An aminoglycoside is a molecule composed of a sugar group and an amino group. Streptomycin is an Antibiotic drug the first of a class of drugs called Aminoglycosides to be discovered and was the first antibiotic remedy for Tuberculosis Amines are Organic compounds and Functional groups that contain a basic Nitrogen Atom with a Lone pair. [1]
Several aminoglycosides function as antibiotics that are effective against certain types of bacteria. In modern usage an antibiotic is a Chemotherapeutic agent with activity against Microorganisms such as Bacteria, fungi or Protozoa The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have They include amikacin, gentamicin, kanamycin, neomycin, netilmicin, paromomycin, rhodostreptomycin[2], streptomycin, tobramycin, and apramycin. Amikacin is an Aminoglycoside Antibiotic used to treat different types of Bacterial Infections Amikacin works by binding to the bacterial Gentamicin is an Aminoglycoside Antibiotic, used to treat many types of bacterial infections particularly those caused by Gram-negative Kanamycin sulfate is an Aminoglycoside Antibiotic, available in both oral and Intravenous forms and used to treat a wide variety of Infections Neomycin is an Aminoglycoside Antibiotic that is found in many topical medications such as creams ointments and eyedrops Netilmicin is a member of the Aminoglycoside family of Antibiotics These antibiotics have the ability to kill a wide variety of Bacteria. Paromomycin sulfate (brand name Humatin) is a Aminoglycoside based drug that fights intestinal infections such as Cryptosporidiosis and amoeba infection Streptomycin is an Antibiotic drug the first of a class of drugs called Aminoglycosides to be discovered and was the first antibiotic remedy for Tuberculosis Tobramycin sulfate is an Aminoglycoside Antibiotic used to treat various types of Bacterial infections particularly Gram-negative infections Apramycin (also Nebramycin II) is an Aminoglycoside Antibiotic.
Anthracyclines are another group of aminoglycosides. Anthracyclines (or anthracycline antibiotics) are a class of drugs used in cancer chemotherapy. These compounds are used in chemotherapy. Chemotherapy, in its most general sense refers to treatment of disease by chemicals that kill cells specifically those of micro-organisms or Cancer.
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Nomenclature
Aminoglycosides that are derived from bacteria of the Streptomyces genus are named with the suffix -mycin, while those which are derived from Micromonospora are named with the suffix -micin. Streptomyces, the largest Genus of Actinobacteria and type genus of the family Streptomycetaceae. A genus (plural genera from Γένος Latin genus "descent family type gender" is a low-level Taxonomic Micromonospora is a genus of bacteria of the family Micromonosporaceae.
This nomenclature system is not specific for aminoglycosides. For example vancomycin is a glycopeptide antibiotic and erythromycin, which is produced from a defunct species of Streptomyces along with its synthetic derivatives clarithromycin and azithromycin are macrolides - all of which differ in their mechanism of actions. Vancomycin ( INN) (ˌvæŋkoʊˈmaɪsɪn is a Glycopeptide Antibiotic used in the Prophylaxis and treatment of infections caused by Glycopeptide antibiotics are a class of Antibiotic drugs. The class is composed of a glycosylated cyclic or polycyclic Nonribosomal peptides Erythromycin is a Macrolide Antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of Penicillin, and is often used for people Streptomyces, the largest Genus of Actinobacteria and type genus of the family Streptomycetaceae. Clarithromycin is a Macrolide Antibiotic used to treat Pharyngitis, Tonsillitis, acute maxillary Sinusitis, acute bacterial exacerbation Azithromycin is an Azalide, a subclass of Macrolide Antibiotics. The macrolides are a group of drugs (typically Antibiotics) whose activity stems from the presence of a macrolide ring, a large macrocyclic
Mechanism of action
Aminoglycosides work by binding to the bacterial 30S ribosomal subunit (some work by binding to the 50S subunit), inhibiting the translocation of the peptidyl-tRNA from the A-site to the P-site and also causing misreading of mRNA, leaving the bacterium unable to synthesize proteins vital to its growth. Note Sometimes the ' 30s is used as shorthand for the 1930s, the 1830s, or other such decades in various centuries Events and Trends Ribosomes ( from ribo nucleic acid and "Greek soma ( meaning body") are complexes of RNA and Protein that Note Sometimes the ' 50s is used as shorthand for the 1950s, the 1850s, or other such decades in various centuries Events and Trends They kill bacteria by inhibiting protein synthesis as they bind to the 16S rRNA and by disrupting the integrity of bacterial cell membrane. [3] However, their exact mechanism of action is not fully known.
There is a significant relationship between the dose administered and the resultant plasma level in blood. TDM, therapeutic drug monitoring, is necessary to obtain the correct dose. These agents exhibit a post-antibiotic effect in which there is no or very little drug levels detectable in blood, but there still seems to be inhibition of bacterial re-growth. This is due to strong, irreversible binding to the ribosome, and remains intracellular long after plasma levels drop. This allows a prolonged dosage interval. Depending on their concentration they act as bacteriostatic or bacteriocidial agents. Bacteriostatic Antibiotics limit the growth of bacteria by interfering with bacterial Protein production DNA replication or other aspects of A bactericide or bacteriocide is a substance that kills bacteria and preferably nothing else
The protein synthesis inhibition of aminoglycosides does not usually produce a bactericidal effect, let alone a rapid one as is frequently observed on susceptible Gram-negative bacilli. Aminoglycosides competitively displace cell biofilm-associated Mg2+ and Ca2+ that link the polysaccharides of adjacent lipopolysaccharide molecules. "The result is shedding of cell membrane blebs, with formation of transient holes in the cell wall and disruption of the normal permeability of the cell wall. This action alone may be sufficient to kill most susceptible Gram-negative bacteria before the aminoglycoside has a chance to reach the 30S ribosome[4]. "
Spectrum of activity
Aminoglycosides are useful primarily in infections involving aerobic, gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. An aerobic organism or aerobe is an Organism that has an Oxygen based Metabolism. Gram-negative bacteria are those Bacteria that do not retain Crystal violet dye in the Gram staining protocol Pseudomonas is a Genus of gamma Proteobacteria, belonging to the larger family of Pseudomonads Recently 16S rRNA sequence Acinetobacter is a Gram-negative Genus of bacteria belonging to the Phylum Proteobacteria. Enterobacter is a genus of common Gram-negative, facultatively-anaerobic, rod-shaped Bacteria of the family Enterobacteriaceae In addition, some Mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Mycobacterium is a Genus of Actinobacteria, given its own family the Mycobacteriaceae Tuberculosis (abbreviated as TB for tubercle bacillus or T u' b' erculosis Bacillus --> is a common The most frequent use of aminoglycosides is empiric therapy for serious infections such as septicemia, complicated intraabdominal infections, complicated urinary tract infections, and nosocomial respiratory tract infections. Usually, once cultures of the causal organism are grown and their susceptibilities tested, aminoglycosides are discontinued in favor of less toxic antibiotics.
Streptomycin was the first effective drug in the treatment of tuberculosis, though the role of aminoglycosides such as streptomycin and amikacin has been eclipsed (because of their toxicity and inconvenient route of administration) except for multiple drug resistant strains.
Infections caused by gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. In the past the aminoglycosides have been used in conjunction with beta-lactam antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis. Endocarditis is an Inflammation of the inner layer of the Heart, the Endocardium. One of the most frequent combinations is ampicillin (a beta-lactam, or penicillin-related antibiotic) and gentamicin. Often, hospital staff refer to this combination as "amp and gent" or more recently called "pen and gent" for penicillin and gentamicin.
Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses.
Experimentation with aminoglycosides as a treatment of cystic fibrosis (CF) has shown some promising results. Cystic fibrosis (also known as CF, mucoviscoidosis, or mucoviscidosis) is a hereditary disease affecting the exocrine (mucus glands of the lungs CF is caused by a mutation in the gene coding for the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance Cystic fibrosis transmembrane conductance regulator ( CFTR) is an ABC transporter -class Protein and Ion channel that transports Chloride In approximately 10% of CF cases the mutation in this gene causes its early termination during translation, leading to the formation of is truncated and non-functional CFTR protein{{Fact}. Translation is the first stage of Protein biosynthesis (part of the overall process of Gene expression) It is believed that gentamicin distorts the structure of the ribosome-RNA complex, leading to a mis-reading of the termination codon, causing the ribosome to "skip" over the stop sequence and to continue with the normal elongation and production of the CFTR protein. Gentamicin is an Aminoglycoside Antibiotic, used to treat many types of bacterial infections particularly those caused by Gram-negative In the Genetic code, a stop codon (or termination codon) is a Nucleotide triplet within Messenger RNA that signals a termination of translation Ribosomes ( from ribo nucleic acid and "Greek soma ( meaning body") are complexes of RNA and Protein that The treatment is still experimental.
Toxicity
The toxicity of these agents are dose-related, and therefore every individual can get these side effects provided the dose is sufficiently high enough. Because of their potential for ototoxicity and nephrotoxicity (kidney toxicity), aminoglycosides are administered in doses based on body weight. Ototoxicity is damage of the Ear ( oto) specifically the Cochlea or auditory nerve and sometimes the Vestibulum, by a Toxin Nephrotoxicity (from Greek nephros "kidney" is a Poisonous effect of some substances both Toxic chemicals and Medication, on the Kidney The kidneys are complicated organs that have numerous biological roles Toxicity is the degree to which a substance is able to damage an exposed organism Vestibular damage, hearing loss and tinnitus are irreversible, so care must be taken not to achieve a sufficiently high dose. Concomitant administration of a cephalosporin may lead to increased risk of nephrotoxicity while administration with a loop diuretic increases the risk of ototoxicity. The cephalosporins (ˌsɛfələˈspɔrən/ /ˌkɛfə- are a class of β-lactam antibiotics. Loop diuretics are Diuretics that act on the ascending Loop of Henle in the Kidney. Blood drug levels and creatinine are monitored during the course of therapy, as there is a highly variable dose to plasma level in blood. Creatinine is a break-down product of Creatine phosphate in Muscle, and is usually produced at a fairly constant rate by the body (depending on muscle mass Serum creatinine measurements are used to estimate how well the kidneys are functioning and as a marker for kidney damage caused by these drugs. They may react with and prolong the actions of neuromuscular agents. Impaired renal function necessitates a reduced dose.
Routes of administration
Since they are not absorbed from the gut, they are administered intravenously and intramuscularly. Intravenous therapy or IV therapy is the giving of Liquid substances directly into a Vein. Intramuscular injection is the injection of a substance directly into a Muscle. Some are used in topical preparations for wounds. Oral administration can be used for gut decontamination (e. g. in hepatic encephalopathy).
Citations
- ^ MeSH Aminoglycosides
- ^ Massachusetts Institute of Technology. Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books "Bacterial 'Battle For Survival' Leads To New Antibiotic. " ScienceDaily 27 February 2008. 28 February 2008 <http://www.sciencedaily.com /releases/2008/02/080226115618. htm>.
- ^ Aminoglycosides versus bacteria--a description of the action, resistance mechanism, and nosocomial battleground. J Biomed Sci. 2008 Jan;15(1):5-14.
- ^ Lorian, Victor. "Antibiotics in Laboratory Medicine". Williams & Wilkins Press, 1996 (pp. 589-590)
External links
- MedlinePlus drug information - Aminoglycosides (Systemic)
- Science Daily Bacterial 'Battle for Survival' - Rhodostreptomycin
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