Excretion elderly patients

In addition to treating insomnia, gabapentin has been used to treat epilepsy, anxiety disorders, and bipolar disorder. It is generally well tolerated with sedation and headaches being the only prominent side effects. Because gabapentin is excreted unchanged in urine, it does not require metabolism by the liver. It is therefore easily eliminated by elderly patients and those with liver disease, although it should be used with caution in those with poor renal (kidney) function. 

Elderly Fenofibric acid is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, take care in dose selection. 

Elderly Clinical studies of nalidixic acid did not include sufficient numbers of subjects 65 and years of age and older to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Observe caution when using nalidixic acid in elderly patients. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be higher in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, take care in dose selection it also may be useful to monitor renal function. 

Age-related alterations in pharmacokinetics (absorption, distribution, metabolism, and excretion) have received considerable attention. Thus, physiological changes in elderly patients, when taken together, may contribute to impairments in drug clearance in this segment of the population (Table 6.5). 

Mechanism of Action A third-generation cephalosporin that binds to bacterial cell membranes and inhibits cell wall synthesis. Therapeutic Effect Bactericidal. Pharmacokinetics Well absorbed from the G1 tract (food increases absorption). Protein binding 21%-40%. Widely distributed. Primarily excreted unchanged in urine. Partially removed by hemodialysis. Half-life 2.3 hr (increased in impaired renal function and elderly patients). 

Pharmacokinetics Lepirudin is eliminated primarily by renal excretion (renal clearance 65 to 115ml/min). Dose adjustment based on creatinine clearance is recommended. The total clearance of lepirudin is 195ml/min, its elimination half-life is 1.3 hours, and its volume of distribution is 12.2 to 18.0 hters.The systemic clearance of lepirudin in women is about 25% lower than in men. In elderly patients the systemic clearance of lepirudin is 20% lower than in younger patients. Distribution is limited to extracellular space. As the intravenous dose is increased over the range of 0.1 to 0.4mg/kg, the maximum plasma concentration and the area-under-the-curve increase proportionally. 

Mivacurium is a mixture of three stereoisomers, the two short-acting cis-trans and trans-trans isomers comprising about 94% of the mixture. Both have very short half-lives of about 2 minutes, while the much less potent c/s-c/s isomer has about one-tenth the neuromuscular blocking potency of the other two isomers. The c/s-c/s isomer undergoes some renal excretion as well as being broken down by plasma cholinesterase with a half-life of about 50 minutes (Table 6.4). The short-acting isomers are broken down almost entirely by plasma cholinesterase with a high rate of clearance and a short duration of action. The duration of action of mivacurium is increased when there is a reduction in plasma cholinesterase activity as in patients with marked renal and hepatic disease. The same is true for elderly patients. 

In this hereditary disease up to 1 - 2 g of methylmalonic acid per day (compared to a normal of <5 mg/day) is excreted in the urine, and a high level of the compound is present in blood. Two causes of the rare disease are known/ One is the lack of functional vitamin B12-containing coenzyme. This can be a result of a mutation in any one of several different genes involved in the synthesis and transport of the cobalamin coenzyme.6 Cultured fibroblasts from patients with this form of the disease contain a very low level of the vitamin B12 coenzyme (Chapter 16), and addition of excess vitamin B12 to the diet may restore coenzyme synthesis to normal. Among elderly patients a smaller increase in methylmalonic acid excretion is a good indicator of vitamin B12 deficiency. A second form of the disease, which does not respond to vitamin B12, arises from a defect in the methylmalonyl mutase protein. Methylmalonic aciduria is often a very severe disease, frequently resulting in death in infancy. Surprisingly, some children with the condition are healthy and develop normally.3 1... 

The function of the kidney decreases with age, and in the elderly the ability to excrete substances is reduced. Therefore drugs and their breakdown products can accumulate in the bodies of elderly patients if they take repeated doses of a drug (see box on Opren, page 29). 

Overdose, which may be absolute or relative (due to impaired renal excretion or in elderly patients who develop adverse effects at lower dosages), leads to severe hypotonia, mental confusion and somnolence, respiratory depression, and eventually apnea, bradycardia, cardiac conduction abnormalities, hypotension, and coma. Convulsions can occur and hypertension has been reported. It is possible that during recovery the picture may be complicated by an acute withdrawal syndrome, with agitation, psychosis, tremor and dystonic movements, convulsions, and hallucinations (SEDA-11, 126) (36 0). 

The effect of COX-2 specific inhihitors on renal function, including sodium excretion, has heen assessed in prostaglandin dependent patients. Catella-Lawson et al. [26] enrolled 36 healthy elderly patients for her study, which evaluated not only sodium excretion and glomerular filtration rates, but also changes in body... 

Collectively, these studies suggest that COX-2 plays a dominate role in the regulation of salt and water excretion in prostaglandin dependent patient, while the role of COX-1 seems to involve the regulation of renal hemodynamics, including GFR. The Swan et al. [127] study suggests that COX-2 may also play a role in regulating GFR however, the combination of elderly patients who are salt depleted may have provided a more severe hemodynamic stress than was present in the other three studies. 

Sodium bicarbonate is metabolized to the sodium cation, which is eliminated from the body by renal excretion, and the bicarbonate anion, which becomes part of the body s bicarbonate store. Any carbon dioxide formed is eliminated via the lungs. Administration of excessive amounts of sodium bicarbonate may thus disturb the body s electrolyte balance, leading to metabolic alkalosis or possibly sodium overload with potentially serious consequences. The amount of sodium present in antacids and effervescent formulations has been sufficient to exacerbate chronic heart failure, especially in elderly patients. ... 

Elderly patients are susceptible to adverse side effects from medication because, as the body ages, the ability to absorb, metabolize, distribute, and excrete medication decreases and results in pooling of medication. Here are additional factors that influence the adverse side effects from medication in elderly people ... 

PK studies in renal-impaired patients if the drug or metabolites are renally excreted. If the NME is excreted and/or metabolized by the liver, a hepatic-impaired study should be undertaken. These studies do not have to be done in elderly patients (they are usually done on a new NME anyway). 

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