e.g. penicillins G and V)
• Natural- antibiotics occur in nature, they are produced by one micro-organism to selectively inhibit the growth of others (Penicillium chrysogenum produces Penicillins)- chemically unchanged
• Semi-synthetic- Antibiotics are chemically modified natural antibiotics (e.g. ampicillin)- based on the natural product but we modify the structure to give better properties in terms of pharmaceutical profile
• Some agents are not produced naturally, they are totally synthetic (e.g. trimethoprim)
• No single anti-microbial can be used to treat all kinds of infection (e.g. bacteria, fungi, protozoa, viruses); Some are broad spectrum and some narrow spectrum (e.g. vancomycin)

Question 3

Selective toxicity- penicillin example

Answer 3

• The aim is to kill microbe without affecting host
• Paul Ehrlich (1854-1915)- “Magic Bullet” (Arsphenamine)
• Example: Penicillin
• Good for: Many Gram-positive Gram-negative bacteria
• Less effective in some cases: Gram-negative bacteria (limited selectivity)
• Not effective for Mycobacteria, fungi, viruses
• Other toxicity/Problems: e.g. Guinea pigs (penicillins kill guinea pigs very quickly) and rabbits, also neurotoxicity on direct application

Question 4

Selective toxicity

Answer 4

• Phylogenic tree= when different species split from each other
• Bacteria was the first to spilt, this is why there are lots more antibiotics
• Fungi diverged from animals far later, this means many of the metabolic processes are the same, DNA, protein is similar to us, therefore, is harder to find differences between us which we can target to give the selective toxicity

Question 5

Selective toxicity- Therapeutic index

Answer 5

• Therapeutic index (ratio) = LD₅₀ / ED₅₀
• LD₅₀= Lethal dose- Dose at which kills 50% of organisms you give it to
• ED₅₀ = Effective dose- Dose which cures 50% of organisms
• It shows how selective the drug is, the smaller the difference between the LD and ED the less selective the drug
• FOR HUMANS TD₅₀/ED₅₀
• Toxic dose

Question 6

Selective toxicity examples

Answer 6

• Penicillin
  
  • 15g/kg to a mouse
  • 50mg/kg to a rabbit
• Prescription
  
  • Normal 250-500mg (5mg/kg) QDS for 7-14 days
  • Gonorrhoea 3.5g ampicillin (50mg/kg + Probenecid)
• Vancomycin
  
  • ED approx 10-20 mg/L
  • LD approx 30-40 mg/L
  • Patient must have IV and constant monitoring due to small therapeutic index

Question 7

Selective toxicity- genomes