Aminoglycosides glomerular filtration

Example. Kanamycin is a member of the aminoglycoside class of antibiotics, all of which are eliminated exclusively by glomerular filtration. Creatinine is a natural body substance that is cleared almost exclusively by glomerular filtration, and creatinine clearance rate is frequently used as a diagnostic tool to determine glomerular filtration rate. The relationship... 

Excretion is by glomerular filtration, largely as unchanged drug thus, high urine levels are attained. Aminoglycosides are removed by hemodialysis (4 to 6 hours removes approximately 50%) and peritoneal dialysis (range, removal of 23% in 8 hours to only 4% in 22 hours). 

Toxicity Aminoglycosides are associated with significant nephrotoxicity or ototoxicity. These agents are excreted primarily by glomerular filtration thus, the serum half-life will be prolonged and significant accumulation will occur in patients with impaired renal function. Toxicity may develop even with conventional doses, particularly in prerenal azotemia or impaired renal function. 

All aminoglycosides are poorly absorbed after oral administration, are more active in alkaline pH and are excreted unchanged by glomerular filtration. Since... 

Abnormal clearance may be anticipated when there is major impairment of the function of the kidney, liver, or heart. Creatinine clearance is a useful quantitative indicator of renal function. Conversely, drug clearance may be a useful indicator of the functional consequences of heart, kidney, or liver failure, often with greater precision than clinical findings or other laboratory tests. For example, when renal function is changing rapidly, estimation of the clearance of aminoglycoside antibiotics may be a more accurate indicator of glomerular filtration than serum creatinine. 

Aminoglycosides have a low volume of distribution and are excreted by glomerular filtration, which is followed by active reuptake via a high-capacity, low-affinity transport system. The aminoglycosides remain in the kidney longer than in other exposed tissues such as the liver. Thus, with gentamycin, the time for the tissue concentration to be reduced by half is... 

Fate Metabolism of the aminoglycosides does not occur in the host. All are rapidly excreted into the urine, predominantly by glomerular filtration. Accumulation occurs in patients with renal failure, and requires dose modification (Figure 31.6). 

Elimination. Glomerular filtration, tubular secretion and reabsorption are low in the neonate (even lower in preterm babies) only reaching adult values in relation to body surface area at 2-5 months. Therefore drugs that are eliminated by the kidney (e.g. aminoglycosides, penicillins, diuretics) must be given in reduced dose after about 6 months. 

Elimination. Renal blood flow, glomerular filtration and tubular secretion decrease with age above 55 years, a decline that is not signalled by raised serum creatinine concentration because production of this metabolite is diminished by the age-associated diminution of muscle mass. Indeed, in the elderly, serum creatinine may be within the concentration range for normal young adults even when the creatinine clearance is 50 ml/min (compared to 127 ml/min in adult male). Particular risk of adverse effects arises with drugs that are eliminated mainly by the kidney and that have a small therapeutic ratio, e.g. aminoglycosides, chlorpropamide, digoxin, lithium. 

Drugs and xenobiotics that have glomerular filtration as their major way of renal etimination will accumulate rapidly during acute or more chronic declines of glomerular filtration. If in addition the therapeutic/ toxic window is narrow, the accumulation will result very quickly in toxic effects (e.g. aminoglycosides). 

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