Gentamicin belongs to the aminoglycoside antimicrobial agents. It is a bactericidal agent with a wide spectrum of activity against Gram-negative and Gram-positive organisms. It irreversibly inhibits protein biosynthesis by acting directly on the ribosome. Gentamicin binds receptors on the 30S subunit of the bacterial ribosome and inhibits protein synthesis through interference with the initiation complex, misreading of the code on the mRNA template, and causing polysomes to dissociate into nonfunctional monosomes.

Ototoxicity and nephrotoxicity are the most serious adverse effects of gentamicin. Ototoxicity is manifested as vestibular dysfunction, which may be due to destruction of hair cells. If renal failure is present, the probability of ototoxicity is greater.

Nephrotoxicity is more common with gentamicin than with any of the other aminoglycosides. It can produce acute renal insufficiency and tubular necrosis.

The amino glycoside antibiotics include gentamicin, streptomycin, neomycin, tobramycin, kanamycin, amikacin, and netilmicin. All these drugs contain amino sugars linked to an aminocyclitol ring by glycosidic bonds. They are used primarily to treat infections caused by aerobic gram-negative bacteria, where they act to interfere with protein synthesis. The aminoglycosides diffuse through channels in the outer membrane of the bacteria and enter the periplasmic space. Subsequently, the drugs are transported across the cytoplasmic membrane by an energy-dependent transport system, which requires the bacteria to utilize oxygen. Once inside the bacterium, they bind to the 30 S ribosomal subunit and block the initiation of protein synthesis. Bacteria may acquire resistance to the action of the aminoglycosides by several different mechanisms. Penetration of the drug through the pores in the outer membrane may become retarded, but resistance of this type is unimportant clinically. Natural resistance to the aminoglycoside antibiotics can be caused by the failure of the drug to penetrate the cytoplasmic membrane. As the transport mechanism requires the utilization of oxygen, this explains the resistance of anaerobic bacteria and facultative bacteria grown under anaerobic conditions. However, the importance of this mechanism on clinically-important acquired-resistance does not appear to be significant. Resistance resulting from alterations in ribosomal structure is less clinically relevant for most infections. While an alteration in ribosomal structure can prevent binding of the drug, these alterations are not widespread. The most clinically relevant mechanism for acquired-resistance to the aminoglycoside antibiotics is the plasmid-mediated elaboration of inactivating enzymes. These enzymes may phosphorylate, adenylate, or acetylate the aminoglycoside, resulting in loss of function. This has become a source of special concern with regard to enterococcal infections, many of which are highly resistant to all aminoglycosides.

Initial treatment for pulmonary or extrapulmonary tuberculosis is isoniazid (INH), rifampin (RMP), and pyrazinamide (PZA) as a short-course intensive daily regimen for 2 months, followed by INH and RMP for 4 more months. The most common side effects of rifampin are reddish urine and stool, saliva, sweat, tears, diarrhea, joint pain, back pain, swelling of feet and/or legs, and blood in urine. Hyperuricemia is a major toxic effect of pyrazinamide; other toxic effects include fever, indigestion, urticaria, photosensitivity, and joint pain. Isoniazid can cause polyneuropathy, jaundice, muscle pain, confusion, and unsteady walk.

Tenofovir is categorized as a nucleoside analogue reverse transcriptase inhibitor (NRTIs). An NRTI’s mechanism of action is to block reverse transcriptase, an enzyme that enables the human immunodeficiency virus 1 (HIV-1) to flourish. This enzyme aids the HIV virus in making a copy of DNA from the viral RNA, and this DNA is incorporated into the host genome. The effectiveness has been found in a review conducted by the Centers for Disease Control and Prevention to be so effective that “pre-exposure prophylaxis can potentially be a vital option for HIV prevention in pearly at very high risk for infection, whether through sexual transmission or injecting drug use.”

In regards to Post-Exposure Prophylaxis (PEP), The United States Public Health Service recommend the use of tenofovir, emtricitabine, or a combination drug of these two medications—plus raltegravir for PEP in occupational exposure scenarios.

All of the drugs are antifungal agents but only flucytosine has been associated with bone marrow suppression and synergizes with other drugs which suppress bone marrow functions. Miconazole and ketoconazole may produce hepatotoxicity, gastro-intestinal upset and headaches. Amphotericin B may produce nephrotoxicity while itraconazole is associated with gastro-intestinal upset and rare liver dysfunction.

The tetracycline antibiotics possess a wide range of antimicrobial activity against gram-positive and gram-negative bacteria, as well as Rickettsia, Mycoplasma, Chlamydia, Ureaplasma, some atypical mycobacteria, and amoebae. These drugs are primarily bacteriostatic and act by inhibiting microbial protein synthesis. The tetracyclines, after active transport into the cell, bind to the 30 S ribosomal subunit. This prevents the access of aminoacyl tRNA to the acceptor site on the mRNA-ribosome complex, inhibiting the addition of amino acids to the growing peptide chain. This effect is, for the most part, reversible and removal of the drug results in loss of action.

The other mechanisms listed are utilized by other antimicrobial agents. For example, all beta-lactam drugs are selective inhibitors of cell wall synthesis, and therefore active against growing bacteria. Sulfonamides are structural analogs of PABA that is necessary for folic acid synthesis. By competitive inhibition, the drug interferes with folic acid synthesis. Folic acid is an important precursor to the synthesis of nucleic acids. Quinolones are examples of antibiotics which inhibit bacterial DNA synthesis by blocking of the DNA gyrase. Antibiotics—polymyxin and colistin—and the antifungal agent amphotericin B act by inhibiting cell membrane function.

Amantadine only works after viral attachment to the cell, preventing viral uncoating. It is also believed to interfere with viral mRNA production. Amantadine is effective against influenza virus A.

Transport antibiotics act as carriers of ions across membranes (e.g. valinomycin) or by forming channels in the membrane that allow ions to cross the membrane (example-gramicidin A). Gramicidin affects cell membrane permeability while polymyxin B interferes with bacterial cell wall production. These transport antibiotics, also called ionophores, are secreted by many microorganisms and disable other species by making their membranes permeable to ions. These antibiotics show high specificity for specific ions. Carriers bind ions on one side of the membrane and shuttle the ion across the membrane. The carrier antibiotics are donut shaped with a hydrophilic center where the ion binds and a hydrophobic periphery that allows the antibiotic to traverse the membrane.

The channel forming antibiotics form a β-helix that forms a "hole" in the membrane through which ions can move. These channels open and close and the accompanying ion movements can be detected by measuring the conductance across the membrane. The transport antibiotics have been a very useful tool for cell biologists and physiologists studying the movement of ions across biological membranes under a variety of conditions. Both types of antibiotics insert into the lipid bilayer but do not alter the composition of the membrane lipids. Penicillin is an antibiotic that acts by inhibiting cell wall synthesis by inhibiting the enzyme glycopeptide transpeptidase. Neomycin is an aminoglycoside antibiotic that binds to the 30S subunit of the ribosome inhibiting protein synthesis.

3'-azido-3'-deoxythymidine (AZT) is a nucleoside analog that blocks HIV replication by inhibiting the RNA-dependent polymerase, HIV-DNA polymerase. The DNA polymerase from HIV is 100-fold more sensitive to AZT than the host polymerase. AZT is a pyrimidine analog that is phosphorylated to AZT-triphosphate by cellular enzymes and acts as a competitive inhibitor of the reverse transcriptase. AZT can be incorporated into viral DNA and cause chain termination because its structure lacks the 2' hydroxyl needed for addition of the next nucleotide by the polymerase.

In addition to nucleoside analogues, HAART also contains non-nucleoside reverse transcriptase inhibitors and protease inhibitors that block cleavage of the precursors of the viral coat proteins, preventing proper viral assembly. Maraviroc blocks a specific cell receptor needed by HIV to enter the host cell.

Amikacin binds to the 30S ribosomal sub-unit, not the 50S.

Enzymatic hydrolysis by % lactamase-producing bacteria targets penicillins.

Bacterial resistance to amikacin can be mediated through loss of a receptor by which amikacin binds the 30S ribosomal subunit, interference with membrane transport, and bacterial acetylation, adenylation, or phosphorylation.

Amikacin is resistant to peroxidase.

Amikacin is only marginally soluble in the bacterial cell membrane to begin with.