Esketamine: Difference between revisions
From Pharmacopedia
More actions
| [checked revision] | [pending revision] |
MDElliottMD (talk | contribs) Comprehensive categorization: +Arylcyclohexylamines, Dissociative Anesthetics, General (IV) Anesthetics, NMDA Receptor Antagonists, Antidepressants |
Sentence-case category link per house style (NMDA_Receptor_Antagonists → NMDA_receptor_antagonists) |
||
| (2 intermediate revisions by one other user not shown) | |||
| Line 1: | Line 1: | ||
{{MedTemplate | {{MedTemplate | ||
| brand = Spravato | |||
| brand | | classes = NMDA receptor antagonist (uncompetitive), dissociative | ||
| mechanism = The S-enantiomer of racemic ketamine. Uncompetitive NMDA receptor antagonist (binds open channel). Proposed antidepressant mechanism: NMDA blockade on GABA interneurons disinhibits glutamate burst → AMPA receptor activation → BDNF/VEGF release → mTOR-mediated synaptogenesis and dendritic spine formation within hours. Also binds sigma-1, opioid receptors (controversial μ-opioid contribution to antidepressant effect debated). | |||
| classes | | uses = Treatment-resistant depression (TRD) in adults, as adjunct to oral antidepressant (FDA-approved March 2019). Depressive symptoms in adults with MDD with acute suicidal ideation or behavior (FDA-approved Aug 2020). | ||
| mechanism | | starting_dose = Induction (TRD): 56 mg intranasal twice weekly × 4 weeks. Maintenance: 56-84 mg once weekly × 4 weeks, then 56-84 mg every 1-2 weeks. For acute suicidality: 84 mg twice weekly × 4 weeks. Administered under medical supervision in REMS-certified site. | ||
| uses | | preparations = 28 mg/device (each dose uses 2 devices) | ||
| starting_dose | | fda_max = 84 mg per session | ||
| preparations | | routes = Intranasal (under direct medical supervision) | ||
| fda_max | | onset = Within hours of first administration | ||
| routes | | duration = Acute effect ~24 hours; cumulative effect builds with repeated dosing | ||
| onset | | halflife = ~7-12 hours | ||
| duration | | bioavailability = ~48% intranasal | ||
| halflife | | pregnancy = Avoid; may cause fetal harm | ||
| bioavailability | | legal = Rx, Schedule III (US). REMS program required. | ||
| pregnancy | | intro = '''Esketamine''' (brand name Spravato) is the S-enantiomer of ketamine, FDA-approved as an intranasal medicine for treatment-resistant depression (March 2019) and for major depression with acute suicidal ideation or behavior (August 2020). The S-enantiomer has approximately 4-fold higher NMDA receptor affinity than the R-enantiomer; Spravato delivers it via a nasal spray under direct medical supervision in a REMS-certified setting due to risks of dissociation, sedation, and abuse. | ||
| legal | |||
| intro | Mechanism: uncompetitive NMDA receptor antagonism on GABA interneurons disinhibits glutamatergic output, leading to AMPA receptor activation, BDNF/VEGF release, and rapid synaptogenesis through mTOR pathway activation. Antidepressant onset within hours is striking compared to monoaminergic antidepressants (4-6 weeks). Patients must be monitored ≥2 hours after dose due to dissociation, sedation, and blood pressure elevation. | ||
| pharmacodynamics= Uncompetitive NMDA receptor antagonist with channel-trapping action. Sigma-1 receptor binding. Possible weak μ-opioid agonism (mechanism contribution debated; naltrexone-blockade studies have given conflicting results). | |||
| pharmacodynamics | | effects = Dissociation, sedation, dizziness, nausea, vertigo, blood pressure elevation, anxiety, sedation. Long-term risks include abuse/dependence, cognitive effects. | ||
| | | interactions = <pharmaInteractions/> | ||
| interactions | |||
}} | }} | ||
| Line 35: | Line 26: | ||
[[Category:Dissociative Anesthetics]] | [[Category:Dissociative Anesthetics]] | ||
[[Category:General (IV) Anesthetics]] | [[Category:General (IV) Anesthetics]] | ||
[[Category:NMDA | [[Category:NMDA receptor antagonists]] | ||
[[Category:Antidepressants]] | [[Category:Antidepressants]] | ||
[[Category:Dissociatives]] | |||