Geriatric Pharmacology

Geriatric patients have many pharmacokinetic and pharmacodynamic changes, due to the aging process. This includes changes in body weight, body composition, volume of distribution, and renal clearance. A 'start low and go slow' approach is recommended.

Based on all the pharmacokinetic changes with age, for any given dose of a medication, an older adult may have a higher brain concentration of the drug and thus may need a lower dose given at less frequent intervals compared to younger adults.

Age-associated Changes in Pharmacokinetics

Adapted from: Reuben DB, et al. Geriatrics At Your Fingertips: 2016, 18th Edition. The American Geriatrics Society
Age Effect Disease, Factor Effect Prescribing Implications
Absorption • Absorption rate and extent are usually unaffected, but may be slightly decreased
• There is decreased gastric pH.
Concurrent medications, tube feedings Drug-drug and drug-food interactions are more likely to alter absorption. Generally absorption is not of clinical significance
Distribution • Lower volume of distribution
• Greater blood-brain barrier (BBB) permeability
• Increase in fat:water ratio
• Decreased plasma protein, particularly albumin
Heart failure, ascites, and other conditions increase body water • Fat-soluble (lipophilic) drugs (e.g. - diazepam) have a larger volume of distribution, will remain in the body longer, lead to a longer half-life, and may be erratically released).
• Highly protein-bound drugs (e.g. - tricyclics) have a greater (active) free concentration.
Metabolism • Decreased liver mass and liver blood flow, leading to decrease drug metabolism and clearance
• May be age-related changes in CYP2C19, while CYP3A4 and CYP2D6 are not affected
Smoking, genotype, concurrent drug treatment, alcohol and caffeine intake may have more effect than aging Lower dosages may be therapeutic
Elimination • Age-related decrease in GFR
• Muscle mass ↓, while fat stores ↑, leading to longer elimination half-lives of lipophilic drugs
Kidney impairment with acute and chronic diseases; decreased muscle mass results in less Cr production Serum Cr not a reliable measure of kidney function; best to estimate CrCl using formula
  • Kidney function normally declines with age - nearly every individual older than 80 years has a glomerular filtration rate less than 60 mL/min/1.73m2

Pharmacokinetic considerations with age include:

  • Individuals may differ in tissue response to a given concentration of drug
  • There is an age-related decline in receptor reserve, increasing susceptibility to clinical and adverse effects (e.g. - risk of falls with use of benzodiazepines, antidepressants and antipsychotics) and here is a narrower therapeutic index with certain medications (especially lithium)

Age-associated Changes in Pharmacodynamics

Adapted from: Reuben DB, et al. Geriatrics At Your Fingertips: 2016, 18th Edition. The American Geriatrics Society
Age Effect Disease, Factor Effect Prescribing Implications
Pharmacodynamics Less predictable and often altered drug response at usual or lower concentrations Drug-drug and drug-disease interactions may alter responses Prolonged pain relief with opioids at lower dosages; increased sedation and postural instability to benzodiazepines; altered sensitivity to β-blockers

Citalopram, escitalopram and sertraline have fewest drug interactions. SSRIs have fewer cardiovascular and anticholinergic side-effects compared with TCAs. However, main concerns are: SIADH/hyponatremia, inhibition of platelet aggregation (bleeding risk), falls, and fractures.

Beware of anticholinergic medications (in particular low-potency antipsychotics with greater anticholinergic profile). There is increased risk of tardive dyskinesia with age (60% risk within 3 years with typical antipsychotics age greater than 45 years; 30% risk with haldol versus 4% for risepridone over 9-month period). Antipsychotics may also increase the risk of dementia and are common causes of QTc prolongation.

Benzodiazepines can decrease memory consolidation in the elderly. Certain benzodiazepines have greater side effects (e.g. - diazepam), compared to lorazepam. Benzodiazepines increase the risk of functional disability, postural sway and falls, and have dependence and abuse potential. Older adults with dementia may also develop paradoxical reactions.

Certain benzodiazepines continue to exert their action after metabolism, via their active metabolites. For example, diazepam produces the active metabolites oxazepam, desmethyldiazepam, and temazepam. These metabolites increase the duration of drug action and can have an impact in older adults and in those with extensive hepatic disease. On the other hand, midazolam produces no active metabolites.[1]

Another result of the proportional increase in body fat with aging is that highly lipophilic benzodiazepines such as diazepam are rapidly taken up by the body's fat storage sites. The serum concentrations can thus fall quickly below the minimum effective threshold with one-time dosing. On the other hand, with repeated dosing, there can be significant accumulation of the drug in fat stores. This means the drug may be released erratically and lead to fluctuating serum levels over time. Thus, diazepam is not recommended in older adults or the elderly.

Older adults should have lithium started at lower doses (eg. - 300mg). They may respond to lower blood levels (eg. - 0.4- 0.7) compared to usual targets in younger adults. Pay attention for medications that may effect lithium clearance (NSAIDS, diuretics).