Chemotherapy of Infection Flashcards
What is the chemotherapeutic index?
The ratio between the dose that will cure something (minimum currative
If the dose of salvarisan that will cure syphillis is 5mg/kg/day and the dose that is lethal is 15mg/kg/day what is the therapeutic index?
15/5 = 3
Describe chemotherapy?
The use of chemical agents to inhibit/kill infectious cells and inhibit the growth of malignant cells
What are the three key differences between bacterial cells and mammalian cells?
- bacterial cells use PABA and mammalian cells do not
- bacterial cells have cell walls and mammalian cells do not
- bacterial cell ribosomes have 30S and 50S subunits and mammalian cells have 40S and 60s subunits
What antibacterial agents deprive bacterial cells of PABA?
sulphonamides
What antibacterial agents inhibit cell wall synthesis in bacterial cells?
Penicillin
How do bacterial cells use PABA?
To synthesised folic acid
What enzyme is involved in the conversion of PABA to folic acid by bacterial cells?
dihydropterate synthases
What is folic acid converted to?
tetrahydrofolic acid
What enzyme converts folic acid to tetrahydrofolic acid?
dihydrofolate reductase
What is tetrahydrofolic acid essential for?
The synthesis of amino acids, pyrimidine nucleotides and therefore DNA, RNA and protein
What is it about sulphonamide that it can inhibit the synthesis of PABA?
It has a similar structure to PABA and is therefore accepted by the enzyme that converts it to folic acid
Sulphonamides are bacteriostatic; what does this mean?
They inhibit the bacterias growth but do not kill them
Is sulphonamies are bacteriostatic what actually kills the bacterial cells?
the hosts immune system
What are two examples of sulphonamides
suphACETamide and sulphaMETHOXAZOLE
What kind of bacteria does penicillin effect?
bacteria that are actively growing
Penicillin kills the bacteria; what is it then known as?
bacteriocideal
Why is the baterial cell wall called the peptidoglycan wall?
Because it is glycen units cross-linked by peptides
What two things does penicillin do that inhibits cells wall synthesis?
- Inhibits the enzyme that cross links the chains in the cell wall
- Activation of an enzyme involved in the cell wall turnover leading to increased breakdown of the cell wall
What antibacterial agent inhibit bacterial protein synthesis?
Tetracycline and Streptomycin and aminoglycosides
How does tetracycline inhibit protein synthesis?
Competes with tRNA for the binding site on the 30S subunit
Are tetracycline bacterial agents bacteriostatic or bacteriocidal?
Bacteriostatic
How do streptomyocin and the aminoglycosides inhibit bacterial cell protein synthesis?
They enter gram -ve bacteria via porin channels and bind to the 30S subunit
Define resistance
The development of bacterial defences against antibacterial agents
What is the main mechanism of bacterial resistance?
Transfer of bacterial resistance genes between bacteria by plasmid transfer
How much faster is bacterial generation time than humans?
100,000 times faster
What do bacteria do to resist sulphonamides?
They create a dihydropteroate synthase that has high affinity for PABA but low affinity for sulphonamides
How do bacteria cells resist penicillin?
Produces B-lactamase to destroy penicillin
How was the bacterial resistance to penicillin overcome?
combine pencillin with clavulamic acid which inhibits B-lactamase
How do bacteria cells resist tetracycline?
bacteria produces ABC transporters to pump tetracycline out of the membrane
What are 4 examples of quinolines?
CHLOROquine, quinINE, MEFLOquine and AMODIAquine