Kanamycin toxicity

Kreis B (1966) Kanamycin toxicity in adults. Ann NY Acad Sci 132/2 957 Kronig B, Fiegel P, Weihrauch T, Hoffler D, Jahnecke J, Amdthauser A (1972) A case of severe repeated immunological reactions to intermittent rifampicin treatment. Eur J Clin Pharmacol 5 53-57... 

The answer is a. (Hardman, pp 1105-1108.) The activity of streptomycin is bactericidal for the tubercle bacillus organism. Other aminoglycosides (e.g., gentamicin, tobramycin, neomycin, amikacin, and kanamycin) have activity against this organism but are seldom used clinically because of toxicity or development of resistance. 

Certain antibiotics such as the tetracyclines, streptomycin, neomycin and kanamycin can cripple the tubules if taken in excessive amounts. Toxic damage to the kidneys can affect not only their filtration functions, but can alter the organs control over blood levels of certain critical molecules. A complex biochemical-hormonal system controlling blood pressure and volume, for example, is regulated by the kidneys, so that chronic kidney damage can inflict damage on the... 

Capreomycin has a pronounced suppressive effect against Mycobacterium tuberculosis and Mycobacterium bovis. Most strains of Mycobacterium kansasii are also sensitive to kanamycin, while other, nontuberculous strains are not sensitive to it. It is often used upon necessity of using parentemal therapy through deep intramuscular injections. Capreomycin is less toxic than kanamycin and has somewhat more of a bacteriostatic effect. Synonyms of this drug are capromycin, capastat, ogostal, and others. 

Renal toxicity - Renal toxicity may be characterized by decreased creatinine clearance, cells or casts in the urine, decreased urine specific gravity, oliguria, proteinuria, or evidence of nitrogen retention. Renal damage is usually reversible. The relative nephrotoxicity of these agents is estimated to be Kanamycin = Amikacin = Gentamicin = Tobramycin Streptomycin. 

Amikacin and kanamycin (see Chapter 46) have been used in the treatment of tuberculosis. Amikacin is very active against several mycobacterium species however, it is expensive and has significant toxicity. It is considered in the treatment of MDR tuberculosis after streptomycin and capreomycin. An additional use of amikacin is in the treatment of disseminated MAC in AIDS patients. There is no cross-resistance between streptomycin and other aminoglycosides most M. tuberculosis strains that are resistant to streptomycin are... 

The aminoglycosides decrease the fidelity of translation by binding to the 30S subunit of the ribosome. This permits the formation of the peptide initiation complex but prohibits any subsequent addition of amino acids to the peptide. This effect is due to the inhibition of polymerization as well as to the failure of tRNA and mRNA codon recognition. Aminoglycosides are ototoxic (i.e., may produce partial deafness), damaging the auditory nerve. Kanamycin is less toxic. Since aminoglycosides are concentrated in the kidney, they may occasionally cause kidney damage. 

Neomycin and kanamycin are now limited to topical and oral use. Neomycin is too toxic for parenteral use. With the advent of more potent and less toxic aminoglycosides, parenteral administration of kanamycin has also been largely abandoned. Paromomycin has recently been shown to be effective against visceral leishmaniasis when given parenterally (see Chapter 52), and this serious infection may represent an important new use for this drug. 

The aminoglycoside antibiotics are discussed in Chapter 45. Kanamycin has been used for treatment of tuberculosis caused by streptomycin-resistant strains, but the availability of less toxic alternatives (eg, capreomycin and amikacin) has rendered it obsolete. 

Apart from its ototoxic and nephrotoxic potential, kanamycin may also cause liver disturbances and both peripheral and central neuropathies including encephalopathy, lethargy, and convulsions. Cochlear toxicity is more frequent... 

Neomycin is particularly ototoxic and nephrotoxic when given parenterally. As with gentamicin and kanamycin, the nephrotoxicity may be reversible but the ototoxicity is usually irreversible and deafness may occur following oral administration, instillation into cavities, or topical use. It may block neuromuscular action and respiratory depression has been reported. Local treatments may cause hypersensitivity, rashes, pruritus, and anaphylaxis. Neomycin is not geno-toxic. 

The PDA found that kanamycin and neotnyciu are very toxic antibiotics and as such have very limited oral clinical use and are used only in situations where patients are not consuming food. There is also 100 little of the essential cofactor. ATP, present in food for the enzyme to degrade a significant amount of antibiotic. 

Aminoglycosides are a group of bactericidal antibiotics originally obtained from various streptomyces species and sharing chemical, antimicrobial, pharmacologic, and toxic characteristics. The group includes streptomycin, neomycin, kanamycin, amikacin, gentamicin, tobramycin, sisomicin, netilmicin, and others. 

The toxicity of aminoglycosides in the kidney and other organs is concentration-dependent. Antibiotics such as kanamycin and gentamycin have their half-lives doubled in elderly patients. The elderly commonly suffer from osteoarthritis and (less commonly) rheumatoid arthritis. NSAIDs must be carefully used in geriatric patients, as they cause GI toxicity. For example, aspirin causes GI irritation... 

Chloramphenicol (9) is liable to breakdown by chloramphenicol acetyl-transferases [185]. Fluoro derivatives (57, 58) resist enzymatic attack but little has been heard of these, apparently because of their toxicity [319], Aminoglycoside antibiotics (AGACs) may be chemically modified by AMEs. Some derivatives (e.g. amikacin, 43) are more recalcitrant than others, e.g. kanamycin (42) (see Figure 4.2). Other enzyme-resistant AGACs of low toxicity are needed. 

The same spectrum of toxicity (ototoxicity and nephrotoxicity) is shared by all members of the group, The more important and frequent interactions are pharmacodynamic. Streptomycin and gentamicin produce predominantly vestibular effects, whereas amikacin, kanamycin and neomycin primarily affect auditory function. All are rapidly excreted by the kidney,... 

There are interesting differences in the toxicity patterns of aminoglycosides in animals. Gentamicin and tobramycin affect the cochlear and vestibular systems to a similar extent, while amikacin, kanamycin, and neomycin preferentially damage the cochlear and streptomycin the vestibular system. Netilmicin appears to be the least toxic (26,27). 

Kanamycin causes mainly cochlear damage (2). After prolonged administration (for example 1 g for periods of 30-180 days) the frequency of this adverse reaction is higher than 40%. Vestibular toxicity occurs in less than 10% of cases treated with usual doses and is generally reversible soon after withdrawal. 

Presurgical bowel preparation with oral kanamycin is seldom practiced and can be followed by an intestinal malabsorption syndrome (3). Only negligible amounts of kanamycin are absorbed through an intact intestinal mucosa, but increased systemic availability and potential toxicity can result from the presence of ulcerated or denuded areas. 

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