AMINOGLYCOSIDE

ANTIBIOTICS
 Tetra cyclines
Aminoglycosides

Macrolids

Chloramphenicol
  Structure
Glycosidic Aminocyclitol

Aminosugar - O - 2-deoxystreptamine - O- Aminosugar

Streptomycin
N-methyl-L-
Strepose
Streptidine - O - aminosugar
- O - glucosamine
aminosugar

Streptobiosamine
MECHANISM OF ACTION

Aminoglycosides Penetrate Bact. Cell Wall To Periplasmic Space

Transport Across Cytoplasmic Membrane

(Oxygen Dependent)

Bind To 30s Ribosomal Units

Prevent Formation of ‘Initiation Complex’

Misreading of Genetic Code on mRNA

Incorrect Amino Acids into Peptide Chain

Inhibits Protein Synthesis

 All derived from an actinomycete or are
semisynthetic derivatives
 Bactericidal action
 Are highly polar compounds
 GIT poor absorption so IV/IM
 More active in alkaline pH
AMINOGLYCOSIDES

• STREPTOMYCIN (1944) • KANAMYCIN (1957 )

• GENTAMICIN (1964) • AMIKACIN

• SISOMICIN • NEOMYCIN

• NEITILMICIN • FRAMYCETIN

• TOBRAMYCIN 1967
 Suffix-“Mycin”- Streptomyces

 “Micin’-Micromonospora
Post Antibiotic Effect
 Half life 1-3hr.

 Concentration depended killing

 Single daily dose result in higher tissue

concentration

 Interval 8-12hr
MECHANISM OF RESISTANCE

1. Plasmid Mediated Bacterial Transferase

Enzymes

2. Deletion of Porin Channels

3. Alteration of Receptor Protein on 30s

Ribosomal Unit
PHARMACOKINETICS

• Very Poor Oral Bioavailability

• Poor Distribution

• Do Not Cross BBB

• Excreted Through Kidney

• Excretion is directly proportion to creatine

clearence
ANTIMICROBIAL SPECTRUM

• AEROBIC G-ve BACILLI

• ENTEROBACTERIACEAE

• NOT EFFECTIVE AGAINST :

G +ve BACILLI
G –ve COCCI
ANAEROBES
TOXICITIES

OTOTOXICITY:-
AG causes impairment of 8th cranial nerve.,
accumulate in the endolymph and perilymph of the
inner ear leading to vestibular and cochlear damage.
• Irrversible

NEUROMUSCULAR BLOCKADE
TOXICITIES
NEPHROTOXICITY
Inhibition of intracellular Phospholipase A2 in renal
brush border

Leads to lysosomal distension ,rapture

Release acid hydrolases & AG

Free drug binds to other cellular organelles

Leading to degeneration and necrosis

 STREPTOMYCIN
 Spectrum :
Y. Pestis, Brucella, F.Tularensis, M.Tuberculosis
 TOXICITY : Vestibular > Auditory
Lowest Nephrotoxicity
 USES :
• Tuberculosis
• SABE
• Plague
• Tularemia & Brucellosis
 GENTAMICIN
 Spectrum :
Pseudomonas, Proteus, E. Coli, Klebsiella, Enterobacteria & Seretia.
 TOXICITY :
More Nephrotoxic
 USES :
• Respiratory Infection in Critically Ill Pt.
• Pelvic Infection
• SABE
• UTIs
• Pseudomonal Infections
• Infected Wounds, Burns, & Conjunctivitis
 SISOMYCIN

 Clinically & PK similar to Gentamicin

 Susceptible to Aminoglycoside Inactivating Enzymes

 Used Interchangeably with Gentamicin

 NETILMICIN

 Semi synthetic Derivative of SISOMYCIN

 Resistant to Inactivating Enzymes

 Lesser Ototoxicity

 Used in Gentamicin Resistant Infections

 TOBRAMYCIN

 Identical To Gentamicin

 2-4 times More Active Against Pseudomonas &

Proteus

 Ototoxicity & Nephrotoxicity < Gentamicin

 Reserve Alternative to ‘G’

 AMIKACIN
 RESISTANT TO BACTERIAL ENZYMES
 USED against Gentamicin & Tobramycin Resistant
Infections
 USES:
• Multi drug Resistant TB
• Hospital Acquired Infections

 Hearing loss > Vestibular loss

 NEOMYCIN

 HIGHLY TOXIC

 UESE
• Infected Wounds, Ulcers, Burn
• External Ear & Eye Infections
• Preoperative Intestinal Antiseptic
• Hepatic Coma