Introduction
Sedatives and hypnotics are medicines that calm the mind and help a person sleep. A sedative reduces excitement and produces relaxation, while a hypnotic induces sleep similar to natural sleep. These medicines are widely used for anxiety, insomnia and during medical procedures.
Sleep and Its Stages
Normal sleep has two phases—NREM (non-rapid eye movement) and REM (rapid eye movement). NREM sleep has five stages (0 to 4), of which stage 2 occupies nearly half of total sleep time. Stages 3 and 4 form deep or “slow wave” sleep. REM sleep usually forms about 30% of the sleep cycle and is important for learning and memory.
Classification of Sedatives and Hypnotics
- Benzodiazepines (BZDs): Diazepam, lorazepam, clonazepam, alprazolam, midazolam, nitrazepam, triazolam, temazepam
- Barbiturates: Phenobarbitone, pentobarbitone, thiopentone
- Non-benzodiazepine hypnotics: Zolpidem, zaleplon, zopiclone, eszopiclone, etizolam
- Others: Melatonin, ramelteon, tasimelteon, suvorexant
Benzodiazepines
Benzodiazepines are the most commonly used sedative–hypnotic medicines. They act on the midbrain, brainstem and limbic system.
Mechanism of Action
They enhance the effect of GABA, an inhibitory neurotransmitter in the brain. This causes relaxation, sedation and sleep. They do not mimic GABA; instead, they facilitate GABA’s natural action.
Pharmacological Actions & Uses
1. Sedation & Hypnosis
- Decrease time required to fall asleep (shorter sleep latency)
- Prolong NREM stage 2 and reduce night awakenings
- Cause near-normal sleep with fewer hangover effects than barbiturates
2. Anticonvulsant
- Diazepam and lorazepam are used in status epilepticus
- Clonazepam is useful for absence seizures
3. Pre-anaesthetic Medication
BZDs reduce anxiety and cause amnesia before surgery. Midazolam is commonly used.
4. Diagnostic and Minor Procedures
Used intravenously for procedures like endoscopy because they cause sedation, amnesia and muscle relaxation.
5. Antianxiety
Diazepam, lorazepam and alprazolam are commonly used for short-term anxiety management.
6. Muscle Relaxation
Useful in conditions like tetanus, cerebral palsy and muscle spasms.
7. Alcohol Withdrawal
Diazepam and chlordiazepoxide reduce tremors and prevent seizures.
8. Conscious Sedation
Maintains patient cooperation without loss of consciousness. Used in dentistry and minor procedures.
Pharmacokinetics
BZDs are well absorbed orally and distributed widely. Many produce active metabolites and may accumulate. They cross the placenta and can affect newborns.
Adverse Effects
- Drowsiness, confusion, blurred vision
- Memory problems (amnesia)
- Tolerance and dependence with long-term use
- Withdrawal symptoms: tremors, agitation, insomnia
- Floppy baby syndrome when used late in pregnancy
- Paradoxical reactions: agitation, anxiety or convulsions (rare)
Benzodiazepine Antagonist – Flumazenil
Flumazenil reverses BZD overdose or sedation. It is given intravenously. It may cause withdrawal symptoms in dependent patients.
Barbiturates
Barbiturates are older sedative–hypnotics and stronger CNS depressants. They act on many brain sites including the reticular activating system.
Mechanism of Action
They enhance GABA action and at high doses directly open chloride channels (GABA-mimetic effect). This makes them more dangerous than BZDs.
Uses
- Insomnia (rarely used now) due to high toxicity
- General anesthesia induction: Thiopentone
- Anticonvulsant: Phenobarbitone for seizures
- Neonatal jaundice: Phenobarbitone increases bilirubin metabolism
Adverse Effects
- Severe hangover, drowsiness
- Respiratory depression
- Hypersensitivity reactions
- High risk of dependence & tolerance
- Enzyme induction → multiple drug interactions
- Contraindicated in porphyria
Barbiturate Poisoning
- Coma, respiratory depression, hypotension
- Treated with airway support, activated charcoal and alkaline diuresis
Non-Benzodiazepine Hypnotics
These include zolpidem, zopiclone, zaleplon and eszopiclone. They act mainly on sleep pathways and have lower abuse potential.
Zolpidem
- Decreases sleep latency and improves sleep quality
- Minimal hangover effects
- Less chance of dependence
- Antagonized by flumazenil
Zopiclone
- Used for short-term insomnia
- Side effects: headache, metallic taste
Zaleplon
- Very short-acting
- Useful for sleep-onset insomnia
Eszopiclone
- Short- and long-term insomnia treatment
Other Agents
Melatonin & Ramelteon
Melatonin regulates sleep–wake cycle. Ramelteon is a melatonin receptor agonist useful for sleep-onset insomnia. Causes minimal dependence.
Tasimelteon
Used in blind patients with circadian rhythm disorder.
Suvorexant
Blocks orexin receptors to promote sleep. Useful in chronic insomnia.
Detailed Notes:
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