AMINOGLYCOSIDE
S
Dr Madhav
Associate Professor
Pharmacology
AIMSR.
Competency: Describe the antibacterial spectrum,
Mechanisms of action, resistance, therapeutic uses
and adverse effects of aminoglycosides. (PH 1.42)
SLOs
• Enlist aminoglycosides and describe their mechanism of
action, spectrum and resistance
• Describe the pharmacokinetics, adverse effects and
interactions of aminoglycosides
CONTENTS
• CLASSIFICATION OF AMINOGLYCOSIDES
•GENERAL PHARAMCOLOGICAL
PROPERTIES
•MECHANISM OF ACTION
•USES
•ADVERSE EFFECTS
AMINOGLYCOSIDES
• Aminoglycosides are mainly used to treat Gram
Negative bacillus infections.
• Antibacterial spectrum:-
• *They are primarily effective against Gram
Negative aerobic bacilli:-E.coli, enterococcus,
proteus, pseudomonas, klebsiella, shigella,
yersinia , francisella tularaemia
* Only few against Gram Positive Cocci:-
Staphylococcus aureus, staphylococcus viridans
•Not effective against Gram positive bacilli, Gram
negative cocci & Anaerobes
Classification-
• SystemicAMINOGLYCOSIDES
aminoglycosides Topical aminoglycosides
• Streptomycin Neomycin
• Amikacin Framycetin
• Gentamicin
• Sisomicin
• Kanamycin
• Netilmicin
• Tobramycin
• Paromomycin
PHARMACOLOGICAL
PROPERTIES
1. All are used as sulfate salts, which are
highly water soluble; solutions are stable
for months.
2. They ionize in solution; are not
absorbed orally;
distribute only extracellularly; do not
penetrate brain
or CSF.
3. All are excreted unchanged in urine by
glomerular
filtration.
5. They act by interfering with
bacterial protein synthesis.
6. All are active primarily against
aerobic gram-negative bacilli and do
not inhibit anerobes.
7. There is only partial cross
resistance among them.
8. They have relatively narrow margin
of safety.
9. All exhibit ototoxicity and
MECHANISM OF ACTION
• Aminoglycosides binds
to the 30s ribosomal
subunit & interfere
with protein synthesis
in the following
ways :-
1.They block formation
of the initiation
complex
2.They cause
misreading of the
code on the m-RNA
Dosing Regimens:
Considering the short t½ (2–4 hr) of aminoglycosides the daily doses are conventionally
divided into 3 equal parts and injected i.m. (or i.v. slowly over 60 min) every 8 hours.
A single total daily dose regimen for patients with normal renal function.
•Aminoglycosides exert concentration dependent
bactericidal action and a long as well as concentration
dependent post-antibiotic effect .
Therefore higher plasma concentrations attained after the single daily dose will be equally
or more effective than the divided doses.
• With the single daily dose, the plasma
concentration will remain subthreshold for
ototoxicity and nephrotoxicity for a longer period
each day allowing washout of the drug from the
endolymph and the renal cortex.
USES OF AMINOGLYCOSIDES
• Severe aerobic gram -negative bacillary
infections:- Urinary tract infections,
pneumonia, osteomyelitis, septicaemia,
meningitis, infected burns -due to
Pseudomonas, Klebsiella,E.coli,Proteus
etc..,
• Bacterial endocarditis due to S.viridans
& Enterococcus:- Pencillin
G+Gentamycin for
S.Viridans ,Ampicillin+Gentamicin for
Enterococcus
•Plague:-
Streptomycin/Gentamycin
•Tularaemia:-Streptomycin
/Gentamycin
•Preparation of bowel for
surgery:-Neomycin
•Hepatic encephalopathy:-
Neomycin
•Gentamycin, tobramycin,
neomycin, sisomicin, framycetin
ADVERSE EFFECTS
OTOTOXICITY: VestibularStreptomycin&
Gentamycin AuditoryAmikacin&Kanamycin
• NEPHROTOXICITY
• NEUROMUSCULAR BLOCKADE
• HYPERSENSITIVITY REACTIONS
• OTOTOXICITY IN FETUS
1. Ototoxicity :
• Dose & duration dependant
• Vestibular / cochlear
• Cochlear :loss of hearing of high frequency → low
frequency
• Elderly & pre–existing hearing defects
• Tinnitus first → progressive hearing loss.
Vestibular toxicity
• Headache first
• Nausea , Vomiting, Giddiness, Nystagmus, vertigo,
ataxia
• Poor recovery -elderly
Nephrotoxicity
• Tubular damage
• Loss of urine conc. power
• Low GFR
• Nitrogen retention
• Albuminuria & casts
• Elderly & pre-existing renal disease: more prone
NMB
• ↓ Ach release
• ↓ the sensitivity of the muscle end plates to ACh
Streptomycin
• Streptomyces griseus
AMS :Narrow
• Myco. tuberculosis. E.coli,
Proteus, Shigella,
Pseudomonas, H.influenzae,
H.ducreyi,
Y.pestis, F.tularensis, Brucella,
Nocardia, Klebsiella, Calym,
granulomatis
ADRs:
1. Nephrotoxicty (lowest among Ags)
2. Ototoxicity (vestibular more common)
3. Neuromuscular blockade
4. HS :rashes, eosinophilia, lymphadenopathy,
dermatitis etc
5. CNS : 8th nerve damage
6. Superinfection - rarely
USES :
1. Tuberculosis
2. Tularaemia
3. Plague
4. Brucellosis
5. SABE
Preparation :
Inj : 0.75,1gm powder /vial, I.M
GENTAMICIN
• Micromonospora purpurea
AMS:
E.coli, Proteus, Klebsiella,
Aerobacter, Salmonella, Strepto,
Staph, Pseudomonas
USES
1. UTI
2. RTIs
3. Topically : burns, etc
4. Meningitis
5. SABE
6. Peritonitis
7. Prophylaxis
Preparations
• Inj : 20mg /ml , 80mg/ ml vial
• Eye drops : 0.3%
• Oint. : 0.1%
• Dose : 1-1.5 mg /kg /8th hrly
I.M / I.V
AMIKACIN
• Broadest spectrum
• SS der. of Kanamycin
• Resistant to 8 of 9 Amyno. inactivating
enzymes
• Inj. : 100, 250, 500 mg in 2ml inj.
• Dose : 1.5 mg /kg/day in 1-3 divided doses.
AMS :
E.coli, Proteus, Klebsiella,
Enterobacter, Serratia,
Pseudomonas,
Myco.tuberculosis, certain
Atypical mycobacteria
AMIKACIN
• Broadest spectrum
• SS der. of Kanamycin
• Resistant to 8 of 9 Amyno. inactivating
enzymes
• Inj. : 100, 250, 500 mg in 2ml inj.
• Dose : 1.5 mg /kg/day in 1-3 divided doses.
AMS :
E.coli, Proteus, Klebsiella,
Enterobacter, Serratia,
Pseudomonas,
Myco.tuberculosis, certain
Atypical mycobacteria
SISOMICIN
• Micromonospora inyoensis
• More on pseudomonas
• 50 mg , 10 mg/ml amp
• Oint.
FRAMYCETIN
• Streptomyces lavendulae
• Too toxic for systemic
administration
• Cream 1%, 0.5 %
• Eye drops : 0.5 %
NEOMYCIN
• Streptomyces fradiae
• G-ve & G+ve
• Highly toxic
• Not used systemically
• 0.3 % oint., 0.5 % cream.,
• 350, 500mg tab
USES
1. Topically: wounds, ulcers,
burns etc
2. Orally :
(i)Before bowel surgery
(ii)Hepatic coma
ADRs
1.Damage to int. villi –
malabsorption with diarrhoea
& steatorrhoea
2.Super infection with candida
3.Kidney damage & ototoxicity
Important Note
• Aminoglycosides are mainly active againstaerobic gram
negative bacilli and NOT active against anerobic bacteria
• Streptomycin and kanamycin have limited sprectrum
• For TB Streptomycin, kanamycin and amikacin
• Streptomycin differ from others – not active against
pseudomonas but active against (brucellosis, turalemia
and plague)
• More active against pseudomonas-tobramycin
• THANK YOU!....
