Hepatic drug metabolism and ageing

Woodhouse, K. W.; James, O.F.W.

doi:10.1093/oxfordjournals.bmb.a072387

Cited by 87 publications

(43 citation statements)

References 15 publications

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“…A study based on 1,582 subjects, aged between 20 and 80, was published a decade ago [5]. According to this study, the liver progressively decreased in size with aging and experienced a marked decline in volume occurring after the 6th decade of life as detected by ultrasonography [5]. Wynne et al [6] showed a significant negative correlation between liver volume and age in 65 volunteer subjects aged 24-91.…”

Section: Morphological Changes In Aging Livermentioning

confidence: 99%

“…In the past, human studies of the aging liver were limited and relied on postmortem samples and often used elderly subjects with liver disease. A study based on 1,582 subjects, aged between 20 and 80, was published a decade ago [5]. According to this study, the liver progressively decreased in size with aging and experienced a marked decline in volume occurring after the 6th decade of life as detected by ultrasonography [5].…”

Section: Morphological Changes In Aging Livermentioning

confidence: 99%

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Aging Liver

Anantharaju¹,

Feller²,

Chedid³

2002

Gerontology

167

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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: Morphological Changes In Aging Livermentioning

confidence: 99%

Section: Morphological Changes In Aging Livermentioning

confidence: 99%

Aging Liver

Anantharaju¹,

Feller²,

Chedid³

2002

Gerontology

167

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“…Phase I reactions (oxidation, reduction, and hydroxylation) are thought to be affected to a greater extent than phase II reactions (glucuronidation, acetylation, and sulfation). The decrease in oxidative metabolism (cytochrome P450) of some drugs in the elderly is thought to be due to changes in liver blood flow and liver mass as one ages (15). However, based on very limited information, glucuronidation reactions appear to be spared with aging (5).…”

Section: Clinical Pharmacology Of Aeds In the Elderlymentioning

confidence: 99%

Epilepsy in the Elderly

Leppik

2006

Epilepsia

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Summary: The elderly are the most rapidly growing segment of the population and the incidence of epilepsy is higher in the elderly than in any other age group. They have been subdivided into the “young old,” 65–74 years, “middle old” 75–84 years, and the “old old,” 85 years or older. But further subdivisions are needed: persons with only epilepsy, those with epilepsy and multiple medical problems, and the frail elderly. Thus, when considering therapy, one must tailor the interventions to nine categories: young old healthy, young old with medical problems, frail young old, old healthy, old with medical problems, frail old, old old healthy, old old with medical problems, and frail old old. The prevalence of antiepileptic drug (AED) use in community dwelling elderly is 1.5%; in the nursing home population it is 10%. Surprisingly, 3% have an AED newly prescribed after admission. Overall, 6.2% were using phenytoin, 1.8% carbamazepine, 0.9% valproic acid, 1.7% phenobarbital, and others combined, 1.2%. AEDs rank fifth among all drug categories as a cause of adverse reactions. There are very few data regarding the clinical use of AEDs in the elderly. The paucity of information makes it very difficult to recommend specific AEDs with any confidence that the outcomes will be optimal. An appropriate for elderly healthy may not be appropriate for elderly with multiple medical problems, and in frail elderly variable absorption may be a major problem. One of the major advantages of some newer AEDs is lack of drug interactions. Cost is an advantage of the older AEDs. Regardless of the AED chosen, one must use doses appropriate to the clearance of the drug, and AED levels, especially unbound (free) levels, must be monitored. The elderly nursing home resident may be more frail, be taking many medications, and have several concomitant illnesses, making them difficult to treat. The most commonly used AED, phenytoin, may not be the easiest or safest AED to prescribe in the elderly with multiple medical problems or the frail elderly.

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“…11 Similarly, the hepatic clearance of many drugs is reduced in the elderly, mainly because of a decrease in liver size (as little as mid-life size 40%) and a reduction in hepatic blood flow. 12 The ageing liver also has a decreased capacity to recover from injury. 13 …”

Section: Pharmacokinetic Changesmentioning

confidence: 99%

Pharmacotherapy for Skin Disorders in Older People

Shen¹,

Kelly

2012

Pharmacy Practice and Res

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Human skin is a visible indicator of age. Structural and physiological changes that occur intrinsically with ageing skin combined with the effects of cumulative extrinsic damage can result in a marked susceptibility to cutaneous disorders in older patients. The progressive degeneration of ageing skin results in atrophy of the vasculature, deterioration of supporting dermis and erosion of normal immune function. Changes from the intrinsic and extrinsic effects of ageing skin have a wide clinical expression, e.g. xerosis, eczema, seborrheic dermatitis and contact dermatitis. Although rarely fatal, these cutaneous disorders can cause morbidity and reduce quality of life. Primary skin malignancies resulting from cumulative solar damage also carry considerable mortality. There have been exciting advances in the diagnosis and treatment of skin diseases in older people. However, comorbidities, polypharmacy and altered pharmacokinetics seen in older people pose significant challenges to effective treatment. Managing skin disorders in older people is often less than optimal because their special needs and limitations are not adequately addressed. This review provides an overview of treatments available for managing skin conditions commonly encountered in older people. J Pharm Pract Res 2012; 42: 150-4.

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Hepatic drug metabolism and ageing

Cited by 87 publications

References 15 publications

Aging Liver

Aging Liver

Epilepsy in the Elderly

Pharmacotherapy for Skin Disorders in Older People

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