K2iv: Serotonin Syndrome
- Serotonin = monoamine neurotransmitter
- SS = potentially life threatening condition associated with ↑serotonergic activity within CNS
Synthesis & Metabolism
- From precursor L-tryptophan
- 2 sites of synthesis:
- ENTEROCHROMAFFIN cells of gut mucosa
- Serotonergic neurons of CNS
- Stored in 3 sites:
- Serotonergic neurons of CNS & myenteric plexus
- Enterochromaffin cells of gut mucosa
- Platelets (rely on uptake)
Role of Serotonin
- CNS →attention, behaviour, thermoregulation
- PNS →GI motility, VC, uterine contraction, bronchoconstriction
- Platelets →platelet aggregation
Serotonin Syndrome
A triad of neuro-excitatory features
- NM hyperactivity: tremor, clonus, myoclonus, hyperreflexia, pyramidal rigidity
- Autonomic hyperactivity: diaphoresis, fever, tachycardia, tachypnoea
- Altered mental status: agitation, excitement, confusion
→Features to distinguish it in a DDx are myoclonus, clonus & hyperreflexia & acute onset over 24hrs
Drugs Implicated
- SS occurs when there is a combination of drug ingestion which affects serotonergic transmission
- Stimulation of 5HTIA & 5HT2A receptors have been implicated, but no single receptor is solely responsible
1) ↑ Serotonin Synthesis
- L-tryptophan
2) ↑ Serotonin Release
- NMDA (ecstasy)
3) Inhibit Serotonin Reuptake
- SSRIs (fluoxetine)
- Phenylpinedine opioids →weak serotonin reuptake Is (pethidine, fentanyl, methadone, tramadol)
- TCAs (amitriptyline) →inhibits MAO uptake mechanisms
4) Inhibit Serotonin Metabolism
- Fever & rev MAO inhibitors (phenelzine)
5) Directly Stimulate Serotonin Receptors
- Lithium
NB: Pethidine + phenelzine →Libby Zion Law
Treatment
- Admit to ICU early
- Discontinue serotonergic agents
- Supportive care
- Sedation with benzos
- Serotonin antagonists
- Chlorpromazine (5HT1 & 5HT2 antagonist – also antagonist at dopamine receptors, histamine receptors & α1/α2 receptors ∴ advise fluid loading to prevent ↓BP)
- Cyproheptadine (histamine, 5HT1 & 5HT2 antagonist)