Anxiolytics and Hypnotics

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Overview & Classification - The Chill Pill Intro

  • Anxiety: Apprehension from anticipation of danger (source often unknown).
  • Insomnia: Difficulty initiating/maintaining sleep, or non-restorative sleep.

Key Neurotransmitters & Roles:

NeurotransmitterRole in Anxiety/Sleep
GABAMajor inhibitory; ↓excitability, promotes calm/sleep
Serotonin (5-HT)Regulates mood, sleep, anxiety; SSRI target
Norepinephrine (NE)Mediates stress/arousal; ↑ in anxiety
MelatoninPineal hormone; regulates circadian rhythm, sleep onset
  • Anxiolytics: Benzodiazepines (BZDs), SSRIs, Buspirone.
  • Hypnotics: Z-drugs, BZDs, Melatonin agonists.

GABA-A receptor structure and binding sites

⭐ GABA is the principal inhibitory neurotransmitter in the CNS, and its potentiation is a common mechanism for anxiolytics.

Benzodiazepines - GABA's Best Buds

  • Mechanism: Allosteric modulators of GABA-A receptors; ↑ frequency of $Cl^-$ channel opening, enhancing GABAergic inhibition. GABA-A receptor with benzodiazepine binding site

  • Classification & Key Uses:

    DurationExamples (📌 Mnemonic)Primary Uses
    ShortMidazolam, Oxazepam (📌 M.O.)Procedural sedation, Insomnia
    IntermediateLorazepam, Alprazolam (📌 L.A.)Anxiety, Insomnia, Status Epilepticus
    LongDiazepam, Clonazepam (📌 D.C.)Alcohol withdrawal, Seizures, Spasms
    (📌 M.O.: "Mostly Over"; L.A.: "Lasts Awhile"; D.C.: "Doesn't Cease")
  • Other Clinical Uses: Panic disorder, Muscle relaxation, Pre-anesthetic sedation.

  • Adverse Effects: Sedation, Ataxia, Anterograde amnesia (📌 "Forget me drug"), Dependence, Withdrawal syndrome (rebound anxiety, seizures), Respiratory depression (↑ risk with opioids).

  • Contraindications: Myasthenia gravis, Sleep apnea, Acute narrow-angle glaucoma. ⚠️ Caution in elderly.

  • Antidote: Flumazenil (competitive antagonist). Dose: 0.2 mg IV, repeat prn (max 1-3 mg).

⭐ > Flumazenil can precipitate seizures in BZD-dependent patients or those with tricyclic antidepressant (TCA) overdose.

  • BZD Withdrawal Management:

Non-BZD Anxiolytics - Beyond Benzos

DrugMoAOnsetDependenceKey UsesCommon Side Effects
Buspirone5-HT1A partial agonistDelayed (2-4 wks)LowGADDizziness, nausea, headache
SSRIs/SNRIsSerotonin/Norepinephrine reuptake inhibitorDelayed (2-4 wks)LowChronic anxiety (GAD, Panic, SAD), OCD, PTSDGI upset, sexual dysfunction, insomnia
Beta-blockers (Propranolol)Beta-adrenergic antagonistRapid (30-60 min)LowPerformance anxiety, somatic symptoms (tremor, palpitations)Bradycardia, hypotension, fatigue
  • SSRIs/SNRIs: First-line for most chronic anxiety disorders.
  • Buspirone: Good for GAD, especially if BZD concerns; no immediate effect.
  • Beta-blockers: Best for situational/performance anxiety with prominent physical symptoms. 📌 "Propranolol Performs under Pressure"

Non-BZD & Other Hypnotics - Sleepy Time Squad

📌 ZZZs for sleep (Zolpidem, Zaleplon, Zopiclone/Eszopiclone).

Drug ClassMoAPrimary UseKey AEsDependence Risk
Z-drugs (Zolpidem, Zaleplon, Eszopiclone)Selective GABA-A $\alpha1$ modulatorShort-term insomniaComplex sleep behaviors, amnesia, shorter duration vs BZDsLow
Melatonin Agonists (Ramelteon, Tasimelteon)MT1/MT2 receptor agonistSleep-onset insomniaDizziness, nausea; non-addictiveVery Low
Antihistamines (Diphenhydramine, Hydroxyzine)H1 antagonismSedation, InsomniaAnticholinergic effects, next-day drowsinessLow

⭐ Z-drugs are preferred over benzodiazepines for short-term insomnia due to their selectivity for the $\alpha1$ subunit of the GABA-A receptor, leading to fewer disruptions in sleep architecture.

High‑Yield Points - ⚡ Biggest Takeaways

  • Benzodiazepines (BZDs) act via GABA-A receptors; Flumazenil is the antidote.
  • Buspirone, a 5-HT1A partial agonist, has delayed onset and low abuse potential.
  • Z-drugs (e.g., Zolpidem) selectively target alpha-1 GABA-A subunits for insomnia.
  • SSRIs/SNRIs are first-line for chronic management of most anxiety disorders.
  • Propranolol (beta-blocker) manages somatic symptoms of performance anxiety.
  • Barbiturates have high abuse potential and cause enzyme induction; largely obsolete.
  • Pregabalin is effective for Generalized Anxiety Disorder (GAD) by modulating calcium channels.
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_____ is the first FDA-approved oral medication specifically for the treatment of postpartum depression

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_____ is the first FDA-approved oral medication specifically for the treatment of postpartum depression

Zuranolone

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Anxiolytics and Hypnotics - Free Indian Medical PG Review