TIS

Chapter 5
Geriatrics - Pharmacology of Aging


Social and Environmental effects of age on drug effect

1. Increased drug use leads to increased side effects and interactions

Old people take many more drugs and thereby suffer greater risk

2. Medicalization of social and psychological problems

Loneliness, fear, anger and social dislocation are all problems that often get interpreted as disease and treated pharmacologically, usually inappropriately.

3. Compliance and memory

Old people and young people are about equally compliant with medications. Young people are too busy or don't believe the doctor, while old people tend to follow Doctors' direction, but more often are unable to remember and take medication.

4. Enlightened non-compliance

A number of elderly people will not take medication because they have experienced negative effect of the medication and don't want to take it for that reason. They are usually right. This is called enlightened, or intelligent non-compliance.

Physiological effects of age on drug effect

1. Pharmacokinetic effects

A. Alteration in absorption:

Most authorities state that drug absorption is unaffected by aging but there are some reasons to doubt this: It is known that pH of the stomach is changed; that the thickness of the villous layer of the small intestine is decreased; and that some drugs are incompletely absorbed in the elderly. It is unlikely that these factors have no effect on absorption, but since most drugs have increased potency in the elderly, the factors that increase drug effect are emphasized.

B. Distribution

1. Less water, more lipid

So lipid soluble drugs, which includes almost all psychotropic drugs have larger volumes of distribution and therefore longer half-lives although they may not have higher concentrations in the elderly.

2. Protein binding

Highly protein bound drugs tend to have higher free drug concentrations in the elderly because the elderly tend to have lower levels of albumin and other binding proteins. You should note that frail and old old people show this much more than the merely old.

3. Elimination

1. Change in kidney function
Everybody should be familiar with the Cruikshank formula:

CrCl=(140 - Age [yr])(Body weight [kg]) / 72 (Serum creatinine [mg/dl])

For women, multiply this figure by 0.85.
As a rule of thumb, figure that for normal people the kidneys will cease functioning entirely at age 140 and they reach their peak at about 20 and interpolate from there.
Not everybody follows this curve exactly.
Drugs which are actively excreted by the kidney like Penicillin may show other effects.

2. Liver changes are more complicated.
Liver function itself cannot be measured. The liver enzymes only show active cell damage and bilirubin levels reflect effects on the bile management system but not necessarily what the drug metabolizing efficiency of the liver might be.
The liver can be impaired by passive congestion from heart failure, deficiencies of blood supply as well as intrinsic liver disease. Furthermore common drug interactions have their effects in the liver.

2. Pharmacodynamics:

Pharmacodynamics refers to changes in the effect of a drug at the receptor site. In practical terms, pharmacodynamic changes are reported when there is a change in the effect of a drug when the blood level is the same for different classes of people Pharmacodynamic changes because of aging are actually fairly unusual; pharmacokinetic changes are more important. A well established pharmacodynamic change due to aging is the increased effect, at the same blood levels, of sedatives, including alcohol, on the aged.

3. Impaired compensating homeostatic mechanisms

4. Highlights of Changes with Particular Classes of Drugs

A. Anti hypertension drugs

1. Thiazide diuretics remain useful but complicate renal impairment. Thiazide diuretics are, if anything, more effective in older people who have intact renal function, but if creatinine clearance drops below about 30cc/minthiazides both loose effectiveness and tend to exacerbate renal disease.

2. ACE inhibitors are particularly useful when CHF generally gain favor.

3. Furosemide and the other loop diuretics, unlike most drugs, are somewhat less potent in elderly people, milligram for milligram; the decreased number of nephrons leaves fewer sites for furosemide to have its effect. It remains the mainstay of CHF treatment and loop diuretics may be used instead of thiazides when renal function falls below 50cc of GFR.

4. Beta blockers have numerous side effects but remain usefuldrugs and even have a place in heart failure, especially when the ejection fraction is normal (diastolic heart failure.) Like the loop diuretics, there is evidence that beta blockers are somewhat less potent in old people.

B. Sedatives and Hypnotics

Sedatives are a difficult area in everybody, but especially in geriatrics. Reserve capacity of the central nervous system is frequently diminished in older people and any further impairment to brain function can cause delirium. On the other hand, anxiety, insomnia and agitation are among the most common and troubling complaints of the elderly and their care givers.
The benzodiazepines, are good anti anxiety agents but exacerbate dementia and can worsen agitation by their disinhibiting effects. Chronic use is well tolerated but ineffective and withdrawal from long-term effects can cause delirium in elders. Diazepam (Valium) should be avoided because the half-life is too long and accumulation is a risk. Of the class, oxazepam (Serax) or lorazepam (Ativan) are the preferred agents.
Trazodone (Desyrel) is a good sedative although originally marketed as an antidepressant. It is relatively free of withdrawal and delirium producing effects, but lacks the potency of the benzodiazepines as a sedative. It should be given in small doses but can be used in the daytime forsedation.
A number of other classes of drugs are occasionally used including beta-blockers, anti-seizure drugs and anti-histamines.


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