Altered Pharmacodynamics of Cardiovascular Drugs and Their Relation to Altered Pharmacokinetics in Elderly Patients

doi:10.1016/S0749-0690(18)30617-7

Clinics in Geriatric Medicine

Volume 6, Issue 2, May 1990, Pages 285-292

https://doi.org/10.1016/S0749-0690(18)30617-7 Get rights and content

Pathophysiologic changes of aging and hypertension alter pharmacodynamic responses to cardiovascular drugs. For beta-adrenergic antagonists and calcium antagonists these changes do not develop in parallel with the pharmacokinetic changes of aging for these drugs. Only with a linked understanding of altered pharmacodynamics and pharmacokinetics can the elderly patient be optimally treated with these drugs.

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Impact of ageing on the pharmacokinetics and pharmacodynamics of the drugs
2022, Pharmacokinetics and Toxicokinetic Considerations - Vol II
Ageing is associated with multiple comorbidities and frequently requires many medications to treat the ailments. Ageing is associated with the change in the physiology of the body. This altered physiology plays a vital role in changing drug pharmacokinetics and pharmacodynamics. In some cases, the drug concentration will be reduced and requires a higher dose to compensate for the loss of the drug to show its therapeutic efficacy. On the other hand, some drug plasma concentrations rise due to altered physiological conditions in elderly patients and show adverse drug reactions. Polypharmacy is also considered one of the major concerns for elderly patients as they administer multiple medications simultaneously. Hence, a systematic, holistic approach needs to be designed shortly to define medication prescription for elderly patients. The geriatric population’s current state of the art is deplorable and needs more investigations to standardize geriatric pharmacology.
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Background: Older individuals experience physiologic changes in organ function related to aging or to specific disease processes. These changes can affect drug pharmacodynamics in older adults.
Objective: The goal of this article was to review age-related changes in pharmacodynamics and their clinical relevance.
Methods: PubMed and International Pharmaceutical Abstracts were searched (January 1980-June 2006) for the following combination of terms: pharmacodynamic and elderly, geriatric or aged. References cited in other reviews were also evaluated. The current review focused on age-related pharmacodynamic changes in agents affecting the central nervous system (CNS), cardiovascular, and endocrine functions.
Results: Older adults frequently demonstrate an exaggerated response to CNS-active drugs. This is in part due to an underlying age-related decline in CNS function and in part due to increased pharmacodynamic sensitivity for some benzodiazepines, anesthetics, and opioids. The most important pharmacodynamic differences with age for cardiovascular agents are the decrease in effect for J3-adrenergic agents. This decline in response in vascular, cardiac, and pulmonary tissue may be due to a decrease in Gs protein interactions. Most studies indicate there is no decrease in cx-receptor sensitivity with age. Angiotensin-converting enzyme inhibitors do not show age-related differences in elderly patients. With the dihydropyridine calcium channel blockers, there was a slight increase in effect for older adults, but this was only for treatment-naive patients and was transient. Nondihydropyridines did not show an age- associated change in pharmacodynamic effect; however, in the elderly, there appeared to be a decrease in the PR interval prolongation normally seen with these agents. Studies of diuretics indicated that the changes in diuretic and natriuretic effects seen in the elderly were associated with pharmacokinetic changes and were not pharmacody- namic in nature. There was a lack of consistent evidence regarding whether sulfonylureas show age-related changes in pharmacodynamic effect.
Conclusions: There is a general trend of greater pharmacodynamic sensitivity in the elderly; however, this is not universal, and these age-related changes must be investigated agent-by-agent until further research yields greater understanding of the molecular mechanisms underlying the aging process.
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2004, American Journal Geriatric Pharmacotherapy
Physiologic changes and disease-related alterations in organ function occur with aging. These changes can affect drug pharmacokinetics in older persons.
This article reviews age-related changes in pharmacokinetics and their clinical relevance.
A PubMed search was conducted using the terms elderly and pharmacokinetics. Other reviews were also included for literature searching. The review includes literature in particular from 1990 through April 2004. Some particles from before 1990 were included to help illustrate principles of age-related pharmacokinetics.
There are minor changes in drug absorption with aging. The effect of aging on small-bowel transporter systems is not yet fully established. Bioavailability of highly extracted drugs often is increased with age. Transdermal absorption may be delayed, especially in the case of water-soluble compounds. Fat-soluble drugs may distribute more widely and water-soluble drugs less extensively in older persons. Hepatic drug metabolism shows wide interindividual variation, and in many cases, there is an age-related decline in elimination of metabolized drugs, particularly eliminated by the cytochrome enzyme system. Any decrement in cytochrome enzyme metabolism appears nonselective. Synthetic conjugation metabolism is less affected by age. Pseudocapillarization of the sinusoidal endothelium in the liver, restricting oxygen diffusion, and the decline in liver size and liver blood flow may influence age-related changes in rate of hepatic metabolism. Frailty, physiological stress, and illness are important predictors of drug metabolism in older individuals. Inhibition of drug metabolism is not altered with aging, but induction is reduced in a minority of studies. Renal drug elimination typically declines with age, commensurate with the fall in creatinine clearance. Renal tubular organic acid transport may decline with age, while the function of the organic base transporter is preserved but may be less responsive to stimulation.
Changes in pharmacokinetics occur due to age-related physiologic perturbations. These changes contribute to altered dose requirements in older persons, particularly in the case of drugs eliminated by the kidney. Interindividual variation, disease, frailty, and stress may overshadow age-related changes.
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: Supported in part by USPHS Grant No. AG-08226

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