AMINOGLYCOSIDES

Definition
Aminoglycoside, any of several natural and semisynthetic compounds that are used to treat bacterial
diseases. The term aminoglycoside is derived from the chemical structure of these compounds, which
are made up of amino groups (NH2) attached to glycosides (derivatives of sugar). The first
aminoglycoside, the antibiotic streptomycin, was discovered in 1943 by American biochemists
Selman Waksman, Albert Schatz, and Elizabeth Bugie, who isolated the compound from Streptomyces
griseus, a strain of soil bacteria. Streptomycin was found to inhibit the growth of a variety of bacterial
organisms, including the organism that causes tuberculosis (Mycobacterium tuberculosis). Waksman
later isolated a second aminoglycoside,neomycin, from another species of soil bacteria, Streptomyces
fradiae. In the following decades, natural aminoglycosides, such as gentamicin and tobramycin, and
semisynthetic aminoglycosides, such as netilmicin and amikacin, were identified and developed.

Nomenclature
Aminoglycosides that are derived from bacteria of the Streptomyces genus are named with the
suffix mycin, whereas those that are derived from Micromonospora are named with the
suffix micin. However, this nomenclature system is not specific for aminoglycosides, and so
appearance of this set of suffixes does not imply common mechanism of action. (For
instance, vancomycin, a glycopeptide antibiotic, and erythromycin, a macrolide antibiotic produced
by Saccharopolyspora erythraea, along with its synthetic derivatives clarithromycin and azithromycin,
all share the suffixes but have notably different mechanisms of action).

Kanamycin A
Kanamycin (also known as kanamycin A) is an aminoglycoside bactericidal antibiotic, available
in oral, intravenous, and intramuscular forms, and used to treat a wide variety of infections.
Kanamycin is isolated from the bacterium Streptomyces kanamyceticus and its most
commonly used form is kanamycin sulfate.
Kanamycin interacts with the 30S subunit of prokaryotic ribosomes. It induces substantial
amounts of mistranslation and indirectly inhibits translocation during protein synthesis.
Kanamycin is a mixture of three main components: kanamycin A, B, and C. Kanamycin A is the
major component in kanamycin. The effects of these components do not appear to be widely
studied as individual compounds when used against prokaryotic and eukaryotic cells.

Amikacin

Tobramycin

Dibekacin

Amikacin (formerly Apothecon's Amikacin) is an aminoglycoside antibiotic used to treat

different types of bacterial infections. Amikacin works by binding to the bacterial 30S
ribosomal subunit, causing misreading of mRNA and leaving the bacterium unable to
synthesize proteins vital to its growth.
It is on the World Health Organization's List of Essential Medicines, a list of the most important
medication needed in a basic health system.
Amikacin is most often used for treating severe, hospital-acquired infections with multidrugresistant Gram-negative bacteria such as Pseudomonas aeruginosa, Acinetobacter, and
Enterobacter. Serratia marcescens and Providencia stuartii are also included in the spectrum.
Amikacin can also be used to treat non-tubercular mycobacterial infections and tuberculosis (if
caused by sensitive strains) when first-line drugs fail to control the infection.
Amikacin may be combined with a beta-lactam antibiotic for empiric therapy for people with
neutropenia and fever.

Tobramycin is an aminoglycoside antibiotic derived from Streptomyces tenebrarius and used to

treat various types of bacterial infections, particularly Gram-negative infections. It is especially
effective against species of Pseudomonas.

Analog of kanamycin with antitubercular as well as broad-spectrum antimicrobial properties.

Pharmacological action: antibiotics, aminoglycoside, antibiotics, antitubercular.

Gentamicin

Sisomicin

Gentamicin is an aminoglycoside antibiotic composed of a mixture of related gentamicin

components and fractions and is used to treat many types of bacterial infections, particularly
those caused by Gram-negative organisms. However, gentamicin is not used for Neisseria
gonorrhoeae, Neisseria meningitidis, or Legionella pneumophila. Gentamicin is also ototoxic
and nephrotoxic, with this toxicity remaining a major problem in clinical use.
Active against a wide range of human bacterial infections, mostly Gram-negative bacteria
including Pseudomonas, Proteus, Serratia, and the Gram-positive Staphylococcus. Gentamicin
is not used for Neisseria gonorrhoeae, Neisseria meningitidis or Legionella pneumophila
bacterial infections (because of the risk of the patient going into shock from lipid A endotoxin
found in certain Gram-negative organisms). Gentamicin is also useful against Yersinia pestis,
its relatives, and Francisella tularensis (the organism responsible for Tularemia seen often in
hunters and/or trappers).
Some Enterobacteriaceae, Pseudomonas spp., enterococci,
Staphylococcus aureus and other staphylococci are resistant to Gentamicin Sulfate, USP to
varying degrees.

Sisomicin (bactoCeaze or Ensamycin) is an aminoglycoside antibiotic, isolated from the

fermentation broth of a new species of the genus Micromonospora. It is a newer broadspectrum aminoglycoside most structurally related to gentamicin.
Sisomicin is the most predictably active aminoglycoside against gram-positive bacteria. Like
most other aminoglycosides, Sisomicin is bactericidal for sensitive clinical isolates. The
Minimum Bactericidal Concentrations (MBC) have been found to be equivalent or very close to
the Minimum Inhibitory Concentrations (MIC). Like other aminoglycosides, most clinical
isolates of Pseudomonas aeruginosa remain susceptible to sisomicin. Resistance to sisomicin
may enzymatically or non-enzymatically be mediated. Sisomicin is inactivated by the same
enzymes as gentamicin but it is active against many, not all, organisms that resist gentamicin
by non-enzymatic mechanisms.

Some studies show that sisomicin has been effective in the treatment of infections that either
had failed to respond to other drugs or were due to microorganisms resistant in vitro to other
aminoglycosides.

Netilmicin

Neomycins B, C

Netilmicin is a member of the aminoglycoside family of antibiotics. These antibiotics have the
ability to kill a wide variety of bacteria. Netilmicin is not absorbed from the gut and is therefore
only given by injection or infusion. It is only used in the treatment of serious infections
particularly those resistant to gentamicin.

Neomycin is an aminoglycoside antibiotic found in many topical medications such as creams,

ointments, and eyedrops. The discovery of neomycin dates back to 1949. It was discovered in
the lab of Selman Waksman, who was later awarded the Nobel Prize in Physiology and
medicine in 1951. Neomycin belongs to aminoglycoside class of antibiotics that contain two or
more aminosugars connected by glycosidic bonds. Due to the inherent oto- and nephrotoxicity
of these substances, systemic use has declined, as safer alternatives have become available.

Neomycin E (paromomycin)
Paromomycin is an aminoglycoside antibiotic, first isolated from Streptomyces krestomuceticus
in the 1950s. It was discovered by Parke Davis now Pfizer and introduced as Humatin in 1960.
It is also called monomycin and aminosidine;
It is on the World Health Organization's List of Essential Medicines, a list of the most important
medication needed in a basic health system.
It is an antibiotic used to treat intestinal infections such as cryptosporidiosis and amoebiasis,
and other diseases such as leishmaniasis. Paromomycin was demonstrated to be effective
against cutaneous leishmaniasis in clinical studies in the USSR in the 1960s, and in trials with
visceral leishmaniasis in the early 1990s.

Streptomycin
Streptomycin is an antibiotic (antimycobacterial) drug, the first of a class of drugs called
aminoglycosides to be discovered, and it was the first cure for tuberculosis. It is derived from
the actinobacterium Streptomyces griseus. Streptomycin is a bactericidal antibiotic. Adverse
effects of this medicine are ototoxicity, nephrotoxicity, fetal auditory toxicity, and
neuromuscular paralysis.

It is on the World Health Organization's List of Essential Medicines, a list of the most important
medication needed in a basic health system.

Mechanisms of action
Streptomycin in complex with a bacterial ribosome. X-ray crystallographic structure of the 30S
ribosomal subunit with bound drug (purple, space-filling representation, at center) protein secondary
structure elements such as alpha-helices in bright green, and the RNA phosphodiester backbone
shown in orange (and the ladder of base pairs in dark green and blue)
Aminoglycosides display concentration-dependent bactericidal activity against "most gram-negative
aerobic and facultative anaerobic bacilli" apart from some bacilli and methicillin-resistant
staphylococci, but not against gram-negative anaerobes and most gram-positive bacteria. They
require only short contact time, and are most effective against susceptible bacterial populations that
are rapidly multiplying. These activities are attributed to a primary mode of action as protein
synthesis inhibitors, though additional mechanisms are implicated for some specific agents, and/or
thorough mechanistic descriptions are as yet unavailable.
The inhibition of protein synthesis is mediated through aminoglycosides' energy-dependent,
sometimes irreversible binding, to the cytosolic, membrane-associated bacterial ribosome (image at
right, mouse-over for legend). (Aminoglycosides first cross bacterial cell wallslipopolysaccharide in
gram-negative bacteria)and cell membranes, where they are actively transported.) While specific
steps in protein synthesis affected may vary somewhat between specific aminoglycoside agents, as
can their affinity and degree of binding, aminoglycoside presence in the cytosol generally perturbs
peptide elongation at the 30S ribosomal subunit, giving rise to inaccurate mRNA translation and so
biosynthesis of proteins that are truncated or that bear altered amino acid compositions at particular
points. Specifically, binding impairs translational proofreading leading to misreading of the RNA
message, premature termination, or both, and so to inaccuracy of the translated protein product. The
subset of aberrant proteins that are incorporated into the bacterial cell membrane may then lead to
changes in its permeability and then to "further stimulation of aminoglycoside transport". The aminosugar portion of this class of molecules (e.g., the 2-deoxystreptamine in kanamycins, gentamicins,
and tobramycin, see above) are implicated in the association of the small molecule with ribosomal
structures that lead to the infidelities in translation (ibid.). Inhibition of ribosomal translocationi.e.,
movement of the peptidyl-tRNA from the A- to the P-sitehas also been suggested.[citation needed]
(Spectinomycin, a related but distinct chemical structure class often discussed with aminoglycosides,
does not induce mRNA misreading and is generally not bactericidal.)

Finally, a further "cell-membrane effect" also occurs with aminoglycosides; "functional integrity of the
bacterial cell membrane" can be lost, later in time courses of aminoglycoside exposure and transport

Routes of administration
Since they are not absorbed from the gut, they are administered intravenously and intramuscularly.
Some are used in topical preparations for wounds. Oral administration can be used for gut
decontamination (e.g., in hepatic encephalopathy). Tobramycin may be administered in a nebulized
form.

Clinical use
The recent emergence of infections due to Gram-negative bacterial strains with advanced patterns of
antimicrobial resistance has prompted physicians to reevaluate the use of these antibacterial agents.
This revived interest in the use of aminoglycosides has brought back to light the debate on the two
major issues related to these compounds, namely the spectrum of antimicrobial susceptibility and
toxicity. Current evidence shows that aminoglycosides do retain activity against the majority of Gramnegative clinical bacterial isolates in many parts of the world. Still, the relatively frequent occurrence
of nephrotoxicity and ototoxicity during aminoglycoside treatment makes physicians reluctant to use
these compounds in everyday practice. Recent advances in the understanding of the effect of various
dosage schedules of aminoglycosides on toxicity have provided a partial solution to this problem,
although more research still needs to be done in order to overcome this problem entirely.
Aminoglycosides are in pregnancy category D, that is, there is positive evidence of human fetal risk
based on adverse reaction data from investigational or marketing experience or studies in humans,
but potential benefits may warrant use of the drug in pregnant women despite potential risks.
Aminoglycosides can exacerbate weakness in patients with myasthenia gravis, and use is therefore
avoided in these patients.

QUESTIONS
1- What is it an aminoglycoside?
- Aminoglycoside is any of several natural are used for the treatment of bacterial diseases.
2- What is the function meets streptomycin?
- Streptomycin was found to inhibit the growth of a variety of bacterial organisms.
3- How named aminoglycosides?
- Bacteria of the Streptomyces genus are named with the suffix mycin.
4- What is it used kanamycin A?
It is used to treat a wide variety of infections. Kanamycin is isolated from a bacterium.
5- What are the three components of kanamycin A?
-Kanamycin is a mixture of three main components: kanamycin A, B, and C.
6- With that is the Antibiotic amikacin combined?
-Amikacin may be combined with a beta-lactam antibiotic for empiric therapy.
7- What is Amikacin?
-Amikacinis is an aminoglycoside antibiotic used to treat different types of bacterial infections.
8- What isnt type of bacteria uses gentamicin?
-The gentamicin is not used for Neisseria gonorrhoeae or Neisseria meningitides.

9- What function meets the Sisomicin?

- Sisomicin is bactericidal for sensitive clinical isolates.
10- When discovered Neomycin E?
- It was discovered by Parke Davis and introduced as Humatin in 1960.
11.-what is uses neomycin E?
-It is an antibiotic used to treat intestinal infections such as cryptosporidiosis and amoebiasis.
12- For neomycin used?
- These agents exhibit which there very little drug level detectable in blood.
13- What are the routes of administration?
- Since they are not absorbed from the gut, they are administered intravenously.
14- How Tobramycin is supplied?
-Tobramycin may be administered in a nebulized form.
15- What are the side effects of Aminoglycosides?
-Aminoglycosides can exacerbate weakness in patients with myasthenia gravis.

KEY TERMS
1 Aminosides: It is a group of bacteriostatic antibiotics that stop bacterial growth.
2 Amikacin: It is an aminoglycoside, tends to be particularly effective against resistant
organisms.
3 Bactericidal: It is any substance capable of killing bacteria, usually by lysis of the
wall.
4 Amino sugar: It is a substance that being a sugar, containing one or more amino
groups, giving them a basic character
5 Renal failure: It is a damage that occurs when the kidneys are unable to adequately
filter.
6 Cystic fibrosis: It is a genetic autosomal recessive disease that primarily affects the
lungs.
7 Bacilli: It is a bacteria found in different environments and can only be seen with a
microscope.
8 The synovial membrane: It is the inner lining of the diartrosis or synovial joints.
9 Tobramycin: It is an antibiotic specially designed for gram negative bacteria of genital
tract of women.
10 Acetyltransferase: It is a transferase enzyme whose catalytic activity is to transfer
an acetyl group.
11 Nephrotoxicity: It is toxicity exerted on the kidneys, organs whose functional
integrity is essential for the maintenance of homeostasis.
12 Neomycin: It is a drug that is used clinically as an antibacterial antibiotic
13 Enterococci: It is a coconut Gram-positive that are presented in pairs or chains
14 Gentamicin: It is an aminoglycoside used as an antibiotic to eradicate eye infections
15 Paromomycin: It is an antibiotic indicated for the treatment of infections intestinal.