Aminoglycosides

Dr Haseena.K.A.
Associate Professor of Pharmacology
Govt Medical College, Thrissur.
 Aminoglycosides
 Antibiotics-Soil Actinomycetes
Aminoglycosides
 Aminosugars linked to an aminocyclitol ring
by glycosidic bonds
 Source & Members
 Natural & Semisynthetic
 Streptomycin
 Gentamicin
 Tobramycin
 Kanamycin
 Neomycin
 Sisomicin
 Netilmicin- from Sisomicin
 Amikacin – from Kanamycin
 Paramomycin
 Streptomyces - mycin
 Micromonospora - micin
Topical
 Neomycin
 Framycetin
 Paramomycin
 Mechanism of action

 Inhibits bacterial protein synthesis

 Bactericidal
 Primarily active against aerobic Gm-ve bacilli
Protein Synthesis
Mechanism of action

 Passive diffusion via porin channels across the

outer membrane
 Then actively transported across the cell
membrane into the cytoplasm
 Irreversible inhibition of protein synthesis
Binds to 30 S subunit

1. Interfere with the initiation complex of peptide

formation
2. Misreading of mRNA , leads to incorporation of
incorrect amino acid resulting in a non functional
or toxic protein
3. Breaking up of polysomes into non functional
monosomes
 Mechanism of Resistance
 Drug inactivation by microbial enzymes
 Failure of antibiotic to penetrate intracellularly
 Low affinity of the drug for bacterial ribosome
 Antimicrobial Spectrum
 Primarily active against aerobic Gm-ve bacilli
 No activity against anaerobes and Gm+ve
bacilli
 Little effect on Gm+ve cocci
 Exhibits synergism with cell wall active
agents
 Antimicrobial Spectrum
 E.coli, Proteus, Klebsiella, Pseudomonas,
Enterobacter, Serratia
 Streptomycin – M.Tuberculosis, F.Tularensis,
Yersinia pestis
 Pharmacokinetics
 All are highly polar cations
 Very poorly absorbed from GIT
 Do not penetrate brain or CSF
 Administration – I/M or I/V
 Excreted unchanged in urine by glomerular
filtration
 Very short t1/2 2-3hours
 Route & dosage schedule

 Given only parenterally, either im or iv

 Traditionally given 8 hourly
 Can be given once daily- More effective & less toxic
 Bactericidal action is concentration dependent
 Post antibiotic effect also depends on plasma
concentration
 Adverse effects

1. Ototoxicity

2. Nephrotoxicity

3. Neuromuscular blockade
 Ototoxicity

 Irreversible
 Progressive destruction of vestibular & cochlear sensory
cells
 Auditory damage- tinnitus & high frequency hearing loss
 Vestibular damage- vertigo, ataxia & loss of balance
 Kanamycin & Amikacin- cochleo toxic
 Strepto & Genta – vestibulo toxic
 Nephro toxicity

 Dose dependent & reversible

 Proximal tubular damage  loss of urinary
concentrating power, low GFR ,nitrogen
retention & casts
 More in elderly& those with kidney disease
 Neo, Tobra & Genta most nephrotoxic
 Neuromuscular blockade
 Inhibits prejunctional release of Ach
 Decreases postjunctional sensitivity to Ach
 Myaesthenia gravis patients more susceptible
 Rx-I/V admn of a calcium salt
Precautions & Interactions
1.Avoid in pregnancy risk of foetal ototoxicity

2.Avoid concurrent use of ototoxic drugs like

frusemide, minocycline etc

3.Avoid concurrent use of other nephro toxic drugs

like Amphotericin B, Cisplatin etc
 Precautions & Interactions

4. Cautious use in elderly and in those with kidney

damage
5.Cautious use of muscle relaxants
6.Do not mix with any drug– in same syringe or
infusion bottle

7.Needs TDM: since very low therapeutic index

 Gentamicin

 Most commonly used AG

 Useful in serious Gm-ve bacillary infections
 Restricted to life threatening infections owing to
nephrotoxicity
 Highly effective against Pseudomonas
 Relatively cheap
 Gentamicin
 Genta + Penicillin(cell wall active agent)
Rationale
 To expand the antimicrobial spectrum
 To provide synergistic bacterial killing
 To prevent the emergence of resistance
 Uses
 Urinary tract infections
 Pneumonia
 Meningitis
 Bacterial endocarditis
 Sepsis
 Topical – eye, skin
 SEPTOPAL-(GM-PMMA)-Osteomyelitis
 Gentamicin

 Dose calculated according to body weight and

renal function
 Adult with normal renal function Dose 3-
5mg/kg/day as a single daily dose or three
equally divided doses
 Streptomycin
 Oldest aminoglycoside
 Extensively used in the past
 Now restricted to TB treatment
 Less potent & relatively narrow spectrum
 Cross resistance-partial & often uni directional
 Streptomycin-Indications
 Plague-Effective for all forms of plague
 Tularemia-1st choice drug
 Tuberculosis
 Bact endocarditis-in combn with
Penicillin.Genta has largely replaced strepto for
this indicn
 Amikacin
 Outstanding feature-Resistant to bacterial
aminoglycoside inactivating enzymes
 Widest spectrum
 Reserve drug for hospital acquired infections
resistant to genta&tobra
 Effective in TB-2nd line agent along with
kanamycin
 Neomycin
 Highly ototoxic & nephrotoxic
 Not used systemically
 Topical-ulcers,infected wound etc
 Orally for
1. Preparation of bowel before surgery
2. Hepatic coma
Paramomycin
 Earlier used as luminal amoebicide orally
 Kala-azar resistant to SSG-I/M
 Spectinomycin

 Aminocyclitol antibiotic with no aminosugars

& glycosidic bonds
 Used as an alternative to Penicillin for resistant
gonorrhea- Single dose 2gm im
THANK YOU