Sedative-Hypnotic Drugs Overview

Sedative-Hypnotic Drugs

• Sedative-hypnotic drugs are a group of drugs that depress the central nervous system (CNS).
• They produce dose-dependent effects, meaning the effects increase with the amount of drug taken.
• Sedatives reduce excitement and calm the person.
• Hypnotics produce sleep resembling normal sleep.

Benzodiazepines

• Benzodiazepines are a major subgroup of sedative-hypnotic drugs.
• Other sedative-hypnotic drugs include barbiturates and miscellaneous agents.

Key Terms

• Addiction: A state where the drug user feels compelled to use the drug and experiences anxiety without it.
• Anesthesia: Loss of consciousness with no response to pain.
• Anxiolytic: A drug that reduces anxiety, a type of sedative.
• Dependence: A state where removing the drug causes unpleasant, potentially life-threatening symptoms, often the opposite of the drug's effects.
• REM Sleep: Phase of sleep with rapid eye movements; most dreaming takes place during REM sleep.
• Tolerance: A decrease in drug effect requiring an increase in dosage to maintain the same response.

Neurotransmitters

• Excitatory Neurotransmitters: Activate nerve cells.
  • Acetylcholine
  • Glutamate
• Inhibitory Neurotransmitters: Inhibit nerve cell activity.
  • GABA (Gamma-Aminobutyric Acid)
  • Glycine

Barbiturates

• Barbiturates are a class of sedative-hypnotic drugs.
• Different types of barbiturates have varying durations of action:
  • Phenobarbital: Long-acting
  • Secobarbital: Short-acting
  • Thiopental: Ultra-short-acting

Mechanism of Action (Barbiturates)

• Barbiturates depress neuronal activity in the midbrain reticular formation, enhancing and prolonging the inhibitory effects of GABA receptors.
• They bind to multiple isoforms of the GABA A receptor.
• Barbiturates increase the duration of GABA-mediated chloride (Cl-) channel opening (hyperpolarization).
• They may also block the excitatory neurotransmitter glutamic acid and, at high concentrations, sodium channels.

GABA Receptor

• Barbiturates activate GABA receptors.
• Activation of GABA receptors opens chloride channels.
• Increased duration of GABA-gated channel opening leads to hyperpolarization of cells.
• Hyperpolarization of cells results in CNS depression.

Clinical Applications (Barbiturates)

• Anesthesia (Thiopental).
• Insomnia and sedation (Secobarbital).
• Seizure disorders (Phenobarbital).

Pharmacokinetics (Sedative-Hypnotics)

• Most sedative-hypnotic drugs are lipid-soluble and well absorbed from the gastrointestinal tract.
• They distribute well to the brain.
• The CNS effects of thiopental are terminated by rapid redistribution of the drug from the brain to other highly perfused tissues.
• Renal excretion eliminates the drug from the body.

Adverse Effects (Barbiturates)

• Drowsiness, severe respiratory and cardiovascular depression.
• Tolerance: The body needs more of the drug to have the same effect.
• Dependence liability: Higher than benzodiazepines.
• Enzyme induction: Can lead to multiple drug interactions.
• Withdrawal symptoms are more severe than opioid withdrawal and can be fatal (no antidote).
• Contraindicated in pregnancy.

Experimental Methods (Sedative-Hypnotic Drug Effects)

• Mouse/Rat Experiment:
  • Weigh two mice or rats.
  • Inject one animal with normal saline (control) and the other with Phenobarbital (50 mg/kg) or Thiopental (30 mg/kg).
  • Record the observations and time of occurrence in a table.