Pharmacy & Therapeutics - March 2008 - (Page 166) CONTINUING EDUCATION CREDIT Pain Associated with Diabetic Peripheral Neuropathy A Review of Available Treatments Erin L. St. Onge, PharmD, and Shannon A. Miller, PharmD Educational Objectives After reviewing this article, readers should be able to: I Describe the pathophysiology of diabetic peripheral neuropathy. I Evaluate pharmacotherapy for diabetic peripheral neuropathy. I Compare current medications used to treat diabetic peripheral neuropathy. I Formulate recommendations for the treatment of diabetic peripheral neuropathy. cohol consumption, hypertension, hypercholesterolemia, and taller height (the longer the nerve fibers, the greater the susceptibility to damage from external trauma or vascular complications).1,3 Most practitioners are aware of the severe pain that accompanies DPN, but only 10% to 30% of patients experience painful symptoms. Instead, the disorder begins as a change in or loss of sensation that can be detected only by clinical tests. Symptoms associated with sensory loss are more common; these include an inability to feel, identify, or manipulate small objects; a loss of ability to judge temperature or painful stimuli; and muscle atrophy, which may lead to physical deformities.1 The pathophysiology of DPN is multifactorial (Figure 1).4 Increased oxidative stress, increased sorbitol, decreased nitric oxide, and increased homocysteine have been identified as the primary factors involved. Elevated blood glucose levels can lead to glycosylated proteins that are easily harmed by free radicals. These proteins may then combine with fats to produce advanced glycosylated end-products that have been linked to abnormalities in vascular tissue, lipid metabolism, and platelets.1,4 Increased sorbitol results from passive diffusion of glucose into nerve cells. After the glucose is inside the cell, it is converted to sorbitol (and other polyols). Sorbitol does not diffuse out of the cell very easily and thus accumulates within the neuron. Studies of diabetic rats suggest that nitric oxide deficiency ↑Advanced glycosylated End-products (AGEs) ↓(Na+/K+)–ATPase activity ↓Free carnitine and myo-inositol Introduction Diabetic peripheral neuropathy (DPN) affects 20% to 30% of patients with diabetes and is a significant cause of morbidity and mortality. Although the true prevalence of DPN is difficult to determine, it may be responsible for up to 75% of nontraumatic amputations. 1 These alarming statistics emphasize the need for practitioners to adopt the following primary recommendations from the American Diabetes Association’s Standards of Medical Care 2007:2 • Patients should be screened for DPN at their baseline examination and annually. • After a diagnosis of DPN has been made, specialized foot care should be instituted to decrease the risk of amputation • If decreased sensation occurs in the feet, the feet should be inspected every three to six months. Hyperglycemia is an important risk factor for the development of peripheral neuropathy. Other risk factors include the duration of diabetes, the patient’s age, cigarette smoking, alDr. St. Onge is Assistant Dean/Director of the University of Florida College of Pharmacy–Orlando Campus, in Apopka, Florida. Dr. Miller is a member of the Pharmacotherapy Faculty at Florida Hospital Family Practice Residency in East Orlando. ↑Oxidative stress ↑Sorbitol ↓Nitric oxide ↑Homocysteine Impaired endothelial function Figure 1 Pathophysiology of diabetic peripheral neuropathy. (Reproduced with permission from Head KA. Altern Med Rev 2006;11(4):294–329. Courtesy of Thorne Research, Inc.4) Accepted for Continuing Education Credit February 20, 2008. 166 P&T® • March 2008 • Vol. 33 No. 3
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