Presented by: Mehrdad Ayati, MD
Clinical Assistant Professor, Medicine
April 24, 2013
In 1950, 8 percent of the U.S. population was 65 and older; by 2050, thanks to increased longevity and a dwindling birth rate, that number is expected to increase to 21 percent. In developing nations, the growth rate of the senior population is even more pronounced, opening up important questions about how these countries’ infrastructures and cultural traditions will need to change to accommodate a virtual tidal wave of older citizens.
Modern medication is a key reason why people are living so much longer. About a third of all medications today are prescribed to patients 65, and it’s projected that more than half will be prescribed to seniors by 2030. Part of this increase is because chronic diseases that arise in a person’s 30s and 40s tend to show complications at age 60-70. In addition, comorbidities tend to arise over time, which often leads to multiple medications, also known as polypharmacy. Comorbidities refers to more than one disease that develops in addition to a primary disease.
In today’s health care system, a patient may have several physicians, which can result in a situation known as a prescription cascade. A cascade occurs when a new medicine is prescribed to treat an adverse reaction to another drug because it appears that a new medical condition requiring treatment has developed. A second drug can cause another adverse reaction or increase the severity of the first response, according to Mehrdad Ayati, MD, a clinical professor of medicine, who spoke at a presentation sponsored by the Stanford Hospital Health Library.
Dr. Ayati described the process: A patient has trouble with sleeping and is prescribed a sleeping pill. Feeling drowsy, she receives a stimulant, which gives her heart palpitations. Her doctor prescribes a beta blocker for her racing heart, which make her depressed. She is prescribed an antidepressant.
“In six months a person like this could be on six medications,” he said, “though the real problem was simply the first drug. It’s a very typical situation, especially for older people.”
Polypharmacy can lead to a greater possibility of adverse drug events, which account for between 5 and 28 percent of acute admissions to both hospitals and clinics. Adverse drug events include errors in the way the medicine is used and reactions from the pharmacological properties of the drug itself, either alone or in combination with other medicines.
“The best prevention of an adverse drug event is knowing what is happening in the body,” Dr. Ayati said.
Pharmacodynamics is the study of the biochemical and physiological effects of drugs on the body. Pharmacokinetics is how the body reacts to the drug and includes the processes of absorption, metabolism, distribution, and elimination. While absorption in the stomach and small intestine is the same biologically for both young and old, as you age, steady changes that can affect your ability to absorb medications, from changes in Ph balance to ongoing stress.
Most drugs are metabolized in the liver, which Dr. Ayati described as the body’s “central post office” organizing drug delivery by “Zip codes.” The liver’s cytochrome (CYP) system is responsible for 75 percent of drug metabolism by activating different enzymes that inhibit or metabolize a drug. Different metabolic rates will determine the effect of a drug, and a physician needs to know how fast a person’s metabolism is to avoid overprescribing and to avoid interactions that could lead to an adverse drug reaction.
“Slow metabolizers means that the drug stays active longer, so less is needed. In fast metabolizers the drug will dissipate quickly,” he said. “There’s not a universal response to a medication. For pain medication, for example, some people may need more frequent or larger dosages—which does make them drug addicts. Their body simply metabolizes differently.”
Important steps are being made toward personalized medicine—technology that uses a person’s unique genetic makeup to predict, monitor, and treat disease, including prescribing medication based on genetic background. Personalized medicine can identify people who have certain mutations in their CYP system, allowing physicians to know in advance how fast they will metabolize a drug.
Drug-to-drug interactions (DDI) occur in more than 80 percent of patients taking more than six medications at a time and in about 13 percent of patients using two medications or more. Interactions can be caused by over-the-counter medications, such as multivitamins, fish oil supplements, baby aspirin, or herbal remedies like St. John’s wort, garlic, echinacea, or gingko biloba. Herbal medicines are not regulated by the FDA and almost a third of them cause a drug-to-drug interaction. Even diet can affect a drug’s efficacy: Grapefruit is known to inhibit CYP for short periods after consumption.
“People often don’t realize that over-the-counter medications are pharmaceutical agents. There’s such an enormous number that no doctor can know them all,” Dr. Ayati said.
Once a drug is absorbed it is distributed around the body in the bloodstream. Drug distribution is affected by the changes in body composition associated with age, such as more body fat and lower hydration. The decreased muscle and tissue mass that accompanies aging also influences the distribution of certain drugs, as will the reduced blood flow to tissues and organs. And even healthy adults lose some renal function as they age, which affects elimination.
Drugs that require high levels of water and muscle to be absorbed may require lower dosages that are increased slowly or current dosages may need to be reduced as a patient ages. Drugs that are distributed through fat may require a larger volume for distribution and may take longer to be eliminated. Other drugs need to bind to albumin, a protein in the blood plasma; since older adults have less of this protein medications can compete for the available resource, making one stronger and the other impotent.
To optimize drug therapy, Dr. Ayati advised that patients and physicians work together to develop the most beneficial approach. “Start slow and low,” he said, “and don’t start to medications at the same time.”
Patients should ask some fundamental questions:
- Is this medication necessary?
- Will I die if I don’t take it?
- What is the benefit?
- What is the risk?
- How can I assess the benefit?
- What is the potential DDI?
Patients should also let all their doctors know of all their medications, prescribed and over-the-counter, and bring their prescriptions with them to office visits to avoid prescription cascade.
About the Speaker
Mehrdad Ayati, MD, is a Board Certified geriatrician. He is the Stanford medical director of the Sunnyvale Health Center and the Los Altos Subacute & Rehabilitation and Palo Alto Rehabilitation centers. He received his medical training from the Iran (Tehran) University of Medical Sciences and did his residency in the UC-Davis School of Medicine and his fellowship at Stanford.
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