A 44-year-old woman with a history of breast cancer comes to the office due to persistent back pain. The patient was recently started on radiation treatment for several vertebral metastases. She has taken acetaminophen and nonsteroidal anti-inflammatory drugs but continues to have severe pain. On physical examination, she has tenderness over several lumbar vertebrae. Neurologic examination is unremarkable. The patient is started on oral morphine therapy. Which of the following is the most likely direct effect of this medication on the spinal cord neurons of this patient?

Question

A 44-year-old woman with a history of breast cancer comes to the office due to persistent back pain.  The patient was recently started on radiation treatment for several vertebral metastases.  She has taken acetaminophen and nonsteroidal anti-inflammatory drugs but continues to have severe pain.  On physical examination, she has tenderness over several lumbar vertebrae.  Neurologic examination is unremarkable.  The patient is started on oral morphine therapy.  Which of the following is the most likely direct effect of this medication on the spinal cord neurons of this patient?

Quizplus · Accepted Answer

11ec160b_3c15_8fd4_9249_014d1402bf8e_MD0001_00 Morphine is an opiate analgesic that is commonly used to treat severe chronic pain in patients with cancer. There are 3 main opiate receptor subtypes (eg, mu, delta, kappa) that mediate analgesia at the spinal and supraspinal levels. All of these transmembrane receptors are coupled to inhibitory G proteins. Morphine and other commonly used opiates have an especially high affinity for the mu receptor, which exerts the strongest analgesic effects. In the spine, opiates bind to mu receptors on the primary afferent neuron, resulting in closure of voltage-gated calcium channels, reduced calcium influx, and decreased excitatory neurotransmitter release (eg, acetylcholine, norepinephrine, serotonin, glutamate, substance P) from the presynaptic terminal (Choice C). Opiates also bind to mu receptors on the postsynaptic membrane, which opens potassium channels and leads to membrane hyperpolarization due to potassium efflux. Opiate-induced inhibition of synaptic activity in the central nervous system attenuates pain transmission, producing analgesia. (Choice A) Digoxin is a cardiac glycoside that inhibits the sodium-potassium ATPase pump in myocardial cells, resulting in a mild increase in intracellular sodium and indirect inhibition of the sodium-calcium exchanger. This leads to increased intracellular calcium and cardiac contractility, which can help reduce symptoms in patients with advanced systolic heart failure. (Choice B) Local anesthetics (eg, lidocaine) reduce pain transmission by blocking voltage-dependent sodium channels, which decreases sodium influx and action potential propagation. They are typically used for minor surgical procedures and spinal anesthesia. (Choice D) Benzodiazepines are sedative-hypnotics that may be indicated for anxiety, panic attacks, or insomnia. They work by increasing chloride influx at GABA-A receptors in the thalamus, limbic structures, and cerebral cortex. Educational objective: Opiate analgesics reduce pain by binding to mu receptors and inhibiting synaptic activity in the central nervous system. Activation of presynaptic mu receptors on the primary afferent neuron leads to closure of voltage-gated calcium channels and reduced excitatory neurotransmitter release. Binding to mu receptors on the postsynaptic membrane causes opening of potassium channels and membrane hyperpolarization. __________ References: Molecular mechanisms of opioid receptor-dependent signaling and behavior. (http://www.ncbi.nlm.nih.gov/pubmed/22020140)

A 44-Year-Old Woman with a History of Breast Cancer Comes