It is important to monitor and alter psychotropic medications and dosages in older patients as needed. This slideshow serves as quick reference on the effects of pharmacokinetic and pharmacodynamic changes in the elderly.
It is important to monitor and alter psychotropic medications and dosages in older patients as needed. This slideshow highlights facts on the effects of pharmacokinetic and pharmacodynamic changes in the elderly.
1. How quickly a drug is absorbed determines in part how quickly it takes effect. The rate of absorption may be affected by reduced gastric motility or delayed emptying due to diseases (eg, diabetes) or drugs (eg, antacids). In the absence of significant disease, however, the extent of absorption is little affected in the elderly.
2. In the liver, the drugs can travel unchanged into the general circulation by way of hepatic veins. Alternatively, drugs can be metabolized in the liver before entering the circulation, via first-pass metabolism.
3. Parenteral administration will make a drug nearly 100% bioavailable. Intravenous administration of drugs in geriatric patients should be approached with caution, because dangerous adverse effects can emerge quickly. In addition, intramuscular administration of drugs is not recommended for geriatric patients with small muscle mass, because this leads to erratic absorption and painful injection.
4. Distribution to peripheral storage sites is significantly affected by aging. As lean body mass decreases, there is a relative increase in fat stores. This is true even for thin elderly patients. These changes create a larger volume of distribution for fat-soluble drugs (including most psychotropics) and a smaller volume of distribution for water-soluble drugs, such as lithium.
5. Cytochrome P-450 (CYP450) is one of the most important drug-metabolizing enzymes. Drug metabolism occurs by phase 1 (oxidation) and/or phase 2 (primarily glucuronidation) processes. The most important drug-metabolizing enzymes are the phase 1 CYP450 enzymes and the phase 2 UGT enzymes. In general, phase 1 oxidation processes are more affected by aging than are UGT processes.
6. The two CYP enzymes important to psychotropic prescribing that decline substantially with age are CYP1A2 and CYP3A. Aging also brings a gradual reduction in liver mass, reduced blood flow, and reduced hepatic metabolic rate.
7. On average, the glomerular filtration (GFR) rate falls linearly with aging at a rate of 1 mL/min/1.73 m2 of body surface. Most drugs and metabolites are excreted from the body by the kidneys at a rate determined by the GFR.
8. Although oxidative metabolism may be reduced in old age, a more significant factor is decreased hepatic blood flow. In the elderly, there may be a decrease of as much as 50% in hepatic blood flow, which impacts drug clearance. Clearance of a drug from the circulation is a function not only of renal excretion but also of hepatic metabolism.
9. Most psychotropic drugs act at postsynap-tic sites; some also interact with autorecep-tors on the presynaptic neuron. In general, the mechanism for these drugs includes drug-receptor binding, signal transduction, and cellular response.
10. Drug interactions are more frequent in elderly patients because more medications are taken. In addition, drug interactions may be more serious because of insufficient physiological reserves. When new medications are started or stopped in elderly patients, it is very important to take note of potential interactions with other drugs or foods.
This slideshow was originally posted Oct. 27, 2014 and has since been updated.
For more information on this topic, please see "Effects of Pharmacokinetic and Pharmacodynamic Changes in the Elderly," by Sandra Jacobson, MD, on which this slideshow was based.