Serotonin and norepinephrine reuptake inhibitors

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Serotonin and norepinephrine reuptake inhibitors

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USMLE® Step 1 style questions USMLE

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A 49-year-old woman comes to her outpatient provider because of a depressed mood that has persisted for several months. She also cites reduced sleep, frequent nighttime awakenings, reduced appetite, and a 2 kg (4.4 lb) weight loss. Her partner notes that she has been irritable and no longer enjoys going camping or playing with her dogs. Her maternal uncle died by suicide at the age of 30, and her mother has a history of generalized anxiety disorder. Past medical history is notable for hypercholesterolemia, hypertension, and type II diabetes mellitus. She smokes one pack of cigarettes per day. Her temperature is 37.0°C (98.6°F), her pulse is 80/min, respirations are 16/min, and her blood pressure is 155/77 mmHg. Which of the following additional findings in this patient would make duloxetine the treatment of choice?  

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Serotonin norepinephrine reuptake inhibitors, or SNRIs, are mainly used to treat major depressive disorder. This disorder causes a persistent feeling of sadness and loss of interest in everyday activities. Even though the exact cause of depression is still unknown, there's some evidence that suggests it’s related to low levels of neurotransmitters like serotonin, norepinephrine, and dopamine. Serotonin norepinephrine reuptake inhibitors work by increasing the levels of serotonin and norepinephrine to alleviate the symptoms of depression.

Alright, now within the brain, there are many different types of neurons, but we’re going to focus only on two: serotonergic neurons which produce serotonin, and noradrenergic neurons which produces norepinephrine. Each of these neurons synthesizes and stores their neurotransmitters in small vesicles. So, when an action potential reaches the presynaptic membrane, these vesicles fuse with the membrane, releasing neurotransmitters in the synaptic cleft. Once released, serotonin or 5-HT binds to 5-HT2 receptors on the postsynaptic membrane, thereby increasing neural stimulation and regulating mood, feeding, and reproductive behavior. On the other hand, norepinephrine binds to norepinephrine receptors on the postsynaptic membrane, boosting alertness. As long as there’s a high enough concentration of neurotransmitters in the synaptic cleft, the postsynaptic neurons will continue to fire. Now, serotonergic neurons on their presynaptic membrane have serotonin transporters or SERT, while noradrenergic neurons have norepinephrine transporters or NET. These membrane proteins transport the serotonin and norepinephrine in the synaptic cleft back into presynaptic neurons. This leads to decreased neurotransmitter concentration within the synaptic cleft, causing the postsynaptic neurons to stop firing.

Summary

Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant medications used to treat major depressive disorder and other mental health conditions such as anxiety disorders, obsessive-compulsive disorder, and attention deficit hyperactivity disorder. SNRIs work by preventing serotonin and norepinephrine reuptake from the synaptic cleft, thus enhancing the effect of both neurotransmitters on the postsynaptic neuron. SNRIs can cause a few dangerous side effects like increased risk of suicide and life-threatening serotonin syndrome.

Sources

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