High extraction drugs are dependent on blood flow and are termed flow limited in their clearance. High extraction drugs are those that are essentially “cleared” as they pass through the liver, whereas low extraction drugs are those whose concentration is little changed after passage through the liver. 4Taken together, these alterations in the cardiovascular system can make elderly patients more sensitive to fluid shifts and blood loss. 3In addition, blunted baroreflexes make geriatric patients less able to respond normally to hypovolemia and much more susceptible to orthostatic hypotension with drug therapy. This makes elderly patients much more susceptible to fluid overload. Myocardial hypertrophy, along with increased collagen content, creates a stiff left ventricle that depends on adequate preload to maintain cardiac output. 2For example, blood vessel distensibility is drastically decreased in elderly patients and, combined with increased intimal thickness and endothelial dysfunction, will increase systolic blood pressure, as well as left ventricular workload. 1In addition, as humans age, protein structure is altered, and this likely accounts for physiologic changes of old age. There are numerous theories of aging, including cellular senescence (cells are unable to replicate DNA and divide normally) and oxidative stress (inability to protect against reactive metabolic molecules, e.g. , free radicals).
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