Elimination elderly

Host factors can help to ensure selection of the most appropriate antimicrobial agent. Age is an important factor in antimicrobial selection. With regard to dose and interval, renal and hepatic function varies with age. Populations with diminished renal function include neonates and the elderly. Hepatic function in the neonate is not fully developed, and drugs that are metabolized or eliminated by this route may produce adverse effects. For example, sulfonamides and ceftriaxone may compete with bilirubin for binding sites and may result in hyperbilirubinemia and kernicterus. Gastric acidity also depends on... 

Elderberry is not only nourishing, it also promotes a healthy metabolism. It helps break up mucus congestion, helps prevent free radicals from damaging healthy cells, treats constipation by loosening old fecal matter lodged in the colon and helps to stimulate natural peristaltic movement. Elder also helps eliminate water and fat that is unnecessarily stored in the body. 

The main rout of excretion of the drug and its metabolites is the kidney with a half-life of 9-18 h in human. In contrast to human, animal models have a lower elimination half-life ranging from 0.6-9 h [78]. The elimination half-life of valproic acid and some metabolites was found to be much longer in the neonates (40-50 h) than adult subjects (9-18 h) [78,81]. One study reported no difference between the elimination half-life between elderly and young subjects (15.4 and 13.0 h, respectively) while other found an increase in for older patients (14.9 versus 7.2 h for young patients) [78,90], Insignificant amounts of valproic acid are found in breast milk, approximately 3% of maternal drug levels [84]. 

In the elderly, doses should be low, and short-elimination half-life agents prescribed. 

There is an association between falls and hip fractures and the use of long-elimination half-life benzodiazepines thus, flurazepam and quazepam should be avoided in the elderly. 

The elimination half life of a drug will thus increase if the volume of distribution is increased as for lipophilic drugs in the elderly or if the clearance is affected, the latter mainly hepatic metabolism or renal excretion. 

Some dmgs are bound to plasma proteins in blood. Plasma protein levels in blood may be decreased in the elderly, but this is most often not clinically relevant since a drug s elimination increases when the free, unbound drug concentration is enhanced (Turnheim 1998). The plasma albumin level may however be markedly decreased in elderly suffering from malnutrition or severe disease. For those patients the concentration of the free unbound drug can reach toxic levels (Waiter-Sack and Klotz 1996). 

Klotz U, Avant GR, Hoyumpa Aet al. (1975) The effects of age and liver disease on the disposition and elimination of diazepam in adult man. J Clin Invest 55(2) 347-359 Kompoliti K and Goetz CG (1998) Neuropharmacology in the elderly. Neurol Clin 16(3) 599-610 Lanctot KL, Best TS, Mittmann N et al. (1998) Efficacy and safety of antipsychotics in behavioral disorders associated with dementia. J Clin Psychiatry 59(10) 550-561 Landi F, Onder G, Cesari M et al. (2005) Psychotropic medications and risk for falls among community-dwelling frail older people an observational study. J Gerontol A Biol Sci Med Sci 60(5) 622-626... 

The benzodiazepines that have been most commonly marketed as sedative-hypnotics include temazepam (Restoril), estazolam (ProSom), flurazepam (Dalmane), quazepam (Doral), and triazolam (Halcion). Of these five, temazepam is the most easily metabolized and eliminated. Therefore, temazepam is preferred for elderly and medically ill patients to minimize the risk of drug accumulation. 

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. 

The metabolism and elimination of TCAs takes several days to occur, the elimination half-life ranging from 20 hours for amitriptyline to 80 hours for protriptyline. The half-life values for the desmethylated metabolites such as desmethylimipramine and nortriptyline are approximately twice those of the parent compounds imipramine and amitriptyline. It is also well established that the half-life values of the TCAs are considerably greater in the elderly, which predisposes such patients to a greater possibility of severe side effects. 

In general, the lowest effective dose of the drug should be used, particularly in elderly patients. Dose titration should be undertaken slowly. Similarly, on discontinuation of a drug, the dose should be reduced slowly, the rate of decrease being decided by the elimination half-life of the drug. Some psychotropic drugs produce a discontinuation syndrome that can usually be avoided by slow withdrawal. In particular, sedatives, anxiolytics and antidepressants can cause withdrawal effects. 

Triazolam (ti/2 of elimination -1.5-5.5 h) is especially likely to impair memory (anterograde amnesia) and to cause rebound anxiety or insomnia and daytime confusion. The severity of these and other adverse reactions (e.g., rage, violent hostility, hallucinations), and their increased frequency in the elderly, has led to curtailed or suspended use of triazolam in some countries (UK). 

For a drug that is to be developed for a disease that occurs mainly in the elderly, it is often advisable to evaluate tolerability and pharmacokinetics in healthy elderly volunteers before clinical trials in the patient population. Dosage may need to be reduced and particular care taken when the kidney is the major organ of elimination, which should be established in the healthy young before administration to the elderly. It should be remembered that the GFR in the healthy elderly with normal plasma creatinine and urea is generally much lower than that in the young. One reason why healthy elderl/ studies have... 

Elderly Delayed elimination of enoxaparin and tinzaparin may occur. 

Hepatic function impairment The elimination half-life of tolterodine was longer in cirrhotic patients (mean, 8.7 hours) than in healthy, young, and elderly volunteers (mean, 2 to 4 hours). The clearance of oral tolterodine was substantially lower in cirrhotic patients (approximately 1.1 L/h/kg) than in the healthy volunteers (approximately 5.7 L/h/kg). 

Pharmacokinetics Oral hydroxyzine is rapidly absorbed from the Gl tract clinical effects are usually noted within 15 to 30 minutes after administration. Mean elimination half-life is 3 hours half-life may be longer in elderly patients. Hydroxyzine is mainly metabolized by the liver. 

Pharmacokinetics Non-ergot dopamine agonists are rapidly absorbed. The absolute bioavailability is more than 90%. Steady-state concentrations are achieved within 2 days of dosing. Terminal half-life is about 8 hours (about 40 minutes for apomorphine) in young healthy volunteers and about 12 hours in elderly volunteers. Urinary excretion is the major route of elimination. 

Elderly The elimination rate of omeprazole was somewhat decreased in the elderly and the bioavailability increased (see Pharmacokinetics). 

Norfloxacin - Absorption is rapid. Food or dairy products may decrease absorption. Steady-state norfloxacin levels will be attained within 2 days of dosing. Norfloxacin is eliminated through metabolism, biliary excretion, and renal excretion. Renal excretion occurs by glomerular filtration and tubular secretion. In healthy elderly volunteers, norfloxacin is eliminated more slowly because of decreased renal function. In patients with Ccr rates 30 mL/min/1.73 m or less, the renal elimination decreases so that the effective serum half-life is 6.5 hours dosage alteration is necessary. 

Ofloxacin - Maximum serum concentrations are achieved 1 to 2 hours after an oral dose. Steady-state concentrations are achieved after 4 doses. Ofloxacin is widely distributed to body tissues and fluids. Elimination is mainly by renal excretion 4% to 8% is excreted in the feces. A longer plasma half-life of about 6.4 to 7.4 hours was observed in elderly subjects, compared with 4 to 5 hours for young subjects. Dosage adjustment is necessary for patients with impaired renal function (Ccr 50 mL/min or less). 

Hepatic function impairment There are no data in patients with severe cirrhosis. Dosage adjustment is recommended in patients with mild-to-moderate cirrhosis. Eideriy Norfloxacin is eliminated more slowly because of decreased renal function. The apparent half-life of ofloxacin is 6 to 8 hours, compared to approximately 5 hours in younger adults. Lomefloxacin plasma clearance was reduced by 25% and the AUC was increased by approximately 33% in the elderly. 

More hydrophilic /3-blockers, such as atenolol, bisoprolol, celiprolol, pindolol and sotalol are predominantly eliminated via the kidney. In elderly patients this may require adaptation of the dosage. Most of the shorter acting /3-blockers are available as slow release preparations. Accordingly, when used as antihypertensives /3-blockers are usually administered once daily. For other applications such as angina pectoris a twice daily dosage may be required. 

Gabapentin Unclear 5-7 1-2 days Slow escalation of dose reduces the risk of adverse reactions. Renal elimination - observe possible need for dose reduction in elderly. Evidence of effect in zoster pain and in neuropathic pain. Not first choice... 

It is important to appreciate that these tubular transport mechanisms are not as well developed in the neonate as in the adult. In addition, their functional capacity may be diminished in the elderly. Thus, compounds normally eliminated by tubular secretion will be excreted more slowly in the very young and in the older adult. This age dependence of the rate of renal drug secretion may have important therapeutic implications and must be considered by the physician who prescribes drugs for these age groups. 

Amantadine is rapidly and completely absorbed from the gastrointestinal tract, and peak blood levels are achieved in 2 to 5 hours. The serum half-life of amantadine averages 17 hours in young adults and 29 hours in the elderly. Most of the drug (90%) is eliminated unchanged by glomerular filtration and tubular secretion. 

Rimantadine is well absorbed following oral administration, with peak blood levels achieved in 5 to 7 hours. Its elimination half-life averages 25 hours in young adults and 32 hours in the elderly. Less than 25% of the dose is excreted in the urine as unchanged drug the remainder is eliminated as hydroxylated or conjugated metabolites. 

Pharmacokinetics Rapidly and almost completely absorbed from fhe G1 fract. Distributed mainly in liver, lungs, G1 tract, and bile. Metabolized in the liver to active metabolite and undergoes extensive first-pass metabolism. Eliminated in urine and feces. Half-life 27 hr (increased in the elderly and in renal or hepatic impairment). 

Pharmacokinetics-. Well absorbed after PO administration. Metabolizedby the liver to inactive metabolite. Eliminated in urine. Half-life 4.4 hr (increased in hepatic impairment and the elderly (older than 65 yr). 

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