Chapter 79 - Serotonin syndrome

Question 1

Define serotonin syndrome

Answer 1

Drug-induced condition resulting from excess serotonergic agonism of the central and peripheral nervous system serotonin receptors, characterized by a clinical triad of mental status changes, autonomic instability, and neuromuscular abnormalities.

Question 2

Name 5 classes of drugs implicated in serotonin syndrome (give examples)

Answer 2

• Serotonin production stimulator (ex: L-tryptophan)
• Metabolism of serotonin inhibitor (ex of monoamine oxidase inhibitor: tranylcypromine)
• Serotonin releasing agents (ex: amphetamines, MDMA, cocaine)
• Serotonin reuptake inhibitors (ex of selective SRI: fluoxetine, tramadol, methadone, fentanyl / ex of tricyclic antidepressant: amitriptyline, trazodone, mirtazapine)
• Serotonin agonists (ex: lithium, LSD, sumatriptan)

Question 3

Where is serotonin produced and stored ?

Answer 3

Production: Enterochromaffin cells and myenteric plexus in the GI tract, neurons mostly located on the midline raphae nuclei of the lower pons and medulla (serotonin does not cross the BBB)
Storage: platelets, lungs, vesicles qt the nerve terminal

Question 4

What are the peripheral nervous system effects of serotonin and clinical signs associated?

Answer 4

Vasoconstriction, platelet aggregation, uterine contraction, intestinal peristalsis, bronchoconstriction

Mostly GI signs: vomiting, diarrhea, abdominal pain, ptyalism, flatulence, bloat.
Autonomic instability (tachycardia, bradycardia, hypertension, hypotension), respiratory distress, DIC, hyperthermia (muscular activity)

Question 5

What are the central clinical signs associated with serotonin syndrome?

Answer 5

Mydriasis, transient blindness, disorientation, hyperesthesia, hyperreflexia, tremors, ataxia, paresis, seizures, coma

Question 6

Which essential aminoacid is hydroxylated and decarboxylated to form serotonin?

Answer 6

Tryptophan

Question 7

How many families of serotonin receptors have been identified?

Answer 7

7 (5-HT1 to 5-HT7)

Question 8

What are the recommended treatments for serotonin syndrome?

Answer 8

• If overdose: emeis or gastric lavage within 15 minutes
• If absorption: activated charcoal q6 (minimize absorption and enterohepatic circulation)
• (Diuresis does not enhance excretion because those drugs are highly protein bound)
• If neurologic signs: diazepam, phenobarbital
• If hyperthermia: active or passive cooling (no NSAIDS -> no fever)
• Hypotension: norepinephrine, phenylephrine, epinephrine)
• Tachycardia, hypertension: short-acting beta-blocker (esmolol, nitroprusside)
• Serotonin receptor antagonist: cyproheptadine 5-HT1A and 5-HT2 (PO, IR), chlorpromazine 5-HT2
• Intravenous lipid emulsion: unproven