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Lecture notes

Pharmacology 7: Antimicrobials
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Lecture notes from Imperial College London, Medical Biosciences BSc, 2nd year, Pharmacology module PHAR 7 on antimicrobials: we will consider drugs that are used in the treatment of microbial infection, exploiting key differences in biochemistry that permit treatments with varying degrees of sel...

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  • September 25, 2023
  • 6
  • 2022/2023
  • Lecture notes
  • Toby athersuch
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Antimicrobials
Introduction to microorganisms
- microorganismal infections: pathogenic/ toxic microorganism because wrong place, activity, quantity
=> exhaust critical resources, invade/ kill cells, produce toxins...
=> stop growth/ kill microorganisms to prevent/ treat infection
=> good risk: benefit ratio (side-effects, toxicity...) => selectively toxic to microorganisms

Broad comparison of microorganisms
- microorganism = microbe = bacteria, fungi, viruses, protoazoa, helminths, algae, prions...
=> unicellular/ multicellular, single cells/ colonies, Archaea/ Bacteria/ Eukarya


/comparison
to animal
(single cell
alls 10 microbes)




- antimicrobial = natural/ synthetic agents that target microorganisms (inhibit/ kill)
=> antibiotics = microorganism-produced (natural) substances that target another microorganism
penicillin
=> antibacterial = natural/ synthetic agents that target bacteria (inhibit/kill)
ex :




=> bacteriostatic = prevents growth of bacteria
=> bactericidal = kills bacteria

Introduction to bacteria
~




- prokaryotic life => Archaea & Bacteria
- unicellular with no membrane-bound nucleus/ organelles
- bacterial ribosomes => synthesise oligopeptides, proteins
- can symbiose w/ animal cells (ex: in gut) => commensal
relationship (only 1 benefits from interaction ≠ mutualistic )
-

no harm to host sometimes)

, - can be pathogenic (but membranes, fluid compo, pH, innate immune system try to prevent it)
- human body = 30 trillion human cells + 40 trillion bacterial cells
- shape diversity:




- diversity in cell walls: ≠ layers of petidoglycan (see after) => different responses to antibacterials
- evolution over time: many environmental niches colonised by bacteria (found everywhere)
=> 1st one: archaebacteria 4000 million years ago (still exist)


Magic bullets
- Paul Ehrlich found that arsenic-containing compounds cure syphilis (caused by treponema pallidum)
=> synthesised the organoarsenic salvarsan
- “Magic Bullet” = ideal therapeutic agent that affect the target organism selectively (no side-effects)
- antibacterials target (look at previous table)
=> genetic material replication
=> nucleic acid synthesis
=> structural integrity: cell wall synthesis
=> membrane needed for growth synthesis
=> protein synthesis

Introduction to antibacterial agents
- class I: target production of precursors using glucose
Istructural integrity

derived ATP => restrict downstream processes
- class II: target production of small molecules
from class I precursors
Ex: trimethoprim...
- class III: target production of macromolecules
from small molecule substrates
Ex: penicillin, ciprofloxacin...

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