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Aminoglycosides
- 1. AMINOGLYCOSIDES PRESENTED BY : G. SANTHANA KUMAR
- 2. INDEX INTRODUCTION CLASSIFICATION MOA ANTIBACTERIAL SPECTRUM PHARMACOKINETICS POST ANTIBIOTIC EFFECT BACTERIAL RESISTANCE ADVERSE EFFECTS OF A.G. A.G DRUGS
- 3. INTRODUCTION Aminoglycoside are bactericidal antibiotic which interfere with ribosomal functions leading to inhibition of protein synthesis of bacteria. They are obtained from bacteria genus Streptomyces and Micromonospora species. The term “ aminoglycoside” was coined be cause structure characterized by two amino sugars joined to a aminocyclitol(non-sugar) by a glycosidic bond. In majority of aminoglycosides. The aminocyclitol moiety is 2- deoxystreptamine which is centrally connecting the two groups. However, in streptomycin- streptidine (aminocyclitol) is placed laterally to streptobiosamine amino sugar.
- 4. CLASSIFICATION: - BASED ON MICROBIAL SOURCE
- 5. CLASSIFICATION - BASED ON ROUTE OF ADMINISTRATION
- 6. Mechanism of action
- 7. ANTIBACTERIAL SPECTRUM Aerobic G-ve bacteria ( Citrobacter, Enterobacter, E. coli, proteus, shigella, proteus, Pseudomonas, Enterococci and Staph aureus ) They are not effective against G+ve bacilli, G-ve cocci and anaerobes. Aminoglycosides are not effective against anaerobes because the penetration of aminoglycoside across porin channel depend upon polarized membrane and oxygen dependent active process, since lack of oxygen make them ineffective against anaerobes
- 8. PHARMACOKINETICS: A: Aminoglycosides are highly polar , basic drugs which do not permit their membrane permeability because of which they have very poor oral bioavailability. Therefore, they are given parenterally or applied locally. D & M : They are poorly distributed and have poor protein binding ability so fail to enter cellular components to get distributed. They get distributed in serous fluids found in synovial ,pleural and peritoneal. E : AG get excreted through kidney by glomerular filtration, resulting in high concentration in urine which makes them useful in UTI. Its excretion is directly proportional to creatinine clearance ,so dose adjustment in done renal insufficiency is done.
- 9. POST-ANTIBIOTIC EFFECT : Aminoglycosides exhibit concentration dependent killing . Increased conc. Can kill more bacteria at rapid rate They also possess significant Post-antibiotic effect and continue to suppress bacterial growth several hours after fall in MIC(Minimum Inhibitory Concentration). Single daily dosing at least as effective as and no more toxic than multiple dosing.
- 10. ANTIBACTERIAL RESISTANCE: Synthesis of plasmid mediated bacterial transferase enzyme that Inactivate aminoglycosides ↓ transport into bacterial cytosol Deletion/alteration of receptor protein on 30 S ribosomal unit by mutation: prevents attachment
- 11. ADVERSE EFFECTS : 1. Ototoxicity: Vestibular and cochlear part affected with aminoglycosides. These drugs get concentrated in labyrinthine fluid. Ototoxicity is greater when plasma concentration of drug is high. Vestibular/cochlear sensory cells get destructive changes, aminoglycoside ear drops are contraindicated . Cochlear damage: Hearing defect, deafness, tinnitus appears, on stopping drug tinnitus disappears. Vestibular damage: Headache, nausea, vomiting, dizziness, nystagmus, ataxia, vertigo. 2. Nephrotoxicity: Tubular damage resulting in loss of urinary concentrating power, low GFR, nitrogen retention, albuminuria. It can be seen in patients having rise serum creatinine levels > 1.5 mg/dl. 3. Neuromuscular blockade: All aminoglycosides reduce Ach release from motor nerve ending, they have curare like action and cause neuromuscular blockade that can cause paralysis and fatal respiratory arrest. They may cause apnea on iv injection, the blockade if severe can be effectively treated by neostigmine.
- 12. STREPTOMYCIN Streptomycin develops a faster resistance when used alone in combination with penicillin /tetracycline. Pharmacokinetics Neither absorbed nor destroyed in git. Absorption from injection site in muscle is rapid. Distributed extracellularly, volume of distribution 0.3 L/kg .Attains low concentration in synovial, pleural fluid. It is not metabolized. Excreted unchanged in urine .Plasma half life is 2-4 hrs. Adverse effects: Vestibular disturbances, auditory disturbances ,Nephrotoxicity ,Hypersensitivity are rare- rashes, eosinophilia, dermatitis ,Pain at injection CONTRAINDICATION: pregnancy causes fetal ototoxicity USES: 1.TB 2. SABE: given with penicillin/ampicillin/vancomycin for 4-6 weeks 3. Plague: rapid cure within 7-12 days 4. Tularemia: Streptomycin cures it in 7-10 days
- 13. GENTAMICIN: On comparing with streptomycin Gentamicim is more potent • It has broader spectrum of action and effective against P. aeruginosa and most strains of Proteus, E.coli, Klebsiella, enterobactor, Serratia It is not effective against M. tuberculosis, Str.pyogenes , Str. Pneumoniae, and some Str. Aureus . It is more nephrotoxic. Uses: 1. In Gm-ve bacillary infections like Septicaemia, sepsis, fever in immunocompromised patients used with penicillins /cephalosporins 2. Pelvic infections : with metronidazole. 3. SABE: with Penicillin G or ampicillin or vancomycin, where gentamicin dose is 1mg/kg for 8 hrs i.m . 4. Coliform infection: with ampicillin or ceftriaxone 5.Pseudomonal infections: with ticarcillin 6. Meningitis by Gm-ve bacilli : III generation cephalosporin alone or with gentamicin 7.Topical-infected burns, wounds, skin lesions.
- 14. NEOMYCIN Neomycin has a wide spectrum active against Gm-ve bacilli and some Gm+ve cocci and obtained from S.fradiae Pseudomonas and strep. pyogenes are not sensitive Too toxic for parenteral use , limited to topical use . USES : Topically used in skin, eye and external ear infections combined with bacitracin or polymyxin-B to widen antibacterial spectrum and to prevent emergence of resistant strains
- 15. OTHER DRUGS; Framycetin (soframycin) :Obtained from S. lavendulae . Similar to neomycin .Toxic for systemic administration , used topically on eye,skin and ear. Paromomycin: Properties similar to neomycin Effective against visceral leishmainiasis by parentral route .Used in Intestinal infections, Treatment of hepatic encephalopathy, Treatment of amoebiasis. Other drugs : tobramycin, sisomicin, kanamycin and amikacin
- 16. USES
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