Sedative-hypnotic drugs

Benzodiazepines

Agents

• Short-acting (half-life 1–12 hours): Triazolam, Oxazepam, and Midazolam
• Intermediate-acting (half-life 12–40 hours): lorazepam, clonazepam, alprazolam, temazepam
• Long-acting (half-life > 40 hours): diazepam, chlordiazepoxide,

Mnemonic

• All contain AZE from Benzodiazepine
• Separate short , intermediate , and long-acting benzodiazepines with the phrase:
  • TOM moved fast , to lure the CAT , but still took several días (Spanish for days) .

Adverse effects

Benzodiazepine overdose

• Clinical features
  • Sedation with normal vital signs
  • Slurred speech, ataxia
• Treatment
  • Antidote: flumazenil
    • Mechanism of action: competitive antagonism at GABA receptor

Benzodiazepine dependence

Warning

Benzodiazepine dependence can already develop after a few weeks of use. Therefore, benzodiazepines should only be prescribed when strongly indicated.

• Withdrawal symptoms
  • Autonomic nervous system
    • Diaphoresis
    • Nausea, vomiting, and anorexia
    • Tachycardia
    • Hypertension
  • Neurological
    • Seizures
      • Less sensitive/fewer GABA receptors → CNS hyperexcitability
    • Tremors
    • Memory impairment
  • Psychiatric
    • Anxiety
    • Depressive mood
    • Insomnia

Mnemonic

Flum-AZE-NIL = turns benzos into nothing

Barbiturates

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Feature	Barbiturates	Benzodiazepines
Mechanism of Action	Act on GABAA receptors, enhancing GABA activity	Act on GABAA receptors, enhancing GABA activity
Potency	Generally more potent	Generally less potent
Safety Profile	Higher risk of overdose and addiction	Lower risk of overdose and addiction
Sedative Effect	Strong sedative effects	Moderate sedative effects
Duration of Action	Short to long duration depending on the type	Short to intermediate duration
Metabolism	Metabolized by liver enzymes	Metabolized by liver enzymes
Indications	Historically used as sedatives, anesthetics, and anticonvulsants	Primarily used as anxiolytics, sedatives, and muscle relaxants
Withdrawal	Severe withdrawal symptoms, including seizures	Generally milder withdrawal symptoms
Risk of Dependence	High risk of physical and psychological dependence	Lower risk of physical and psychological dependence
Examples	Phenobarbital, Pentobarbital, Secobarbital, Primidone: essential tremor	Diazepam, Alprazolam, Lorazepam, Clonazepam

Nonbenzodiazepine hypnotics (Z-drugs)

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Agents

• Zolpidem (imidazopyridine): half-life ∼ 2 hours
  • Brand name: Stilnox
• Zaleplon (pyrazolopyrimidine): half-life ∼ 1 hour
• Eszopiclone: half-life ∼ 6 hours

Mechanism of action

• Similar to benzodiazepines
• Selectivity for GABA_A receptors with α1 subunits (corresponding to the BZ1 subtype)
• Short-acting due to fast metabolization by liver enzymes

Melatonin agonists

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Agents

• Ramelteon
• Tasimelteon
• Agomelatine

Mnemonic

Ramelteon, tasimelteon, and agomelatine are melatonin receptor agonists.

Mechanism of action

• Activation of MT1 and MT2 receptors in suprachiasmatic nuclei of the hypothalamus → quicker sleep onset
• Do not cause dependence

Indications

• Insomnia, especially in older adults
  • Because of its low risk of adverse effects, rameleton is a preferred option in older patients, who are particularly sensitive to the adverse reactions of sedative pharmacotherapy.

Adverse effects

• Headache
• Dizziness
• Fatigue
• Nausea