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Effect of Medication on the body, and body's effect on medication in relation to aging

Posted Jun 10 2009 6:43pm
Effect of medication on the body, and body’s effect on medication in relation to aging.
Pujan J. Dave PharmD Candidate 2008 (U of F)

According to the US Bureau of the Census, it has been reported that in the present decade in the United States, there will be a large increase in the number of individuals 85 years of age and older. This change will give rise to the number of medications prescribed as well as new knowledge about the effect of the aging process on drug action and interaction. It is well known that the pathophysiologic changes that occur in the transition from middle age to old age alter responsiveness to medication. According to Col and Fenale, in the United States as many a 28% of hospital admissions of elderly patients are the direct result of drug-related problems. The physiologic response to drugs is dependent on several factors, including the time course of drug adsorption, distribution, metabolism, and elimination in the body (pharmacokinetics (PK)) and the effect of drugs on the target receptor (specific location where the drug binds and has its effect - pharmacodynamics (PD)). Understanding PK and PD in relation to aging can help decrease the potential of adverse drug reaction (ADR), which leads to increase in hospital admissions amongst the elderly.
The PK process of absorption is unlikely to be significantly affected by the intrinsic physiology of aging. The rate of absorption of orally administered medication is delayed in the elderly due perhaps to decreased gastric pH, a decrease in the number of mucosal cells, a delay in gastric emptying time, a decrease in splanchnic blood flow. The extent of drug distribution or Volume of distribution (Vd) does change with age. There is a significant change since, in the elderly, the lean body mass (muscle) can decrease by as much as 12% to 19% and fat tissue mass can increase 14% to 35%. The total body water content decreases, which further affects drug distribution. Fat-soluble drugs readily cross membranes and are take up by fat tissue, whereas water-soluble medications, there is a decline of distribution with age. In the elderly population there is also a significant decline in the albumin (protein) which can lead to increase in drug that is not bound to protein. This means an increase in amount of active drug, thus an increase in the drug’s concentration and potentially its toxicities as well.
The PK processes of metabolism and elimination are greatly impacted because there is a significant decrease in blood flow due to a decrease in cardiac output for the most part. As stated by O’Malley and colleagues, there is a 40% reduction in hepatic (liver) blood flow in the elderly. Since, the liver is considered to be the primary organ in metabolism of drugs it can be understood how half –life (time it takes for half of a medication to be used up by the body) of medication can increase due to the severe reduction in delivery of the drug to the liver. Elimination is also greatly impacted by the aging process. Duthrie et al. found that there is a significant change in renal plasma flow, renal tubular clearance, and creatinine clearance (used to estimate kidney function). It is also said that there is a 50% decline in average clearance from age 25 to age 85, despite a serum creatinine (see May’s newsletter) level that remains unchanged at approximately 1.0 mg/dl. There are two significant outcomes that can occur with the decline in renal function: One- the amount of time the drug stays active in the body increased; Second- the amount of active drug in the body can increased because it is not being eliminated. If the drug that is being eliminated has a very small range of concentration between effectiveness and toxicity that it should be within the body then it can potentially lead to life threatening side effects.
Aging can impact the PD process as well. Age-related changes at the receptor level (level at which drug molecules bind to proteins or certain cells) can affect how drugs function in the elderly patient. This has been shown more prominently in a class of drugs that work on the beta- adrenergic system. Aging also leads to a decrease in homeostatic set point which can inturn exacerbate the adverse effects of certain medications, an example of which is taking drugs that lower arterial blood pressure which leads to significant changes in blood pressure. According to Turnheim et al, there is also a decrease in dopamine production and dopamine receptors seen in the elderly, leading to an increased incidence of extrapayramidal symptoms (Parkinson like) with neuroleptic drug use. Finally, a particularly important PD effects of aging concerns the cardiac QT interval which can be prolonged by certain medications. The QT-prolongation is the development of life-threatening ventricular tachyarrhythmias. QT-prolongation is a particular concern when a patient is being administered multiple medications that can prolong the QT interval.
The majority of medications are approved based upon clinical trials in younger patients. Therefore, appropriate modifications must be made for the elderly patients based on PK and PD changes. As a rule of thumb, the use of medication should be kept to a minimum especially in elderly, and certain medications known to causes significant side-effects should be avoided. To avoid medication related problems, a review of prescriptions and the medical record should be undertaken as warranted by the best qualified health care professional to identify, prevent and resolve medication-related problems, such as a Senior Care Pharmacist.
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