A pharmacodynamic basis for changes in drug activity associated with aging in the adult

Bender, A. Douglas

doi:10.1016/0531-5565(65)90008-2

Cited by 22 publications

(7 citation statements)

References 39 publications

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“…Over the past ten years, evidence has accumulated which supports an already generally accepted view that the probability of experiencing adverse drug reactions increases with age (1, 2). During this same period, it has become increasingly appreciated that the activities of some drugs are modified in the geriatric patient and that these variations should be acknowledged in therapeutic regimens prescribed for patients in this age group (3)(4)(5)(6)(7)(8)(9)(10)(11).…”

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confidence: 99%

Pharmacodynamic Principles of Drug Therapy in the Aged*

Bender¹

1974

J American Geriatrics Society

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The geriatric patient responds differently to some drugs than does the younger adult, and consequently certain precautions should be taken when prescribing a therapeutic regimen for the elderly. Increasing age is accompanied by functional changes in many of the systems that control the way a drug is metabolized and the response that it evokes. Apparently it is these changes which underlie the modified effect seen clinically in geriatric patients. Age tends to reduce and delay the absorption of substances from the gastrointestinal tract, impair and delay drug clearance and excretion by the kidneys, and reduce the rate of enzyme destruction. The plasma half‐life of penicillin, digoxin, antipyrine, or phenylbutazone is extended significantly in the aged so that higher circulating concentrations are maintained for longer periods. Other age‐related changes influence the effect of a drug once it has combined with its receptor. These include an altered number of receptor sites, a decrease in the transmitter content of affected tissues, an increase in the rigidity of responsive tissues, and an overall decline in homeostatic capability.

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confidence: 99%

Pharmacodynamic Principles of Drug Therapy in the Aged*

Bender¹

1974

J American Geriatrics Society

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“…The author is aware of the dangers of oversimplification. Other aspects such as the number of responsible cells, the lipoid/water partition coefficient of drugs, and the increased or decreased susceptibility to the effects of a drug (44–49) have not been covered in the scope of this paper. However, the number of drugs used in geriatric patients in multiple dosing, and with which there is danger of overdosing and hence severe side effects such as nephrotoxicity, is limited.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Approach to Drug Dosing in the Aged

Ritschel

1976

J American Geriatrics Society

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Data in the literature show that there is a constant ratio of total body fluid to lean cell mass with increasing age (1.15 for males and 1.31 for females). Since the drug receptors usually are found in the tissues, and since cell mass and total body fluid apparently decrease at a constant rate, it would seem that the volume of distribution of drugs decreases proportionally with increasing age. Kidney function, as measured by the glomerular filtration rate and transport maximum, apparently decreases with increasing age according to zero-order kinetics. Based on these data, correction factors were established for the change in volume of distribution and renal functions with increasing age. Equations were derived for calculating the loading dose and maintenance dosage of drugs in multiple-dose therapy in females and males. Equations are presented for drugs following the minimal inhibitory concentration (MIC) pattern and the log dose-response pattern, respectively. The MIC pattern is recommended in the use of bacteriostatic drugs, for which it is essential to maintain recommended in the use of bacteriostatic drugs, for which it is essential to maintain during the entire course of therapy a minimum inhibitory concentration. The log dose-response pattern is recommended for bactericidal and antiarrhythmia drugs, for which it is essential to obtain an average therapeutic steady-state concentration. Based on this pharmacokinetic approach, it would seem that elderly patients, during multiple-dose therapy, are exposed to dose sizes that are too large if no correction is made.

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“…We believe, therefore, that factors other than renal impairment must also be involved, such as age 7 and the ability of the older patient to adjust to his interna 1 environment. 8 Delayed excretion of triamterene and redistribution of body potassium in favor of the extracellular component could be factors. Triamterene is excreted primarily as the sulfuric acid ester of 2,4,7-triamino-6-p-hydroxyphenylpteridine.…”

Section: Discussionmentioning

confidence: 99%

Changes in serum potassium levels occurring in patients treated with triamterene and a triamterene‐hydrochlorothiazide combination

Hansen

Bender

1967

Clin Pharma and Therapeutics

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This report summarizes the changes in serum potassium levels in 583 patients treated with triamterene alone, 484 treated with a combination of triamterene and hydrochlorothiazide, and 82 treated with hydrochlorothiazide. The incidence of hypokalemia <3.5 mEq. per liter) in patients treated with a combination of triamterene and hydrochlorothiazide was 6 per cent. Hyperkalemia (>5.4 mEq. per liter) developed in 7.5 per cent of subfects to whom the combination was given, in 12 to 19 per cent of subfects treated with triamterene, and in 4 per cent of patients, especially the severely ill, treated with hydrochlorothiazide.

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A pharmacodynamic basis for changes in drug activity associated with aging in the adult

Cited by 22 publications

References 39 publications

Pharmacodynamic Principles of Drug Therapy in the Aged*

Pharmacodynamic Principles of Drug Therapy in the Aged*

Pharmacokinetic Approach to Drug Dosing in the Aged

Changes in serum potassium levels occurring in patients treated with triamterene and a triamterene‐hydrochlorothiazide combination

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