Sedatives

(Hypnotics; Anxiolytics)

ByGerald F. O’Malley, DO, Grand Strand Regional Medical Center;
Rika O’Malley, MD, Grand Strand Medical Center
Reviewed/Revised Dec 2022
View Patient Education

Sedatives include benzodiazepines, barbiturates, and related drugs. High doses can cause decreased level of consciousness and respiratory depression, which may require intubation and mechanical ventilation

The therapeutic benefit of sedatives is well-established, but their value in alleviating stress and anxiety is also probably the reason that they are abused so frequently. Abused anxiolytics and sedatives include benzodiazepines, barbiturates, and other drugs taken to promote sleep.

Pathophysiology of Sedative Toxicity

Benzodiazepines and barbiturates bind gamma-aminobutyric acid (GABA)-A receptors, increase the affinity of the receptor to GABA, and promote inhibitory neurotransmitter effects.

Chronic effects

> 3 months or 500 to 600 mg/day for 1 month may induce a withdrawal syndrome when the drug is stopped.

Tolerance and tachyphylaxis develop irregularly and incompletely; thus, considerable behavioral, mood, and cognitive disturbances persist, even in regular users, depending on the dosage and the drug’s pharmacodynamic effects. Some cross-tolerance exists between alcohol and sedatives, especially drugs that act on GABA-A receptors. Barbiturates and alcohol are similar in the dependence, withdrawal symptoms, and chronic intoxication they cause. Physiologic dependence develops over weeks to months in chronic users.

Pregnancy

Teratogenicity has been associated with benzodiazepine use during pregnancy, but the evidence is inconclusive. Prolonged use of barbiturates during pregnancy can cause barbiturate withdrawal in the neonate1

Pathophysiology reference

  1. 1.Veroniki AA, Cogo E, Rios P, et al: Comparative safety of anti-epileptic drugs during pregnancy: A systematic review and network meta-analysis of congenital malformations and prenatal outcomes. BMC Med 15 (1):95, 2017. doi: 10.1186/s12916-017-0845-1

Symptoms and Signs of Sedative Toxicity

Acute toxicity or overdose

The signs of sedative intoxication are depression of deep tendon reflexes, fine lateral-gaze nystagmus, slightly decreased alertness with coarse or rapid nystagmus, ataxia, slurred speech, and postural unsteadiness.

Increasing toxicity can cause nystagmus on forward gaze, miosis, somnolence, marked ataxia with falling, confusion, stupor, respiratory depression, and, ultimately, death. Overdose of a benzodiazepine rarely causes hypotension, and these drugs do not cause arrhythmias.

Withdrawal

When intake of therapeutic doses of sedatives is stopped or reduced below a critical level, a self-limited mild withdrawal syndrome can ensue. After only a few weeks of use, attempts to stop using the drug can exacerbate insomnia and result in restlessness, disturbing dreams, frequent awakening, and feelings of tension in the early morning.

Withdrawal from benzodiazepinesalcohol withdrawal.

Withdrawal from barbiturates is also similar to alcohol withdrawal. In people who chronically take in large doses of barbiturates, as well as in those who stop or decrease the dosage abruptly, a potentially life-threatening withdrawal syndrome similar to delirium tremens may occur. Occasionally, even after properly managed withdrawal over 1 to 2 weeks, a seizure may occur. Without treatment, withdrawal of a short-acting barbiturate can cause the following:

  • Within the first 12 to 20 hours: Increasing restlessness, tremulousness, and weakness

  • By the 2nd day: More prominent tremulousness, sometimes increased deep tendon reflexes, and increased weakness

  • During the 2nd and 3rd days: Seizures (in 75% of patients who were taking 800 mg/day), sometimes progressing to status epilepticus and death

  • From the 2nd to the 5th day: Delirium, insomnia, confusion, frightening visual and auditory hallucinations, and often hyperpyrexia and dehydration

Diagnosis of Sedative Toxicity

  • Usually a clinical diagnosis

drug screens. However, detecting drugs on such screening tests may not reflect the patient's condition and usually does not alter clinical management; even if the results are positive, if patients do not have a clear history of sedative ingestion, other causes of the patient's symptoms should be ruled out.

Treatment of Sedative Toxicity

  • Supportive care

Toxicity or overdose

hemodialysis (1).

Urinary alkalinization

Withdrawal and detoxification

Severe acute withdrawal of sedatives requires hospitalization for close monitoring of withdrawal symptoms, preferably in an intensive care unit, and use of appropriate doses of IV benzodiazepines. Oral benzodiazepines may be used if withdrawal symptoms are mild.

One approach for managing sedative dependence is to withdraw the drug on a strict schedule while monitoring signs of withdrawal. Often, switching to a long-acting drug, which is easier to taper, is better. The timing of dose reduction depends on the presence and severity of withdrawal symptoms.

Treatment reference

  1. 1. Hoyland K, Hoy M, Austin R, et alBMJ Case Rep 2013: bcr2013010011, 2013. doi: 10.1136/bcr-2013-010011

More Information

The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

  1. Findtreatment.gov: Listing of licensed US providers of treatment for substance use disorders

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