Pawitra Pulbutr M.Sc. in Pharm (Pharmacology) Aminoglycosides Pawitra Pulbutr M.Sc. in Pharm (Pharmacology)
วัตถุประสงค์เชิงพฤติกรรม เข้าใจและอธิบายถึงกลไกการออกฤทธิ์, กลไกการดื้อยา, เภสัชจลนศาสตร์, อาการไม่พึงประสงค์ที่เกิดจากการใช้ยา, การนำไปใช้ประโยชน์ทางคลินิก รวมทั้งข้อดีและข้อเสียของยาต้านแบคทีเรียในกลุ่ม aminoglycosides และ spectinomycin
Aminoglycosides Macromolecule … Polycations +++ Major effective on gram negative Streptomycin Amikacin Gentamicin Tobramycin Sisomicin Netilmicin Neomycin Kanamycin
Mechanism of action Bacterial protein synthesis inhibitors Passive diffusion through outer membrane Active O2 dependent transport through cell membrane Bind at 30s subunit ribosome Inhibit initiation complex formation Miscoding of mRNA … non-function/ toxic peptide Block of ribosome translocation … Breakdown of polysome into monosome Irreversible … Bactericidal**
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Synergism & antagonism Synergism with beta-lactam antibiotics beta-lactam act on cell wall increase AGs penetration Antagonism with beta-lactam antibiotics form complex with beta-lactam ring loss of activity Should not mix together in drug preparation
Once daily Aminoglycosides Concentration dependent killing Higher peak … Higher effect Prolong Post Antibiotic Effects (PAEs) Can be given OD Less toxicity >>> nephrotoxicity*** Concentration dependent … Saturation Time dependent Saturation of tubular uptake
ADRs Ototoxic & Nephrotoxic Ototoxic … auditory damage & vestibular damage >>> irreversible Nephrotoxic … decrease CLcr >>> reversible Continuing use > 5 days High dose Elderly patient Renal insufficiency Use with nephrotoxic agents … loop diuretics, vancomycin, amphotericin B, cidofovir
<PLUS Penicillins> Clinical use Gram negative enteric bacteria infection <PLUS Penicillins> Enterococcal endocarditis Viridans streptococcal endocarditis Staphylococcal endocarditis Others >>> Mycobacterium tuberculosis (TB)
Spectinomycin Aminoglycosides like No amino sugar & glycosidic bonds Alternative for gonorrhea in penicillin hypersensitivity in pregnancy*** IM inj. No cross resistance with other drugs used in gonorrhea ADRs … pain at injection site, fever, nausea, nephrotoxic, anemia
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