A 62-year-old man comes to the office for follow-up. The patient has a 10-year history of type 2 diabetes mellitus. Over the past 2 years, he has had burning pain and pins and needle sensations in his feet, which is worse at nighttime. Nortriptyline was prescribed, and the dosage was gradually increased. Currently, the patient takes the maximal recommended dose but states the symptoms are not well controlled. He reports no drug adverse effects. Other medical history includes hypertension and hyperlipidemia. Blood pressure is 124/70 mm Hg and pulse is 68/min. Physical examination shows decreased light touch and pain sensation in the feet. Ankle reflexes are decreased bilaterally. His most recent hemoglobin A1c level is 7.0%. Appropriate foot care is advised, and additional pharmacotherapy for the patient's symptoms is planned. Which of the following medications would provide additional benefit through a different mechanism with no drug-drug interaction?

Question

A 62-year-old man comes to the office for follow-up.  The patient has a 10-year history of type 2 diabetes mellitus.  Over the past 2 years, he has had burning pain and pins and needle sensations in his feet, which is worse at nighttime.  Nortriptyline was prescribed, and the dosage was gradually increased.  Currently, the patient takes the maximal recommended dose but states the symptoms are not well controlled.  He reports no drug adverse effects.  Other medical history includes hypertension and hyperlipidemia.  Blood pressure is 124/70 mm Hg and pulse is 68/min.  Physical examination shows decreased light touch and pain sensation in the feet.  Ankle reflexes are decreased bilaterally.  His most recent hemoglobin A1c level is 7.0%.  Appropriate foot care is advised, and additional pharmacotherapy for the patient's symptoms is planned.  Which of the following medications would provide additional benefit through a different mechanism with no drug-drug interaction?

Quizplus · Accepted Answer

11ec160b_3c0d_044d_9249_a345e472d322_MD0001_00 First-line therapy for painful diabetic neuropathy includes the following three classes of medications: Tricyclic antidepressants (TCAs) (eg, nortriptyline, amitriptyline) modulate pain transmission by inhibiting voltage-gated sodium channels in sensory nerves and increasing norepinephrine signaling in the central nervous system (CNS). Serotonin-norepinephrine reuptake inhibitors (SNRIs) (eg, duloxetine, venlafaxine) alter central transmission of pain by increasing norepinephrine in the central synapses. Anticonvulsants (eg, gabapentin, pregabalin) inhibit the release of excitatory neurotransmitters by binding to voltage-gated calcium modulators on nerve terminals. This patient is being treated with nortriptyline, a TCA drug. His symptoms are uncontrolled; therefore, an additional medication with a different mechanism of action should be added to avoid additive or potentially even synergistic adverse effects. Gabapentin does not inhibit serotonin and norepinephrine in the CNS but rather inhibits the release of excitatory neurotransmitters, so it is less likely to compound the adverse effects of a TCA. (Choices A and B) Amitriptyline and desipramine, like nortriptyline, are both TCAs and should not be used concurrently because the combination can result in excess toxicity (eg, delirium, arrhythmias, seizures). (Choices C and E) Duloxetine and venlafaxine are both SNRIs, which, like TCAs, inhibit serotonin and norepinephrine uptake in the CNS; therefore, TCAs and SNRIs are not typically used in combination. Educational objective: Pain due to diabetic neuropathy may be difficult to control and require multiple medications. To reduce the risk of adverse effects and improve pain control, medications should work through different mechanisms. One such combination may include a tricyclic antidepressant (eg, nortriptyline) and an anticonvulsant (eg, gabapentin).

A 62-Year-Old Man Comes to the Office for Follow-Up