aminoglycosides PowerPoint Presentation.pptx

Aminoglycosides
M.Pharm sem II Pharmacology

1. PRESNTED BY- GANESH VASUDEV MAHAJAN M.PHARM 1 ST YEAR SEM-2 DEPARTMENT –PHARMACOLOGY RAJARSHI SHAHU COLLEGE OF PHARMACY, buldana AMINOGLYCOSIDE 1/19

2. FLOW OF PRESENTATION INTRODUCTION. GRAM POSITIVE AND NEGATIVE BACTERIA CLASSIFICATION OF AMINOGLYCOSIDES MECHANISM OF ACTION PHARMACOKINETICS ANTIBACTERIAL RESISTANCE ANTICATERIAL SPECTRUM USES AMINOGLYCOSIDES TOXICITY DRUG INTERACTION 2/19

3. INTRODUCTION Amino glycosides are natural product or semi-synthetic derivatives of highly water soluble compounds produced by a variety of soil actinomycetes. Streptomycin was first number discovered in 1944 by waksman and his colleagues. Amikacin a derivatives of kanamycin and netilmicin ,a derivatives of sisomicin,are semisynthetic product. 3/19

4. Aminoglycosides ( gentamicin , tobracymycin , amikamycin , netilmycin , kanamycin , streptomycin , Paromomycin , and neomycin) are used primarily to treat infections caused by aerobic gram-negative bacteria. Streptomycin and amikacin are the important agents for the treatment of mycobactrial infections and paromomycin is used orally for intestinal amebiasis . Widely in combination with a β - lactum antibiotics - serious infection with gram-negative bacteria 4/19

5. -combination with vancomycin gram-negative endocarditis . Treatment of tuberculosis Aminoglycosides are bacterial inhibitors of protein synthesis. 5/19

6. GRAM POSITIVE&NEGATIVE BACTERIA 6/19

7. CLASIFIACTON OF AMINOGLYCOSIDES SYSTEMIC -TOPICAL STREPTOMYCIN -NEOMYCIN GENTAMYCIN -FRAMYCETIN KANAMYCIN AMIKACIN SISOMYCIN NETILMICIN 7/19

8. MECHANISM OF ACTION Aminoglycosides binds to 30s ribosomal units of bacteria Prevents the formation of initiation complex , which is the prerequisites for peptide synthesis Lack of the formation of initiation complex causes the 30s sub unit to misread the genetics code on mRNA Incorrect amino acids thus incorporated into the growing peptide chain which is are of no use for bacterial growth Leads to bacterial death 8/19

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10. Aminoglycosides also act... Formed improper initiation complex blocks the movement of ribosome's resulting in a mRNA attached with single ribosome's Thus amino glycosides also interfere in the assemble of p0lysomes Results in the accumulation of non functional ribosome's 10/19

11. Pharmacokinetics ABSORPTION – amino glycosides are highly polar so they have poor oral bioavailability Therefore they given parenterally (IM route ) or applied locally METABILOSM - these are poorly distributed and poorly protein bound when given parenterally they failed to reach intraocular fluid or CSF 11/19

12. METABOLISM –as they do not penetrate more cellular compartment they do not under go any significant metabolism EXCRETION- Mainly by kidney through glomerular filtration. Resulting in fairly high urinary concentration so they can be used in the treatment of URINARY TRACT INFECTIONS. Their excretion directly proportional to creatinine clearance Normal half life varies from 1.5 hrs, it may increased to 24-48 hrs in patients with renal insufficiency 12/19

13. Anti bacterial resistance Synthesis of plasmid mediated bacterial transferase enzymes ( acetyl transferases , phoshotransferases and adenyl transferases) that can inactive aminoglycosides by acetylation, phosphorylation and adenylation respectively. By development of mutation or deletion of porin channels. Alteration of receptor proteins on 30s ribosomal units. 13/19

14. Anti bacterial spectrum Activity is primarily directed against gram negative aerobicbacilii ( Ecoli , klebsiella , shingella , ) Only a few gram positive cocci are inhibited (staphylococcus aureas ,streptococcus viridians and faecalis ) These are not effective against gram positive BACILLI , gram negative COCCI and ANAEROBES. 14/19

15. Aminoglycosides uses 15/19

16. Aminoglycosides toxicity Nephrotoxicity Inhibition of intracellular lysosomal phospholipase A2 in renal brush border and of free aminoglycosides into cytosol Then this free drug blocks the calcium transport in mitochondria by displacing calcium Leading to mitochondria degradation and necrosis Causes chronic renal failure Nephrotoxicity 16/19

17. Ototoxicity (irreversible) Aminoglycosides causes impairment of 8 th cranial nerve function They accumulate in endolymph ( vetibular ) , perilymph ( cohlear ) and causes ireeversible damage Vestivbular damage is characterised by vertigo ataxia and loss of balance where as cochlear damage leads to hearing loss and tinnitus And neuromuscular blocking effect ( Ach release) 17/19

18. Drug interaction Aminoglycosides + local anaesthetics/skeletal muscle relaxants Leads to paralysis Aminoglycosides should not be given with ototoxic and nephrotoxic drug like tetracycline, furosemide , amphotericin B 18/19

19. Thank you 19/19