Pharmacokinetics in old age

Tregaskis, B; Stevenson, I. H.

doi:10.1093/oxfordjournals.bmb.a072397

Cited by 26 publications

(8 citation statements)

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“…Physiologic changes known to play a role in the pharmacokinetics of a drug in the elderly include [50,51]: decline in total body size, total body water, lean body mass, kidney mass and function, liver mass, liver blood flow and function, serum albumin and increase in body fat stores. Polypharmacy, drug interactions and compliance also play a major role in drug therapy in the elderly.…”

Section: Drug Handling By the Aging Livermentioning

confidence: 99%

“…Hepatic metabolism of drugs depends on phase I and phase II reactions [51]. Phase I reactions comprise oxidation, reduction, demethylation and hydrolysis, rendering the compounds less lipophilic.…”

Section: Liver Drug-metabolizing Enzymesmentioning

confidence: 99%

“…Phase I reactions comprise oxidation, reduction, demethylation and hydrolysis, rendering the compounds less lipophilic. Phase II reactions additionally serve to expose or to add functionally reactive sites to which polar groups may be conjugated by reactions of glucoronidation, methylation, sulfation, or acetylation [51].…”

Section: Liver Drug-metabolizing Enzymesmentioning

confidence: 99%

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Aging Liver

Anantharaju¹,

Feller²,

Chedid³

2002

Gerontology

163

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Aging is characterized by a progressive decline of cellular functions. The aging liver appears to preserve its function relatively well. Aging is associated in human liver with morphological changes such as decrease in size attributable to decreased hepatic blood flow. Ultrastructural analysis of the human liver has revealed that the integrity of mitochondria and enzymatic activity remain mostly unchanged with aging. Reactive oxygen species (ROS) are involved in the aging process and result mainly from nonenzymatic processes in the liver. Endogenous free radicals are generated within mitochondria and suspected to cause severe injury to mitochondrial DNA. This damaged DNA accumulates with aging. In addition, polyunsaturated fatty acids, highly sensitive to ROS, decrease in liver mitochondria from human centenarians, a feature acquired during evolution as a protective mechanism to favor longevity. Diet is considered the main environmental factor having effect on lifespan. It has a major impact on aging liver, the central metabolic organ of the body. The ubiquitin proteolytic pathway in the liver serves to destroy many proteins, among them p21 which is encoded by abundant mRNA in senescent cells, can inhibit cell proliferation and favors DNA repair. Drug therapy in the elderly may be complicated by several factors such as decline in body weight, renal function, liver mass and hepatic blood flow, making adverse drug reactions more frequent. Hepatic drug metabolism is mainly mediated by the cytochrome P₄₅₀system and drug interactions in the elderly are likely related to the progressive decline of this system after the fifth decade of life and another decrease in individuals aged >70. Antihypertensive therapy in the elderly depends upon either hepatic or renal function and should be adjusted accordingly. Finally, telomerases are the biological clocks of replicative lifespan. Shortening of telomeric ends of chromosomes correlates with aging and decline in the replicative potential of the cell: replicative senescence. Telomere DNA of human somatic cells shortens during each cell division thus leading to a finite proliferation. Transfection of the telomerase reverse transcriptase gene results in elongation of telomeres and extension of lifespan. This also applies to humans. Replicative senescence in human cells evolved as a mechanism to protect them from continuous divisions leading to multiple mutations. Longer-lived species such as humans had to develop replicative senescence to ensure that they would have the increased protection that their longevity necessitates.

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Section: Drug Handling By the Aging Livermentioning

confidence: 99%

Section: Liver Drug-metabolizing Enzymesmentioning

confidence: 99%

Section: Liver Drug-metabolizing Enzymesmentioning

confidence: 99%

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Aging Liver

Anantharaju¹,

Feller²,

Chedid³

2002

Gerontology

163

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“…The' volume of distribution for digoxin is smaller due to a reduction in total body water content. Thus, a smaller loading dose is required in the elderly to provide adequate utilisation and avoid potential toxicity (Tregaskis & Stevenson 1990). Conversely, for lipidsoluble drugs such as lidocaine and thiopentone, the volume of distribution rises because of the relative increase in body fat.…”

Section: Body Compositionmentioning

confidence: 99%

Adverse Drug Reactions An Overview of Special Considerations in the Management of the Elderly Patient

Brawn

Castleden²

1990

Drug Safety

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The incidence of adverse drug reactions increases with aging, and the elderly are more likely to suffer serious or fatal reactions. Thus, morbidity and mortality are considerable in old patients, with 15% of those in hospital suffering a reaction, and many admitted as a consequence of one. The greater propensity of older patients for adverse drug reactions largely reflects the prescription of drugs to them, although over-the-counter purchases must also play a part. The elderly take more drugs per se (which is a reflection of multiple pathology), and more drugs with a narrow therapeutic index associated with a high risk of dangerous adverse reactions and drug interactions. They also have a reduced ability to withstand any reactions due to concomitant disease, and an altered pharmacokinetic and -dynamic response which tends to increase drug effects. The recommendation must be to use fewer drugs in older patients, perhaps trying alternative medicine first in nonacute conditions. Starting doses can often be reduced in the elderly, and clinical and therapeutic monitoring of effect is mandatory. The use of diuretics, antihypertensives, anti-Parkinsonian drugs and anticoagulants emphasise these points, and is discussed in detail together with digoxin, analgesics and nonsteroidal anti-inflammatory drugs. Clear guidelines are given for the use of each of these classes of drug.

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“…Conversely, the amount of body water decreases from 61% to 53% (The Royal Melbourne Hospital Pharmacy Department, 1987). These changes in body composition mean that fat-soluble drugs such as diazepam and lidocaine have an increased volume of distribution and a longer duration of chemical action (Tregaskis & Stevenson, 1990). Likewise, the reduction of total body water and mass decreases the distribution volume and increases the initial plasma level of water-soluble drugs such as acetaminophen and ethanol (Montamat, Cusack, & Vestal, 1989).…”

Section: Physiologic Changes Of Agingmentioning

confidence: 99%

Geropharmacology: An Individualized Approach

Wright¹

1991

Journal of the American Academy of Nurse Practitioners

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Pharmacologic care of the elderly is a multifaceted problem. This article approaches geropharmacology from an individualized perspective. The practitioner should plan and prescribe health care for the aged, with a knowledge of physiologic changes in the elderly, an understanding of the pharmacokinetic and pharmacodynamic mechanisms of iatrogenic drug reactions, and an awareness of the social and ethical issues related to geropharmacology.

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Pharmacokinetics in old age

Cited by 26 publications

References 0 publications

Aging Liver

Aging Liver

Adverse Drug Reactions An Overview of Special Considerations in the Management of the Elderly Patient

Geropharmacology: An Individualized Approach

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