Flashcards
Antibiotics I: Antimetabolites
Flashcards do conjunto (21)
- 1What did Ehrlich discover about altering structure of compounds?Related compounds may have curative action increase independent of toxicity
- 2What are the two types of effect antibiotics can have?Bactericidal= kills bacteria
bacteriostatic= stops growth - 3what are the 4 main sites of antibiotic action-metabolism (antimetabolites)
-cell wall synthesis
-protein synthesis
-nucleic acid synthesis - 4what was the first sulphonamide antibacterial
- 5what is prontosil structure
- 6What are the functional groups of a sulphonamide-amino terminus (cannot be changed or modified)
-benzene ring (more active than other aromatics)
-sulphonamide terminus (can be modified- swap hydrogens for other groups) - 7what molecule are sulphonamides similar to? what is this similarity called?pAB (para-amino benzoic acid)
isosterism - 8what is pAB used forfolate synthesis
- 9how do sulphonamides workincorporated instead of pAB, creates a false product, prevents folate synthesis
- 10why does incorporation of a sulphonamide prevent folate synthesis-next step after pAB is glutamate addition
-glutamate can't be added to sulphonamide group - 11what is folic acid used for'one-carbon metabolism'- transfer of methyl groups (e.g. dUMP-->dTMP)
- 12why are sulphonamides selectively toxic to bacteria?Humans do not synthesise folate, sulphonamides block a pathway that is present in bacteria but not humans
- 13what is the sulphonamide general structure
- 14why do sulphonamides work so well?-they generate a false product- prevents a build up before the block (competition=overcome block)
-bacteria have no uptake mechanisms for end-product
-we don't synthesise folate- pAB not present in our cells - 15what blocks the action of sulphonamidesend products of folate metabolism (serine, thymine etc)
- 16what effect do sulphonamides have on bacteriausually bacteriostatic (become bacteriocidal in absence of thymine- 'thymineless death')
- 17how is sulphonamide resistance achieved-inc pAB levels
-inc folate uptake
-reduced uptake of drug
-metabolism of drug - 18what are sulphonamides used forUTIs, meningitis, and in veterinary medicine
- 19what types of bacteria do sulphonamides affectbroad spectrum- Gram -ve and +ve
- 20what are 2 related drugs that act by the same mechanism-dapsone (used in combi therapy for leprosy)
-p-amino salicyclic acid (tuberculosis) - 21what are some other drugs which target folate synthesisdihydrofolate reductase inhibitors (enzyme also present in humans so toxic):
-methotrexate (anticancer)
-trimethoprim - selective for bacterial enzyme (bacterial IC50=0.01µM, mammalian IC50=300µM)