Claudia E. Tomaselli

Pharmacotherapy in the geriatric population* Thegeriatric population constitutes the largest group of consumers of medications in this country. Changes in the pharmacokinetic response to medications of this population are less predictable than in younger age groups, thereby resulting in adverse reactions and drug interactions in multidrugusers. Dentists need to be aware of these changes as well as alterations in therapeutic responses t o the medications most commonly used in dental treatment: sedatives, local anesthetics, analgesics, and antibiotics.

This paper won First Prize in the Eleventh Annual Arthur Elfenbaum Essay Award Contest sponsored by the American Society for Geriatric Dentistry. Ms. Tomaselli is a junior dental student at the University of Pennsylvania School of Dental Medicine.

he geriatric patient may require special considerations and precautions when any medications in the dental practice are given or prescribed, the significance of which will depend on the patient's present medical condition and current medications. Another factor that will play an important role is the change in pharmacokinetics, due to deterioration of certain organs, that accompanies aging.' According to the latest census figures, the elderly population in the United States numbers 31 million and is projected to reach approximately 35 million by the year 2000.2 Of the present number, 86% suffer from one disease, and 50% suffer from two or more chronic illnesses3 Multi-drug therapy is common practice for the clinical management of these patients? More than 80% are receiving at least one medication daily, not including the non-prescribed drugs usually taken by these individual^.^ From the patients already on medications, 87% are taking multiple drugsS The geriatric population accounts for 25% of the total consumption of medications in the United States.b This paper emphasizes the possible complications associated with the medications dispensed by the practicing dentist and enhances an awareness on the part of the dental profession about the challenges associated with multi-drug therapy in the elderly. The most common medications received by geriatric patients are cardiovascular agents, analgesics, sedatives, and tranquilizem6 As with all medications, these therapeu-

tic agents have documented adverse effects and known drug interactions. Several studies have demonstrated that the elderly are more susceptible to adverse reactions when compared with younger individual^.^,' Also, it is not surprising that the numbers of adverse reactions increase with an increase in the number of medications taken. These adverse reactions can be an important factor in the morbidity and mortality of the elderly and must be considered in the pharmacologic management of the geriatric patient. With the advances made in health care, these patients have increased potential life spans*, and by showing an increase in dental awareness, they are also preserving more of their dentitions and seeking treatment more often'. It is, then, very important for the practicing dentist to be aware that the medications used in dentistry could possibly interact with the patient's multiple drug therapy, induce diseases, or worsen any existing illness.

Pharmacokinetic changes in the geriatric population Pharmacokinetics refers to the absorption, distribution, metabolism, and excretion of a drug and its pharmacokinetic response.',I0 In the younger population, pharmacokinetics can predict the response of the medications taken, but with aging it becomes less reliable due to changes in body composition, organ function, and receptor ~ensitivity.~ These changes can be the result of an agerelated alteration in normal physiology or can be due to a pathologic entity.6

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Absorption The elderly usually have an impairment in gastro-intestinal (GI) tract mobility, a reduction of gastric acid and pepsin secretion, as well as a reduction in splenic blood This will reduce the solubility and ionization of the drug in the GI tract;'j however, drug absorption does not seem to be a f f e ~ t e d . ' , ~ J ~ , ' ~ There is also a decrease in the active transport mechanism of nutrients, which usually does not play a role in most situations since most medications are absorbed by passive diffusion.Is Distribution Geriatric patients also present with a change in body composition, in that body fat can increase up to 30-4070.'~ This change affects the distribution of medications that are highly soluble in lipids, increasing their duration of action. Examples of such medications are diazepam and phen~barbital.'~,'~ On the other hand, water-soluble drugs such as acetaminophen and aminoglycosides will have decreased distribution and therefore shorter durations of action.".lh In the elderly, distribution is also altered due to a decreased number of protein-binding site^.^,'^ If the medication is a highly bound drug and the prescribed dose does not account for this change, a portion of the dose will remain unbound. Depending on the medication and the dose, the level of unbound medication may reach toxic level^.'^,^^

Metabolism The liver is considered the primary site of biotransformation for the majority of medication^.'^,^' Liver metabolism in the geriatric patient is also decreased due to a reduced liver blood flow, a reduced liver mass, and a reduced production of hepatic enzyme^.'^^^^ This reduction in metabolism will specifically effect drug metabolization in the liver. This will be especially important in the dysfunction of microsomal enzyme activity associated with liver disease, where a reduction in the dosage of the medication is almost always neces-

sary.2' If this reduction in dosage is not taken into account, it can lead to drug toxi~ity.'~ Nevertheless, the effects of the reduced metabolism due to aging remain to be determined.'

Excretion Many medications are excreted via the kidneys.' In the geriatric population, renal function is reduced in about 35% and,isprobably the most important factor responsible for altered levels of medications in this group of patients.I9 This decrease in renal function is important for medications eliminated by glomerular filtration or active tubular secretion. In this situation, medications and their metabolites can accumulate, resulting in an increase in adverse and/or sideeffects, increasing the toxicity and possibly leading to an If adjustment of drug dosage is necessary, the patient's physician should be c~nsulted.'~ Changes in therapeutic response due to aging The aging process affects the pharmacologic management of the geriatric patient in important ways that influence therapeutic results. The therapeutic responses of the medications prescribed in dentistry can be altered due to the aging process. Most commonly, drugs used by the dental practitioner-ie., sedatives, local anesthetics, analgesics, and antibiotics-may be at risk of being affected by this mechanism. Sedatives Barbiturates are not recommended in the pharmacologic management of the geriatric patient. Hazards associated with the use of barbiturates include depression, excitement, and confusion.Ib However, benzodiazepines-such as lorazepam, oxazepam, temazepam, and triazolam-are recommended for the geriatric population. The benzodiazepines are the medication of choice due to their short half-life and nonactive metabolites.22Nevertheless, the dose of the selected benzodiazepine should be reduced when it is used alone and especially when it is used in combination with another CNS

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depressant. For instance, diazepam has been shown to produce a greater degree of CNS depression in the elderly.23The half-life for diazepam can increase from 20 hours in the young patient to 80 hours in the geriatric patient.24

Local anesthetics In general, geriatric patients require less local anesthetic than younger patients due to a decrease in nerve fiber number, a reduced neuronal supply, and a decreased clearance of the local anesthetic at the site of injection.2sThe maximum dose for an adult patient is 300 mg (8.3 dental cartridges of a 2% lidocaine solution), but because of the changes mentioned above, no more than 108 mg (three cartridges of a 2% lidocaine solution) should be given in one appointment.2b Due to variability of individuals, this recommendation should not be considered as a general rule. More research concerning the use of local anesthetics in the elderly should be presented before a guideline can be established. Analgesics When analgesics are prescribed to the geriatric patient, the dose may be reduced to compensate for changes in pharmacokinetics and differences in pain perception.'s Due to a decrease in clearance, the administration of a normal adult dose of aspirin to the geriatric patient would result in an increase in the half-life, possibly causing the blood levels to become excessive. Other analgesics, such as ibuprofen and combinations of opiates with aspirin or acetaminophen, have been reported to cause frequent adverse reactions.Is The analgesic of choice for the geriatric patient is acetaminophen, which seems to have the fewest side-effects. Antibiotics The more common antibiotics administered in dentistry are penicillins, cephalosporins, tetracyclines, and erythromycin. Usually, no adjustment of dosage is necessary due to their substantial margin of safety. Only when renal failure is present is an adjustment of the dosage of the

Table. Drug interactions encountered.*

Drug Administered Sedatives

Barbiturates

Local Anesthetic Components

Benzodiazepines Chloral Hydrate Epinephrine

Lidocaine Analgesics

Acetorninophen

Meperidine

NSAIDs

Propoxyphene

Salicylates

Antibiotics

Cephalosporins Erythromycin Metronidazole Penici11ins

Tetracyclines

Other Drug Alcohol Corticosteroids MA0 Inhibitors Oral Anticoagulants Levodopa Oral Anticoagulants MA0 Inhibitors Guanethidine Digitalis Tri-cyclic Antidepressants Beta-adrenergic Blockers Reserpine Methyldopa Beta-adrenergic Blockers Cimetidine Anticholinergics Barbiturates Oral Anticoagulants MA0 Inhibitors Phenothiazine Tri-cyclic Antidepressants Anti-hypertensives Lithium Corticosteroids Oral Anticoagulants Levodopa Carbamazepine CNS Depressants Alcohol Corticosteroids Anticoagulants Methotrexate NSAIDs Oral Hypoglycemics Gentamicin Lasix Theophylline Penicillin Alcohol Disulfiram Tetracyclines Oral contraceptives Probenecid Coumadin Tandearil Cournadin Antacids, Milk products Oral contraceptives Penicillins

Adverse Effect Enhanced CNS depression Increased activity of Corticosteroids Increased CNS depression Decreased activity of Oral anticoagulants Decreased activity of Levodopa Prolonged bleeding Enhanced CV effects HTN, Cardiac arrhythmias Cardiac arrhythmias Cardiac arrhythmias HTN and/or bradycardia and hypotension Enhanced CV effects Enhanced CV effects Increased toxicity of Lidocaine Increased toxicity of Lidocaine Delayed analgesia Increased risk of liver toxicity Prolonged bleeding HTN and excitement Enhanced sedation and respiratory depression Enhanced sedation and respiratory depression Reduced hypertensive response Lithium toxicity GI ulceration and bleeding Prolonged bleeding CNS stimulation, anxiety, and mental confusion Increased toxicity of Carbamazepine Enhanced CNS depression Increased GI bleeding GI ulceration and bleeding Prolonged bleeding Increased toxicity of Methotrexate GI ulceration and bleeding Increased hypoglycemic effects Increased renal toxicity Increased renal toxicty Increased toxicity of Theophylline Decreased effectiveness of Penicillin ”Antabuse” reaction to alcohol Psychotic episodes Interferes with action of Penicillin Decreased effectiveness of oral contraceptives Enhanced effectiveness of Penicillin Prolonged bleeding Enhanced effectiveness of Tandearil Prolonged bleeding Decreased effectiveness of Tetracycline Decreased effectiveness of oral contraceptives Decreased effectiveness of Penicillin

*Adapted from BeckeF and Ciancio and Bourgault24

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penicillins, cephalosporins, and most tetracyclines necessary.27

Drug interactions and adverse reactions The dentist as a health care provider must be aware of the interactions between medications prescribed in dentistry and the medications the patient may be taking. It has been shown that about 25% of the medications taken by the elderly will have some interaction with drugs given in dentistryF8 The interactions most often encountered with the medications used in dentistry are shown in the Table (adapted from references 21 and 29). Concurrent administration of several medications can result in interactions affecting the absorption, biotransformation,distribution, and elimination of the prescribed drugs. These interactions can either enhance or decrease the effect of a specific medication, which can lead to complications such as excessive therapeutic effects or adverse pharmacological reactions.(' The elderly population is most susceptible to these interactions because of their multiple drug therapy.I4 Studies have demonstrated that drug interactions and adverse reactions play an important role in the increase of the hospitalization rate in the geriatric population.m Drug-induced illnesses It has been reported that 30%of the geriatric population is more susceptible to the development of complications following the administration of one or more The more common complications are urinary problems, mood /sleep disorders, GI problems, equilibrium disturbances, skin rashes, and muscular discomfort.6J5,20 In addition, one study showed that when compared with younger patients, older individuals were less aware of drug-related symptoms and reported fewer druginduced Complications arising from medications can be manifested in the oral cavity. Manifestations that should signal the dentist include oral ulcerations, xerostomia, candidiasis, discloration of &heoral mucosa,

lichenoid reactions, taste disturbances, pain and swelling of the salivary glands, and oral dyskinesias.' Disease exacerbation due to drug interaction

Certain medications can precipitate disease exacerbation that had been under control or in remission. An example of this complication is the exacerbation of a peptic ulcer when aspirin is prescribed. Other conditions precipitated by the administration of drugs include hypertension32 and peptic ulcersT3with the use of non-steroidal anti-inflammatory drugs. The dental practitioner has to be aware of drug-disease interactions in order to avoid an unnecessary increase in the morbidity or mortality of these patients.

Conclusion Guidelines should be established for the pharmacologic treatment of the geriatric population in the dental practice. Nevertheless, due to the variability in their health status, it is very difficult for any set rules to be instituted. Each and every patient should be approached as a different individual. However, the pharmacokinetic changes as well as the drug interactions have to be considered. It is evident that the alteration in the normal physiology due to aging as well as multi-drug therapy can compromise dental pharmacologic treatment. The general practitioner should be aware of the possible complications as well as the alternatives in the pharmacologic treatment and be prepared to meet the challenge associated with the dental treatment of the geriatric population. 1 would like to thank my husband, Dr. Dante L. Tomaselli, for his never-ending help and support. I would also like to thank Dr. Ron Feldman for his outstanding assistance in the preparation of the manuscript.

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Special Can, in Dentistry, Vol12 No 3 1992 l l l

Pharmacotherapy in the geriatric population.

The geriatric population constitutes the largest group of consumers of medications in this country. Changes in the pharmacokinetic response to medicat...
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