This document provides information on various aminoglycoside antibiotics, including their classification, mechanisms of action, resistance, and side effects. It discusses several specific aminoglycosides - streptomycin, gentamicin, amikacin, neomycin, kanamycin, and framycetin. All aminoglycosides are bactericidal, acting by binding to bacterial ribosomes and inhibiting protein synthesis. Resistance can occur via enzymatic modification or decreased drug accumulation in bacteria. Adverse effects include ototoxicity and nephrotoxicity.

1. PRESENTATION ON:
AMINOGLYCOSIDE
INTEGRAL UNIVERSITY,LUCKNOW
Session: 2016-2017
Presented by: Under the guidence of:
Mohd Muztaba Dr .Anuradha Mishra
M.Pharm 1st year
Pharmacology

2.  These are a group of natural and semisynthetic antibiotics
having polybasic amino groups linked glycosidically to two or
more aminosugar (strephdine2-deoxy streptamine garosamine)
residue.
 Unlike penicilline which was a chance discovery
aminoglycosides are products of deliberate search for drugs
effective against gram-negative bacteria.
 All aminoglycosides are produced by soil actinomycetes

3. CLASSIFICATION
 Systemic aminoglycosides
Streptomycine, Amikacin
Gentamicin, Sisomicin
Kanamycin
 Topical aminoglycosides
Neomycin , Framycetin

4.  MECHANISM OF ACTION
 The aminoglycosides are bactericidal antibiotic
 Transport of the aminoglycosides through bacterial cell wall &
cytoplasmic membrane (diffusion-outer coat-Gm –ve via porin
channel)
 Irreversibly Binding to ribosomes (mostly 30s and 50s,30s
&50s interface) resulting in inhibition of protein synthesis.

6. MECHANISM OF RESISTANCE
 Production of a transferase enzyme or enzymes inactivates the
aminoglycoside by acetylation, or phosphorylation. This is
the principal type of resistance encountered clinically
 There is impaired entry of aminoglycoside into the cell. This
may be genotypic, resulting from mutation or deletion of a
proteins involved in transport and maintenance of the
electrochemical gradient; or phenotypic, eg, resulting from
growth conditions under which the oxygen-dependent
transport process described above is not functional
 The receptor protein on the 30S ribosomal subunit may be
deleted or altered as a result of a mutation.

7.  CONTRAINDICATIONS : hypersensitivity to aminoglycosides
or bisulfites
 DRUG INTERACTION :
• Inactivated by penicillins and cephalosporins when
coadministered to pateints with renal insufficiency.
• Increased incidence of ototoxicity with loop diuretics.
• Increased incidence of nephrotoxicity with other nephrotoxic
drugs.
 SIDE EFFECTS : nausea,vomiting,urticaria,muscles
weakness,rash etc.
 ADVERSE EFFECTS: vertigo,myocarditis,thrombocytopenia,
leukemia,hepatic necrosis,muscle paralysis, etc.
 TOXICITY : ototoxicity,nephrotoxicity

8. STREPTOMYCIN
• It is older antibiotics and obtained by Streptomyces griseus,
used in past but now used for treatment of TB
 M.O.A
• Inhibit initiation of translation by binding to 16s rRNA.
 MECHANISM OF RESISTANCE
• Mutations in (16sRNA) or (ribosomal protein) which produce
alterations in the streptomycin binding site
Cross resistance:
• Partial or unidirectional cross resistance occur.

9. Pharmacokinetics
• Neither absorbed nor destroyed in git.
• Absorption from injection site in muscle is rapid.
• Distributed extracellularly, volume of distribution 0.3 L/kg
• It is not metabolized. Excreted unchanged in urine
• Plasma half life is 2-4 hrs
Adverse effects
• Vestibular disturbances, auditory disturbances
• Nephrotoxicity
• Hypersensitivity are rare-rashes, eosinophilia, dermatitis
• Pain at injection site

10. CONTRAINDICATION: pregnancy causes foetal
ototoxicity
DOSE: Tb – 1g or 0.75 g i.m OD or thrice weekly for
30-60 days
Acute infection: 1g i.m OD or BD for 7-10 days
USES: TB, given with
pencillin/ampicillin/vancomycin for 4-6 weeks
• Plague: rapid cure within 7-12 days
• Tularemia: Streptomycin cures it in 7-10 days

11. GENTAMYCIN
 Gentamicin is an aminoglycoside isolated from
Micromonospora purpurea . It is effective against both gram-
positive and gram-negative organisms
Antimicrobial Activity
 Gentamicin sulfate inhibits in vitro many strains of
staphylococci and coliforms and other gram-negative bacteria.

12. RESISTANCE
 gentamicin in combination with vancomycin or a penicilline
produces a potent bactericidal effect, which in part is due to
enhanced uptake of drug that occurs with inhibition of cell wall
synthesis
 Resistance to gentamicin rapidly emerges in staphylococci
during monotherapy owing to selection of permeability
mutants. Ribosomal resistance is rare. Among gram-negative
bacteria, resistance is most commonly due to plasmid-encoded
aminoglycoside-modifying enzyme
 Gram-negative bacteria that are gentamicin-resistant usually
are susceptible to amikacin, which is much more resistant to
modifying enzyme activity.

13. AMIKACIN
 It is a semisynthetic aminoglycoside
 It is effective against several gram negative organism
including
Escherichia coli
Mycobacterium tuberculosis
 It is bactericidal effect Amikacin in highly effective against
pseudomonas
 RESISTANCE
 decreased uptake and/or accumulation of the drug in bacteria
the bacterial expression of enzymes which modify the
antibiotic and thereby inactivate it

14. ADVERSE EFFECT
• Vertigo
• Ataxia
• Ototoxicity
• Nephrotoxicity
USE
• Rt i
• Bone and joint infection
• Skin and soft tissue infection

15. INTRACTION
 Amphoterecin b may leads to increase nephrotoxicity and
reduce the clearance of amikacin when use in together
 Increse risk of ototoxicity with potent diuretics

16. NEOMYCIN & KANAMYCIN
 wide spectrum active against Gm-ve bacilli and some gm+ve
cocci and obtained from Streptomyces.fradiae
Antimicrobial Activity & Resistance
 Drugs of the neomycin group are active against gram-positive
and gram-negative bacteria and some mycobacteria.and
streptococci are generally resistant. Mechanisms of
antibacterial action and resistance are the same as with other
aminoglycosides.
 The widespread use of these drugs in bowel preparation for
elective surgery has resulted in the selection of resistant
organisms and some outbreaks of enterocolitis in hospitals.
Cross-resistance between kanamycin and neomycin is
complete.

17.  USES:Topically used in skin, eye and external ear
infections combined with bacitracin or polymyxin-B to
widen antibacterial spectrum and to prevent emergence of
resistant strains
Orally
 Preparation of bowel before surgery 1 gm TDS
ADVERSE EFFECT
 Applied topically neomycin has low sensitizing potential
However, rashes do occur.
 Oral neomycin has a damaging effect on intestinal villi-
prolonged treatment can induce malabsorption syndrome with
diarrhoea
 It can decrease the absorption of digoxin and many other
drugs, as well as bile acids.

18. FARAMYCETIN
 it is very similar to neomycin. It is too toxic for systemic
administration and is used topically on skin, eye, ear in the
same manner as neomycin.

19. THANK YOU