6. aminoglycosides

1. AMINOGLYCOSIDE ANTIBIOTICS

2. Aminoglycosides Tetra cyclines Chloramphenicol Macrolids

3. Structure Streptomycin Aminosugar O Aminosugar 2-deoxystreptamine O - - - - Glycosidic Aminocyclitol N-methyl-L-glucosamine aminosugar - - O Strepose aminosugar O - - Streptidine Streptobiosamine

4. 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

5. 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

6. AMINOGLYCOSIDES STREPTOMYCIN (1944) GENTAMICIN (1964) SISOMICIN NEITILMICIN TOBRAMYCIN 1967 KANAMYCIN (1957 ) AMIKACIN NEOMYCIN FRAMYCETIN

7. Suffix-“Mycin”- Streptomyces “Micin’- Micromonospora

8. Post Antibiotic Effect Half life 1-3hr. Concentration depended killing Single daily dose result in higher tissue concentration Interval 8-12hr

9. MECHANISM OF RESISTANCE Plasmid Mediated Bacterial Transferase Enzymes Deletion of Porin Channels Alteration of Receptor Protein on 30s Ribosomal Unit

10. PHARMACOKINETICS Very Poor Oral Bioavailability Poor Distribution Do Not Cross BBB Excreted Through Kidney Excretion is directly proportion to creatine clearence

11. ANTIMICROBIAL SPECTRUM AEROBIC G-ve BACILLI ENTEROBACTERIACEAE NOT EFFECTIVE AGAINST : G +ve BACILLI G –ve COCCI ANAEROBES

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

13. NEPHROTOXICITY Inhibition of intracellular Phospholipase A 2 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 TOXICITIES

14. STREPTOMYCIN Spectrum : Y. Pestis, Brucella, F.Tularensis, M.Tuberculosis TOXICITY : Vestibular > Auditory Lowest Nephrotoxicity USES : Tuberculosis SABE Plague Tularemia & Brucellosis

15. 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

16. SISOMYCIN Clinically & PK similar to Gentamicin Susceptible to Aminoglycoside Inactivating Enzymes Used Interchangeably with Gentamicin

17. NETILMICIN Semi synthetic Derivative of SISOMYCIN Resistant to Inactivating Enzymes Lesser Ototoxicity Used in Gentamicin Resistant Infections

18. TOBRAMYCIN Identical To Gentamicin 2-4 times More Active Against Pseudomonas & Proteus Ototoxicity & Nephrotoxicity < Gentamicin Reserve Alternative to ‘G’

19. AMIKACIN RESISTANT TO BACTERIAL ENZYMES USED against Gentamicin & Tobramycin Resistant Infections USES: Multi drug Resistant TB Hospital Acquired Infections Hearing loss > Vestibular loss

20. NEOMYCIN HIGHLY TOXIC UESE Infected Wounds, Ulcers, Burn External Ear & Eye Infections Preoperative Intestinal Antiseptic Hepatic Coma