AMINOGLYCOSIDES
Presented by Professor Dr. Imad A-J ThanoonThe group include: Gentamicin, Amikacin, Tobramycin Kanamycin, Streptomycin , Netilmicin Framycetin, Neomycin, Sissomycin Paromomicin,Isepamicin,arbekacin
AMINOGLYCOSIDES
PHARMACOKINETICS Structurally related amino sugars attached by glycosidic linkages Polar compounds Not absorbed orallyGeneral character of Aminoglycosides group
Formulations are Sulfate or hydrochloric salts Formulations are water soluble and stable Highly polar basic drugs. Ionize during dissolution Distribution inside the cells is minimal Penetration through BBB is minimal Least metabolized by hepatic enzymes Excretion is mainly renal (unchanged form, through glomerular filtration)(Not absorbed from GIT)
Bactericidal in nature More active in alkaline pH MOA is by interfering with protein synthesis Attach with 30S ribosomal subunit (ATT) Concentration dependent (PAE) Mainly gram negative (plus tuberculosis by streptomycin, Kanamycin, Amikacin) Cross resistance is partial Therapeutic index is narrow
AMINOGLYCOSIDES
PHARMACOKINETICS Given intramuscularly or intravenously for systemic effects Limited tissue penetration Do not readily cross the blood-brain barrier, what about usage in meningitis?!AMINOGLYCOSIDES
PHARMACOKINETICS Major mode of excretion Glomerular filtration Plasma levels are affected by changes in renal functionAMINOGLYCOSIDES
PHARMACOKINETICS Excretion is directly proportional to creatinine clearance With normal renal function, elimination half-life is 2-3 hAMINOGLYCOSIDES
PHARMACOKINETICS Dosage adjustment must be made in renal insufficiency to avoid toxic accumulation Monitoring plasma levels is needed for safe and effective dosage selection and adjustmentAMINOGLYCOSIDES
PHARMACOKINETICS For traditional dosing regimens 2 or 3 times dailyAMINOGLYCOSIDES
Buy AT 30 and CEL at 50 MECHANISM OF ACTION Bactericidal (irreversible) inhibitors of protein synthesis. Bind to 30S ribosomal unit Interfere with protein synthesisClinical Uses of Aminoglycosides: 1. Gram negative bacillary infections particullarly , septicemia, pelvic and abdominal sepsis. Gentamicin remains the drug of choice but tobramycin should be preferred for infections caused by Pseudomonas aeroginosa.
2. Bacterial Endocarditis : Aminoglycosides are used in combination ( penicillinG + gentamicin IV) with Penicillins for the treatment of Enterococcal, Streptococcal or Staphylococcal endocarditis. 3. Streptomycin is used for the treatment of brucellosis, tularemia, plague and tuberculosis.
4. Biliary tract infections. 5. Meningitis ( gentamicin intrathecally ). 6. UTIs. 7. Prophylaxis of surgical infections. 8. Topically: Gentamicin and framycetin as creams ,ointments and solutions for the treatment of infected burns, wounds or skin lesions.
Adverse Effects: 1. Ototoxicity: Both vestibular (streptomycin & gentamycin) and auditory damage (amikacin,kanamycin &neomycin) may occur causing hearing loss, vertigo, tinnitus, headache, dizziness or nausea, 2. Nephrotoxicity: All aminoglycosides are nephrotoxic . It is more likely to occur with large doses, high blood levels, long duration of therapy, in elderly patients, renal disease and in patients receiving furosemide diuretic. Most nephrotoxic Gentamicin and tobramycin
AMINOGLYCOSIDES
The NEPHROTOXICITY is More common in elderly patients Patients concurrently receiving Amphotericin B Cephalosporins Vancomycin Nephrotoxicity is reversible Verapamil and Ca++ can Reduce nephrotoxic potential But Also reduce antibacterial effect3. Neuromuscular Blockade: Aminoglycosides may impair neuromuscular transmission and aggravate myasthenia gravis or cause a transient myasthenia syndrome. 4. Aminoglycosides may cause: Skin rashes (8% when neomycin is applied topically.