How Do Sedative/Hypnotics Work?

Sedative/hypnotics are medications for induction and maintenance sleep in people with insomnia. Sedative/hypnotics induce sedation by depressing the central nervous system (CNS), in particular, the sensory cortex of the brain, which is responsible for processing the sensory inputs from the body, such as touch, pain and temperature.

Sedative/hypnotics depress the limbic system of the brain, which regulates emotional and behavioral responses, and reticular formation which regulates sleep and consciousness. Sedative/hypnotics produce sedation by enhancing the activity of gamma-aminobutyric acid (GABA), a neurotransmitter that inhibits electrical activity in the brain.

Neurotransmitters are chemicals that nerve cells (neurons) release to transmit nerve signals. Neurotransmitters bind to specific types of receptors, which are protein molecules on neuronal membranes that initiate action within the cell when stimulated by the neurotransmitter.

Sedative/hypnotics are believed to enhance GABA’s effects by binding to GABA-A receptors, and opening the chloride channels in the neuronal membrane. When the chloride ions flow into the neuron, they change the electrical polarity within the neuron and reduce its excitability to nerve impulses.

Some of the sedative/hypnotics are barbiturates, another class of medications that also work by enhancing GABA activity. Barbiturates are mostly used in clinical settings for sedation and are no longer commonly prescribed because of their high potential for addiction, overdose and use as illegal street drugs.

Some of the medications used as sedative/hypnotics work in other ways which include:

• Melatonin receptor agonists: Melatonin receptor agonists bind to melatonin receptors M1 and M2 and enhance their activity. Melatonin performs many essential functions including regulation of sleep/wake cycle, and enhancing melatonin activity in the night improves nighttime sleep.
• Orexin antagonists: Orexin antagonists promote sleep by blocking orexin activity. Orexin, also known as hypocretin, is a neurotransmitter that has many functions including regulation of sleep/wake states. Orexin is secreted in the hypothalamus region of the brain in two forms, orexin A and B, which bind to OX1 and OX2 receptors and promote arousal and wakefulness.
• Antihistamines: Antihistamines promote sleep by binding to H1 histamine receptors in the central nervous system, and blocking the activity of histamine which plays a role in wakefulness. Antihistamines are also combined with non-steroidal anti-inflammatory drugs (NSAIDs) to treat occasional sleeplessness caused by mild-to-moderate pain.

Sedative/hypnotics may be administered through the following routes:

• Oral: Tablets, capsules, caplets, sublingual tablets placed under the tongue, and oral sprays.
• Injections: Intravenous (IV) and intramuscular (IM)

Uses of sedative/hypnotics include:

• Treatment of insomnia, to induce and maintain sleep
• Treatment of occasional sleeplessness caused by mild-to-moderate pain
• Relief from anxiety
• Pre-procedure sedation
• Barbiturate coma (medically induced coma)
• Non-24-hour sleep-wake disorder (a circadian rhythm sleep disorder, more common in completely blind people who cannot perceive light)
• Smith-Magenis syndrome (a rare genetic disorder that causes many cognitive and behavioral abnormalities, including sleep disturbances)

Side effects of sedative/hypnotics may include the following:

• Somnolence (drowsiness)
• Headache
• Asthenia (weakness)
• Neuromuscular and skeletal weakness
• Ataxia (impaired coordination, balance and speech)
• Dizziness
• Lethargy
• Lightheadedness
• Sedation 
• Fatigue
• Hangover
• Vertigo
• Dysgeusia (taste disorder)
• Diarrhea
• Nausea
• Vomiting
• Abdominal pain
• Dyspepsia (indigestion)
• Constipation
• Anorexia (loss of appetite)
• Colitis (inflammation of the colon)
• Xerostomia (dry mouth)
• Confusion
• Euphoria
• Nervousness
• Anxiety
• Agitation
• Hallucinations
• Depersonalization
• Disorientation
• Abnormal thinking
• Hostility
• Irritability
• Mania
• Paradoxical reactions such as:
  • Onset or worsening of insomnia
  • CNS stimulation
• Depression
• Cognitive decline in elderly people
• Sleep disorders
• Nighttime sleep disturbances in Smith-Magenis syndrome
• Abnormal dreams and nightmares
• Sleep-related behavior such as sleep driving, sleep cooking or sleep eating
• Accidental injury
• Memory disorder/impairment
• Amnesia (loss of memory)
• Anterograde amnesia (difficulty in making new memories)
• Traveler’s amnesia (temporary episodes of memory loss, especially when combined with alcohol)
• Paresthesia (abnormal skin sensations)
• Hypesthesia (reduced skin sensation)
• Hypokinesia (slow movements)
• Hyperkinesia (excessive movement)
• Psychomotor hyperactivity (restlessness with unintentional physical movements)
• Tremor
• Seizure
• CNS depression
• Anticholinergic effects such as:
  • Reduced gastric movement
  • Decreased secretions
  • Blurred vision
• Eye pain
• Visual disturbances
• Diplopia (double vision)
• Epistaxis (nasal bleeding)
• Ear pain
• Hyperacusis (high sensitivity to sounds)
• Tinnitus (ringing in the ears)
• Dysosmia (smell disorder)
• Dysphagia (swallowing difficulties)
• Dryness of nose and throat
• Thick sputum
• Cough
• Dysmenorrhea (painful menstrual periods)
• Flushing
• Palpitations
• Tachycardia (rapid heartbeat)
• Chest pain
• Hypertension (high blood pressure)
• Bradycardia (slow heartbeat)
• Hypotension (low blood pressure)
• Syncope (fainting)
• Respiratory depression
• Apnea (cessation of breathing)
• Postoperative atelectasis (partial or complete collapse of a lung)
• Oral ulcers, blisters and inflammation with sublingual tablets
• Injection site reactions
• Hypersensitivity reactions such as:
  • Rash
  • Urticaria (hives)
  • Pruritus (itching)
  • Angioedema (swelling in the tissue under the skin or mucous membranes)
  • Photosensitivity
  • Stevens-Johnson syndrome (a rare medical emergency with flu-like symptoms and a painful rash)
  • Anaphylaxis (severe allergic reaction)
• Alopecia (hair loss)
• Asthma
• Peripheral edema
• Neuralgia (nerve pain)
• Myalgia (muscle pain)
• Neck pain
• Muscle spasms and cramps
• Fever
• Flu-like symptoms
• Sinusitis (inflammation of the sinuses)
• Pharyngitis (throat inflammation)
• Cystitis (inflammation of the bladder)
• Genitourinary complaints
• Dysuria (painful urination)
• Urinary retention
• Urinary tract infections
• Upper respiratory infections
• Bleeding
• Blood dyscrasias (disorders)
• Agranulocytosis (low granulocytes, immune cells with granules)
• Megaloblastic anemia (anemia caused because of a condition in which the bone marrow produces a deficient number of large, abnormal immature red blood cells)
• Systemic lupus erythematosus (an inflammatory disease)
• Hypercholesterolemia (high blood levels of cholesterol)
• Hypokalemia (low blood level of potassium)
• Elevated liver enzymes such as AST, ALT, bilirubin and alkaline phosphatase (rare)
• Hepatotoxicity (toxicity to the liver)
• Liver damage
• Jaundice
• Drug dependence
• Withdrawal symptoms upon drug discontinuation

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of sedative/hypnotic drugs include:

• Advil PM
• Ambien
• Ambien CR
• amobarbital?
• Belsomra
• butabarbital?
• chloral hydrate?
• diphenhydramine/ibuprofen
• Doral
• doxylamine
• Edluar
• estazolam
• eszopiclone
• flurazepam
• Halcion
• Hetlioz
• Hetlioz LQ
• Intermezzo
• Lunesta
• Nembutal
• pentobarbital
• quazepam
• ramelteon
• Restoril
• Rozerem
• secobarbital?
• Seconal?
• Sonata
• suvorexant
• tasimelteon
• temazepam
• triazolam
• Unisom
• zaleplon
• zolpidem
• Zolpimist