Sedatives, Hypnotics, and Centrally Acting Muscle Relaxants

Sedatives and Hypnotics

Introduction

Sedatives and hypnotics are medications that act on the central nervous system (CNS) to induce relaxation, reduce anxiety, promote sleep, or produce a hypnotic state.

Sedatives have a calming effect, while hypnotics induce and maintain sleep. These drugs can help manage insomnia, anxiety disorders, and certain medical procedures requiring sedation.

Pharmacology of Sedative-Hypnotic Drugs

Mechanism of Action

Sedative-hypnotic drugs enhance the activity of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS. They bind to  GABA A receptors, increasing the influx of chloride ions into neurons, leading to neuronal hyperpolarization and suppression of neuronal activity.

Fig GABAergic neurotransmission

Fig Hyperpolarization

Sedatives and hypnotic drugs can be classified into different categories based on their chemical structure and pharmacological properties. Here is a classification of commonly used sedatives and hypnotics

1. Benzodiazepines:

Examples: Diazepam, Lorazepam, Alprazolam, Oxazepam, Temazepam, Triazolam

The drugs differ in selectivity, and the clinical usefulness of individual drug thus varies considerably. As the dose of benzodiazepine is increased sedation progress to hypnosis.

Mechanism of Action: Benzodiazepines acts at GABA A receptors by binding to a specific site that is different from GABA binding site. Benzodiazepines allosterically enhance the binding of GABA to GABAA receptor and increase the frequency chloride channel opening, leading to CNS depression and relaxation.

Clinical Applications: Anxiety disorders, insomnia, sedation before medical procedures.

Side effects: Light headedness, lassitude, increased reaction time, motor incoordination, impairment of mental and motor functions, confusion, and anterograde amnesia. Chronic use may lead to drug dependence and abuse.

2. Non-Benzodiazepine Sedative-Hypnotics (Z-Drugs):

Examples: Zolpidem, Eszopiclone, Zaleplon

Mechanism of Action: Act on the same GABA receptor complex as benzodiazepines, promoting sleep initiation and maintenance.

Clinical Applications: Short-term treatment of insomnia.

Side effects: Morning sedation, delayed reaction time, anterograde amnesia.

3. Barbiturates:

Examples: Phenobarbital, Secobarbital, Pentobarbital

Mechanism of Action: Enhance the effects of GABA by increasing the duration of chloride channel opening, leading to sedation and hypnotic effects.

Clinical Applications: General anesthesia, epilepsy, sedation.

Side Effects: Drug dependence, drowsiness, motor incoordination, repspiratory depression, allergic reactions, enzyme induction (drug interaction and tolerance development). In some individual may cause excitement instead of depression.

4. Melatonin Receptor Agonists:

Example: Ramelteon

Mechanism of Action: Act on melatonin receptors in the brain to regulate the sleep-wake cycle.

Clinical Applications: Treatment of insomnia, particularly for individuals with difficulty falling asleep.

5. Orexin Receptor Antagonists:

Example: Suvorexant

Mechanism of Action: Block the activity of orexin receptors, promoting sleep. It promotes sleep through the binding inhibition of orexin A and B, neuropeptides that promote wakefulness.

Clinical Applications: Treatment of insomnia.

6. Antidepressants with Sedative Properties:

Examples: Trazodone, Mirtazapine

Mechanism of Action: Modulate neurotransmitter systems involved in mood regulation and promote sedation.

Clinical Applications: Treatment of depression and insomnia.

Centrally Acting Muscle Relaxants

Centrally acting muscle relaxants are a class of medications that act on the CNS to reduce skeletal muscle tone and induce relaxation. These drugs are commonly used in the management of muscle spasms, spasticity, and for facilitating surgical procedures that require muscle relaxation. Here are some examples of centrally acting muscle relaxants:

Benzodiazepines

Examples: Diazepam, Lorazepam

Mechanism of Action: Enhance the inhibitory effects of GABA, a neurotransmitter that reduces neuronal activity, leading to muscle relaxation.

Clinical Applications: Management of muscle spasms, spasticity, and as an adjunct in the treatment of certain neurological conditions such as multiple sclerosis and cerebral palsy.

Baclofen

Mechanism of Action: Acts as a GABA-B receptor agonist, reducing the release of excitatory neurotransmitters and decreasing spinal reflex activity.

Clinical Applications: Treatment of muscle spasms and spasticity associated with conditions such as multiple sclerosis, spinal cord injury, and cerebral palsy.

Tizanidine

Mechanism of Action: Alpha-2 adrenergic agonist that inhibits the release of excitatory neurotransmitters, resulting in muscle relaxation.

Clinical Applications: Management of muscle spasms and spasticity associated with conditions such as multiple sclerosis, spinal cord injury, and stroke.

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