1) Aminoglycosides are polybasic amino groups linked glycosidically to aminosugar compounds. They are highly water soluble and excreted unchanged in urine. 2) They are bactericidal, inhibiting protein synthesis by binding to the 30S/50S interface of bacterial ribosomes. This causes misreading of mRNA and nonfunctional protein formation. 3) Common adverse effects include ototoxicity (hearing loss) and nephrotoxicity. Individual drugs vary in their specific toxicities.

1. AMINOGYCOSIDE
ANTIMICROBIALS
Dr. Sahil Kumar
Department of Pharmacology
Maulana Azad Medical College

2. AMINO + GYCOSIDE
Polybasic amino groups linked
glycosidically to two or more aminosugar.

3. GENERAL PROPERTIES
 Highly water soluble, so not absorbed orally.
More active at alkaline pH.
Excreted unchanged in urine.
 Bactericidal, inhibit protein synthesis.
 Active against gram negative bacteria.
 Resemble each other in PK, therapeutic and toxic
properties.

4. MECHANISM OF ACTION
 Passive diffusion via porin channels across outer
membrane
 Decrease extra cellular pH
 Anaerobic conditions Transport
 Cell wall active drugs : (Penicillin, Vancomycin)
Transport Synergism
 Active transport across cell membrane into

5. Bind to 30s/ 50s/ 30s-50s interface of
ribosome:
 Interfere with initiation complex of peptide
formation.
 Induce misreading of mRNA-amino acid
peptide: toxic/non functional protein.
 Break up of polysomes to nonfunctional
monosomes.
MECHANISM OF ACTION

6.  Irreversible inhibition of protein synthesis
 Bactericidal
 Concentration dependent killing.
 “Post antibiotic effect” (once daily dosing)
MECHANISM OF ACTION

7. POST ANTIBIOTIC EFFECT
Antibacterial activity persists beyond the time
during which measurable conc is present.
Slow recovery after reversible nonlethal damage to
cell structures.
 Drug bound to receptor-periplasmic space.
 Time taken for enzyme synthesis for cell growth.

8. POST ANTIBIOTIC EFFECT
 Once daily dosing of aminoglycoside.
 High doses give once daily.
 Less toxicity, lower monitoring costs.

9. MECHANISM OF
RESISTANCE
 Drug inactivation -Bacteria elaborate
tranferase enzyme or adenylylating,
acetylating, phosphorylating enzyme: plasmid
mediated.
 Impaired entry – Mutation/Deletion of porins or
oxygen dependent transport process disrupted.
 Altered Binding Protein - 30s ribosomal unit
altered/ deleted:-mutation.

10. Mechanism of resistanceMechanism of resistance
produces enzymesproduces enzymes
Altered ribosomal subunitAltered ribosomal subunit
Changes of PorinsChanges of Porins
Active efflux systemActive efflux system

11. PHARMACOKINETICS
 Poor oral absorption from intact GIT mucosa
 After i/m. inj. peak conc. in 30-60 min.
 Highly polar, mainly extra cellular
 Cleared by kidneys: Excretion directly proportional
to creatinine clearance
 Normal half life in serum : 2-3 hrs
 Can cross placenta – fetal hearing loss.
C/I pregnancy.

12. CLASSIFICATION
Systemic Aminoglycosides
Streptomycin
Gentamicin
Kanamycin
Tobramycin
Topical Aminoglycosides
Neomycin
Framycetin
 Amikacin
 Sisomicin
 Netilmicin
 Paromomycin

13. SHARED ADVERSE
EFFECTS
Ototoxic :(Hearing Loss, Tinnitus)
Auditory (Cochlear damage) Vestibulotoxic: (Streptomycin,
(Neomycin, Kanamycin, Gentamicin)
Amikacin)
Nephrotoxic: Neomycin,Tobramycin,Gentamicin
Curare like effect : Resp paralysis, N.M. Blockade
Reversible: Calcium Gluconate or Neostigmine

14. ADVERSE DRUG REACTIONS
Cochl
ear
Vestib
ular
Nephrotoxic Clinical Uses
Streptomycin + ++ + T.B.
Gentamicin + ++ + More active
against
Pseudomonas
Tobramycin ++ ++ + ”
Netilmicin + + + In Gentamicin
resistant cases
Neomycin ++ + +++ Topical ,Oral
Framycetin ++ + +++ Topical
Kanamycin ++ + +++ T.B.
Amikacin ++ + +++ In Gentamicin
resistant Cases

15. STREPTOMYCIN
 Less active against Gram –ve bacilli than others.
 I/m. inj.
 Inactivating enzymes, Ribosomal resistance-limited
use as single agent.
Therapeutic uses:
 Bacterial Endocarditis:
Synergistic with penicillin - Enterococci, Gp.D
streptococci, Oral strept. viridans gps.
Strept + Penicillin G : 4 weeks

16.  Tularemia: 1-2g (15-25mg/kg/day) ×7 -10 d
 Plague: Most effective, 1-4g/day × 7-10 d
 Tuberculosis:15mg/day, i/m inj 2-3 months in
combination with other A.T. drugs
ADVERSE EFFECTS:
 Least nephrotoxic (not accumulated in renal cortex)
 Disturbance of vestibular fn. - vertigo
 Disturbance of auditory fn. – less common
 Fever,Rash,Allergic Reactions.
 C/I in pregnancy (deafness in newborn)

17.  From micromonospora purpurea
 Low cost, most reliable against resistant infections
 Mostly active against Gram –ve, some gram +ve &
not against anaerobes
 Alone or synergistic : Proteus, Enterobacter,
Klebsiella
Gentamicin, Amikacin, Tobramycin, Netilimicin:
used interchangeably
GENTAMICIN

18. RESISTANCE:
 Streptococci & enterococci resistant to
Gentamicin (failure of drug to penetrate)
 Resistance of staphylococcus due to
selection of permeability mutants
 Gram-ve plasmid mediated
aminoglycoside modifying enzymes

19. THERAPEUTIC USES
 Sepsis, Pneumonia: Gram-ve organisms, -
Pseudomonas, Enterobacter, Proteus.
 In Immunocompromised patients can be given
with cephalosporin/ penicillin
 Endocarditis Penicillin G + Genta:
 Topical Adm: Creams, Ointments 0.1-0.3%,
Burns, I.V. Catheter infection
 Meningitis by serious gram –ve with or without
3rd
gen cephalosporins .
Adverse effects: same as others

20. KANAMYCIN
 Used in past
 Toxic : Hepatoxicity ++
Auditory toxicity ++
Vestibular +
 Use: Tuberculosis (2nd
line), Hepatic coma

21. TOBRAMYCIN
 PK similar to Gentamicin
 i/m or i/v
 Superior activity against pseudomonal
infections, Proteus along with beta lactams .
 Ineffective against mycobacterium.
 Alternative to Gentamicin.
 5-6 mg/kg i/m or i/v 3 divided doses.
 S/E :Ototoxic ,Nephrotoxic (slightly less)

22. AMIKACIN
 Semisynthetic derivative of Kanamycin, less toxic.
 Resistant to enzyme inactivation.
 Given in Genta/ Tobra resistant infections of
Gram –ve bact.-Proteus, Pseudomonas, Serriatia:-
500mg i/m 12 hourly(15 mg/kg/day)
 Multi drug resistant T.B. (7.5-15mg/kg/day once
daily/2-3 ×weeks)

23. SISOMICIN
 From Micromonospora inyoensis.
 Similar to Genta but more potent on
Pseudomonas, Beta hemolytic Strept and
G –ve.
 Sub Acute Bacterial Endocarditis (SABE)
– with Penicillin.
 Susceptible to inactivating enzymes.

24. NETILMICIN
 Like Gentamycin & Tobramycin
(interchangeable with these)
 Resistant to most inactivating enzymes
 Similar toxicity
 5-7 mg/kg/day

25. PARAMOMICIN
 Related to Neomycin.
 Activity against protozoan parasites.
 Intestinal Amoebiasis: 1g/6 hourly× 2 weeks,
orally
 Alternative to Neomycin for Hepatic
Encephalopathy.
 Visceral Leishmaniasis.

26. NEOMYCIN
Uses
Oral :
• 1) Hepatic coma suppresses Coliforms
• 2) Gut surgery
Topically for infected wound, buns, ulcers, external
ear infections, conjunctivitis.
Toxicity:
Malabsorption, Super infection
Nephrotoxic, Ototoxic

27.  Extracted from Strept. lavendulae.
 Similar to Neomycin but too toxic for systemic
use.
 Used topically (same as Neomycin).
FRAMYCETIN

28. THANK YOU