Selective serotonin reuptake inhibitors

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Selective serotonin reuptake inhibitors

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Questions

USMLE® Step 1 style questions USMLE

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USMLE® Step 2 style questions USMLE

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A 61-year-old woman is brought to the emergency room by her neighbor after being found in an obtunded state with an empty bottle of medication next to her. Past medical history is significant for hypertension, type II diabetes mellitus, and major depressive disorder. Family history is noncontributory. Her temperature is 37.6 C (99.8 F), pulse is 88/min, respirations are 17/min, and blood pressure is 110/75 mm Hg. Physical examination is unremarkable. Serum chemistry and ECG findings are shown below. Which of the following medications most likely contributed to this patient’s presentation? 

 Laboratory value     Result    
 Serum chemistry    
 Sodium      142 mEq/L    
 Potassium      mEq/L    
 Chloride      95 mEq/L    
 Creatinine      1.2 mg/dL    

Reproduced from Wikimedia Commons 

External References

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Bulimia nervosa p. 584

SSRIs for p. 593

Depression

SSRIs for p. 593

Generalized anxiety disorder (GAD) p. 579, 580

selective serotonin reuptake inhibitors (SSRIs) for p. 593

Obsessive-compulsive disorder (OCD) p. 580

SSRIs for p. 593

Panic disorder p. 579, 580

SSRIs for p. 593

Post-traumatic stress disorder (PTSD) p. 579, 581

SSRIs for p. 593

Selective serotonin reuptake inhibitors (SSRIs)

Social anxiety disorder p. 580

SSRIs for p. 593

SSRIs (selective serotonin reuptake inhibitors) p. 593

Transcript

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Selective Serotonin Reuptake inhibitors, or SSRIs, 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. Selective serotonin reuptake inhibitors work by increasing the levels of serotonin to alleviate the symptoms of depression.

Now, serotonin is a neurotransmitter that helps regulate mood, emotions and feeding behavior. Presynaptic serotonergic neurons use the amino acid tryptophan to synthesize serotonin, which is also called 5-hydroxytryptamine, or 5-HT. Once synthesized, serotonin is stored in small vesicles within the presynaptic neuron. When an action potential reaches the presynaptic membrane, the vesicles fuse with the membrane and release the serotonin into the synaptic cleft. The serotonin drift around until they bind to 5HT2 receptors on the postsynaptic neuron, and cause it to fire off its own action potential. As long as there’s a high enough concentration of serotonin in the synaptic cleft, the postsynaptic neuron will continue to fire. On the presynaptic neuron, there are serotonin reuptake transporters or SERTs. This protein functions like a little trap door on the cell membrane; when a sodium, a chloride and a serotonin binds to the surface of this protein on the extracellular side, it flips over and sends the serotonin and the ions into the cell. When a potassium ion binds to the protein on the intracellular side, the trapdoor resets again, so more serotonin can attach. This way, serotonin is taken back into the presynaptic neuron, its concentration in the synaptic cleft decreases, and the postsynaptic neuron stops firing.

Now, in conditions such as major depressive disorder, where there’s a low serotonin level, selective serotonin reuptake inhibitors are the first-line therapy due to their milder side effects. Common medications in this class include escitalopram, fluoxetine, fluvoxamine, sertraline, paroxetine, and citalopram. They bind to serotonin reuptake transporters and inhibits them, which increases the serotonin level within the synaptic cleft. It's important to note that these medications are slow-acting because it takes time for serotonin to accumulate within the synaptic cleft. Because of this, it usually takes 4-6 weeks before improvements can be seen. Other conditions that can be treated with SSRIs include chronic anxiety, post traumatic stress disorder, or PTSD, obsessive-compulsive disorder, or OCD, and eating disorders like bulimia.

Summary

Selective serotonin reuptake inhibitors, or SSRIs, are a class of antidepressant medications commonly used in the treatment of major depressive disorders, post-traumatic stress disorder, obsessive-compulsive disorder, chronic anxiety disorders, and eating disorders like bulimia. SSRIs work by preventing serotonin reuptake from the synaptic cleft, thus increasing the amount of serotonin binding to 5HT2 receptors. SSRIs have a few dangerous side effects like increased risk of suicide and life-threatening serotonin syndrome.

Sources

  1. "Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)
  2. "Rang and Dale's Pharmacology" Elsevier (2019)
  3. "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)
  4. "Neuroleptic malignant syndrome and serotonin syndrome" Thermoregulation: From Basic Neuroscience to Clinical Neurology, Part II (2018)
  5. "Mechanism of action of antidepressant medications" J Clin Psychiatry (1999)
  6. "Selective Serotonin Reuptake Inhibitors" Antidepressants (2018)
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