Sedative and Hypnotic

sedative or transquilliser

These are the substance that induces sedation (sleep) by reducing irritability or excitement.

They are CNS depressants and interact with brain activity.

hypnotic or soporific

Hypnotic or soporific drugs, commonly known as sleeping pills.

These are a class of psychoactive drugs whose primary function is to induce sleep and to be used in the treatment of insomnia.

Hypnotic- sedative drugs

The term sedative describes drugs that serve to calm or relieve anxiety.

The term hypnotic generally describes drugs whose main purpose is to initiate, sustain sleep.

Because these two functions frequently overlap they are often referred to collectively as sedative-hypnotic drugs.

stages of sleep

The different phases of sleep and their characteristics are-

1. Stage 0 (awake)– From lying down to falling asleep ,eye movements can be seen.
2. Stage 1 (dozing) -Eye movement are reduced but there may be burst of rolling Neck muscles relax.
3. Stages 3 & 4 – characterized as the deep stages of sleep, and are often the hardest to wake up from so they will make disoriented and groggy for minutes after they awake. These periods of slow wave sleep (SWS).
4. REM sleep (paradoxical sleep) – These are marked, irregular and fast eye movements; dreams and nightmares

CLASSIFICATION OF DRUGS

1. Barbiturates –

• Phenobarbitone
• Thiopentone
• Methohexitone
• Butobarbitone
• Pentobarbitone

2. Benzodiazepines

• Diazepam
• Flurazepam
• Nitrazepam
• Alprazolam
• Temazepam
• Triazolam
• Chlordiazepoxide
• Oxazepam
• Lorazepam
• Clonazepam

3. Newer nonbenzodiazepine hypnotics-

• Zaleplon
• Zolpidem

BARBITURATES

Barbiturates are not used now to promote sleep or to calm patients,these are most popular sedative and hypnotic.

However,they are described first because they are the prototype of CNS depressants.

Barbiturates are substituted derivatives of barbituric acid

Barbiturates have variable lipid solubility, the more soluble ones are more potent and short acting.

PHARMACOLOGICAL ACTIONS

Barbiturates are general depressants for all excitable cells, the CNS is most sensitive.

1. CNS effects:

Barbiturates produce dose-dependent

sedation → sleep then anaesthesia → coma.

• Hypnotic dose shortens the time taken to fall asleep and increases sleep duration, Night awakenings are reduced.

The effects on sleep become progressively less marked if the drug is taken every night consecutively.

Hangover (dizziness, distortions of mood, irritability and lethargy) may occur in the morning after a nightly dose.

• Sedative dose (smaller dose of a longer acting barbiturate) given at day time can produce drowsiness, reduction in anxiety and excitability.

Barbiturates can impair learning, short- term memory and judgement.

They have no analgesic action and anticonvulsant property.

2. Other systems

• Respiration is depressed by relatively higher doses.
• Hypnotic doses of barbiturates produce a slight decrease in BP and heart rate.
• Toxic doses produce market fall in BP due to vasomotor centre depression, ganglionic blockade and direct decrease in cardiac contractility.
• However, the dose producing cardiac arrest is about 3 times larger than that causing respiratory failure.

• Skeletal muscle- Hypnotic doses have little effect but anaesthetic doses reduce muscle contraction by action on neuromuscular junction.

• Kidney- Barbiturates tend to reduce urine flow by decreasing BP and increasing ADH release.

• .Smooth muscles Tone and motility of bowel is decreased slightly by hypnotic doses.

PHARMACOKINETICS

Barbiturates are well absorbed from the GI tract. They are widely distributed in the body.

The rate of entry into CNS is dependent on lipid solubility. Highly-lipid soluble thiopentone has practically instantaneous entry, while less lipid-soluble ones pentobarbitone take longer;

phenobarbitone enters very slowly.

Barbiturates cross placenta and are secreted in milk; can produce effects on the foetus and suckling infant.

USES

• Except for phenobarbitone in epilepsy and thiopentone in anaesthesia other barbiturate is used now.

• They are occasionally employed in psychosomatic disorders. Eg; Phenobarbitone 30-60 mg oral

contraindication of barbiturates

Hangover was common after the use of barbiturates as hypnotic.

Mental confusion, impaired performance and traffic accidents,excitement etc.

Rashes, swelling of eyelids, lips, etc. Hypersensitivity is common.

Acute barbiturate poisoning Mostly suicidal, sometimes accidental.

BENZODIAZEPINES (BZD)

Definition

Benzodiazepines are man-made medications that cause mild to severe depression of the nerves within the brain (central nervous system) and sedation.

Seizures, anxiety, and other diseases that require benzodiazepine treatment may be caused by excessive activity of nerves in the brain.

Work

Chlordiazepoxide and diazepam were introduced as antianxiety drugs, has replaced barbiturates as hypnotic and sedative.

Hypnotic doses do not affect respiration or cardiovascular functions. Higher doses produce mild respiratory depression and hypotension which is problematic only in patients with respiratory insufficiency .

Fall in BP in case of diazepam and lorazepam is due to reduction in cardiac output while that due to midazolam is due to peripheral resistance.

A specific BZD antagonist flumazenil is avaiable which can be used in case of poisoning.

Generalized anxiety disorder

Benzodiazepines have efficacy to cure short-term management of generalized anxiety disorder (GAD), but were not shown effective in producing long-term improvement overall.

Panic disorder

Because of their effectiveness, tolerability, and rapid onset of anxiolytic action, benzodiazepines are frequently used for the treatment of anxiety associated with panic disorder .

Seizures

Prolonged convulsive epileptic seizures are a medical emergency that can usually be dealt with effectively by administering fast-acting benzodiazepines, which are potent anticonvulsants.

Nonbenzodiazepine

Nonbenzodiazepine drugs are much more selective than the older benzodiazepine producing effective relief of anxiety/panic with little or no sedation or anticonvulsant effects, and are thus potentially more precise than older, anti-anxiety drugs.