Anxiolytics, sedatives, and hypnotics

Anxiolytics

Anxiolytics are medications used to treat anxiety symptoms associated with disorders such as generalized anxiety disorder, PTSD, agoraphobia, panic disorder, and phobias.

Anxiolytics include:

• Beta-blockers (especially propranolol)
• Buspirone
• Certain antihistamines (e.g., hydroxyzine [Atarax] and diphenhydramine [Benadryl])
• Antidepressants
• Sedative-hypnotics

Buspirone (BuSpar, Vanspar) modulates serotonin and dopamine levels in the brain.

Adverse effects include:

• Dizziness
• Nausea
• Diarrhea
• Headache
• Confusion
• Rash
• Weakness
• Increased sweating

Buspirone should not be taken with grapefruit juice and is contraindicated with MAOIs.

Sedative-hypnotics

Sedatives and hypnotics are drugs used to decrease stress and anxiety and to treat insomnia. They’re also called tranquilizers or sleeping pills.

They include:

• Barbiturates
• Benzodiazepines
• Other drugs (e.g., zolpidem)

Barbiturates increase GABA (gamma aminobutyric acid) activity in the brain, which promotes sleep and calmness.

Examples include:

• Phenobarbital (Sezaby)
• Pentobarbital
• Amobarbital (Amytal sodium)

Barbiturates have a high addiction and dependence potential, so they aren’t preferred as sedative-hypnotics. They’re mainly used as anesthetics and antiepileptics. They may cause respiratory depression. Barbiturates are controlled substances and are classified under Schedules II to IV.

Benzodiazepines activate GABA-A receptors in the brain and affect conductances of chloride channels. GABA-A slows brain impulses, which can lead to:

• Increased sleep
• Seizure control
• Muscle relaxation
• Reduced stress

Benzodiazepines can have serious and life-threatening adverse effects, including respiratory depression (especially when combined with alcohol or other respiratory depressant medications). Other adverse effects include:

• Dependence
• Drowsiness
• Confusion
• Headache
• Nausea
• Vomiting
• Coma

Patients taking benzodiazepines chronically may develop tolerance to their effects.

Benzodiazepines differ by their half-lives, which affects how long the drug remains in the body.

Those with short to intermediate half-lives (5-20 hours) include:

• Alprazolam
• Midazolam
• Bromazepam
• Clonazepam
• Lorazepam
• Oxazepam
• Temazepam

Those with long half-lives (above 20 hours, with some as high as 80-100 hours) include:

• Diazepam
• Clorazepate
• Chlordiazepoxide

Commonly prescribed benzodiazepines include:

• Diazepam (Valium)
• Alprazolam (Xanax)
• Triazolam (Halcion)
• Lorazepam (Ativan)
• Clonazepam (Klonopin)
• Estazolam (Prosom)
• Flurazepam (Dalmane)
• Temazepam (Restoril)
• Midazolam (Versed)

Benzodiazepines are controlled substances and are classified under DEA Schedule IV.

Flumazenil

Flumazenil (Anexate, Mazicon, Lanexat, Romazicon) is an antagonist at benzodiazepine receptors. It’s used to reverse benzodiazepine overdose.

It may cause:

• Seizures
• Slow heart rate
• Agitation
• Sweating
• Confusion
• Blurred vision
• Hypertension

Flumazenil is contraindicated with TCAs because it can induce seizures and is not effective at reversing benzodiazepine overdose.

Other sedative-hypnotics

Some sedative-hypnotics are not barbiturates or benzodiazepines.

Common examples include:

• Zolpidem (Ambien)
• Eszopiclone (Lunesta)
• Zaleplon (Sonata)
• Ramelteon (Rozerem)
• Suvorexant (Belsomra)

Common adverse effects of sedative-hypnotics include drowsiness, dizziness, and tiredness. Alcohol enhances the adverse effects of all sedatives and hypnotics and is dangerous to take together.

Zolpidem has a mechanism of action similar to benzodiazepines because it modulates GABA receptor activity in the brain. It has a high abuse and misuse potential. Dangerous sleep behaviors have been observed, including sleepwalking, memory loss, and unusual activities while not fully awake (e.g., driving, cooking) that the patient does not recall.

Eszopiclone has a similar mechanism of action and adverse effect profile to zolpidem.

Zaleplon is a short-acting drug with a mechanism resembling benzodiazepines, but it is more selective for the receptor type. Adverse effects are similar to zolpidem.

Suvorexant is an orexin receptor antagonist. Orexin promotes wakefulness, and suvorexant blocks this effect to cause sleepiness. Unusual adverse effects include temporary inability to speak and temporary leg weakness (sleep paralysis).

Ramelteon is a melatonin receptor agonist. It may cause a severe allergic reaction and angioedema with difficulty breathing.