Streptomycin toxicity

Dosing of capreomycin is the same as that of streptomycin. Toxicity is reduced if 1 g is given two or three times weekly after an initial response has been achieved with a daily dosing schedule. 

Sreptomycin. Streptomycin is usually administered daily as a single IM injection. The preferred site is the upper outer quadrant of the buttock or die midlateral thigh. The deltoid area is used only if die area is well developed. In patients 60 years of age or older, the dosage is reduced because of die risk of increased toxicity. 

In the absence of an AGAC the ribosomes will prodnce the artificial polypeptides, polyphenylalanine (as specified by the codon UUU) or polyproline (as specified by the codon CCC). However, when streptomycin is added, the ribosomes prodnce a mixture of polythreonine (codon ACU) and poly serine (codon UCU). The misreading of the codons does not appear to be random U is read as A or C and C is read as A or U. If such misreading occurs in whole cells the accumulation of non-functional or toxic proteins would eventually prove fatal to the cells. There is some evidence that the bacterial cell membrane is damaged when the cells attempt to excrete the faulty proteins. 

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. 

Gentamicin should be added if tolerance or moderately susceptible (MIC >0.1 g/mL) organisms are encountered streptomycin is used but can be more toxic. 

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... 

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. 

Mycobacterium tuberculosis Add streptomycin or ethambutol as a fourth drug in a regimen containing isoniazid (INH), rifampin, and pyrazinamide for initial treatment of tuberculosis unless the likelihood of INH or rifampin resistance is very low. Streptomycin also is indicated for therapy of tuberculosis when one or more of the above drugs is contraindicated because of toxicity or intolerance. 

Streptomycin usually is administered daily as a single IM injection. Give a total dose of not more than 120 g over the course of therapy unless there are no other therapeutic options. In patients older than 60 years of age, reduce dosage because of the risk of increased toxicity (see Warning Box). 

Aminoglycosides accumulate in otolymph and can cause both vestibular and auditory ototoxicity, both of which can be irreversible. Uptake is driven by the concentration gradient between blood and the otolymph this process is saturable. Sustained high concentrations in otolymph first destroy hair cells that are sensitive to high-frequency sounds. Streptomycin is more likely to cause vestibular toxicity than ototoxicity. The severity... 

Ototoxicity and nephrotoxicity are the major concerns during administration of streptomycin and other aminoglycosides. The toxic effects are dose related and increase with age and underlying renal insufficiency. All aminoglycosides require dose adjustment in renal failure patients. Ototoxicity is severe when aminoglycosides are combined with other potentially ototoxic agents. 

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... 

Streptomycin Eightii nerve toxicity (deafness) in child... 

The overdose toxicity occurs when the high dose of drug is required for the specific treatment or the drug is taken accidentally or with the intention of suicide. The effects are predictable and dose related. For example delirium by the use of atropine and respiratory failure by morphine occur due to their overdoses. The well known antitubercular drug, streptomycin causes vestibular damage and deafness on prolonged use. 

It is used in the treatment of tuberculosis caused by streptomycin resistant strains but since agents with lesser toxicity e.g. capreomycin and amikacin are available, its use is obsolete. 

Inside the cell, aminoglycosides bind to specific 30S-subunit ribosomal proteins (S12 in the case of streptomycin). Protein synthesis is inhibited by aminoglycosides in at least three ways (Figure 45-3) (1) interference with the initiation complex of peptide formation (2) misreading of mRNA, which causes incorporation of incorrect amino acids into the peptide and results in a nonfunctional or toxic protein and (3) breakup of polysomes into nonfunctional monosomes. These activities occur more or less simultaneously, and the overall effect is irreversible and lethal for the cell. 

Pain at the injection site is common but usually not severe. The most serious toxic effect with streptomycin is disturbance of vestibular function—vertigo and loss of balance. The frequency and severity of this disturbance are in proportion to the age of the patient, the blood levels of the drug, and the duration of administration. Vestibular dysfunction may follow a few weeks of unusually high blood levels (eg, in individuals with impaired renal function) or months of relatively low blood levels. Vestibular toxicity tends to be irreversible. Streptomycin given during pregnancy can cause deafness in the newborn and therefore is relatively contraindicated. 

Streptomycin is ototoxic and nephrotoxic. Vertigo and hearing loss are the most common adverse effects and may be permanent. Toxicity is dose-related, and the risk is increased in the elderly. As with all aminoglycosides, the dose must be adjusted according to renal function (see Chapter 45). Toxicity can be reduced by limiting therapy to no more than 6 months whenever possible. 

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. 

Streptomycin Prevents bacterial protein synthesis by binding to the S12 ribosomal subunit (see also Chapter 45) Bactericidal activity against susceptible mycobacteria Used in tuberculosis when an injectable drug is needed or desirable and in treatment of drug-resistant strains IM, IV renal clearance (half-life 2.5 h) administered daily initially, then 2 x week Toxicity Nephrotoxicity, ototoxicity... 

Prescott B, Kauffman G, James WG. Further studies on effect of glycerine on toxicity of isoniazid-streptomycin mixtures in mice. Antibiot Chemother 1958 8 225. 

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