Pharmacodynamics* in the older patient

The increasing number of elderly people in the world, presents multiple challenges for provision of care. Many biological changes occur with ageing such as decrease in physiological fitness, reduction of homeostatic capabilities and decline in functional reserves.

Drug absorption^[1]

Drug dissolution is affected by the ageing of the gastrointestinal mucosa in the elderly and the decrease of gastric acid secretion (25% – 20% reduction). As a result drugs stay longer in the gastrointestinal tract, which is conducive to greater drug absorption.

Drug distribution^[1]

Due to a decrease in the amount of plasma proteins, an increase of fat percentage and decrease of lean tissues (skeletal muscle, liver, brain, kidney, etc.), when the same dose of drug is used in elderly and young people, it has a high level of free state and greater functionality in the elderly. The elderly are therefore more prone to toxic reactions.

Drug metabolism^[1]

As the activity of drug metabolism enzymes in the liver decrease, the half-life of the drug gets prolonged. Also, the age associated reduction of parenchymal cells in the liver and a reduction of liver blood flow affects the ability of the liver to metabolise drugs. These factors further compound the drug scavenging capacity of the elderly, causing drug effect enhancement and more adverse reactions.

Drug excretion^[1]

The kidney is the main organ involved in drug excretion; therefore the pharmacokinetics of ageing induced change mainly results from reduced kidney functionality. It is the most important factor in producing toxic drug reactions in the elderly.

Consequently, in older patients, the effects of drug concentrations at the site of action may be greater or smaller than those in younger people. These differences may be due to changes in^[2]:

• drug-receptor interaction
• post receptor events
• or adaptive homeostatic responses
• pathologic changes in organs (in frail patients)

Older adults with cognitive impairment, are particularly prone to central nervous system (CNS) adverse effects of drugs e.g., tricyclic antidepressants, sedating antihistamines, urinary antimuscarinic agents, some antipsychotic drugs.

Below are some recommendations^[3] for appropriate drug prescribing:

• First, special caution should be taken when prescribing drugs to elderly patients, notably drugs with a narrow therapeutic window. These drugs commonly require regular monitoring to prevent overdose, toxicity and drug-drug interactions.
• Second, physicians must be familiar with pharmacokinetic^ and pharmacodynamic changes for drugs prescribed to the elderly, and drug-drug interactions must be anticipated.
• Third, dose should be adjusted for some drugs. For others, careful upwards titration of drug dosage is needed.
• Fourth, some drugs must be avoided in elderly. The benefit/risk profile of every prescribed medication should be frequently reassessed.
• Fifth, physicians, pharmacists and nurses must consult elderly patients regarding the potential adverse consequences of drugs when using alone or together with other medications.

Polypharmacy$ can also modify pharmacokinetic and pharmacodynamic effects of drugs due to drug-drug interactions.

*Pharmacodynamics is defined as what the drug does to the body or the response of the body to the drug; it is affected by receptor binding, post receptor effects, and chemical interactions.

^The term pharmacokinetics describes the fate of a drug in the body and encompasses absorption across the gut wall, first pass metabolism in gut wall and liver, protein binding, distribution throughout the body and elimination by kidney, liver or other routes. Many changes occur with ageing which could theoretically affect these variables4.

$Polypharmacy is the prescribing of multiple drugs for multiple diseases. In the older patient this can lead to problems with drug compliance and is also directly related to the incidence of side effects.

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