أدوية مهدئة ومنوّمة

Sedative and Hypnotic Drugs

• Sedatives calm and reduce anxiety without inducing sleep (produce drowsiness).
• Hypnotics induce sleep and maintain the sleep state (mimic natural sleep).
• High doses of hypnotics can induce anesthesia.
• Sedatives and hypnotics cause central nervous system (CNS) depression.
• Dosage determines use: low dose = sedative, high dose = hypnotic.

Classification of Hypnotics and Sedatives

Barbiturates

• Were common sedative-hypnotics in the past, but now less preferred.
• Derivatives of barbituric acid (not a hypnotic itself).
• Names typically end in "al" or "one" (e.g., Phenobarbital).
• Classified by duration of action:
  • Ultra-short acting (e.g., Thiopental):
    • High lipid solubility
    • Rapid CNS entry, used for anesthesia
  • Short acting (e.g., Pentobarbital): 3 hours
  • Intermediate acting (e.g., Amobarbital): 4 hours
  • Long acting (e.g., Phenobarbital): 6-8 hours

Mechanism of Action

• Act at GABA-BZD receptors, chloride channel complex.
• Potentiate GABAergic inhibition by prolonging chloride channel opening time.
• Increase GABA neurotransmitter inhibition, reduce excitation.

Pharmacokinetics

• Absorption: Varies among different barbiturates, from alimentary tract.
• Distribution: Throughout the body (brain, liver, kidneys).
• Metabolism: Primarily in the liver by oxidation, mainly at C5, degradation rate slower for long-acting.
• Excretion: Unchanged in urine.

Pharmacological Actions

• CNS: Sedation, hypnosis, anesthesia, analgesia, anticonvulsant effects.
• CVS: Low oral doses slightly reduce blood pressure and heart rate; high doses (IV) cause sharp drops in blood pressure. Acute poisoning leads to severe hypotension (vasomotor center and direct vasodilation depression).
• Respiratory: Potent respiratory depressants due to depression of the respiratory center.
• Uterus: Reduce frequency and force of contractions during labor; cross placenta and depress newborn's respiratory center.

Therapeutic Uses

• Largely replaced by benzodiazepines (BZDs) as hypnotics and anxiolytics.
• Still used for: Epilepsy (Phenobarbital), anesthesia (thiopental), hyperbilirubinemia/kernicterus in neonates.

Adverse Effects

• Hangover, confusion, impaired performance, tolerance, dependence, potential withdrawal.
• Hypersensitivity reactions.
• Psychological disturbances.

Acute Barbiturate Poisoning

• Mostly suicidal, sometimes accidental.
• Manifestations: Excessive CNS depression (flaccid coma); shallow, failing respiration; decreased blood pressure; cardiovascular collapse; renal shutdown; potentially fatal.

Treatment of Acute Poisoning

• Gastric lavage.
• Supportive measures.
• Forced alkaline diuresis.
• Hemodialysis and hemoperfusion.

Chronic Barbiturate Poisoning

• Amnesia, skin rash, and other adverse effects.

Drug-Drug Interactions

• Barbiturates induce metabolism of many drugs, reducing their effectiveness (e.g., Warfarin, oral contraceptives, tolbutamide, griseofulvin, chloramphenicol, theophylline).
• Sodium valproate increases phenobarbital plasma concentration.
• Phenobarbital decreases griseofulvin absorption from the gastrointestinal tract.