Aminoglycosides.

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Presentation transcript:

Aminoglycosides

Aminoglycosides Streptomycin Neomycin Kanamycin Amikacin Gentamycin Tobramycin Sisomicin Netilmicin Are used for gram-negative bacteria in bacteremia or sepsis In combination with vancomycin or a penicillin for the treatment of endocarditis In tuberculosis treatment

Aminoglycosides Streptomycin is the prototype of this group. Gentamycin, tobramycin and amikacin are most widely used aminoglycosides at present. Neomycin and kanamycin are largely limited to topical use. Aminoglycosides show synergy when combined with beta-lactams or vancomycin. Aminoglycosides may complex w/ beta-lactams and inactivate. Therefore, they should not be mixed together for administration.

Mechanism of Action Binds specifically to 30 S ribosomal subunit. Protein synthesis is inhibited by aminoglycosides in at least three ways. Interfere the initiation complex of peptide formation. Induce misreading of mRNA results in systhesis of nonfunction or toxic protein. Break up of polysomes into non functional monosomes. Bacterial protein synthesis is irreversibly inhibited and bacteria dies.

Protein synthesis is inhibited by aminoglycosides in at least three ways.

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Aminoglycosides Pharmacokinetics Absorption from GIS is poor. IM or IV route is prefered. Distribution in the body is poor. Excreted by kidneys, thus dose should be reduced in renal failure.

Aminoglycosides Adverse effects All are ototoxic and nefrotoxic. Especially when therapy is longer at high doses. Neomycin, kanamycin and amikacin are the most ototoxic agents in the group. Neomycin, tobramycin and gentamycin are the most nephrotoxic agents in the group. Streptomycin and gentamycin are vestibulotoxic (vertigo, ataxia, lost of balance). Curare-like effect at high doses.

Aminoglycosides Clinical Use Mostly used against gram-negative enteric bacteria and suspicion of sepsis, Enterecoccal, staphyloccal and streptococcal endocarditis in combination with a beta-lactam antibiotic.

Aminoglycosides Streptomycin Isolated from streptomyces griseus. Resistance has emerged in most species severely limiting its use today. Mycobacterial infections Is mainly used as the second line agent for the treatment of tuberculosis. The dosage is 0,5-1 g /day IM or IV. It should be used in combination with other anti tuberculosis drugs in order to prevent the resistance development. Nontuberculosis infections. In plague, tularemia and brucellosis, streptomycin is given IM in combination with an oral tetracyclin.

Aminoglycosides Streptomycin continued. Adverse reactions Hypersensitivity (fever, skin rash) Pain at the injection site Disturbance of the vestibular function (vertigo, loss of balance) If used in pregnancy, can cause deafness therefore contrindicated in pregnancy.

Aminoglycosides Gentamycin Isolated from Micromonospora purpurea. Effective against both gram-positive and gram-negative organisms. Active on the following bacteria alone or in combination w/ beta-lactams: peudomonas, proteus, enterobacter, klebsiella, serratia, stenotrophomonas Like all aminoglycosides no activity against anaerobes.

Aminoglycosides Gentamycin continued At present, gentamycin is employed mainly in severe infections (eg. Sepsis, pneumonia) caused by gram-negative bacteria that are likely to be resistant to other drugs. Is given intravenously. Should not be used as a single agent to treat staphylococcal infections. Because resistance develops rapidly. Renal functions should be monitored if administered more than few days. Ointments, creams or solutions are used for topical treatment of infected burns, wounds, skin lesions and prevention of catheter infections.

Aminoglycosides Amikacin Tobramycin Semisynthetic derivative of kanamycin. Less toxic than kanamycin. Strains of multidrug resistance Mycobacterium tuberculosis are usually susceptible to amikacin. Nefrotoxic and ototoxic. Tobramycin Similar to gentamycin.

Aminoglycosides Netilmisin Neomycin and Kanamycin Similar to gentamycin and tobramycin. Neomycin and Kanamycin Too toxic for parenteral use. Mainly used for bowel preperation for surgery.