Intro to Antimicrobial Chemotherapy Flashcards
What is chemotherapy?
+ The use of chemicals (natural or synthetic) to inhibit the growth/replication of ‘invading organisms’ or cancerous cells within the body
+ Antibiotics and anti-bacterials can be used interchangeably
What are features of Salvarsan?
+ Kills trypanosomes
+ Trypanosomes can become resistant (trypanosomes resistant to one agent remain susceptible to others)
What is prontosil?
+ A red dye that inbibits bacteria (antibacterial)
+ Metabolises sulphanilamide: not a dye but still reactive to bacteria
How was streptomycin discovered?
+ Antibiotic discovery based on theory that soil organisms may have produced agents to kill mycobacteria derived from soil organisms
+ Soil screened for presence of factors that inhibit mycobacteria
+ Mycobacteria discovered
What is selective toxicity?
Central to the use of chemotherapeutic agents:
- when drugs intended to be toxic to the invading organism/cancerous cells but be relatively harmless to the host/normal cells
What does the approach of using drugs with selective toxicity depend upon?
The existence of biochemical differences between the target group of cells and the host
What are examples of different selective toxicity?
+ Penicillins: in the absence of allergy have very low toxicity and high doses can be used
+ Aminoglycosides have a narrow THERAPEUTIC INDEX thus the dose that causes toxicity is very close to the therapeutic dose
+ For anti-tuberculosis drugs such as isoniazid and pyrazinamide a number of patients will develop hepatotoxicity that is not dose related and may require treatment to be stopped
What are the main classes of anti-microbial agents?
+ Beta-lactam and cephalosporin
+ Glycopeptide
+ Cyclicpeptide
+ Phosphonic acids
+ Lipopeptides
What are the main mechanisms of action of beta-lactam and cephalosporin?
Preventing peptidoglycan cross-linking
What is the target of beta-lactam and cephalosporin?
Penicillin bindng proteins
What are examples of beta-lactams and cephalosporins?
+ Penicillin G
+ Flucloxavillin
+ Tazobactam
What is the main mechanism of action of glycopeptides?
Prevents transglycolation and transpeptidation
What is the target of glycopeptides?
C-terminal D-Ala-D-Ala
What are examples of glycopeptides?
+ Vancomycin
+ Teicoplanin
What is the main mechanism of action of cyclic peptides?
Prevents carriage of building-blocks of peptidoglycan bacterial cell wall outside of the inner membrane
What is the target of cyclic peptides?
C55-isoprenyl pyrophosphate
What are examples of cyclic peptides?
+ Bacitracin
+ Polymyxin
What is the main mechanism of action of phosphonic acids?
Inhibits first stage of peptidolycan synthesis
What is the target of phonphonic acids?
murA protein
What is an example of a phosphonic acid?
Fosphomycin
What is the main mechanism of action of lipopeptides?
Calcium-dependent membrane depolarisation
What is an example of a lipopeptide?
Daptomycin
What are the different classes of penicillins?
- Penicillins G and V
- β-lactamase-resistant penicillins
- cloxacillin, oxacillin, nafcillin, dicloxacillin, methicillin - Broad-spectrum penicillins
- ampicillin
- amoxicillin - Extended spectrum penicillins
- carbenicillin
- ticaracillin
- azlocillin
- piperacillin
How are cephalosporins classified?
By generations in the order in which they were developed:
- 1st, 2nd, 3rd
Now can be termed by means of administration:
- oral (cephalexin)
- parenteral (cefuroxime, cefotaxime)
What are bacterial folate antagonists?
Sulphonamides & trimethoprim:
- antibiotics which act through an inhibition of the folate pathway in bacteria
- humans don’t have folate (get it via diet)
- this makes bacteria susceptinble to drugs which interfere with folate metabolism: selective toxicity target
What is the role of amino glycosides work?
INHIBIT PROTEIN SYNTHESIS
- Form ionic bonds at cell surface
- Penetrate cell wall via a transport mechanism across cell membrane
- Diffuse into cytoplasm then bind to bacterial ribosomes
What occurs during the inhibition of protein synthesis by aminoglycosides?
- Bind to ribosomes
(i) at interface between assembled 30S and 50S units
(ii) directly to individual subunits - Inhibits protein synthesis by misreading mRNA
What are examples of aminoglycosides?
+ Streptomycin
+ Kanamycin
+ Neomycon
+ Gentamycin
What are features of tetracyclines?
- They prevent attachment of tRNA to acceptor site on mRNA-ribosomal complex
- This prevents addition of amino acids to peptide chain
- Weakly bound to ribosomes, unlike aminoglycosides
- Differences in activity of individual tetracyclines related to solubility in bacteria lipid membrane
What is the role of chloramphenicol, erythromycin and clindamycin?
+ Prevent addition of new amino acids to growing peptide chain by binding ribosomes
+ This prevents association of peptidyl-transferase with amino acid and no peptide bond formed i.e no transpepidation
+ May also prevent translocation of ribosome down mRNA template (erythromycin)
What are fluoroquinolones?
Synthetic antibiotics
What are the classes of fluoroquinolones?
- Broad spectrum:
- ciprofloxacin, ofloxacin, norfloxacin - Narrower-speectrum
- Cinoxacin, nalidixic acid
How do fluoroquinolones work?
+ Act by inhibiting bacterial Topoisomerase II (DNA gyrase)
+ This enzyme catalyses introductionof negative supercoil in DNA permitting transcription and replication
