Sedative and Hypnotic Drugs Overview

Sedative and Hypnotic Drugs

• Sedatives calm and reduce anxiety without inducing sleep, a state of drowsiness.
• Hypnotics induce drowsiness and promote sleep. Higher doses produce anesthesia.
• Both sedatives and hypnotics cause central nervous system depression.
• The dose determines if a drug is categorized as a sedative or hypnotic.

Classification of Sedative and Hypnotics: Barbiturates

• Barbiturates were common sedatives and hypnotics in the past, but are less used now.

• They are derivatives of barbituric acid, with alkyl or aryl substitutions.

• Barbiturate names often end in "-al" or "-one."

• Classified by duration of action:

  • Ultra-short acting (e.g., Hexobarbital, Thiopental):
    • High lipid solubility allowing rapid CNS entry; used in anesthesia.
  • Short acting (e.g., Pentobarbital , Butobarbital ): duration of action ~ 3 hrs
  • Intermediate acting (e.g., Amobarbital): duration of action ~ 4 hrs
  • Long acting (e.g., Phenobarbital, Barbital): duration of action ~ 6-8 hrs

• Mechanism of Action:

  • Barbiturates act at GABA-BZD receptors, increasing chloride channel opening time. This potentiates GABAergic inhibition and decreases excitation.

• Pharmacokinetics:

  • Absorption: Varies depending on the specific barbiturate.
  • Distribution: Throughout body tissues (brain, liver, kidneys).
  • Metabolism: Primarily occurs in the liver via oxidation at C5. Long-acting barbiturates metabolize slower than short-acting ones.
  • Excretion: Unchanged in urine.

• Pharmacological Actions:

  • CNS: Sedation, hypnosis, anesthesia, analgesia, anticonvulsant effects.
  • CVS: Low doses cause slight blood pressure and heart rate reduction. High (IV) doses can cause sharp drops in blood pressure. Acute poisoning leads to severe hypotension.
  • Respiration: Potent respiratory depressants, due to respiratory center depression.
  • Uterus: Reduce uterine contractions during labor; affect newborn respiratory center.

• Therapeutic Uses:

  • Limited current use except for Phenobarbital (epilepsy) and Thiopental (anesthesia). Once common as hypnotics and anxiolytics, replaced by benzodiazepines.
  • Can be used in neonates for hyperbilirubinemia and kernicterus.

• Adverse Effects:

  • Hangover, confusion, impaired performance
  • Hypersensitivity
  • Tolerance, dependence, withdrawal syndromes

• Acute Barbiturate Poisoning:

  • Mostly suicidal, sometimes accidental.
  • Symptoms due to CNS depression: Coma, shallow/failing respiration, decreased BP, cardiovascular collapse, renal shutdown.
  • Treatment: Gastric lavage, supportive care, forced alkaline diuresis, hemodialysis/hemoperfusion.

• Chronic Barbiturate Poisoning:

  • Amnesia, skin rash.

• Drug Interactions:

  • Barbiturates induce metabolism of other drugs (Warfarin, steroids, tolbutamide, griseofulvin, chloramphenicol, theophylline) reducing their effectiveness.
  • Valproate increases phenobarbital concentration.
  • Phenobarbital can decrease griseofulvin absorption.

Explore the distinctions between sedatives and hypnotics, including their classification and effects on the central nervous system. This quiz also covers barbiturates, their history, and their varying durations of action. Test your understanding of these crucial drugs in pharmacology.