Medications for the elderly

The multiplicity of pathologies, the high risk of destabilization of the condition in patients of older age groups leads to the fact that drugs for the elderly have become increasingly used in geriatrics. Features of pharmacokinetics, pharmacodynamics, therapeutic and toxic effects of drugs in the elderly body, as well as the possibilities of using geroprotectors are studied by geriatric pharmacology.

Age-related features of pharmacokinetics are that in elderly and senile people the absorption of substances from the gastrointestinal tract slows down, the distribution and transport of drugs in the body changes, the rate of biotransformation in the liver decreases, and the excretion of drugs slows down.

Oral medications for the elderly are most frequently used in geriatric practice. The first stage of pharmacokinetics is their absorption in the gastrointestinal tract. With age, the absorption surface of the digestive organs decreases, the secretory function of the digestive glands and the enzymatic activity of digestive juices decrease, the blood flow in the mesenteric vessels decreases - all this leads to a slowdown in the rate of dissolution of the drug and its absorption. Of particular importance is the motor function of the intestine and its change under the influence of medications: constipation and medications for the elderly that contribute to a slowdown in intestinal peristalsis (atropine, platifillin, tricyclic antidepressants, antiparkinsonian agents, phenothiazine neuroleptics, etc.) lead to increased absorption of drugs; frequent loose stools and the use of laxatives and metoclopramide reduce the absorption of simultaneously used drugs.

With subcutaneous and intramuscular administration of drugs, the effect occurs later due to a decrease in cardiac output, a slowdown in blood flow velocity and thickening of the walls of blood vessels.

The second stage of pharmacokinetics is distribution, which depends on the protein composition of the blood, water-electrolyte status, and the level of functioning of the cardiovascular system. In addition, distribution largely depends on the properties of the drug used for the elderly. Thus, water-soluble drugs for the elderly are distributed in extracellular spaces, while lipid-soluble drugs are distributed in intra- and extracellular spaces.

In elderly patients, there is a decrease in albumin content, a decrease in muscle mass and water, an increase in body fat content, as a result of which the distribution and concentration of drugs in the blood changes.

A decrease in blood flow velocity and the intensity of peripheral circulation also increases the duration of circulation of drugs and increases the risk of intoxication.

As is known, drugs for the elderly in the blood are bound by plasma proteins (usually albumins); bound to proteins, they are not active. If there are 2 or more drugs in the blood, the one with a greater ability to bind to proteins displaces the less active one. This, along with an age-related decrease in albumin levels, leads to an increase in the content of the free fraction of the drug for the elderly, which creates a risk of a toxic effect. This is especially true for sulfonamides, benzodiazepines, salicylates, cardiac glycosides, purine antispasmodics, indirect anticoagulants, phenothiazide neuroleptics, oral antidiabetic agents, narcotic analgesics and anticonvulsants.

Shifts in the protein composition of the blood observed with aging may be the cause of altered transport of administered medications and a slower rate of their diffusion through vascular tissue membranes.

A decrease in muscle mass and water in the elderly and old age leads to a decrease in the volume of distribution of drugs, accompanied by an increase in the concentration of water-soluble drugs in the blood plasma and tissues and an increase in the risk of overdose of such drugs as drugs for the elderly, namely: aminoglycolide antibiotics, dipjein, hydrophilic beta-blockers (atenolol, tenormin, nadolol, sotalol), theophylline, H2-histamine receptor blockers.

Due to the relative increase in lipid content in old age, the volume of distribution of fat-soluble drugs increases with a decrease in their concentration in the blood plasma, which leads to a slower onset of the effect, an increased tendency to accumulation, and prolongation of the pharmacological activity of drugs such as tetracycline antibiotics, benzodiazepines, ethanol, phenothiazine neuroleptics, and sleeping pills.

With age, a change in the biotransformation (metabolism) of medicinal substances is also observed, caused primarily by a weakening of the activity of the liver's enzyme systems, a decrease in the number of hepatocytes and a decrease in hepatic blood flow (annually by 0.3-1.5%). At the same time, the biotransformation of drugs slows down, their concentration in the blood and tissues increases, side effects develop more often, and the risk of overdose is higher.

It is important to note that the activity of enzymes that ensure the process of glucuronidation of drugs practically does not change with age, therefore, in the elderly, all other things being equal, it is preferable to prescribe drugs that are inactivated by this route.

It should also be taken into account that in some elderly and senile individuals the rate of biotransformation of medicinal substances is not subject to age-related changes.

The next stage of pharmacokinetics is the elimination of drugs from the body. In geriatric patients, renal blood flow decreases, glomerular filtration decreases, the number of functioning nephrons decreases, tubular secretion is impaired with a decrease in creatinine clearance (in people over 65 years of age, it is 30-40% of the indicators of middle-aged people). The excretion of drugs slows down. This is also facilitated by the prolongation of the enterohepatic circulation of drugs and their metabolites (due to hypokinetic dyskinesia of the biliary tract and increased reabsorption with reduced intestinal peristalsis).

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Basic principles of drug therapy in geriatrics

It is necessary to limit the number of drugs to the smallest possible number (1-2 drugs for the elderly), the intake of which should be as simple as possible (1-2 times a day). Only those drugs whose therapeutic and side effects are well known should be prescribed.

If it is possible to achieve a therapeutic effect using non-drug methods, then, if possible, they should be used.

It is necessary to treat the underlying disease or syndrome that currently determines the severity of the patient's condition.

Strict individualization of treatment is required, as well as selection of optimal doses of medications for a given patient.

Use the rule of small doses (half, one third of the generally accepted dose), then slowly increase it until the therapeutic effect is achieved and adjust the maintenance dose.

It is advisable to prescribe complex medications with multidirectional effects on the patient’s existing diseases.

Use medications for the elderly and a diet that normalize the reactivity, metabolism and functions of the aging organism, reducing the risk of developing side effects: complexes of water- and fat-soluble vitamins, vital micro- and macroelements, amino acids, adaptogens.

It should be remembered that the effect of drugs administered enterally may occur later and be insufficiently pronounced due to age-related deterioration in their absorption in the gastrointestinal tract.

It is necessary to control fluid intake and urine output, the state of kidney function. Insufficient fluid intake can contribute to the development of drug intoxication.

Long-term use of many drugs (sedatives, painkillers, sleeping pills) leads to tachyphylaxis (addiction) and an increase in their dosages, increasing the risk of intoxication. Frequent replacement of drugs and the use of "pulse therapy" are necessary.

In a clinic setting, prescribed recommendations and medications for the elderly should be written down for the patient and given to him.

Among persons receiving polypharmacotherapy, patients with factors of increased risk of toxic, side and paradoxical effects of drugs should be distinguished. This group of persons should include patients with complicated allergic anamnesis, signs of renal or hepatic failure, with reduced cardiac output, progressive decrease in body weight, hypoalbuminemia. Increased risk of complications of pharmacotherapy is observed in patients over 80 years old with altered neuropsychiatric status, reduced hearing and vision.

At each visit, check which medications for the elderly and how much of the prescribed medications the patient takes. Encourage the patient to keep a diary of sensations associated with the treatment.

Regularly monitor the parameters of physiologically important processes (blood pressure, pulse, diuresis, electrolyte composition of the blood), preventing sudden changes in their values.

Age-related changes in physiological processes

Decreased absorption surface of the gastrointestinal tract, decreased mesenteric blood flow, increased pH of gastric contents, slowed peristalsis.

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Malabsorption

Decreased muscle mass, total body fluid, albumin content, increased acidic a-glycoprotein content, fat content, changes in drug-protein bonds.

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Violation of distribution

Decreased hepatic blood flow, liver parenchyma mass, decreased enzyme activity.

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Metabolic disorder

A decrease in the number of functioning nephrons, a decrease in the rate of glomerular filtration and secretory function of the renal tubules, a slow excretion of excreta through the gastrointestinal tract, skin, and lungs.

Excretion disorder

For example, sensitivity to neuroleptics increases, causing confusion, extrapyramidal symptoms, orthostatic hypotension and urinary retention. The use of nitrates and novocainamide is accompanied by a greater decrease in arterial pressure than in middle-aged individuals and possible deterioration of cerebral circulation. Increased sensitivity to anticoagulants has been found.

On the other hand, in elderly people, adrenaline, ephedrine and other adrenomimetics have a weaker effect. Atropine and platifillin have a weaker effect on the heart rate and have a lesser spasmolytic effect (change in the binding of the drug to M-cholinergic receptors).

The anticonvulsant effect of barbiturates is less pronounced. The hypotensive effect of beta-blockers is reduced, and the number of side effects with their use increases.

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Summary of Pharmacokinetic Changes with Aging

Medicines for the elderly are determined not only by their concentration in the body, but also by the functional state of the tissue or target organ and receptors. With aging, the number of receptors in the nervous tissue decreases, functional exhaustion and decreased reactivity occur, which often leads to the development of inadequate to the amount of the administered agent and even paradoxical reactions when using cardiac glycosides, glucocorticosteroids, nitrates, adrenergic and adrenergic blockers, some hypotensive agents, analgesics, barbiturates, benzodiazepine tranquilizers, antiparkinsonian and anticonvulsant drugs. The occurrence of perverted reactions to medications is facilitated by reduced physical activity, a tendency to constipation, vitamin deficiency, deterioration of tissue blood supply and the relative predominance of excitatory processes in the nervous system in old and senile age.