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Basic Pharmacology And Physiology Of Sedative Hypnotic Drug

September 26, 2020Category : Public Health
Basic Pharmacology And Physiology Of Sedative Hypnotic Drug

The unwanted effects of benzodiazepines, especially their abuse and addiction potential are well known and have been described many times. Although some doctors still consider the newer Z-drugs, such as Zolpidem or Zopiclone, as less harmful, evidence shows that it is a false belief. This is also reflected by updated guidelines. That might explain why in many countries, the overall number of prescribed benzodiazepines and Z-drugs (BenzoZ) has decreased over the last decades

Insomnia is a common sleep disorder that can be caused by psychological stress, chronic pain, and medication. A large number of insomnia patients are associated with different degrees of depression and anxiety. These symptoms can occur simultaneously with insomnia, resulting in decreased mental activity, memory loss, slow response, autonomic dysfunction, resulting in decreased immune function and memory loss, Insomnia affects approximately 10–30% of adults worldwide, and 6% are diagnosed with chronic insomnia. Drugs used to treat insomnia include benzodiazepine receptor agonists, non-benzodiazepine receptor agonists, selective melatonin receptor agonists, and sedative antidepressants.

In addition, most of the current targets for anti-insomnia drugs are serotonin (5-HT) receptors, γ-aminobutyric acid (GABA) receptors. However, taking these drugs will be accompanied by “hangover” effect, psychomotor disorder, drug dependence, addiction, tolerance, amnesia, rebound insomnia and other side effects, and their clinical efficacy is still controversial. Therefore, the research on new sedative and hypnotic drugs with fewer side effects and better efficacy is still continuing.

Aromatherapy is currently used to treat chronic pain, depression, anxiety, insomnia, improve cognitive efficiency, relieve stress and other psychological and physiological conditions related disorders. Aromatherapy is the use of essential oils extracted from the flowers, stems, leaves, roots and fruits of various plants.

Phenobarbital is a barbiturate that is widely used as a sedative and an antiseizure medication. Phenobarbital has been linked to rare instances of idiosyncratic liver injury that can be severe and even fatal. Barbiturates are structurally related compounds with sedative and hypnotic activities, some of which (phenobarbital and mephobarital) are also used as anticonvulsants. Phenobarbital has been clearly linked to cases of idiosyncratic acute liver injury, resembling the immunoallergic hepatotoxicity of other aromatic anticonvulsants such as phenytoin and carbamazepine. In contrast, the other conventional sedative barbiturates have not been linked to serum enzyme elevations during therapy and clinically apparent acute liver injury due to the sedative barbiturates is extremely rare, if it occurs at all.

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The typical starting dose in treating seizures in adults is 60 to 100 mg in three divided doses daily. Oral formulations of tablets or capsules of 15, 16, 30, 60, 90 and 100 mg are available in multiple generic forms. Parenteral formations and oral elixirs for pediatric use are also available. Phenobarbital has declined in general use in recent years with availability of more efficacious and better tolerated agents. Its major advantage is low cost, but it is more sedating than other anticonvulsants. Frequent side effects include drowsiness, sedation, hypotension, and skin rash.

Phenobarbital hepatotoxicity is usually rapidly reversible with improvements beginning within 5 to 7 days of stopping the drug and being complete within 1 to 2 months. In cases of severe injury, progression to acute liver failure and death can occur. Corticosteroids have been used but with uncertain effectiveness.

Prolonged cholestasis can occur, but chronic injury and vanishing bile duct syndrome have not been reported from phenobarbital therapy. Cross reactivity with other aromatic anticonvulsants (phenytoin, carbamazepine, primidone, and lamotrigine) is common but not invariable. Patients with hypersensitivity to phenobarbital should be monitored carefully if they are to start other aromatic anticonvulsants.

Uncommon but potentially severe adverse events included severe sedation, dependence, hypersensitivity reactions, Stevens-Johnson syndrome and toxic epidermal necrolysis. Amobarbital, butabarbital, pentobarbital and secobarbital are used as sedatives and hypnotics and not as anticonvulsants. These and several other barbiturates were introduced into medical use in the United States in the 1950s as sedatives, hypnotics (short term treatment of insomnia) and preanesthetic agents.

They are now rarely used, having been largely replaced by more effective and better tolerated sedatives and hypnotics such as the benzodiazepines and benzodiazepine receptor agonists. Amobarbital and butabarbital are currently available, but only as solutions for parenteral administration, being used largely as preanesthetic agents. Secobarbital is available as a 100 mg capsule generically and under the brand name Seconal. Pentobarbital is no longer available in the United States.

Current indications for the barbiturates include short term treatment of insomnia and as a preanesthetic agent. The recommended dose of secobarbital in adults is 100 mg at bedtime or 200 to 300 mg 1 to 2 hours before surgery. Barbiturates that are no longer available in the United States include butalbital, mephobarbital, methohexital and pentobarbital. Secobarbital is classified as a Schedule II substance, indicating that it has definite potential for physical and psychological dependence and abuse. Frequent side effects include drowsiness, sedation, hypotension, nausea, headache and skin rash.

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