Introduction aux hypnotiques

Introduction to Hypnotics

• Hypnotics are substances that induce sedation and sleep in the central nervous system.
• Sleep is characterized by cyclical phases including paradoxical and slow-wave sleep.
• Hypnotics are a diverse group of medications with varying chemical structures, mechanisms of action, and side effects.

Sleep

• Sleep is a natural, recurring state characterized by loss of consciousness, reduced sensory activity, and muscle relaxation.
• It contrasts with wakefulness by a lowered responsiveness to external stimuli.
• It differs from a coma in that it's reversible.
• Insomnia is defined by difficulty falling asleep, or maintaining sleep, or waking up too early, with daytime functional impairment.

Historical Classification of Hypnotics

• Opium-based solutions (Laudanum) were used for centuries as sedatives and hypnotics.
• Bromides and paraldehyde were early hypnotics.
• Chloral hydrate and various alcohol derivatives followed, with barbituates becoming prominent.
• Antihistamines were later discovered to also have sedative properties.
• Benzodiazepines emerged to replace barbituates and other earlier hypnotic agents, due to their greater safety profile.
• More recently, drugs with similar mechanisms of action to benzodiazepines have been developed.

Barbituates

• Barbituates are a class of cyclic ureides derived from malonylurea.

• They are synthesized by condensing urea with malonic acid.

• Substitution on the malonic acid moiety can lead to different durations and intensities of action.

• Barbituates have been widely used, but replaced by benzodiazepines for their higher safety profile.

• Different barbituates have varying durations of action: from short- to long-acting

Benzodiazepines (BZDs)

• BZDs are a class of drugs that act by enhancing the effects of GABA on GABA receptors in the central nervous system..
• These drugs possess a high therapeutic index, less acute toxicity, and fewer side effects compared to the barbituates.
• Benzdiazepinone sub-types: 1-4-benzodiazepinone & 2-3-benzoodiazepinone
• Structures & Nomenclature
• Mechanisms of Action, including their roles in GABAergic transmission.

Newer Hypnotics

• Newer drugs demonstrate structural variations of chemical structure, including cyclopyrrolone or pyrazolopyrimidine sub-types) and imidazopyridine subtypes (like zolpidem).
• These newer hypnotics are often associated with a reduced risk of some adverse effects compared to older drugs like barbiturates.
• Differences in their duration and potency

Antihistamines

• Some antihistamines have sedative properties, often used as sleep aids.
• The sedative effect is due to central histamine inhibition and adrenolytic effects.
• These possess better safety profiles than barbituates, benzodiazepines
• Mechanism of action: antagonism of histamine H1 receptors.

Chloral Hydrate

• Chloral hydrate is a sedative and hypnotic agent.
• Its mechanism of action involves conversion to trichloroethanol by liver enzymes .
• This results in an effect on GABAergic transmission within the central nervous system.
• Important: Chloral hydrate has been linked to increased risk of cancer.