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
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Routinely check CrCl in geriatric patients when starting new medications, I found this to be quite different for eGFR that is automatically reported.
creatinine clearance more important than cr due to decreased muscle mass
Very important to calculate creatinine clearance. Don’t just go by the EGFR /creatinine in lab work
very important information to consider when prescribing medications.
I thought absorption did change with age. I’m glad I know that it does not now.
interesting, I thought so too
have never seen age adjusted eGFR reportsd
Excellent section. Great review.
have to include age
age weight gender simple
will keep a closer eye on water solubility
Very informative page. And I see Mrs. Foxglove is coming back to haunt us…
Thank you for pointing that Cr is not an indication of renal function in elderly person
new information that is great to know.
I will remember and be cautious prescribing to the “little old lady” with normal Cr
One of the few EMR benefits is calculation of these factors
important formula to know
the info about calculating GFR is very helpful.
Pharmacodynamics is fun!
Must KNOW stuff
good to know
Back to basic physiology which we often forget as the foundation . Good recap
drugs are dosed for weight for all our life but are also dosed for age as children or elderly as well. Also persons with chronic conditions that involve the kidneys (elimination) or liver (metabolism) need special medication dosage considerations. Too high of a dosage of some drugs such as gentamycin can serious damage the kidneys.
Really helpful about drug concentrations in water vs fat soluble!
Was so helpful
Makes total sense.
I always use my CrCl app on my iphone!
i use an app to help calc. always surprised at the difference between calculated vs gfr reported
I really liked the liver enzyme explanation and pictures.
really good to have emphasised the importance of CrCl and its fairly easy to calculate esp with app calculators. As mentioned its often a shock to see how poor it is in elderly with “normal” creatinine. The only variable not available to the lab is weight but in the future with electronic patient information systems it may be possible for the lab to automatically calculate and report CrCl.
less is more
Some good comments above to consider
Would be interesting to know impact of illegal drugs, marijuana etc on medications
Age adjusted creatinine clearance is the best indicator of renal function in elderly.
good simple review
any other good apps for creatinine clearance or eGFR?
Good i-phone apps for creatinine clearance.
Thanks for the review, very clearly presented
Med review and dosing consideration should occur regularily
I will be checking clearance Clarence. That’s my new vector Victor.
age means increasing variability in the assumptions you can make for a patients ability to metabolize and excrete
so there is no spoon?
less = more
I don’t think so…
less is more in the elderly
Take intoaccount not only part of the metabolic process but also what the patient presents as sarcopenia affects metabolism
modify drug delivery
se necesita ajustar la dosis
Need to adjust dose..
Difficult to dose properly
EMR warnings on interaction are useful
pharmacy input essential
interesting that females have a noted difference in clearance
thanks NADA for the app.
I have seen age adjusted lab values as a list. Don’t know if labs do it but they should.
http://www.kidney.org is a great tool as well with a free mobile app
While the lab-reported eGFR is considered to be an estimate of renal function (and is a better value to consider than the serum creatinine, often used rather than calculating CrCl), there is sometimes a surprisingly big difference between the eGFR and CrCl. I ask for pharm consult for renal dose adjustment of meds if I am unsure and concerned about renal impairment.
That “eGFR” you get is NEVER age-adjusted ( at least I’ve never seen a hospital where it is.) Use http://www.mdcalc.com/creatinine-clearance-cockcroft-gault-equation/ to calculate the true CrCl the next few times you see an older lady with a “normal” creatinine. You’ll be amazed how poor their CrCl really is! Often the equivalent of a 50 year old with a Cr of 200!
Does any lab not report the age adjusted creatinine clearance?