Sedative Hypnotics

These include 3 types of drugs;

• Benzodiazepines
• Barbiturates
• Miscellaneous agents

Benzodiazepines (BZ)

• These were introduced in 1960.
• These are most commonly used.

Mechanism of Action

• It is based on GABA receptors stimulation.
• GABA (amino acid) binds with receptors and chloride channels open and there is influx of chloride ions which leads to hyper-polarization of membrane and sedation occurs. This is normal phenomenon.
• Benzodiazepines facilitate this mechanism by facilitating the binding of GABA receptors to their receptors which lead to sustained hyper-polarization.
• It is dose dependent effect;
• Low dose…. Sedation
• High dose… Hypnosis
• If GABA concentration is low, BZ are not able to perform their action because these only facilitate binding not the release of GABA.

Classification of BZ

Their classification is based on duration of activity;

Short Acting BZ

• Drugs with half life less than 5 hours and include;
• Midazolam
• Triazolam

Medium Acting BZ

• Drugs with half life b/w 5-24 hours and include
• Alprazolam
• Lorazepam

Long Acting BZ

• Drugs with half life greater than 24 hours and include
• Diazepam
• Chlorodiazep

Flumazenil

• This drug is used to treat the toxicity of BZ b/c it is antagonist of BZ.

Effects of BZ

• These act as anti-convulsants and also reduce the anxiety.
• These are poor analgesic but good muscle relaxant.
• Effects on CVS and respiratory systems are negligible.

Therapeutic Uses

• Sedative and hypnotic
• Anti-convulsants
• Used for sleep disorders
• Pre-anesthetic
• Midazolam can be used as anesthetic agent.

Problem

• If used for longer duration, problem of dependency occurs and abrupt withdrawal leads to anxiety, convulsions and other withdrawal symptoms.

Barbiturates

• These are synthesized from urea and malonic acid.
• Urea and malonic acid combine to form Barbituric acid.
• Barbituric acid is not having hypnotic property.
• When hydrogen at 5^th carbon in Barbituric acid is replaced by other substitutes, then these have hypnotic property.
• If thiaurea is used instead of Urea, Thiobarbiturates are formed which are good lipid soluble. Sodium salts of Thio-barbiturates are used as injectable anesthetics.
• These are having dose dependent effect;
• Low dose…Sedation
• High dose…Hypnosis
• Higher dose…..Anesthesia
• In BZ, higher dose do not lead to anesthesia.
• So Barbiturates are used as general anesthetics.

Classification of Barbiturates

Their classification is also based on duration of activity;

Ultra-short acting

• Drugs with half life b/w 10-30 minutes and include;
• Thiopental
• Thiobarbitone
• hexobarbitone

Short acting

• Drugs with half life b/w 30min-3hours and include;
• Pentobarbitone
• Secobarbitone

Medium acting

• Drugs with half life b/w 3-6 hours and include;
• Butobarbitone
• Amylobarbitone

Long acting

• Drugs with half life more than 6 hours and include;
• Phenobarbitone
• Mephobarbitone

Effects of Barbiturates

• Sedation, hypnosis and anesthesia
• Anti-convulsants
• Poor analgesics
• Higher doses can lead to respiratory failure and death. To treat this, respiratory center stimulants (Doxapram) are used.

Therapeutic Uses

• Sedative, hypnotic and anesthetic
• Anti-convulsants (Phenobarbitone, Primidone)

Miscellaneous Drugs

• Chloral Hydrate through oral route can be given.
• Chlorobutanol
• Bromides
• Ethyl Alcohol
• Cannabis (Bhang)