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Serotonin syndrome (mechanism of disease)

This is a flowchart on serotonin syndrome, covering the etiology, pathophysiology, and manifestations. ADDITIONAL TAGS: Rhabdomyolysis Risk factors / SDOH Cell / tissue damage Structural factors Medicine / iatrogenic Infectious / microbial Biochem / metabolic Immunology / inflammation Signs / symptoms Tests / imaging / labs Environmental, toxin Hereditary / genetic Smooth muscle physiology Pathophysiology Etiology Manifestations Serotonergic drugs: Antidepressants (MAOIs, SSRIs, SNRIs, TCAs, vortioxetine, vilazodone, trazodone) Anticonvulsants (e.g., valproate) Opioids (e.g., tramadol, meperidine) 5-HT3 receptor antagonists (ondansetron) Anxiolytics (e.g., buspirone) NMDAR antagonists (dextromethorphan) Serotonin recep agonist (triptans, ritonavir) Antibiotics (e.g., linezolid) Herbal supplements (e.g., St. John's wort, ginseng, tryptophan) Recreational stimulants (MDMA, cocaine) =2 serotonergic drugs concurrently =1 serotonergic drugs concurrent with certain CYP450 inhibitors ↓ CYP450 activity → ↓ drug clearance → serotonergic drugs accumulate → ↑ serotonergic activity CYP450 inhibitors (e.g., ciprofloxacin) Switching between serotonergic drug without tapering Drug overdose, intentional or accidental Patient-specific pharmacokinetic / -dynamic factors ↓ CYP450 activity Serotonin receptor polymorphisms Excess serotonin ↑ stimulation of the postsynaptic 5-HT1A and 5-HT2A receptors Diaphoresis Tachycardia Hypertension Mydriasis Hyperreflexia Myoclonus Clonus Horizontal ocular clonus Hypertonicity Rigidity (esp in lower extrem) Delirium Psychomotor agitation Coma Autonomic dysfunction Classic triad: Neuromuscular excitability → hyperthermia Altered mental status Nausea, diarrhea, vomiting Anxiety Seizure Hypotension (in MAOi toxicity) Serotonin reaches central nervous system Modulate gastrointestinal motility Bronchoconstriction Acute respiratory distress syndrome Vasoconstriction Acute kidney injury Platelet aggregation Disseminated intravascular coagulation Complications: Serotonin syndrome