Geriatric Pharmacology

·        Increased risk of adverse effects in elderly.

·        Age-related changes in pharmacokinetics.

·        Age-related changes in pharmacodynamic response.

·        NSAIDs.

·        Psychotropic drugs.

·        Benzodiazepines.

·        Heterocyclic antidepressants.

Prescribing for the Elderly

1.    As Singapore ages, the number of elderly patients will increase and physicians will have to develop expertise in the management of such patients.

2.    The incidence of adverse drug reactions rises with age in the adult, especially after 65 years because of:

a.    The increasing number of drugs that they need to take because they tend to have multiple diseases.

b.    Poor compliance with dosing regimens.

c.       Decrease in physiological renal and hepatic functions.

Age-related changes in pharmacokinetics

1.       Absorption of drugs may be slower may be slower because gastrointestinal blood flow and motility are reduced.

2.       Distribution:

a.       There is a significant decrease in lean body mass so that standard adult doses provide a greater amount of drug per kg.

b.    Total body water is less but body fat is increased.

c.       Plasma albumin concentrations may be reduced by chronic disease, leading to greater amount of free unbound drug.

3.       Metabolism:

a.       Metabolism is reduced because liver mass and liver blood flow are decreased.

b.       Metabolic inactivation of drugs is slower.

c.       Drugs that are normally extensively eliminated in first-pass through the liver appear in higher concentration in the systemic circulation and persist in it for longer, e.g. TCAs.

d.       Capacity for hepatic enzyme induction is lessened.

4.       Elimination:

a.       Renal blood flow, glomerular filtration and tubular secretion decrease with age above 55 years.

b.    Risk of adverse effects arises with drugs that are eliminated mainly by the kidney and that have a small therapeutic ratio, e.g. aminoglycosides, chlorpropamide, digoxin, lithium.

Pharmacodynamic response

1.       Drugs that act on the CNS produce an exaggerated response and are more likely to depress respiration because vital capacity is reduced in elderly, e.g. sedatives and hypnotics.

2.       Response to beta-agonists and antagonists is blunted in old age due to reduction in the number of receptors.

3.       Baroceptor sensitivity is reduced leading to the potential for orthostatic hypotension in drugs that reduce blood pressure.

Non-steriodal anti-inflammatory drugs (NSAIDs)

1.       NSAIDs are the main drugs used for the treatment of various forms of arthritis and are commonly used by the elderly.

2.       Central nervous system:

a.       Confusion.

b.       Depression.

c.       Dizziness.

d.       Headache.

e.       Insomnia.

f.       Decreased hearing and tinnitus.

3.       Cardiovascular system:

a.       Cause salt and water retention.

b.       Increase blood pressure.

c.       Antagonize effects of anti-hypertensive drugs like beta-blockers, vasodilators and diuretics.

4.       Gastrointestinal tract:

a.       Ulceration, bleeding and perforation of upper gastrointestinal tract with chronic NSAID use.

b.    Age is one of the risk factors of upper GI toxicity.

5.       Kidneys:

a.       Functional renal insufficiency, nephrotic syndrome, interstitial nephritis and papillary necrosis have been associated with NSAID use.

b.       Functional renal insufficiency is common as NSAIDs inhibit prostaglandin synthesis and prostaglandins are involved in the hemodynamics of the kidneys.

c.       Their vasodilatory action is important in maintaining renal blood flow when there is renal vasoconstriction such as in renal insufficiency due to age, atherosclerosis, etc.

6.       NSAIDs and drug interactions:

a.       Increased risk of bleeding with anticoagulants.

b.       Hyperkalaemia with ACE inhibitors.

c.       NSAID induced convulsions with quinolones.

d.       Enhanced effects of phenytoin and antidiabetic drugs.

Psychotropic drugs

1.    In the elderly patients psychotropic drugs are used to treat behavioral disorders associated with dementia or psychiatric illnesses like depression or psychosis.

2.    In addition, some of these drugs like benzodiazepines are commonly prescribed for the elderly for complaints like insomnia, anxiety, agitation, etc.

3.       Structural or functional changes with aging may result in the elderly being more sensitive to the drug and requiring a lower dose than the younger patient.

4.       Therefore, the dosage for the elderly should be appropriately adjusted.

Benzodiazepines

1.       Sedation:

a.    The common adverse reactions of the benzodiazepines are sedation, drowsiness, ataxia and impaired coordination.

b.       Sedation at night is useful for the elderly with insomnia but if the effect is carried over to the next day it can cause confusion and disorientation.

c.       Drowsiness coupled with incoordination in an elderly increases the risk of falls.

d.       Several studies have shown that the use of benzodiazepines was significantly associated with increased risks of falls and fractures in the elderly.

2.       Psychomotor impairment:

a.       Psychomotor impairment results in poor judgment, slow reaction time, decreased speed and accuracy of motor function.

b.    With increasing age, many older persons may not have good psychomotor function and further impairment induced by drugs will cause distress to the individual and is dangerous for those who still drive a car or operate machinery.

3.       Cognitive impairment:

a.       Some of the symptoms of cognitive impairment associated with benzodiazepine usage include increased forgetfulness, poor attention and anterograde amnesia.

b.       Reduction in memory and attention can be seen even in short-term benzodiazepine usage.

c.    In the elderly who is already suffering from these symptoms chronic benzodiazepine usage may worsen the symptoms resulting in inability to cope with the tasks of daily living.

d.    But the drug should not withdrawn from chronic users abruptly because of the risk of withdrawn symptoms.

4.       Paradoxical effects:

a.       Benzodiazepines may cause increased irritability, depression, aggression or socially unacceptable behavior in some individuals.

b.    In elderly patients these symptoms should not be attributed to aging or to the worsening of behavioral problems as drugs such as benzodiazepines may induce them.

5.       Tolerance and dependence:

a.    The risk of tolerance and dependence on the benzodiazepines in the elderly is the same as for the younger patients.

b.    The factors that are associated with the risk of dependence are the dose and duration of treatment.

Heterocyclic antidepressants

1.       Sedation:

a.    The sedative effect of the heterocyclic antidepressans varies with the individual and is usually more pronounced in the initial phase of treatment.

b.       Sedation at night may be useful if the patient is also suffering from insomnia.

c.       However, sedation during daytime is not desirable as it decreases their activity and also predisposes them to falls and fractures.

2.       Cardiovascular effects:

a.       Cardiotoxicity manifesting as hypotension, arrhythmias and conduction abnormalities are well recognized in tricyclic overdose.

b.    In the patient with no cardiac abnormalities the most common cardiovascular adverse effects of the TCAs are tachycardia and orthostatic hypotension.

c.    To the elderly patient orthostatic hypotension is particularly hazardous as it can result in a stroke or myocardial infarction and falls.

d.    A simple precaution like warning the patient to change posture from supine to upright gradually may help to reduce the risk of sudden hypotension.

3.       Anticholinergic adverse reactions:

a.    The common adverse anticholinergic reactions associated with heterocyclic antidepressant usage include dry mouth, blurring of vision, constipation and urinary retention.

b.    In the elderly patients with dentures dry mouth may cause pain and difficulties in using the dentures.

c.    The mydriatic effect of the antidepressants may aggravate narrow angle glaucoma in the elderly patient.

d.       Many elderly males have prostatic hypertrophy and depending on its severity, the heterocyclic antidepressants may precipitate acute urinary retention.

e.       Constipation is a common complaint among elderly patients and treatment with heterocyclic antidepressants may worsen the situation.

4.    CNS adverse reactions:

a.       Common ones are headache, tremor, ataxia, confusion and delirium.

b.       These drugs may also lower seizure threshold and precipitate convulsions.

5.       Selective serotonin re-uptake inhibitors (SSRIs):

a.       Common adverse effects are constipation, diarrhea, nausea and weight loss.

b.    They may also cause neurological reactions like agitation, insomnia, tremors, dizziness, seizures and extrapyramidal symptoms.

c.       These drugs should be used with greater caution in the elderly patient with Parkinson’s disease.

d.    The use of SSRIs has also been associated with hyponatraemia and elderly patients may be at greater risk.

e.    In addition, SSRIs are hepatic enzyme inhibitors, they may potentiate the effects of codeine, beta-blockers, calcium antagonists and benzodiazepines.

Principles of Prescribing

1.    The benefits of therapy should outweigh the risks of adverse reactions.

2.       Dosage:

a.       Should be individualized for each patient.

b.    To start at the lower end of the dosage range and work upwards titrating with the response of the patient.

3.       Drug-drug interactions: as the elderly patient tend to be on polypharmacy, another addition to the patient’s list of medications should not be made without checking for drug-drug interactions.