aminoglycoside

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