Princicples of Antimicrobial Chemotherapy Flashcards
Define chemotherapy.
The use of chemicals to inhibit the growth of invading organisms or cancerous cells.
What did Ehrlich discover?
Discovered and established the concept of selective toxicity.
What did Ehrlich discover that killed trypanosomes?
Salvarsan.
What did Ehrlich discover about resistance?
Trypanosomes could become resistant. Trypanosomes resistant to one agent remained susceptible to others.
What did Domagk discover?
Prontosil- a red dye that inhibited bacteria.
What was Domagk’s achievement?
Developed the concept of rational design of anti-bacterials.
What did Florey and Chain recognise?
The value of penicillin as a treatment of bacterial infection.
What is selective toxicity?
Drugs intended to be toxic to invading organism/cancerous cells but be relatively harmless to host cells.
What does selective toxicity depend on?
The existence of biochemical differences between the target group of cells and the host.
How are aminoglycosides an example of selective toxicity?
They have a very narrow therapeutic index thus the dose that causes toxicity is very close to the TD.
What are examples of anti-tuberculosis drugs?
Isoniazid and pyrazinamide.
What may tuberculosis patients develop when treated with anti-tb drugs?
Hepatoxicity
What is hepatotoxicity?
The medical term for damage to the liver caused by a chemical.
What are examples of beta lactam and cephalosporin class drugs?
Penicillin G, flucloxacillin and tazobactam.
What are examples of glycopeptide class drugs?
Vancomycin and teicoplanin.
What are examples of cyclic peptide drugs?
Bacitracin and polymyxin.
What are examples of phosphoric acid class drugs?
Fosphomycin
What are examples of lipopeptide class drugs?
Daptomycin
Where are peptidoglycans present?
They make up the cell wall of bacteria and do not occur in eukaryotes.
What are the strands of peptidoglycans made up of?
N-acetylclucosamine and N-acetlymuramic acid dimers.
What forms the cross links between the peptidoglycan strands?
The peptide side chains of the amino acids form a latticework of cross links.
Which drugs prevent peptidoglycan cross-linking?
Penicillin G, flucloxacillin, tazobactam and vancomycin.
What are the early penicillins?
Penicillins g and v.
What are the beta lactamase resistant penicillins?
Methicillin, oxacillin, nafcillin, cloxacillin and dicloxacillin.
What is the penicillin most commonly used in the UK?
Flucloxocillin.
What are the broad spectrum penicillins?
Ampicillin and amoxicillin.
What can broad spectrum penicillins be used against?
Gram negative bacteria.
What are the extended spectrum penicillins?
Carbenicillin, ticarcillin, azlocillin and piperacillin.
Where does cephalosporium acremonium comes from?
Fungus.
How do cephalosporins work?
In the same mechanisms as penicillins.
How is cephalexin given?
Orally.
How is cefuroxime and cefotaxime given?
Parenterally.
How are cephalosporins classified?
By generation (1st, 2nd and 3rd).
What are examples of bacterial folate antagonists?
Sulphonamides and trimethoprim.
How do sulphonamides and trimethoprim work?
They act through an inhibition of the folate pathway in bacteria.
Why are bacteria susceptible to bacterial folate antagonists?
Bacteria must make their own supply of folate, but humans do not.
Which enzyme do sulfonamides interfere with?
Dihydropteroate synthetase.
Which enzyme do trimethoprims interfere with?
Dihydrofolate reductase.
What are examples of aminoglycosides?
Streptomycin, kanamycin, neomycin and gentamycin.
How do aminoglycosides work?
Form ionic bonds at CSM and diffuse into cytoplasm and bind to bacterial ribosomes.
How do aminoglycosides inhibit protein synthesis in bacteria?
They bind to ribosomes: at the interface between the assembled 30s and 50s subunits or directly to the subunits.
How do aminoglycosides actions result in the inhibition of protein synthesis?
Misreading of mRNA.
What is the action of tetracyclines?
They prevent attachment of the tRNA to the acceptor site on the mRNA-ribosomal complex.
How are tetracyclines different to aminoglycosides?
They are only weakly bound to the ribosomes.
What property affects the activity of individual tetracyclines?
Their solubility in the lipid membrane of the bacteria.
What is the action of chloramphenicol, erythromycin and clindamycin?
Prevent the addition of new AAs to the growing peptide chain by binding ribosomes.
What does the actions of chloramphenicol, erythromycin and clindamycin prevent?
Association of the peptidyl-transferase with the AA and no peptide bond is formed.
What specifically might erythromycin prevent?
Translocation of the ribosome down the mRNA template.
What are fluoroquinolones?
Synthetic antibiotics.
What are broad spectrum agent examples of fluoroquinolones?
Ciprofloxacin, ofloxacin and norfloxacin.
What are narrower spectrum drug examples of fluoroquinolones?
Nalidixic acid.
How do fluoroquinolones act?
By inhibiting bacterial DNA Topoisomerase II also known as DNA gyrase.
What does DNA gyrase (topoisomerase II) do?
This enzyme catalyses the introduction of negative supercoil DNA permitting transcription and replication.
What is the use of fluoroquinolones defined by?
The spectrum of activity and by pharmacokinetics.
