Among the many antibiotics isolated from that genus, several are compounds closely related in structure to streptomycin. Six of them kanamycin, neomycin, paromomycin, gentamicin, tobramycin, and netilmicin— currently are marketed in the United States. Amikacin, a semisynthetic derivative of kanamycin A, has been added, and it is possible that additional aminoglycosides will be introduced in the future.

All aminoglycoside antibiotics are absorbed very poorly (less than 1% under normal circumstances) following oral administration, and some of them (kanamycin, neomycin, and paromomycin) are administered by that route for the treatment of GI infections. Because of their potent broadspectrum antimicrobial activity, they are also used for the treatment of systemic infections. Their undesirable side effects, particularly ototoxicity and nephrotoxicity, have restricted their systemic use to serious infections or infections caused by bacterial strains resistant to other agents.

Chemistry Contain 3 parts (3-4)units. Aminoglycosides are so named because their structures consist of amino sugars linked glycosidically. All have at least one amino hexose, and some have a pentose lacking an amino group (e.g., streptomycin, neomycin, and paromomycin). In addition to that each of clinically useful aminoglycosides contains a highly substituted 1,3- diaminocyclohexane central ring; in kanamycin, neomycin, gentamicin, and tobramycin, it is deoxystreptamine(deoxy mean lack OH group), and in streptomycin, it is streptadine.

The aminoglycosides are thus strongly basic compounds that exist as polycations at physiological pH. Their inorganic acid salts are very soluble in water. All are available as sulfates. Solutions of the aminoglycoside salts are stable to autoclaving. The high water solubility of the aminoglycosides contributes to their pharmacokinetic properties.

They distribute well into most body fluids but not into the central nervous system, bone, or fatty or connective tissues. They tend to concentrate in the kidneys and are excreted by glomerular filtration. Aminoglycosides are apparently not metabolized in vivo.

Spectrum of Activity

Under certain circumstances, aminoglycoside and β- lactam antibiotics exert a synergistic action in vivo against some bacterial strains when the two are administered jointly. For example, carbenicillin and gentamicin are synergistic against gentamicin-sensitive strains of P. aeruginosa and several other species of Gram-negative bacilli, and penicillin G and streptomycin (or gentamicin or kanamycin) tend to be more effective than either agent alone in the treatment of enterococcal endocarditis.

The two antibiotic types should not be combined in the same solution because they are chemically incompatible. Damage to the cell wall caused by the β- lactam antibiotic interfere with cell wall syntheses so it increase penetration of the aminoglycoside into the bacterial cell. So we can decrease the dose due to synergistic effect.

Mechanism of Action The aminoglycosides act directly on the bacterial ribosome to inhibit the initiation of protein synthesis and to interfere with the fidelity of translation of the genetic message. They bind to the 30S ribosomal subunit to form a complex that cannot initiate proper amino acid polymerization.

The binding of streptomycin and other aminoglycosides to ribosomes also causes misreading mutations of the genetic code, apparently resulting from failure of specific aminoacyl RNAs to recognize the proper codons on messenger RNA (mRNA) and hence incorporation of improper amino acids into the peptide chain. All of the commercially available aminoglycoside antibiotics are bactericidal, except spectinomycin.

Products Streptomycin Sulfate, Sterile Streptomycin sulfate is a white, odorless powder that is hygroscopic but stable toward light and air. It is freely soluble in water, forming solutions that are slightly acidic or nearly neutral. It is very slightly soluble in alcohol and is insoluble in most other organic solvents. Acid hydrolysis yields streptidine and streptobiosamine, the compound that is a combination of L-streptose and N-methyl-L- glucosamine

Streptomycin acts as a triacidic base through the effect of its two strongly basic guanidino groups and the more weakly basic methylamino group. Aqueous solutions may be stored at room temperature for 1 week without any loss of potency, but they are most stable if the pH is between 4.5 and 7.0. The solutions decompose if sterilized by heating, so sterile solutions are prepared by adding sterile distilled water to the sterile powder. The early salts of streptomycin contained impurities that were difficult to remove and caused a histamine-like reaction. By forming a complex with calcium chloride, it was possible to free the streptomycin from these impurities and to obtain a product that was generally well tolerated.

These are characterized by vertigo, disturbance of equilibrium, and diminished auditory perception. Additionally, nephrotoxicity occurs with some frequency. Patients undergoing therapy with streptomycin should have frequent checks of renal monitoring parameters.

Side effect Chronic toxicity reactions may or may not be reversible. Minor toxic effects include rashes, mild malaise, muscular pains, and drug fever. As a chemotherapeutic agent, streptomycin is active against numerous Gram-negative and Gram-positive bacteria.

One of the greatest virtues of streptomycin is its effectiveness against the tubercle bacillus, M. tuberculosis. By itself, the antibiotic is not a cure, but it is a valuable adjunct to other treatment modalities for TB, used also locally in GIT The greatest drawback to the use of streptomycin is the infection of amoebic dysentery. Because streptomycin is not absorbed when given orally or destroyed significantly in the GI tract, at one time it was used rather widely in the treatment of infections of the intestinal tract. For systemic action, streptomycin usually is given by intramuscular injection.

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