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Transcript of aminoglycoside 2
Aminoglycoside
Introduction
These are a group of natural and semisynthetic antibiotics having polybasic amino groups linked
glycosidically to two or more aminosugar (streptidine, 2-deoxy streptamine, garosamine )
residues.
Unlike penicillin, which was a chance discovery, aminoglycosides are products of
deliberate search for drug effective against gram –negative bacteria. Streptomycin was the first
member discovered in 1944 by Waksman and his colleagues. It assumed gread importance
because it was active against tuberclebacilli. Others have been produced later, now
aminoglycosides are a sizable family. All aminoglycosides are produced by soil actinomycetes
and have many common properties
An aminoglycoside is a molecule or a portion of a molecule composed of amino-modified
sugars[1]
Several aminoglycosides function as antibiotics that are effective against certain types of
bacteria. They include amikacin, arbekacin, gentamicin, kanamycin, neomycin, netilmicin,
paromomycin, rhodostreptomycin,[2] streptomycin, tobramycin, and apramycin[3].
Systemic Aminoglycosides: Streptomycin Amikacin
Gentamicin Sisomicin
Kanamycin Netilmicin
Tobramycin
Topical Aminoglycosides:
Neomycin Framycetin
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 1
Aminoglycoside
Mechanisms of action:
Aminoglycosides have several potential antibiotic mechanisms, some as protein synthesis
inhibitors, although their exact mechanism of action is not fully known:
They interfere with the proofreading process, causing increased rate of error in synthesis
with premature termination.[9]
Also, there is evidence of inhibition of ribosomal translocation where the peptidyl-tRNA
moves from the A-site to the P-site.[9]
They can also disrupt the integrity of bacterial cell membrane. [10]
They bind to the bacterial 30S ribosomal subunit[11][12] (some work by binding to the 50S
subunit[13])
There is a significant variability in the relationship between the dose administered and the
resultant plasma level in blood. Therapeutic drug monitoring (TDM) is necessary to obtain the
correct dose. These agents exhibit a post-antibiotic effect in which there is no or very little drug
level 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 bactericidal agents.
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." [14]
The antibacterial properties of aminoglycosides were believed to result from inhibition of
bacterial protein synthesis through irreversible binding to the 30S bacterial ribosome. This
explanation, however, does not account for the potent bactericidal properties of these agents,
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 2
Aminoglycoside
since other antibiotics that inhibit the synthesis of proteins (such as tetracycline) are not
bactericidal. Recent experimental studies show that the initial site of action is the outer bacterial
membrane. The cationic antibiotic molecules create fissures in the outer cell membrane, resulting
in leakage of intracellular contents and enhanced antibiotic uptake. This rapid action at the outer
membrane, it is presumed, accounts for most of the bactericidal activity. Energy is needed for
aminoglycoside uptake into the bacterial cell. Anaerobes have less energy available for this
uptake, so aminoglycosides are less active against anaerobes.
Aminoglycosides are useful primarily in infections involving aerobic, gram-negative bacteria,
such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some Mycobacteria,
including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. 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. In the past, the
aminoglycosides have been used in conjunction with beta-lactam antibiotics in streptococcal
infections for their synergistic effects, in particular in endocarditis. 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.
Nonsense suppression:
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 3
Aminoglycoside
The interference with DNA proofreading has been exploited to treat genetic diseases that result
from premature stop codes (leading to early termination of protein synthesis and truncated
proteins). Aminoglycosides can cause the cell to overcome the stop code, insert a random amino
acid, and express a full-length protein. [15]
The aminoglycoside gentamicin has been used to treat cystic fibrosis (CF) cells in the laboratory
to induce them to grow full-length proteins. CF is caused by a mutation in the gene coding for
the cystic fibrosis transmembrane conductance regulator (CFTR) protein. 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. 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. [16]
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. [17] 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 Gram-negative 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
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 4
Aminoglycoside
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. [18]
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. [5]
This nomenclature system is not specific for aminoglycosides. For example, vancomycin is a
glycopeptide antibiotic and erythromycin, which is produced from the species
Saccharopolyspora erythraea (previously misclassified as Streptomyces) along with its synthetic
derivatives clarithromycin and azithromycin, is a macrolide. [7][8] All differ in their mechanisms
of action, however.
Streptomycin
Neomycin
Framycetin
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 5
Aminoglycoside
Paromomycin
Ribostamycin
Kanamycin
Amikacin
Arbekacin
Bekanamycin
Dibekacin
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 6
Aminoglycoside
Tobramycin
Spectinomycin
Hygromycin B
Paromomycin sulfate
Gentamicin
Netilmicin
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 7
Aminoglycoside
Sisomicin
Isepamicin
Verdamicin
Astromicin
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 8
Aminoglycoside
Amikacin
Amikacin
Systematic (IUPAC) name
(2S)-4-amino-N-[(2S,3S,4R,5S)-5-amino-2-
[(2S,3R,4S,5S,6R)-4-amino-3,5-dihydroxy-
6-(hydroxymethyl)oxan-2-yl]oxy-4-[(2R,3R,
4S,5R,6R)-6-(aminomethyl)-3,4,5-trihydroxy-
oxan-2-yl]oxy-3-hydroxy-cyclohexyl]-2-hydroxy-
butanamide
Clinical data
Trade names Amikin
AHFS/Drugs.com monograph
MedlinePlus a682661
Pregnancy cat. D(AU) C(US)
Legal status POM (UK) ℞-only (US)
Routes Intramuscular, intravenous
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 9
Aminoglycoside
Pharmacokinetic data
Protein binding 0-11%
Half-life 2-3 hours
Excretion Renal
Identifiers
CAS number 37517-28-5
ATC code D06AX12 J01GB06, S01AA21
PubChem CID 37768
DrugBank APRD00550
ChemSpider 34635
UNII 84319SGC3C
KEGG D02543
ChEBI CHEBI:2637
ChEMBL CHEMBL177
Chemical data
Formula C22H43N5O13
Mol. mass 585.603 g/mol
SMILES eMolecules & PubChem
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.
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 10
Aminoglycoside
Administration
Amikacin may be administered once or twice a day but must be given by the intravenous or
intramuscular route. There is no oral form available as amikacin is not absorbed orally. In people
with kidney failure, dosage must be adjusted according to the creatinine clearance, usually by
reducing the dosing frequency.
Uses
Amikacin is most often used for treating severe, hospital-acquired infections with multidrug
resistant 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.
Resistance
Amikacin has high resistance against bacterial inactivation. It resists attacks by most bacterial
inactivating enzymes, this is accomplished by the L-hydroxyaminobuteroyl amide (L-HABA)
moiety attached to N-3 which inhibits acetylation, phosphorylation and adenylation in the distant
amino sugar ring (C-2,C-3,C-4). To prevent the development of bacterial resistance to this
extremely powerful antibiotic, its use is tightly regulated.
Side effects
Side effects of amikacin are similar to other aminoglycosides. Kidney damage and hearing loss
are the most important effects. Because of this potential, blood levels of the drug and markers of
kidney function (creatinine) may be monitored. Moreover, doses are adjusted specifically based
upon serum Creatinine clearance in clinical settings.
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 11
Aminoglycoside
Apramycin
Apramycin
Systematic (IUPAC) name
(2R,3R,4R,5S,6R)-5-amino-2- [((1R,2R,3R,4R,6R,8R)-8-amino-9- [(1R,2S,3R,4R,6R)-4,6-diamino-2,3- dihydroxy-cyclohexyl]oxy-2-hydroxy- 3-methylamino-5,10- dioxabicyclo[4.4.0]dec-4-yl)oxy]-6-
(hydroxymethyl)oxane-3,4-diol
Clinical data
AHFS/Drugs.com International Drug Names
Pregnancy cat. ?
Legal status ?
Identifiers
CAS number 37321-09-8
ATCvet code QA07AA92 QJ01GB90 QJ51GB90
PubChem CID 3081545
DrugBank DB04626
ChemSpider 2339128
UNII 388K3TR36Z
KEGG D02322
ChEBI CHEBI:2790
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 12
Aminoglycoside
ChEMBL CHEMBL1230961
Chemical data
Formula C21H41N5O11
Mol. mass 539.58 g/mol
SMILES eMolecules & PubChem
InChI[show]
Apramycin (also Nebramycin II) is an aminoglycoside antibiotic used in veterinary medicine. It
is produced by Streptomyces tenebrarius.
Pharmacology:
Indication
For the treatment of bacterial infections in animals.
Mechanism of action
Apramycin stands out among aminoglycosides for its mechanism of action which is based on
blocking translocation and its ability to bind also to the eukaryotic decoding site despite
differences in key residues required for apramycin recognition by the bacterial target. The drug
binds in the deep groove of the RNA which forms a continuously stacked helix comprising non-
canonical C.A and G.A base pairs and a bulged-out adenine. The binding mode of apramycin at
the human decoding-site RNA is distinct from aminoglycoside recognition of the bacterial target,
suggesting a molecular basis for the actions of apramycin in eukaryotes and bacteria.
Arbekacin
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Aminoglycoside
Arbekacin
Systematic (IUPAC) name
(2S)-4-amino-N-[(1R,2S,3R,4R,5S)-5-amino-2-{[(2S,3R,4S,5S,6R)-4-amino-3,5-dihydroxy-6-
(hydroxymethyl)oxan-2-yl]oxy}-4-{[(2R,3R,6S)-3-amino-6-(aminomethyl)oxan-2-yl]oxy}-3-hydroxycyclohexyl]-
2-hydroxybutanamide
Clinical data
AHFS/Drugs.com International Drug Names
Pregnancy cat. ?
Legal status ℞ Prescription only
Routes Intramuscular, intravenous
Pharmacokinetic data
Metabolism Minimal
Excretion Renal
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 14
Aminoglycoside
Identifiers
CAS number 51025-85-5
ATC code J01GB12
PubChem CID 11398765
DrugBank DB06696
ChemSpider 2140
UNII G7V6SLI20L
KEGG D07462
ChEMBL CHEMBL233430
Chemical data
Formula C22H44N6O10
Mol. mass 552.62 g/mol
Arbekacin (INN) is a semisynthetic aminoglycoside antibiotic. It is primarily used for the
treatment of infections caused by multi-resistant bacteria including methicillin-resistant
Staphylococcus aureus (MRSA), Arbekacin was originally synthesized from dibekacin in 1973.
It has been registered and marketed in Japan since 1990 under the trade name Habekacin.
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Aminoglycoside
Arbekacin is no longer covered by patent and generic versions of the drug are also available
under such trade names as Decontasin and Blubatosine.
Pharmacology:
Indication
Arbekacin is used for the short term treatment of multi-resistant bacterial infections, such as
methicillin-resistant Staphylococcus aureus (MRSA).
Pharmacodynamics
Aminoglycosides, such as Arbekacin, work by binding to the bacterial 30S ribosomal subunit,
causing misreading of t-RNA which consequently, leaves the bacterium unable to synthesize
proteins vital to its growth. Energy is needed for aminoglycoside uptake into the bacterial cell.
Anaerobes have less energy available for this uptake, so aminoglycosides are less active against
anaerobes. Aminoglycosides are useful primarily in infections involving aerobic, gram-negative
bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter.
Mechanism of action
Aminoglycosides, such as 'Arbekacin, inhibit protein synthesis in susceptible bacteria by
irreversibly binding to bacterial 30S and 16S ribosomal subunits. Specifically Arbekacin binds to
four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with
decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region
interacts with the wobble base in the anticodon of tRNA. This leads to misreading of mRNA so
incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides
and the breakup of polysomes into nonfunctional monosomes.
Absorption
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 16
Aminoglycoside
Aminoglycosides are not well absorbed from the gastrointestinal tract. Their absorption is
markedly improved by parenteral administration.
Toxicity
Ototoxicity and nephrotoxicity are the most serious adverse effects of aminoglycoside therapy
and are more likely to occur in patients with a history of renal impairment or who are receiving
other ototoxic and/or nephrotoxic drugs. Normal duration of IM or IV aminoglycoside therapy is
7-10 days. Although a longer duration may be necessary in some cases, toxicity is more likely to
occur when aminoglycoside treatment is continued for longer than 10 days.
Affected organisms
Enteric bacteria and other eubacteria
Gentamicin
Gentamicin
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 17
Aminoglycoside
Systematic (IUPAC) name
(3R,4R,5R)-2-{[(1S,2S,3R,4S,6R)-4,6-
diamino-3-{[(2R,3R,6S)-
3-amino-6-[(1R)-
1-(methylamino)ethyl]oxan-2-yl]oxy}-
2-hydroxycyclohexyl]oxy}-5-methyl-
4-(methylamino)oxane-3,5-diol
Clinical data
AHFS/Drugs.com monograph
MedlinePlus a682275
Pregnancy cat. D
Legal status POM (UK)
Routes IV, IM, topical
Pharmacokinetic data
Bioavailability limited oral bioavailability
Protein binding 0-10%
Half-life 2 hrs
Excretion Renal
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 18
Aminoglycoside
Identifiers
CAS number 1403-66-3
ATC code D06AX07 J01GB03 S01AA11 S02AA14 S03AA06 QA07AA91 QG01AA91 QG51AA04 QJ51GB03
PubChem CID 3467
IUPHAR ligand 2427
DrugBank DB00798
ChemSpider 390067
UNII T6Z9V48IKG
KEGG D08013
ChEBI CHEBI:27412
ChEMBL CHEMBL195892
Chemical data
Formula C21H43N5O7
Mol. mass 477.596 g/mol
SMILES eMolecules & PubChem
InChI[show]
(what is this?) (verify)
Gentamicin is an aminoglycoside antibiotic, 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.
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 19
Aminoglycoside
It is synthesized by Micromonospora, a genus of Gram-positive bacteria widely present in the
environment (water and soil). To highlight their specific biological origins, gentamicin and other
related antibiotics produced by this genus (verdamicin, mutamicin, sisomicin, netilmicin,
retymicin) generally have their spellings ending in ~micin and not in ~mycin. Gentamicin is a
bactericidal antibiotic that works by binding the 30S subunit of the bacterial ribosome,
interrupting protein synthesis.
Like all aminoglycosides, when gentamicin is given orally, it is not systemically active. This is
because it is not absorbed to any appreciable extent from the small intestine. It is administered
intravenously, intramuscularly or topically to treat infections. It appears to be completely
eliminated unchanged in the urine. Urine must be collected for many days to recover all of a
given dose because the drug binds avidly to certain tissues.
E. coli has shown some resistance to gentamicin, despite being Gram-negative. Reluctance to use
gentamicin for empirical therapy has led to increased use of alternative broad-spectrum
antibiotics, which some experts suggest has led to the prevalence of antibiotic-resistant bacterial
infections by Golden Staph and other so-called "superbugs".
Gentamicin is one of the few heat-stable antibiotics that remain active even after autoclaving,
which makes it particularly useful in the preparation of some microbiological growth media. It is
used during orthopaedic surgery when high temperatures are required for the setting of cements
(e.g. hip replacements).
Spectrum of activity
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
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 20
Aminoglycoside
certain Gram-negative organisms). Gentamicin is also useful against Yersinia pestis and its
relatives.
Side effects
These aminoglycosides are toxic to the sensory cells of the ear, but they vary greatly in their
relative effects on hearing versus balance. Gentamicin is a vestibulotoxin, and can cause
permanent loss of equilibrioception, caused by damage to the vestibular apparatus of the inner
ear, usually if taken at high doses or for prolonged periods of time, but there are well
documented cases in which gentamicin completely destroyed the vestibular apparatus after three
to five days. A small number of affected individuals have a normally harmless mutation in their
mitochondrial RNA (m1555 A>G), that allows the gentamicin to affect their cells. The cells of
the ear are particularly sensitive to this, sometimes causing complete hearing loss. However,
gentamicin is sometimes used intentionally for this purpose in severe Ménière's disease, to
disable the vestibular apparatus.
Gentamicin can also be highly nephrotoxic, particularly if multiple doses accumulate over a
course of treatment. For this reason gentamicin is usually dosed by body weight. Various
formulae exist for calculating gentamicin dosage. Also trough and peak serum levels of
gentamicin are monitored during treatment, generally before and after the third dose is infused.
Gentamicin, like other aminoglycosides, causes nephrotoxicity by inhibiting protein synthesis in
renal cells. This mechanism specifically causes necrosis of cells in the proximal tubule, resulting
in acute tubular necrosis which can lead to acute renal failure.
Side effects of gentamicin toxicity vary from patient to patient. Side effects may become
apparent shortly after or up to months after gentamicin is administered. Symptoms of gentamicin
toxicity include:
Balance difficulty
Bouncing, unsteady vision
Ringing in the ears (tinnitus)
Difficulty multi-tasking, particularly when standing
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Aminoglycoside
Psychiatric symptoms related to gentamicin can occur. These include anorexia, confusion,
depression, disorientation and visual hallucinations. Immediate professional help should be
sought if any of these symptoms or others appear after administration of aminoglycosides.
General medical practitioners should refer patients with such symptoms to an otolaryngologist,
commonly known as an 'ear, nose, and throat doctor', for comprehensive tests.
A number of factors and determinants should be taken into account when using gentamicin,
including differentiation between empirical and directed therapy which will affect dosage and
treatment period. Many medical practitioners freely administer gentamicin as an antibiotic
without advising patients of the severe and permanent potential ramifications of its use.
Gentamicin is well known to be a cheap, low cost yet old medicine as compared to modern
alternatives, and is typically US$3–6 per dosage less than modern alternatives.
Many people recover from gentamicin toxicity naturally over time if the drug is discontinued,
but they recover slowly and usually incompletely. Sometimes the toxicity of gentamicin can still
increase over months after the last dose. Upon cessation of gentamicin therapy symptoms such as
tinnitus and imbalance may become less pronounced. Sensori-neural hearing loss caused by
gentamicin toxicity is permanent however.
Production and usage in research
Gentamicin is produced by a fermentation procedure. It was discovered by a Chinese
microbiologist, Yue Wang. The majority of the world's gentamicin production takes place in
China and South Korea; the last European producer is Lek, part of Sandoz group.
Gentamicin has been used since the early 1980s in microbiological research. The gentamicin
protection assay enables researchers to quantify the ability of pathogenic bacteria to invade
eukaryotic cells. It takes advantage of the fact that gentamicin is not able to penetrate eukaryotic
cells.
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Aminoglycoside
Kanamycin
Kanamycin
Systematic (IUPAC) name
2-(aminomethyl)- 6-[4,6-diamino-3- [4-amino-3,5-dihydroxy-6-(hydroxymethyl) tetrahydropyran-2-yl]oxy- 2-
hydroxy- cyclohexoxy]- tetrahydropyran- 3,4,5-triol
Clinical data
AHFS/Drugs.com monograph
Pregnancy cat. D
Legal status ?
Routes Oral, intravenous, intramuscular
Pharmacokinetic data
Bioavailability very low after oral delivery
Metabolism Unknown
Half-life 2 hours 30 minutes
Excretion Urine (as unchanged drug)
Identifiers
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 23
Aminoglycoside
CAS number 59-01-8
ATC code A07AA08 J01GB04 S01AA24
PubChem CID 6032
DrugBank APRD00026
ChemSpider 5810
UNII RUC37XUP2P
ChEBI CHEBI:17630
ChEMBL CHEMBL1384
Chemical data
Formula C18H36N4O11
Mol. mass 484.499
SMILES eMolecules & PubChem
InChI[show]
(what is this?) (verify)
Kanamycin sulfate is an aminoglycoside antibiotic, available in oral, intravenous, and
intramuscular forms, and used to treat a wide variety of infections. Kanamycin is isolated from
Streptomyces kanamyceticus.
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Aminoglycoside
Mechanism
Kanamycin interacts with the 30S subunit of prokaryotic ribosomes. It induces substantial
amounts of mistranslation and indirectly inhibits translocation during protein synthesis.
Side effects
Serious side effects include tinnitus or loss of hearing, toxicity to kidneys, and allergic reactions
to the drug.
Use in research
Kanamycin is used in molecular biology as a selective agent most commonly to isolate bacteria
(e.g., E. coli) which have taken up genes (e.g., of plasmids) coupled to a gene coding for
kanamycin resistance (primarily Neomycin phosphotransferase II [NPT II/Neo]). Bacteria that
have been transformed with a plasmid containing the kanamycin resistance gene are plated on
kanamycin (50-100 ug/ml) containing agar plates or are grown in media containing kanamycin
(50-100 ug/ml). Only the bacteria that have successfully taken up the kanamycin resistance gene
become resistant and will grow under these conditions. As a powder kanamycin is white to off-
white and is soluble in water (50 mg/ml).
Mammalian cells and other eukaryotes are screened using G418, a similar aminoglycoside
antibiotic, which KanMX confers resistance against.
At least one such gene, Atwbc19 is native to a plant species, of comparatively large size and its
coded protein acts in a manner which decreases the possibility of Horizontal Gene Transfer from
the plant to bacteria; it may be incapable of giving resistance to kanamycin to bacteria even if
gene transfer occurs.
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Aminoglycoside
Neomycin
Neomycin
Systematic (IUPAC) name
(1R,2R,3S,4R,6S)-4,6-diamino-2-
Clinical data
Trade names Neo-rx
AHFS/Drugs.com monograph
MedlinePlus a682274
Pregnancy cat. ?
Legal status OTC
Routes Topical, Oral
Pharmacokinetic data
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 26
Aminoglycoside
Half-life 2 to 3 hours
Identifiers
CAS number 1404-04-2
ATC code A01AB08 A07AA01, B05CA09, D06AX04, J01GB05, R02AB01,
S01AA03, S02AA07, S03AA01
PubChem CID 8378
IUPHAR ligand 709
DrugBank DB00994
ChemSpider 8075
UNII I16QD7X297
KEGG D08260
ChEBI CHEBI:7508
ChEMBL CHEMBL449118
Chemical data
Formula C23H46N6O13
Mol. mass 614.644 g/mol
SMILES eMolecules & PubChem
InChI[show]
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 27
Aminoglycoside
Neomycin is an aminoglycoside antibiotic that is 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 which contain
two or more aminosugars connected by glycosidic bonds. Neamine (two rings), Ribostamycin
(three rings), Paromomycin (four rings) and Lividomycin (five rings) are some other examples of
aminoglycosides. They have shown tremendous potential as antibacterials. One of them,
Gentamicin has been used extensively in clinical practice. Due to the inherent oto and
nephrotoxicity of these substances, systemic use has declined as safer alternatives have become
available.
Uses
Neomycin is overwhelmingly used as a topical preparation, such as Neosporin. It can also be
given orally, where it is usually combined with other antibiotics. Neomycin is not absorbed from
the gastrointestinal tract and has been used as a preventive measure for hepatic encephalopathy
and hypercholesterolemia. By killing bacteria in the intestinal tract, it keeps ammonia levels low
and prevents hepatic encephalopathy, especially prior to GI surgery. It has also been used to treat
small intestinal bacterial overgrowth. It is not given intravenously, as neomycin is extremely
nephrotoxic (causes kidney damage), especially compared to other aminoglycosides. The
exception is when neomycin is included, in very small quantities, as a preservative in some
vaccines - typically 0.025 mg per dose.
Molecular biology
Neomycin resistance is conferred by either one of two aminoglycoside phosphotransferase genes.
A neo gene is commonly included in DNA plasmids used by molecular biologists to establish
stable mammalian cell lines expressing cloned proteins in culture; many commercially available
protein expression plasmids contain neo as a selectable marker. Non-transfected cells will
eventually die off when the culture is treated with neomycin or similar antibiotic. Neomycin or
kanamycin can be used for prokaryotes, but geneticin (G418) is, in general, needed for
eukaryotes.
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 28
Aminoglycoside
Spectrum
Similar to other aminoglycosides, neomycin has excellent activity against Gram-negative
bacteria, and has partial activity against Gram-positive bacteria. It is relatively toxic to humans,
and many people have allergic reactions to it. See: Hypersensitivity. Physicians sometimes
recommend using antibiotic ointments without neomycin, such as Polysporin.
History
Neomycin was discovered in 1949 by the microbiologist Selman Waksman and his student
Hubert Lechevalier at Rutgers University. It is produced naturally by the bacterium
Streptomyces fradiae.
Neomycin as a DNA binder
Neomycin belongs to the family of aminoglycosides. This family includes many other
medicinally important drugs: streptomycin, paromomycin and kanamycin . Aminoglycosides are
known for their ability to bind to duplex RNA with high affinity. A study done by Daniel Pilch,
Associate Professor Dept. of Pharmacology at Rutgers University, and his coworkers determined
the association constant for neomycin with A-site RNA was found to be in the ~109 range.
However, more than 50 years after its discovery, its DNA-binding properties were still unknown.
In 2000, Dev P. Arya, currently Director of the Laboratory of Medicinal Chemistry at Clemson
University, and his coworkers discovered that neomycin induces enormous thermal stabilization
of triplex DNA while having little or almost no effect on the DNA duplex stabilization. They
also showed that neomycin binds to structures that adopt A-form structure, triplex DNA being
one of them. They later went on to show that neomycin even induces DNA:RNA hybrid triplex
formation.
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 29
Aminoglycoside
Netilmicin
Netilmicin
Systematic (IUPAC) name
(2R,3R,4R,5R)-2-{[(1S,2S,3R,4S,6R)-4-amino-3-{[(2S,3R)-3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-
yl]oxy}-6-(ethylamino)-2-hydroxycyclohexyl]oxy}-5-methyl-4-(methylamino)oxane-3,5-diol
Clinical data
AHFS/Drugs.com monograph
MedlinePlus a605011
Pregnancy cat. ?
Legal status ?
Pharmacokinetic data
Bioavailability ~0%
Half-life 2.5 hours
Identifiers
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 30
Aminoglycoside
CAS number 56391-56-1
ATC code J01GB07 S01AA23
PubChem CID 41859
DrugBank APRD00232
ChemSpider 38195
UNII 4O5J85GJJB
KEGG D08268
ChEMBL CHEMBL1572
Chemical data
Formula C21H41N5O7
Mol. mass 475.58 g/mol
SMILES eMolecules & PubChem
InChI[show]
(what is this?) (verify)
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.
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 31
Aminoglycoside
Available dosage forms
Available dosage forms include:
UK: netilmicin (as Sulphate):
o 10 mg/mL (1.5 mL amp)
o 50 mg/mL (1-mL amp)
o 100 mg/mL(1-mL,1.5-mL & 2-mL amp)
France: Nétilmicin sulfate:
o Amp 25 mg/1 mL
o 50 mg/2 mL
o 100 mg/1 mL
o 150 mg/1.5 mL
Ingredients for 100 mg/mL vial
Netilmicin (as sulphate) 100 mg
Sodium metabisulfite 2.4 mg
Sodium sulfite 0.8 mg
Edetate disodium 0.1 mg
Benzyl alcohol 10 mg
Water for injection qs 1 mL
FDA approval date : February 28, 1983
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 32
Aminoglycoside
Comparison with drugs of the same therapeutic category:
According to the British National Formulary (BNF), netilmicin has similar activity to
gentamicin, but less ototoxicity in those needing treatment for longer than 10 days.Netilmicin is
active against a number of gentamicin-resistant Gram-negative bacilli but is less active against
Ps. Aeuroginosa than gentamicin or tobramycin.
However according to the below-mentioned studies, the above advantages are somehow
controversial:
Netilmicin (Netromycin, Schering-Plough, Netspan- Cipla):
In summary, netilmicin has not been demonstrated to have significant advantages over other
aminoglycosides (gentamicin, tobramycin, amikacin), and it is more expensive; thus, its
potential value is limited. Drug Intelligence & Clinical Pharmacy: Vol. 17, No. 2, pp. 83-91.
Once-daily gentamicin versus once-daily netilmicin in patients with serious infections—a
randomized clinical trial:
We conclude that with once-daily dosing no benefit of netilmicin over gentamicin regarding
nephro- or ototoxicity could be demonstrated. Journal of Antimicrobial Chemotherapy
(1994) 33, 823-835.
Ototoxicity and nephrotoxicity of gentamicin vs netilmicin in patients with serious
infections. A randomized clinical trial:
We conclude that with once-daily treatment no benefit of netilmicin over gentamicin
regarding nephro- or ototoxicity could be demonstrated. Clin Otolaryngol Allied Sci. 1995
Apr;20(2):118-23.
Relative efficacy and toxicity of netilmicin and tobramycin in oncology patients:
We conclude that aminoglycoside-associated ototoxicity was less severe and more often
reversible with netilmicin than with tobramycin. Arch Intern Med. 1986 Dec;146(12):2329-
34.
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 33
Aminoglycoside
Daily single-dose aminoglycoside administration. Therapeutic and economic benefits:
Animal studies have shown that dosing aminoglycosides once daily is more efficient and less
nephrotoxic than the conventional multiple daily dosing regimens. Netilmicin and amikacin
are the drugs most often used in clinical trials of once-daily dosing regimens. Ugeskr Laeger.
1993 May 10;155(19):1436-41.
Comparison of Netilmicin with Gentamicin in the Therapy of Experimental Escherichia coli
Meningitis:
Because of its reduced toxicity and greater in vivo bactericidal activity, netilmicin may offer
an advantage over gentamicin in the therapy of gram-negative bacillary meningitis.
Antimicrob Agents Chemother. 1978 June; 13(6): 899-904.
A comparison of netilmicin and gentamicin in the treatment of pelvic infections:
The microbacteria isolated by standard culture techniques before therapy revealed Neisseria
gonorrhoeae in 69% and 51% of the netilmicin and gentamicin groups, respectively;
anaerobic organisms were cultured in about 75% of each group. Obstetrics & Gynecology
1979;54:554-557.
Netilmicin: a review of toxicity in laboratory animals:
Presently available data suggest that netilmicin offers distinct advantages over older
aminoglycosides. Final conclusions must await prospective randomized double-blind trials in
man. J Int Med Res. 1978;6(4):286-99.
Nonparallel nephrotoxicity dose-response curves of aminoglycosides:
Nephrotoxicity comparisons of aminoglycosides in rats, utilizing large multiples of human
doses, have indicated an advantage for netilmicin. However, no nephrotoxicity advantage of
netilmicin has been demonstrated at the lower doses used in clinics. Antimicrob Agents
Chemother. 1981 June; 19(6): 1024–1028.
Comparative ototoxicity of netilmicin, gentamicin, and tobramycin in cats:
Under the conditions of this study, at least a twofold (vestibular) to fourfold (cochlear)
relative safety margin for ototoxicity was established in favor of netilmicin over tobramycin
and gentamicin. Toxicol Appl Pharmacol. 1985 Mar 15;77(3):479-89.
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 34
Aminoglycoside
Comparison of Netilmicin and Gentamicin Pharmacokinetics in Humans:
In a crossover study, single doses of netilmicin and gentamicin were administered
intramuscularly, each at 1.0 and 2.5 mg/kg. No significant differences were observed
between the two drugs in disposition half-life, rate of distribution and elimination, area under
the serum concentration-time curve, urinary excretion, total body clearance, and renal
clearance. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Feb. 1980, p. 184-187.
Schering-Plough Research Division, Bloomfield, New Jersey 07003.
Paromomycin sulfate
Paromomycin
Systematic (IUPAC) name
(2R,3S,4R,5R,6S)-5-amino-6-[(1R,2S,3S,4R,6S)-
4,6-diamino-2-[(2S,3R,4R,5R)-4-[(2R,3R,4R,5R,6S)-
3-amino-6-(aminomethyl)-4,5-dihydroxy-oxan-2-yl]
oxy-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-
3-hydroxy-cyclohexyl]oxy-2-(hydroxymethyl)oxane-3,4-diol
Clinical data
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 35
Aminoglycoside
AHFS/Drugs.com monograph
MedlinePlus a601098
Pregnancy cat. B(US)
Legal status Rx only U.S.
Routes Oral, intramuscular
Pharmacokinetic data
Bioavailability None
Metabolism None
Half-life ?
Excretion Fecal
Identifiers
CAS number 1263-89-4
ATC code A07AA06
PubChem CID 441375
DrugBank DB01421
ChemSpider 390117
ChEMBL CHEMBL370143
Chemical data
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 36
Aminoglycoside
Formula C23H47N5O18S
Mol. mass 615.629 g/mol
SMILES eMolecules & PubChem
Paromomycin (brand name Humatin) is an aminoglycoside antibiotic, first isolated from
Streptomyces krestomuceticus in the 1950s. It is also called monomycin and aminosidine;
Uses
It is an antibiotic designed to fight intestinal infections such as cryptosporidiosis, amoebiasis,
and leishmaniasis.
The route of administration is intramuscular injection and capsule.
Mechanism
Paromomycin inhibits protein synthesis by binding to 16S ribosomal RNA.
History and availability
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.
It was developed as a therapeutic against visceral leishmaniasis by the Institute for OneWorld
Health. Paromomycin was granted orphan drug status in 2005 and was approved by the Drug
Controller General of India in September 2006 for treatment of visceral leishmaniasis.
As of February 5th, 2008, King Pharmaceuticals is discontinuing the sale of Humatin.
Paromomycin continues to be available in the United States from another manufacturer.[9]
Streptomycin
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 37
Aminoglycoside
Streptomycin
Systematic (IUPAC) name
5-(2,4-diguanidino-
3,5,6-trihydroxy-cyclohexoxy)- 4-[4,5-dihydroxy-6-(hydroxymethyl)
-3-methylamino-tetrahydropyran-2-yl] oxy-3-hydroxy-2-methyl
-tetrahydrofuran-3-carbaldehyde
Clinical data
AHFS/Drugs.com monograph
Pregnancy cat. DM[1]
Legal status POM (UK) ℞-only (US)
Routes Intramuscular, intravenous
Pharmacokinetic data
Bioavailability 84% to 88% (est.)[2]
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 38
Aminoglycoside
Half-life 5 to 6 hours
Excretion Renal
Identifiers
CAS number 57-92-1
ATC code A07AA04 J01GA01
PubChem CID 19649
DrugBank DB01082
ChemSpider 18508
UNII Y45QSO73OB
KEGG D08531
ChEBI CHEBI:17076
ChEMBL CHEMBL1201194
Chemical data
Formula C21H39N7O12
Mol. mass 581.574 g/mol
SMILES eMolecules & PubChem
Physical data
Melt. point 12 °C (54 °F)
(what is this?) (verify)
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. It is derived from the
actinobacterium Streptomyces griseus. Streptomycin is a bactericidal antibiotic. Streptomycin
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 39
Aminoglycoside
cannot be given orally, but must be administered by regular intramuscular injections. An adverse
effect of this medicine is ototoxicity.
Mechanism of action
Streptomycin is a protein synthesis inhibitor. It binds to the small 16S rRNA of the 30S subunit
of the bacterial ribosome, interfering with the binding of formyl-methionyl-tRNA to the 30S
subunit. This leads to codon misreading, eventual inhibition of protein synthesis and ultimately
death of microbial cells through mechanisms that are still not understood. Humans have
structurally different ribosomes from bacteria, thereby allowing the selectivity of this antibiotic
for bacteria. However at low concentrations Streptomycin only inhibits growth of the bacteria by
inducing prokaryotic ribosomes to misread mRNA. Streptomycin is an antibiotic that inhibits
both Gram-positive and Gram-negative bacteria, and is a therefore a useful broad-spectrum
antibiotic.
History
Streptomycin was first isolated on October 19, 1943 by Albert Schatz, a graduate student, in the
laboratory of Selman Abraham Waksman at Rutgers University. Dr. Waksman and his laboratory
discovered several antibiotics, including actinomycin, clavacin, streptothricin, streptomycin,
grisein, neomycin, fradicin, candicidin and candidin. Of these, streptomycin and neomycin found
extensive application in the treatment of numerous infectious diseases. Streptomycin was the
first antibiotic that could be used to cure the disease tuberculosis; early production of the drug
was dominated by Merck & Co. under George W. Merck.
The first randomized trial of streptomycin against pulmonary tuberculosis was carried out in
1946-1947 by the MRC Tuberculosis Research Unit under the chairmanship of Sir Geoffrey
Marshall (1887–1982). The trial was both double-blind and placebo-controlled. It is widely
accepted to have been the first randomised curative trial. Results showed efficacy against TB,
albeit with minor toxicity and acquired bacterial resistance to the drug.
Uses
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 40
Aminoglycoside
Treatment of diseases
Infective endocarditis caused by enterococcus when the organism is not sensitive to
Gentamicin
Tuberculosis in combination with other anti-TB drugs. It is not the first-line treatment,
except in medically under-served populations where the cost of more expensive treatments
are prohibitive.
Plague (Yersinia pestis) has historically been treated with it as the first-line treatment. It is
approved for this purpose by the U.S. Food and Drug Administration.
In veterinary medicine, streptomycin is the first-line antibiotic for use against gram negative
bacteria in large animals (horses, cattle, sheep etc.). It is commonly combined with procaine
penicillin for intramuscular injection.
While streptomycin is traditionally given intramuscularly (indeed, in many countries it is only
licensed to be used intramuscularly), the drug may also be administered intravenously.
Pesticide
Streptomycin is also used as a pesticide, to combat the growth of bacteria, fungi, and algae.
Streptomycin controls bacterial and fungal diseases of certain fruit, vegetables, seed, and
ornamental crops, and controls algae in ornamental ponds and aquaria. A major use is in the
control of fireblight on apple and pear trees. As in medical applications, extensive use can be
associated with the development of resistant strains.
Cell culture
Streptomycin, in combination with penicillin, is used in a standard antibiotic cocktail to prevent
bacterial infection in cell culture.
Tobramycin
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 41
Aminoglycoside
Tobramycin
Systematic (IUPAC) name
(2S,3R,4S,5S,6R)-4-amino-2-{[(1S,2S,3R,4S,6R)-4,6-diamino-3-{[(2R,3R,5S,6R)-3-amino-6-(aminomethyl)-5-
hydroxyoxan-2-yl]oxy}-2-hydroxycyclohexyl]oxy}-6-(hydroxymethyl)oxane-3,5-diol
Clinical data
Trade names Tobrex
AHFS/Drugs.com monograph
MedlinePlus a682660
Pregnancy cat. D (Injection, Inhalation); B (Ophthalmic) (US)
Legal status ?
Routes IV, IM, inhalation, ophthalmic
Pharmacokinetic data
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 42
Aminoglycoside
Protein binding < 30%
Identifiers
CAS number 32986-56-4
ATC code J01GB01 S01AA12
PubChem CID 36294
DrugBank APRD00582
ChemSpider 33377
UNII VZ8RRZ51VK
KEGG D00063
ChEBI CHEBI:28864
ChEMBL CHEMBL1747
Chemical data
Formula C18H37N5O9
Mol. mass 467.515 g/mol
SMILES eMolecules & PubChem
InChI[show]
(what is this?) (verify)
Tobramycin is an aminoglycoside antibiotic used to treat various types of bacterial infections,
particularly Gram-negative infections.
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 43
Aminoglycoside
Mechanism of action
Tobramycin works by binding to a site on the bacterial 30S and 50S ribosome, preventing
formation of the 70S complex. As a result, mRNA cannot be translated into protein and cell
death ensues. Tobramycin is preferred over gentamicin for Pseudomonas aeruginosa pneumonia
due to better lung penetration and bactericidal activity.
Administration
Like all aminoglycosides, tobramycin does not pass the gastro-intestinal tract, so for systemic
use it can only be given intravenously, intramuscularly, eyedrops (commonly with
Dextramethsone), or it can be administered and inhaled via nebuliser. The formulation for
injection is branded Nebcin. Patients with cystic fibrosis will often take an inhalational
(nebulised) form (Tobi) for suppression of Pseudomonas aeruginosa infections. Tobramycin is
also combined with dexamethasone as an ophthalmic solution (TobraDex).
Bausch & Lomb Pharmaceuticals produces a sterile tobramycin solution (eye-drops) with a
tobramycin concentration of 0.3%, which is available by prescription only in the United States
and Canada. (In some countries, such as Italy, it is available over the counter.) It is mixed with
0.01% benzalkonium chloride as a preservative. These concentrations result in 3 mg per ml and
0.1 mg per ml, respectively.
A proprietary formulation of micronized, nebulized tobramycin has been tested as a treatment for
bacterial sinusitis.
Side effects
Like other aminoglycosides, tobramycin can cause deafness or a loss of equilibrioception
(vertigo) in genetically susceptible individuals. These individuals have a normally harmless
mutation in their DNA, that allows the tobramycin to affect their cells. The cells of the ear are
particularly sensitive to this.
Tobramycin can also be highly toxic to the kidneys, particularly if multiple doses accumulate
over a course of treatment.
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 44
Aminoglycoside
For these reasons, when tobramycin is given parenterally, it is usually dosed by body weight.
Various formulae exist for calculating tobramycin dosage. Also serum levels of tobramycin are
monitored during treatment.
References
1. ^ MeSH Aminoglycosides
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 45
Aminoglycoside
2. ^ "Bacterial 'battle for survival' leads to new antibiotic" (Press release). Massachusetts
Institute of Technology. February 26, 2008.
http://web.mit.edu/newsoffice/2008/antibiotics-0226.html. Retrieved December 1, 2010.
3. ^ Ryden, R; Moore (1977). "BJ". J Antimicrob Chemother 3 (6): 609–613.
4. ^ Kroppenstedt RM, Mayilraj S, Wink JM (Jun 2005). "Eight new species of the genus
Micromonospora, Micromonospora citrea sp. nov., Micromonospora echinaurantiaca sp.
nov., Micromonospora echinofusca sp. nov. Micromonospora fulviviridis sp. nov.,
Micromonospora inyonensis sp. nov., Micromonospora peucetia sp. nov.,
Micromonospora sagamiensis sp. nov., and Micromonospora viridifaciens sp. nov". Syst
Appl Microbiol. 28 (4): 328–39. PMID 15997706.
5. ^ Paul M. Dewick (2009). Medicinal Natural Products: A Biosynthetic Approach (3rd ed
ed.). Wiley. ISBN 0470741678.
6. ^ Walter P. Hammes1 and Francis C. Neuhaus (1974). On the Mechanism of Action of
Vancomycin: Inhibition of Peptidoglycan Synthesis in Gaffkya homari. 6. pp. 722–728.
7. ^ Protein synthesis inhibitors: macrolides mechanism of action animation. Classification
of agents Pharmamotion. Author: Gary Kaiser. The Community College of Baltimore
County. Retrieved on July 31, 2009
8. ^ The Mechanism of Action of Macrolides, Lincosamides and Streptogramin B Reveals
the Nascent Peptide Exit Path in the Ribosome Martin Lovmar and Måns Ehrenberg
9. ^ a b Pharmamotion --> Protein synthesis inhibitors: aminoglycosides mechanism of
action animation. Classification of agents Posted by Flavio Guzmán on 12/08/08
10. ^ Shakil, Shazi; Khan, Rosina; Zarrilli, Raffaele; Khan, Asad U. (2007).
"Aminoglycosides versus bacteria – a description of the action, resistance mechanism,
and nosocomial battleground". Journal of Biomedical Science 15 (1): 5–14.
doi:10.1007/s11373-007-9194-y. PMID 17657587.
11. ^ Levison, Matthew E. (July 2009). "Aminoglycosides: Bacteria and Antibacterial
Drugs". Merck Manual Professional.
http://www.merck.com/mmpe/sec14/ch170/ch170b.html.
12. ^ "Aminoglycosides". http://www.aic.cuhk.edu.hk/web8/aminoglycosides.htm.
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 46
Aminoglycoside
13. ^ Champney, W. S. (2001). "Bacterial Ribosomal Subunit Synthesis A Novel Antibiotic
Target". Current Drug Targets - Infectious Disorders 1 (1): 19–36.
doi:10.2174/1568005013343281. PMID 12455231.
14. ^ Lorian, Victor (1996). Antibiotics in Laboratory Medicine. Williams & Wilkins Press.
pp. 589–90. ISBN 0-683-05169-5.
15. ^ Feero, W. Gregory; Guttmacher, Alan E.; Dietz, Harry C. (2010). "New Therapeutic
Approaches to Mendelian Disorders". New England Journal of Medicine 363 (9): 852–
63. doi:10.1056/NEJMra0907180. PMID 20818846.
16. ^ Wilschanski, Michael; Yahav, Yaacov; Yaacov, Yasmin; Blau, Hannah; Bentur, Lea;
Rivlin, Joseph; Aviram, Micha; Bdolah-Abram, Tali et al. (2003). "Gentamicin-Induced
Correction of CFTR Function in Patients with Cystic Fibrosis andCFTRStop Mutations".
New England Journal of Medicine 349 (15): 1433–41. doi:10.1056/NEJMoa022170.
PMID 14534336.
17. ^ Falagas, Matthew E; Grammatikos, Alexandros P; Michalopoulos, Argyris (2008).
"Potential of old-generation antibiotics to address current need for new antibiotics".
Expert Review of Anti-infective Therapy 6 (5): 593–600. doi:10.1586/14787210.6.5.593.
PMID 18847400.
18. ^ Durante-Mangoni, Emanuele; Grammatikos, Alexandros; Utili, Riccardo; Falagas,
Matthew E. (2009). "Do we still need the aminoglycosides?". International Journal of
Antimicrobial Agents 33 (3): 201–5. doi:10.1016/j.ijantimicag.2008.09.001.
PMID 18976888.
External links
MedlinePlus drug information - Aminoglycosides (Systemic) Science Daily Bacterial 'Battle for Survival' - Rhodostreptomycin
SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.) Page 47