Anxiolytics, sedatives, and hypnotics

Anxiolytics, sedatives, and hypnotics

Anxiolytics, sedatives and hypnotics are medicines that work on the central nervous system to relieve anxiety, aid sleep, or have a calming effect.

The benzodiazepines are the main class of drugs that fit into this category. Although there are more than twenty benzodiazepine derivatives, only certain ones have been approved to treat anxiety (eg, alprazolam, clonazepam, diazepam, and lorazepam), sleeplessness (insomnia) (eg, estazolam, flurazepam, quazepam, temazepam and triazolam), or panic disorder (eg, alprazolam). Barbiturates are an older class of medicine that used to be used for these indications as well; however, barbiturates have a narrow therapeutic index (window of effectiveness before toxicity occurs), and are more likely to cause respiratory depression, coma and death, and are very rarely used nowadays. The main issue with use of benzodiazepines is dependence. Benzodiazepines differ in their propensity to cause sedation and in the length of time they act for. All benzodiazepines are thought to work by enhancing the inhibitory action of γ-aminobutyric acid (GABA).

Other drug classes that are also considered effective at relieving anxiety include the SSRIs, SNRIs, tricyclic antidepressants and buspirone; other medicines may also be prescribed off-label. These drugs are often preferred over benzodiazepines for anxiety because they are unlikely to cause dependence; however, they may not work as quickly as benzodiazepines. SSRIs typically have a delayed onset-of-action and may initially worsen anxiety.

Other drug classes that have a sedative effective include first-generation antihistamines, agonists of melatonin receptors, anesthetics, eszopiclone, zaleplon, zolpidem, zopiclone, and several others. Many of these drugs also have a hypnotic effect.

Benzodiazepines

Benzodiazepines are a class of agents that work on the central nervous system, acting selectively on gamma-aminobutyric acid-A (GABA-A) receptors in the brain. GABA is a neurotransmitter that inhibits or reduces the activity of nerve cells (neurons) within the brain. Benzodiazepines open GABA-activated chloride channels, and allow chloride ions to enter the neuron. This makes the neuron negatively charged and resistant to excitation.

All benzodiazepines work in a similar way but there are differences in the way individual benzodiazepines act on the different GABA-A receptor sub-types. In addition, some benzodiazepines are more potent than others or work for a longer length of time. Because of this, some work better than others in particular conditions. Benzodiazepines may be used in the treatment of anxiety, panic disorder, seizures, or sleep disorders. They may also be used as a muscle relaxant, during alcohol withdrawal, or before surgery to induce relaxation and amnesia (memory loss).

Diazepam

Usual Adult Dose for Anxiety
ORAL:
2 to 10 mg orally 2 to 4 times a day
PARENTERAL:
Moderate Anxiety Disorders and Symptoms: 2 to 5 mg IM or IV, repeated in 3 to 4 hours if necessary
Severe Anxiety Disorders and Symptoms: 5 to 10 mg IM or IV, repeated in 3 to 4 hours if necessary
Comments:
-Oral doses should be determined by the severity of symptoms.
-Anxiety associated with the stress of everyday life usually does not require treatment with this drug.
Use: Management of anxiety disorders and short-term relief of anxiety symptoms

Barbiturates

Barbiturates are a class of drugs that have been derived from barbituric acid. Barbituric acid itself has no therapeutic activity; however, its derivatives enhance the action of GABA, a neurotransmitter that inhibits the activity of nerve cells in the brain.

Historically, barbiturates were used in the treatment of anxiety, epilepsy, as anesthetics, and to induce sleep. However, they have a tendency to cause psychological and physical dependence and there is a fine line between a normal dose and a toxic dose. Nowadays, barbiturates have been largely superseded by safer drugs, although some are still used during surgery or to control seizures.

Phenobarbital

Usual Adult Dose for Sedation
Daytime Sedation:
30 to 120 mg orally, IM, or IV in 2 or 3 divided doses
Maximum dose: 400 mg during a 24-hour period
Preoperative Sedation:
Parenteral:
100 to 200 mg IM 60 to 90 minutes before surgery
Comments:
-Frequency of administration should be determined by the patient response.
-Parenteral administration should be reserved for situations in which oral administration is impossible/impractical.
Uses: Daytime sedation; preoperative sedation