Aminoglycosides - a group of natural and semi synthethic antibiotics having aminosugar link to an aminocyclitol ring by glycosidic bond. Includes: streptomycin, neomycin, gentmicin, amicacin, kanamycin and tobramycin. Share many chemical and pharmacological properties and have similar antibacterial spectrum and toxic effects. CHEMISTRY Presence of amino group in the structure imparts basic nature to aminoglycosides Hydroxyl group on sugar provides high water solubility( or poor lipid solubility) MECHANISMS OF ACTION Gram negative organisms allow aminoglycosides to diffuse through porin channel in their outer membrane These organisms also have an oxygen dependent system that transports antibiotic across the cell membrane Antibiotics then binds to 30s ribosomal subunit There it causes 30s subunit of completed ribosome to misread the genetic code which leads to incompletely synthesized protein BACTERIAL RESISTANCE Due to: Decreased uptake of drug when oxygen dependent transport system or porin channels are absent Altered 30s ribosomal subunit aminoglycosides binding site Plasmid associated synthesis of enzymes like acetyltransferase, nucleotidyltransferase and phosphotransferases ADVERSE EFFECTS Nephrotoxicity Occurs as a result of excessive accumulation of aminoglycosides by proximal tubular cells Ototoxicity both vesicular and auditory dysfunction due to accumulation in perilymph and endolymph in the inner ear in the dose and time dependent manner Neuromuscular blockade Due to interference with acetylcholine release from motor nerve endings Other effects Have low tendency to cause allergic reactions, may produce peripheral neuritis and dysfunction of optic nerve. Contact dermatitis is a common reaction to topically applied neomycin. DRUG INTERACTION Shows interactipon with drugs which cause ototoxicity, nephrotoxicity and neurotoxicity Concurrent use of aminoglycosides with loop diuretics( furosemide) and osmotic diuretics(mannitol) aggravate nephrotoxic and ototoxic effect. When used with inhalent anaesthetic or neuromuscular blocking drugs increase risk of neuromuscular blockade and respiratory paralysis Aminoglycosides and halothane aggravates cardiovascular depression Shows synergistic effect with beta -lactam antibiotics. Higher concentrates of carbenicillin, ticarcillin and piperacillin are reported to inactivate aminoglycosides CLINICAL USES Widely used to treating local and systemic infection caused by susceptible bacteria Infused into uterus to treat endometritis and udder to treat mastitis Also topically used ears and eyes CONTRAINDICATIONS: Contradicted in patients those who are hypersensitive to them Should be used with extreme caution in pre existing renal disease, neonate, geriatric and obese animals Should not be given to working dogs due to it’s adverse effect on hearing Cause adverse effect on foetus, so their use during pregnancy is not recommended until mandatory

1. AMINOGLYCOSIDES

2. •Aminoglycosides - a group of natural and semi synthethic
antibiotics having aminosugar link to an aminocyclitol ring
by glycosidic bond.
•Includes: streptomycin, neomycin, gentmicin, amicacin,
kanamycin and tobramycin.
•Share many chemical and pharmacological properties
and have similar antibacterial spectrum and toxic effects.

3. CHEMISTRY
•Presence of amino group in the structure imparts basic
nature to aminoglycosides
•Hydroxyl group on sugar provides high water solubility(
or poor lipid solubility)

4. ANTIBACTERIAL SPECTRUM
CLASSIFICATION DRUGS SUSCEPTIBLE
ORGANISM
Narrow Streptomycin,
dihydrostreptomy
cin
Aerobic gram
negative
Broad Neomycin
Kanamycin
Aerobic gram
negative and
gram positive
Extended Gentamycin Wide range of
gram negative
and gram positive

5. MECHANISMS OF ACTION
•Gram negative organisms allow aminoglycosides to
diffuse through porin channel in their outer membrane
•These organisms also have an oxygen dependent system
that transports antibiotic across the cell membrane
•Antibiotics then binds to 30s ribosomal subunit
•There it causes 30s subunit of completed ribosome to
misread the genetic code which leads to incompletely
synthesized protein

6. BACTERIAL RESISTANCE
Due to:
•Decreased uptake of drug when oxygen dependent
transport system or porin channels are absent
•Altered 30s ribosomal subunit aminoglycosides binding
site
•Plasmid associated synthesis of enzymes like
acetyltransferase, nucleotidyltransferase and
phosphotransferases

7. PHARMACOKINETICS
Administration
•Highly polar, polycationic structure of aminoglycosides
prevents adequate absorption after oral administration
•All (except neomycin) given through parenteral
administration
•Bactericidal effect-: concentration and time dependent

8. Distribution
•Extensively distributed in extracellular fluid, but do not
readily enter into cell due to their polar nature
•Largely excluded from brain, CSF, eye and most body
tissue except kidneys and inner ear
• May cross placental barrier and reach fetal plasma and
amniotic fluid

9. Biotransformation and Excretion
•Not metabolised in body and excreted largely(90%) in
urine by Glomerular filtration
•Plasma half life equals to 2 to 4 hrs in patient with
normal renal function which may increase to 24 to 48 hrs
in patient with renal insufficiency

10. ADVERSE EFFECTS
Nephrotoxicity
Occurs as a result of excessive accumulation of aminoglycosides by
proximal tubular cells
Ototoxicity
both vesicular and auditory dysfunction due to accumulation in
perilymph and endolymph in the inner ear in the dose and time
dependent manner
Neuromuscular blockade
Due to interference with acetylcholine release from motor nerve
endings
Other effects
Have low tendency to cause allergic reactions, may produce
peripheral neuritis and dysfunction of optic nerve. Contact
dermatitis is a common reaction to topically applied neomycin.

11. DRUG INTERACTION
•Shows interactipon with drugs which cause ototoxicity,
nephrotoxicity and neurotoxicity
•Concurrent use of aminoglycosides with loop diuretics(
furosemide) and osmotic diuretics(mannitol) aggravate
nephrotoxic and ototoxic effect.
•When used with inhalent anaesthetic or
neuromuscular blocking drugs increase risk of
neuromuscular blockade and respiratory paralysis

12. •Aminoglycosides and halothane aggravates
cardiovascular depression
•Shows synergistic effect with beta -lactam antibiotics.
•Higher concentrates of carbenicillin, ticarcillin and
piperacillin are reported to inactivate aminoglycosides

13. CLINICAL USES
•Widely used to treating local and systemic infection
caused by susceptible bacteria
•Infused into uterus to treat endometritis and udder to
treat mastitis
•Also topically used ears and eyes

14. CONTRAINDICATIONS:
Contradicted in patients those who are hypersensitive to
them
•Should be used with extreme caution in pre existing renal
disease, neonate, geriatric and obese animals
•Should not be given to working dogs due to it’s adverse
effect on hearing
•Cause adverse effect on foetus, so their use during
pregnancy is not recommended until mandatory

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