Aminoglycosides

Aminoglycosides

Aminoglycosides are a group of bactericidal antibiotics sharing chemical, antimicrobial, pharmacologic and toxic characteristics. (Poorly absorbed from GIT, poor penetration to CSF and eye, highly active against G-ve bacilli, and inactive against anaerobics,

high concentrations in renal cortex, endolymph & perilymph of inner ear, excreted mainly by GF, synergistic effects with penicillins & cephalosporins.

The group include:

·        Gentamicin#, Amikacin, Tobramycin

·        Kanamycin, Neomycin#, Netilmicin

·        Streptomycin ,Framycetin#,sissomicin

·        Paromomicin, Dibekacin.

Mechanism of action:

·        The aminoglycosides act by inhibiting the synthesis of bacterial proteins. This is usually achieved by binding of the drug to 30 S subunit of bacterial ribosomes .The abnormal proteins which result are fatal to the microbe.

·        Resistance: results from several bacterial enzymes that inactivate the aminoglycoside molecule.

·        Note: Amikacin & netilmicin are not affected by such inactiviting enzymes.

Ø Aminoglycosides are active only against aerobic gram negative bacilli and Staphylococci. Activity against Streptococci alone is poor.

Ø  They are poorly absorbed when given orally and must be used parenterally for systemic infections. Also can be applied topically (GFN).

Clinical 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 (penicillin G + 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.

9.     Gentamicin, framycetin and neomycin for the treatment of eye and ear infections.

10.       Neomycin is used orally for bowel preparation before surgery to reduce GIT bacterial populations and to sterilise the bowel of patients who are to receive intense immunosuppressive therapy.

Adverse Effects:

1.     Ototoxicity: Both vestibular and auditory ;(cochear) (KA)damage may occur causing high =pitch tinnitus that can persist up to 2 wks after discontinuation, then auditory impairment occur if the drug continue; vestibular toxicity(GST), there will be headache lasting 1-2 days, then acute stage,as nausea,vomiting & difficulty with equilibrium persist for 1-2 wks, then chronic stage ataxia (recovery may take 1-1.5 years)

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, in patients receiving furosemide diuretic, hypercalcemia, pleural effusion & ascites.

Picture: mild proteinurea, casts & hyaline in urine

G > T > N

3.     Neuromuscular Blockade:

Aminoglycosides may impair neuromuscular transmission and aggravate myasthenia gravis or cause a transient myasthenia syndrome. This can be reversed by??

4.     Aminoglycosides may cause: Skin rashes, hemolytic anemia, paresthesia and peripheral neuropathy.