Protein synthesis machinery, including ribosomes, is somewhat different in bacteria compared to mammalian cells. This accounts for the selectivity of this group of drugs for bacteria. Some textbooks and instructors make a point of having students know which ribosomal subunit a class of drugs binds to. However, this is not of primary importance. If you already know it, try not to forget it. If you are struggling with the antimicrobials at this point, save this fact for later. These drugs require binding to an intracellular protein (ribosomal subunit). Therefore, the drugs need to gain entry into the cell. A major route of resistance for the bacteria is to block the movement of the drugs into the cell.
For the protein synthesis inhibitors, the class names are related to the chemical structure of the compounds in each group, but don’t worry too much about remembering the class name. It is more important to know the individual drug names here.
The aminoglycosides are broad-spectrum antimicrobials. However, anaerobic bacteria are generally resistant to them.
Some bacteria use an oxygen-dependent transport system to bring the aminoglycosides into the cell. The anaerobes (with non–oxygen-based metabolism) do not have this system. Therefore, they are generally resistant to the aminoglycosides.
Notice that the names of the aminoglycosides all end in “-mycin” or “-micin,” except amikacin. However, the drug companies have thrown a curve ball here, because the drug clindamycin and all the macrolides (erythromycin, clarithromycin, etc.) also end in “-mycin.” So take a moment to compare the list of names here with the one included later in the chapter. Be sure that you can recognize which class a particular name belongs to.
Aminoglycosides are poorly absorbed from the gastrointestinal (GI) tract and none cross the blood-brain barrier.
Most aminoglycosides must be administered parenterally. They are highly polar compounds and are relatively insoluble in fat. They do not readily penetrate most cells without help from penicillins or a transport system.
Recall the synergism between penicillins and aminoglycosides that was mentioned in the introduction to chemotherapy (see Chapter 27). The penicillins cause cell wall abnormalities that allow the aminoglycosides to gain entry into the bacteria.
Aminoglycosides have ototoxicity, nephrotoxicity, and neuromuscular toxicity.
The margin of safety with these drugs is small. This means that the toxic concentration is only slightly higher than the therapeutic concentration.
The ototoxicity can be both cochlear (auditory) and vestibular. The symptoms include tinnitus (ringing), deafness, vertigo or unsteadiness of gait, and high-frequency hearing loss. The cochlear toxicity results from selective destruction of the outer hair cells in the organ of Corti.
The nephrotoxicity is related to the rapid uptake of the drug by proximal tubular cells. ...