Bacteria IV Flashcards
What do both these drugs do?
Interfere with the tetrahydrofolate pathway - an important precursor of DNA
What are sulphonamides?
Competitive inhibitors and alternate substrates for DHPS
Why are sulphonamides selective?
We do not perform this reaction
What does trimethoprim target?
Dihydrofolate reductase
Produces THF from DHF
What are the clinical applications of sulphonamides and trimethoprim?
Respiratory tract infections
Urinary tract infections
Digestive tract infections
Combination can be used for treatment/prophylaxis of pneumonia in HIV
How is sulphonamides administered?
Orally (long half lives)
How is trimethoprim administered?
Oral/IV
Which drug can cause Steven johnsons syndrome?
Sulphonamides
Which drugs target DNA topoisomerase?
Quinolones & fluoroquinolones
DNA gyrase and topoisomerase IV
What does gyrase do?
Negative supercoils
What does topoisomerase IV do?
Decatenating activity required for release of daughter chromosome produced during replication
Both enzymes catalyse ATP-dependent DNA double strand breakage-rejoining reactions
What is the primary target in gram negative bacteria?
Gyrase with it being reversed in gram-positive bacteria
What major side effect of quinolones is there?
Arthropathy - erosion of cartilage in joints but only demonstrated in young animals
What is the key part of the nitro heterocyclic drugs?
The core but only differs at the side group - the key part of the molecule is the nitro group
What does metronidazole do?
Potent bactericidal action against most obligate anaerobic bacteria
Active against some anaerobic facultative under anaerobic conditions
What happens to the nitro group in metronidazole?
Nitro group of drug reduced by low redox potential nitroreducatases
What does metronidazole treat?
Intracellular abdominal infection, C.difficile, non-venereal genial infections, etc.
How are nitrofurans activated?
Reduction
Not so dependent on anaerobic conditions
Oral only
What does nitrofurans treat?
Urinary retract infections unable to tolerate beta lactams, sulphonamides and trimethoprim
What does nitrofurans do under anaerobic conditions?
Produces double strand DNA breaks in human cells
What drugs target transcription?
Rifamycin - targets RNA polymerase and binds the beta subunit of prokaryotic RNAP
Interferes with the initiation of transcription through steric hindrance
Does Rifamycin resistance arise quickly?
Yes - by point mutation. Only used in combinations
What does Rifamycin treat?
Tuberculosis, leprosy, penicillin resistance, s.pneumoniae and s.aureus
What drugs target nucleotide metabolism?
Sulphonamides and trimethoprim
What are the three types of nitro heterocyclic drugs?
Nitroimidazoles - metronidazole & tinidazole
Nitrofurans - nitrofurantoin
Nitrothiazoles
What is the pathway for metronidazole?
Entry of drug into the cell
Reductive activation
Toxic effects of reduced intermediate products
Formation of inactive end product
What are the toxic effects of metronidazole?
DNA damage
Oxidation
Strand breaks
Helix destabilisation
What are the formulations for metronidazole?
Oral, IV, topical gel/cream
What does metronidazole treat?
Anaerobic bacterial infections & protozoan infections
What does metronidazole react with?
Alcohol - accumulation of acetaldehyde
Can nitrofurans be used for recurrent urinary tract infections?
Yes
