Continuity of Care: Diabetic Neuropathy: Bridging the Sensation Gap

Dr. Carey is a PGY-1 pharmacy practice resident at Baystate Medical Center in Springfield, Massachusetts. Dr. Throm is an assistant professor at Midwestern University College of Pharmacy? Glendale, Glendale, Arizona.

Diabetic neuropathy (DN) refers to symptoms and signs of peripheral nerve dysfunction in patients with diabetes.¹ Prevalence is a function of disease duration, with approximately 50% of diabetic patients eventually developing neuropathy.^2,3 The pathogenesis behind DN is multifactorial, involving both metabolic, vascular, and inflammatory changes, which are initially triggered by chronic hyperglycemia.^3,4

Several different syndromes of DN have been identified and categorized.^1,3,5 Of these, peripheral diabetic neuropathy (PDN) is the most common presentation of DN, and diabetic autonomic neuropathy (DAN) is the type associated with the greatest risk of morbidity and mortality.^3,6

Peripheral Diabetic Neuropathy

Up to 50% of patients with PDN experience symptoms, such as burning pain, electrical or stabbing sensations, numbness, and deep aching pain.1 Neuropathic pain typically worsens at night, and the symptoms are most commonly experienced in the feet and lower limbs, although the hands also may be affected (also known as stocking-glove distribution).^1,2 Up to half of patients with PDN are asymptomatic; diagnosis is sometimes made on clinical examination or, in some cases, after the patient presents to the hospital or community pharmacy with a painless foot ulcer.¹

Tight glucose control is the primary treatment to prevent the development and slow the progression of DN.^1,7 Pharmacists should emphasize this important aspect of DN when counseling patients and also monitor patients for adherence to their drug therapy regimens.

Because PDN may be asymptomatic or cause loss of sensation in the extremities, patients with diabetes need optimal foot care to prevent foot ulcers and amputation.⁴ In addition to educating patients on the importance of annual foot exams, pharmacists can show patients how to conduct daily foot inspections to check for cuts, blisters, calluses, and reddened areas.^8-10

Pharmacologic treatment of PDN is mainly targeted toward pain management (Table 1). Therapeutic options include antidepressants, anticonvulsants, and opioids. Tricyclic antidepressants like amitriptyline, desipramine, and nortriptyline have been used with good effect but are often associated with adverse effects like sedation, orthostatic hypotension, constipation, dry mouth, dizziness, and blurred vision.^1,4

Duloxetine is a norepinephrinespecific reuptake inhibitor that has an FDA-approved indication for treatment of painful DN. Anticonvulsants like gabapentin and pregabalin also are effective at treating neuropathic pain. Gabapentin is usually started at a low dose and gradually titrated up to avoid adverse effects like stomach upset, dizziness, and drowsiness. Pregabalin, the other FDA-approved medication for treatment of DN, has a similar adverse effect profile as gabapentin, but may be titrated to target dose more rapidly.⁴

Opioids such as oxycodone and tramadol also may be used. Opioids have been proven effective at treating PDN, but clinicians may choose to exhaust other treatment options first before prescribing these medications.² A topical cream that may be used is capsaicin, an alkaloid found in red pepper. Capsaicin depletes substance P, which is an inflammatory mediator important in the sensitization of nerves to painful stimuli. 2 Adjunctive treatments include acupuncture and transcutaneous electrical nerve stimulation, in which electrodes placed on the skin transmit electrical impulses that are believed to relieve neuropathic pain by blocking the pain pathway.^11,12

Diabetic Autonomic Neuropathy

DAN has an insidious onset and presents in a variety of different ways, most commonly affecting the cardiovascular system, gastrointestinal tract, genitourinary system, eyesight, and sweat glands (Table 2).^4,6 Cardiovascular autonomic neuropathy (CAN) is associated with increased risk of mortality, making it a major concern for patients with DAN.^4,6 CAN refers to orthostatic hypotension, silent myocardial infarction, and exercise intolerance, in which increases in physical activity fail to result in increased cardiac output.⁶

Continuity of Care Across the Health Care Spectrum

Community Pharmacy

Pharmacists in the community setting have an important role in recognizing signs of DN in diabetic patients who may present with concerns, such as pain, numbness, or constipation. Patients with foot problems sometimes initially present to the community pharmacy looking for an OTC treatment. In this case, the pharmacist can have an important intervention in referring a patient to his or her physician. Community pharmacists also may assist with formulary management to ensure that the patient receives the most cost-effective treatment. The pharmacist also plays a vital role in providing patient counseling on the importance of adherence to diabetic medications.

Acute Care

Inpatient pharmacists need to educate physicians and nurses about the pharmacologic treatment of DN. Medications used to treat painful DSP, such as tricyclic antidepressants and antiepileptics, are different from the nonsteroidal antiinflammatory drugs and opioids commonly used to treat somatic pain. The inpatient pharmacist should look at the patient medication list to ensure optimal treatment. One important consideration is tolerability; tricyclic antidepressants tend to have less tolerable anticholinergic adverse effects than antiepileptic medications. The inpatient pharmacist must also take into account patientspecific characteristics (eg, an elderly patient with benign prostatic hyperplasia may do better with a medication that limits anticholinergic side effects as first-line therapy).

Rehabilitation Hospital

If a patient is transitioned from an acute care facility to a rehabilitation hospital, which sometimes occurs after amputation, it is important to assess the patient?s pain control therapy. During the acute hospitalization, pain management may not be the primary concern, and this presents pharmacists with an opportunity to evaluate whether the patient had effective pain control prior to admission. A thorough assessment of what the patient?s pain concerns are, which treatments have or have not worked in the past, and what the patient?s pain goals are can be helpful.

Primary Care Provider

The primary care provider (PCP) assists in the long-term management of neuropathy, diabetes, hypertension, and hyperlipidemia. Pharmacists in all settings may assist the PCP in choosing the most cost-effective and safe medication for the patient with DN.

Conclusion

Pharmacists in all health care settings play an important role in the prevention and treatment of DN. Bridging the continuity of care gap ensures that patients understand the importance of medication adherence.

References

• Boulton AJ, Vinik AI, Arezzo JC, et al. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care. 2005;28:956-962.
• Boulton AJ, Malik RA, Arezzo JC, Sosenko JM. Diabetic somatic neuropathies. Diabetes Care. 2004;27:1458-1486.
• Simmons Z, Feldman EL. Update on diabetic neuropathy. Curr Opin Neurol. 2002;15:595-603..
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• Thomas PK. Classification, differential diagnosis, and staging of diabetic peripheral neuropathy. Diabetes. 1997;46(suppl 2):S54?S57.
• Vinik AI, Maser RE, Mitchell BD, Freeman R. Diabetic autonomic neuropathy. Diabetes Care. 2003;26:1553?1579.
• The Diabetes Control and Complications Trial Research Group. The effect of intensive diabetes therapy on the development and progression of neuropathy. Ann Intern Med. 1995;122:561-568.
• Malone JM, Snyder M, Anderson G, Bernhard VM, Holloway GA Jr, Bunt TJ. Prevention of amputation by diabetic education. Am J Surg. 1989;158:520-524.
• Mayfield JA, Reiber GE, Sanders LJ, et al. Preventive foot care in diabetes. Diabetes Care. 2004;27(suppl 1):S63-S64.
• Harley JR. Preventing diabetic foot disease. Nurse Pract. 1993;18:37-44.
• Kumar D, Marshall HJ. Diabetic peripheral neuropathy: amelioration of pain with transcutaneous electrostimulation. Diabetes Care.1997;20:1702-1705.
• Somers DL, Somers MF. Treatment of neuropathic pain in a patient with diabetic neuropathy using transcutaneous electrical nerve stimulation applied to the skin of the lumbar region. Phys Ther. 1999; 79:767-775.