MEDICINE SAFETY IN THE GERIATRIC POPULATION

Dr. Mangala Lahkar, Professor, Dept. of Pharmacology, GMC

Dr. Urmi Choudhury, Associate Professor, Dept. of Pharmacology, GMC

Dr. Anindita Mahanta, Demonstrator, Dept. of Physiology, GMC

In the last century, there has been a rapid increase in the population of persons above 65
years and this trend is expected to continue. The proportion of global population over 65 years old is
expected to rise from 11% in 2010 to 22% in 2050 and 32% in 2100. The population of aged above 80
years in western Europe will increase from 4% in 2010 up to 10% in 2050.

In India , though the percentage of aged population is low in comparison to the figures in
developed countries , but it is projected that by the year 2030 , the population of people aged between
65 – 85 years will increase by 66%.

The process of aging is associated with a number of physiological changes which alter the
pharmacokinetics and pharmaco-dynamics of many drugs. Changes in pharmacokinetics occur mainly
because of change in body weight with aging which affects the volume of distribution and renal
clearance. Drug absorption is not affected significantly so as to require dose adjustments. With
advancing age, there is a reduction in liver mass which decreases the first pass metabolism , resulting in
significant increase in bioavailability of drugs that undergo extensive first pass metabolism such as
opioids and metoclopramide. Such drugs should be started at a low dose in elderly patients. With
advancing age, there is a progressive decrease in the proportion of total body weight and lean body
mass which results in a relative increase in body fat. Consequently, hydrophilic drugs (gentamicin ,
digoxin,lithium and theophyline ) in older people reaches higher serum level requiring a lower loading
dose. On the other hand, half life of lipophilic drugs ( benzodiazepines , morphine , amiodarone ) is
prolonged resulting in long lasting effects and adverse effects after cessation of drug therapy.

Although there is significant reduction in clearance of many drugs metabolized by phase 1

reactions ( oxidation and reduction) in liver , this is not of clinical significance and does not require dose
reduction. The clinical significance of the age-related reduction in GFR which affects the clearance of
drugs such as water soluble antibiotics, diuretics, digoxin , water soluble beta blockers ,NSAIDs, lithium
and newer anticoagulants like dabigatron and rivaroxaban depends on the clearance of the drug. Thus
drugs with a narrow therapeutic index ( aminoglycoside, antibiotics , digoxin ,and lithium ) are likely to
have serious adverse effects ( nephrotoxicity).

Age -related pharmacodynamic effects include:

1. Increased sedation with benzodiazepiness.

 2. Decreased bronchodilatation with beta agonist.
3. Decreased anti hypertensive effects with beta blockers.
4. Increased anti coagulant effects with vitamin K antagonists.
5. Increased analgesic effect with morphine like central analgesics.
6. Increased anti hypertensive effect with verapamil.
7. Increased anesthetic effect with propofol.

Elderly patients are likely to suffer from several chronic disorders , requiring use of more drugs
compared to younger adults. An average elderly patient is likely to be on 4-5 prescription drugs, in
addition to atleast two over the counter drugs. Most commonly used over the counter drugs are
paracetamol ,NSAIDs, anti histaminics and PPIs to treat minor complaints such as pain , colds , GI
symptoms etc. However, use of multiple medications increase the risk of drug interactions and
adverse drug reactions.

Most ADRs are dose related , predictable and potentially avoidable (Type A) and caused by
antibiotics, anti coagulants , digoxin, diuretics , hypoglycemic agents NSAIDs. Idiosyncratic (Type B)
reactions are less common but associated with serious toxicity .

Some ADRs in the elderly include;

1. Drowsiness with anti coagulants.

2. Hallucinations and postural hypotension with anti parkinsonian drugs.
3. Drowsiness and fall with anti-psychotic drugs.
4. Bleeding with vitamin K antagonists.
5. Nausea , bardycardia with digoxin.
6. Hypoglycemia and falls with sulphonylurea anti diabetics.
7. Bradycardia,hypotension,constipation with verapamil and diltiazem.

Taking into account the myriad changes that occur in pharmacokinetics and pharmacodynamics
with aging as well as the increased risk of adverse drug reactions in elderly due to use of multiple drugs,
there is a need for clinical and observational studies in the elderly to help frame appropriate
prescription guidelines for old persons.

Reference: Clinical Pharmacology in Old Persons. Paul AF Jansen and Jacobus R B J Grousers. Scientifica
2012.