AMINOGLYCOSIDE

ANTIBIOSTICS
The aminoglycosides consists of two or more amino
sugar joint in glycosidic linkage to a hexose nucleus,
which is naturally in a central position. They are
basically bacteriocidal in nature and are effective
against gram negative bacteria’s like listeria
,shigella,salmonella,haemophills,bordetella and
brucella,some gram positive bacterias.they are not
absorbed from GIT,therefore,administered parenterally
and excreted through the kidneys.they impain
neuromuscular transmission and contraindicated in
myasthemia like disorders.
Aminoglycoside is a medicinal and bacteriologic
category of traditional Gram-negative antibacterial
therapeutic agents that inhibit protein synthesis and
contain as a portion of the molecule an amino-modified
glycoside (sugar); the term can also refer more
generally to any organic molecule that contains
aminosugar substructures. Aminoglycoside antibiotics
display bactericidal activity against gram-negative
aerobes and some anaerobic bacilli where resistance has
not yet arisen, but generally not against Gram-positive
and anaerobic Gram-negative bacteria. They include the
first-in-class aminoglycoside antibiotic streptomycin
(images at right) derived from Streptomyces griseus, the
earliest modern agent used against tuberculosis, and an
example that lacks the common 2-deoxystreptamine
moiety (image right, below) present in many other class
members. Other examples include the
deoxystreptamine-containing agents kanamycin,
tobramycin, gentamicin, and neomycin.

COMMON PROPERTIES OF
AMINOGLYCOSIDE ANTIBIOTICS
 All are used as sulphate salts ,which are highly
water soluble ,solutions ,are stable for months.
 They ionize in solution ,are not absorbed orally
only extracellulary ,do not penetrate brain or CSF.
 All are bacteriacidal and more active at alkaline
pH.
 All are active primarily against aerobic gram
negative bacilli and do not inhibit anaerobes.
 All exhibit ototoxicity and nephrotoxicity.
 They have relatively narrow margin of safety.

CLASSIFICATION:
1. Systemic amino glycosides:

-Stretomycin -Gentamicin
-Kanamycin -Tobramycin
 -Amikacin -Sisomicin
-Paromomycin -Netilmicin
2.Topical amino glycosides: -Neomycin
-Framycetin

MECHANISM OF ACTION
The amino glycosides are bactericidal antibiotics ,all having
the same general pattern of action which may be described in
two main steps:
(a) Transport of the amino glycoside through the bacterial cell
wall and cytoplasmic membrane.
(b) Binding to ribosomes resulting in inhibition of protein
synthesis.
It can say in other words ,inhibition of bacterial protein
synthesis by binding to 30s subunits of bacteril ribosomes.

ADME:
Administered IM,IV or SC, high concentration is found in
body fluids, cross the placenta ,plasma t1/2 is 2-3
hours,excreted within 24 hours as unchanged from kidney.

CONTRA-INDICATED IN :
-Renal disorders
-Geriatric patients
-Myasthemia gravis
DOSE:
Gentamicin /Tobramycin /Sisomicin /Netilmicin -3-5
mg/kg/day.
Steptomycin /Kanamycin /Amikacin- 7.5-15 mg/kg/day.

ADVERSE EFFECTS:
(a) Ototoxicity
(b) Neuromuscular blockage
(c) Anginoedema
(d) Anaphylactic shock
(e) Nephrotoxicity
(f ) Disfunction of optic nerve
(g) Eosinophilia
PRECAUTIONS AND INTERACTIONS:
(a) Avoid amino glycosides during pregnancy ;risk of foetal
ototoxicity.
(b) Avoid concurrent use of other neprotoxic drugs ,e.g.
,NSAIDs , Amphotericin , Vancomycin ,Cyclosporin
,Cisplatin.
(c) Cautions use of muscle relaxants in patients receiving an
amino glycoside.
(d) Do not mi
x amino glycoside with any drug in the same syringe /infusion
bottles.

USES: Amino glycosides are preferred in the following

causes-
(a) Effective against infections due to gram negative bacterias.
(b) Tuberclosis (streptomycin)
(c) Plague
(d) Urinary tract infections (kanamycin)
(e ) Respiratory tract infections (kanamycin)
(f) Skin and GIT infections (Tramycetin)
(g) Chronic amoebic dysentery (promamycin)
(h) Atherosclerosis (neomycin)
(i) Antiseptic (gentamicin)
(j) Skin elesion (Gentamicin)

PROTOTYPE DRUGS
STREPTOMYCIN
Streptomycin is an antibiotic (antimycobacterial) drug,
the first of a class of drugs called aminoglycosides to be
discovered, and it was the first effective treatment 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.

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. Speculation on this mechanism indicates that the
binding of the molecule to the 30S subunit interferes with 50S
subunit association with the mRNA strand. This results in an
unstable ribosomal-mRNA complex, leading to a frameshift
mutation and defective protein synthesis; leading to cell death.
Humans have ribosomes which are structurally different from
those in bacteria, so the drug does not have this effect in
human cells. At low concentrations, however, 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 therefore a useful broad-spectrum antibiotic.

ADVERSE EFFECTS
 - Fever - Rashes
- Tinnitus - Vertigo
- Ataxia - Nephrotoxicity

Uses
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 is prohibitive.
 Plague (Yersinia pestis) has historically been
treated with it as the first-line treatment. However
It is approved for this purpose only 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.
 Tularemia infections have been treated mostly
with Streptomycin and some other antibiotic
drugs, which is effective, but the infection is
resistant to Penicillin.
While streptomycin traditionally is given
intramuscularly (indeed, in many countries it is only
licensed to be used intramuscularly), the drug may also
be administered intravenously.

GENTAMICIN

Gentamicin, sold under brand names Garamycin among

others, is an antibiotic used to treat many types of bacterial
infections. This may include bone infections, endocarditis,
pelvic inflammatory disease, meningitis, pneumonia, urinary
tract infections, and sepsis among others. It is not effective
for gonorrhea or chlamydia infections. It can be given
intravenously, by injection into a muscle, or topically. Topical
formulations may be used in burns or for infections of the
outside of the eye. In the developed world it is often only
used for two days until bacterial cultures determine what
antibiotics the infection is sensitive to.[3] The dose required
should be monitored by blood testing.
It is obtained from the bacteria Micromonospora purpurea.

Mechanism of action:
Gentamicin is a bactericidal antibiotic that works by
irreversibly binding the 30S subunit of the bacterial
ribosome, interrupting protein synthesis. This
mechanism of action is similar to other
Aminoglycosides. Gentamicin is a bactericidal
antibiotic.

ADVERSE EFFECTS:
Side effects of gentamicin can range from less severe reactions such
as nausea and vomiting to more severe reactions such as:

 Low blood counts

 Allergic responses
 Neuromuscular problems
 Nerve damage
 Kidney damage (nephrotoxicity)
 Ear disorders (ototoxicity)

Kidney damage

Factors that increase risk of nephrotoxicity include:

 Increased age
 Reduced renal function
 Pregnancy
 Hypothyroidism
 Hepatic dysfunction
 Volume depletion
 Metabolic acidosis
 Sodium depletion

Inner ear

Factors that increase risk of inner ear damage include:

  High blood uric acid levels
 Kidney dysfunction
 Liver dysfunction
 Higher doses
 Long courses of therapy
 Elderly
 Also taking strong diuretics (e.g. furosemide)

Uses
Gentamicin is used in the treatment of respiratory tract
infections, urinary tract infections, blood, bone and soft
tissues infections of these susceptible bacteria.
Gentamicin is not used for Neisseria gonorrhoeae, Neisseria
meningitidis or Legionella pneumophila bacterial infections
(because of the risk of the person 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).

Neomycin
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 or 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.

ADVERSE EFFECTS:
Applied topically neomycin has low sensitizing potential.
However, rashes do occur.
Small amounts that are absorbed from the gut or topical sites
are excreted unchanged by kidney.This may accumulate in
patients with renal insufficiency-cause further kidney damage
and ototoxicity. Neomycin is contra indicated if renal
function is impaired.

DOSE:
0.25-1gm QID oral, 0.3-0.5% topical.

USES:
Neomycin is typically 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.

KANAMYCIN

Kanamycin (also known as kanamycin A) is an aminoglycoside

bacteriocidal 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[1] and its most commonly used
form is kanamycin sulfate.

Side effects:
Serious side effects include tinnitus or loss of hearing, toxicity
to kidneys, and allergic reactions to the drug.

Mechanism of action:
Kanamycin interacts with the 30S subunit of prokaryotic
ribosomes. It gives birth to substantial amounts of
mistranslation and indirectly inhibits translocation during
protein synthesis.

Uses:
Kanamycin has been used to treat infections caused by Gram-
negative bacteria including E. coli, Proteus spp., Serratia
marcescens, and Klebsiella pneumoniae.

TOBRAMYCIN

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.

Adverse effects:
Like other aminoglycosides, tobramycin is ototoxic: it can
cause hearing loss, or a loss of equilibrioception, or both in
genetically susceptible individuals. These individuals carry a
normally harmless genetic mutation that allows
aminoglycosides such as tobramycin to affect cochlear cells.
Aminoglycoside-induced ototoxicity is generally irreversible.
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. Specifically, aminoglycosides possess high
affinities for certain portions of RNAs, especially the
prokaryotic rRNA. In addition, aminoglycosides bind to the
hammerhead ribozyme, tRNA(Phe), the Rev response element
(RRE) transcriptional activation region in human
immunodeficiency virus (HIV), the ribozyme from hepatitis
delta virus, and group I self-splicing introns.

DOSE:
3-5mg/kg day in 1-3 doses.

USES:
Like all aminoglycosides, tobramycin does not pass the
gastro-intestinal tract, so for systemic use it can only be given
intravenously or intramuscularly. Ophthalmic (tobramycin
only, Tobrex, or combined with dexamethasone, sold as
TobraDex) and nebulised formulations both have low
systemic absorption. The formulation for injection is branded
Nebcin. The nebulised formulation (brand name Tobi) is
indicated in the treatment of exacerbations of chronic
infection with Pseudomonas aeruginosa in patients diagnosed
with cystic fibrosis. A proprietary formulation of micronized,
nebulized tobramycin has been tested as a treatment for
bacterial sinusitis. Tobrex and TobraDex are indicated in the
treatment of superficial infections of the eye, such as bacterial
conjunctivitis. Tobramycin (injection) is also indicated for
various severe or life-threatening gram-negative infections:
meningitis in neonates, brucellosis, pelvic inflammatory
disease, Yersinia pestis infection (plague).

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;

Mechanism of action:
Paromomycin is a protein synthesis inhibitor in nonresistant
cells by binding to 16S ribosomal RNA.This broad-spectrum
antibiotic soluble in water, is very similar in action to
neomycin. Antimicrobial activity of paromomycin against
Escherichia coli and Staphylococcus aureus has been shown.

USES:
It is an antibiotic used to treat intestinal infections such
as cryptosporidiosis and amoebiasis, and other
diseases such as leishmaniasis.
The route of administration is intramuscular injection
and capsule. Paromomycin topical cream with or
without gentamicin is an effective treatment for
ulcerative cutaneous leishmaniasis, according to the
results of a phase-3, randomized, double-blind, parallel
group–controlled trial.
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ofMedicalPharmacology”, seventh edition,
Published by Japee, New Delhi 110002 India,
Page No- 743-751.
 Sharma D, Cukras AR, Rogers EJ, Southworth DR,

Green R (7 December 2007). "Mutational analysis

of S12 protein and implications for the accuracy
of decoding by the ribosome". Journal of
Molecular Biology 374.
 East, J E; Foweraker, J E; Murgatroyd, F D (2005-

05-01). "Gentamicin induced ototoxicity during

treatment of enterococcal endocarditis:
resolution with substitution by netilmicin"
 Garrod, L.P., et al.: "Antibiotic and
Chemotherapy", page 131. Churchill Livingstone,
1981.
 "Neomycin." Pharmaceutical Manufacturing
Encyclopedia (3rd edition) Volume 3. (2007):
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