Normal changes in the aging body (normal physiology of aging) affect pharmacokinetics.
- Changes that affect drug concentration in the body.
- What the body does to the drug.
- Pharmacokinetics = Absorption/ Distribution/ Metabolism/ Elimination
Absorption (with a few exceptions) does not change significantly with aging.
Check serum albumin levels and adjust the dose of drug accordingly. Example tool for phenytoin correction.
Since with normal aging we lose muscle (think: water) and gain fat (think: fat!) the effect of aging on Volume of Distribution (VD), is significant.
With increasing age, albumin levels decrease which results in higher active drug concentrations of protein-bound drugs. Some examples include warfarin, phenytoin, diazepam and ibuprofen.
If a drug is water soluble:
The volume of distribution in the older body is much less and therefore the serum concentration will be greater than expected for a given dose.
e.g. Digoxin or Hydrochlorothiazide; Penicillins; most Cephalosporins; Sotalol; Lithium.
Revisit the case of Mrs.Foxglove for an example of differences in distribution of a drug.
If a drug is fat soluble:
The volume of distribution in the older body is greater and therefore the serum concentration will be less than expected for a given dose.
e.g. Midazolam or Diazepam (In larger individuals, these benzos will distribute into fat mass and leach out slowly, causing decreased clearance); Nifedipine/Verapamil; Buproprion; Quetiapine (including most other psychotropics); Propranolol; Amiodarone.
Metabolism of drugs happens mostly in the liver. In the older person, the liver maintains all of its enzyme systems but at decreased function and is therefore more easily challenged by the addition of new substrates. If drug A is at steady state at a given dose, adding drug B will require some of the enzymes previously metabolizing drug A, causing higher serum concentrations of both. Remember, metabolites are often active too (eg. diazepam, morphine)– so metabolism isn’t always the same as elimination.
The main organ of elimination is the kidney, which changes significantly with aging. Because both renal mass and blood flow decrease steadily from age 30 on, anyone over 70 should be thought of as having some significant degree of renal impairment. Remember that serum creatinine is not a good guide to renal function in the older patient because of the loss of lean body mass/muscle. You don’t need to calculate Creatinine Clearance/GFR on every older patient but it helps to remember the variables.
So the “little (weight) old (age) lady (gender)” with the normal creatinine, still probably is unable to eliminate drugs adequately.
Creatinine Clearance = ( 140 – age ) x weight x ( 0.85 if female ) / Serum Creatinine
- Indirect variation with age
- Direct variation with weight
- Direct variation with gender
- Indirect variation with serum creatinine