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Bacteriology lecture 11 Miscellaneous Antibiotics


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What type of drugs are the sulfonamides
Broad spectrum, bacteriostatic drugs. Can treat both bacteria and parasitic diseases
What does sulfanilamide do
It is an inhibitor of folic acid synthesis in bacteria. It is a competitive inhibitor of dihydropteroic acid synthetase
What is the mechanism of sulfonamide selective toxicity
Animals obtain folic acid from their diet, while bacteria must metabolize it. Also, folate is not transfered into bacterial cells
What does Trimethoprim do
It acts as a competitive inhibitor of dihydrofolate reductase, which converts dihydrofolate into tetrahydrofolate (folic acid)
What is the selective toxicity of trimethoprim due to
Structural differences between bacterial and host dihydrofolate reductases. Bacterial enzymes have much higher affinity for the drug
How is synergism achieved with sulfonamide and trimethoprim
Sulfonamides inhibit new synthesis and folic acid, and trimethoprim prevents conversion of dihyrofolate to tetrahydrofolate. This double punch immediately delays growth
What are the characteristics of Para-aminosalicylic Acid (PAS)
Mechanism of action similar to the sulfonamides, but different spectrum of action. Effective against Mycobacterium tuberculosis. Difference reflects the differential sensitivities of the individual dihydropteroic acid synthetases.
What antibiotics affect nucleic acid synthesis
Rifampin, Rifabutin, Quinolones
What does Rifampin do
Inhibits RNA synthesis in bacteria. Narrow spectrum, bactericidal. Treats gram positive Neisseria sp. and mycobacteria. Prevents initiation of transcription, but does not inhibit transcription in progress
Why are mitochondria not affected by Rifampin
They contain a DNA-dependent RNA polymerase that is sensitive to the drug, but their membranes are impermeable to it
Rifabutin is a derivative of Rifampin. What does it treat
Infections caused by Mycobacterium avium
What do the quinolone antibiotics do
Inhibit bacterial DNA synthesis by specifically inhibiting the DNA gyrase of prokaryotic organisms.
What are some of the quinolones
Nalidixic acid (narrow spectrum, acts against gram-negative organisms in the urinary tract); Norfloxacin, Ciprofloxacin, Ofloxacin, Levofloxacin, Lomefloxacin, Sparfloxacin
How do bacteria resist the quinolones
Mutate DNA gyrase or alter the porins of gram-negative bacteria
What antibiotics affect cell membranes
Polymyxins, Colistin (polymyxin E), Amphotericin B
What type of drugs are Polymyxins and Colistin (Polymyxin E)
Bactericidal, narrow spectrum against gram negative bacteria (Pseudomonads in urinary tract infection).
How do the Polymxins and Colistin (polymyxin E) work
They contain a lower molecular weight ring with a hydrophobic tail. They insert into the membrane and bind PE or LPS, causing the membrane to become leaky. Active against growing and nongrowing cells
What is resistance to Polymxins and Colistin (polymyxin E) due to
Alterations in the outer membrane
What is the selective toxicity of polymyxins and colistin (polymyxin E) due to
Absence of PE and LPS in host cell membranes
Why type of drugs are Amphotericin B and Nystatin
How is amphotericin B administered
Intravenously for the treatment of systemic mycoses, since it is poorly absorbed through the gut
How does Amphotericin B work
It associates with ergosterol to form a channel through which molecules leak out of the cell
Why does Amphotericin cause toxic side effects
It binds to cholesterol as well as ergesterol, though with a lower affinity
What are some of the negative aspects of amphotericin chemotherapy
Toxic sides effects, such as nausea, vomiting, diarrhea, neprotoxicity, and anemia
Why are the polymyxins primarily effective against gram-negative bacteria
Gram-negative bacteria do not have a complex peptidoglycan layer to protect the cell membrane
Why are the polyene antibiotics ineffective against bacteria
Bacterial cell walls do not contain Ergosterol

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