Depressants

DEPRESSANTS AND INHALANTS

Classification of Psychoactive Drugs

  • Categories include:

    • Stimulants

    • Depressants

    • Examples: Alcohol, Benzodiazepines, Other Sedatives, Sleeping Pills, Inhalants

    • Opioids

    • Cannabinoids

    • Psychedelics

    • Psychiatric Medications

Depressants

  • Definition:

    • A class of drugs that decrease central nervous system (CNS) activity, leading to a widespread effect in the brain.

    • Also called sedatives or hypnotics.

  • Types of Depressants:

    • Sedatives: Treat anxiety

    • Hypnotics: Treat insomnia

Historical Development

  • Before Barbiturates:

    • Chloral Hydrate:

    • First synthesized in 1832, used clinically until about 1870.

    • Dosage: 1-2 grams induce sleep in less than an hour.

    • Cautions: Repeated use leads to gastric irritation.

    • Paraldehyde:

    • Synthesized in 1829; clinically introduced in 1882.

    • Effective with wide safety margin but has an extremely noxious taste and odor.

  • Barbiturates:

    • Introduced in 1903; over 2,500 variations synthesized.

    • Popular examples: Phenobarbital, Amobarbital, Secobarbital.

    • Classification based on Duration of Action:

      • Short-acting: Induce sleep, prescribed in high doses.

      • Long-acting: Reduce anxiety, prescribed in low doses.

Concerns About Barbiturates

  • Overdose Risks:

    • Both intentional and accidental overdoses lead to respiratory depression.

  • Abuse and Dependence:

    • Associated with rapid onset of effects; led to the search for safer alternatives.

Meprobamate

  • Approved in 1955; produced physical dependence similar to barbiturates.

  • Once widely prescribed, now largely replaced by benzodiazepines.

Methaqualone

  • Known brands: Quaalude, Sopor; colloquially referred to as “ludes.”

  • Introduced in the U.S. in 1965 despite issues in other countries.

  • Originally thought to be a safe alternative to barbiturates; later overprescribed and misused.

  • Scheduled as:

    • Schedule II in 1973

    • Schedule I in 1985

Benzodiazepines

  • Introduction: First introduced in 1960, with Librium (Chlordiazepoxide) being the first marketed.

  • Characteristics:

    • Reduces anxiety with less drowsiness than barbiturates.

    • Larger safety margin against overdose.

    • Overdose rare without combination with other CNS depressants/alcohol.

  • Dependency Concerns:

    • Dependence and overdose risks; particularly high when combined with other sedating drugs.

    • Comparison to Barbiturates:

    • Differences exist among benzodiazepines and barbiturates; others are minimal between classes.

Rohypnol

  • 1990s term associated with the “Mickey Finn”; used in the context of sexual assault.

  • Causes profound intoxication when mixed with alcohol.

  • In 1997, reformulated to produce color when dissolved in drinks; similar effects to other CNS depressants.

Nonbenzodiazepine Hypnotics

  • Commonly called “Z-drugs” (e.g. Zolpidem/Ambien).

  • Similar to benzodiazepines but different chemical structure; short duration, rapid onset.

  • Initially thought safer; withdrawal symptoms reported; scheduled as Schedule IV.

Mechanism of Action: Sedatives and Hypnotics

  • Benzodiazepines:

    • Bind to specific receptor sites enhancing GABA's inhibitory effects.

  • Barbiturates:

    • Act on separate binding site near GABA receptors.

  • Nonbenzodiazepine hypnotics:

    • A new class with selective binding to different sites on the GABA receptor complex.

Beneficial Uses of Depressants

  • Anxiolytics:

    • Sedatives for anxiety; four benzodiazepines are top-prescribed in the US: Xanax, Ativan, Klonopin, Valium.

Concerns: Anxiolytics

  • Not suitable for all anxiety disorders (e.g. OCD, specific phobias).

  • Overprescribing issues; many prescriptions not written by psychiatrists for clear anxiety conditions.

Hypnotics (Sleeping Pills)

  • Large doses help individuals sleep faster; a health survey indicated insomnia rates—17% women, 9% men.

  • Proper evaluation for associated depression is recommended during complaints of insomnia.

Concerns: Nonbenzodiazepine Hypnotics

  • Issues include sleepwalking, eating, and driving while semi-conscious; required warning labels.

Anticonvulsants

  • Barbiturates and benzodiazepines prescribed for seizures; alternatives preferred but may be used in combination.

  • Tolerance may complicate finding effective dosages without excessive drowsiness; sudden withdrawal can provoke seizures.

Causes for Concern for Depressants: Abuse Liability

  • Psychological Dependence: Associated with short-acting sedatives.

  • Physical Dependence: Withdrawal syndrome akin to alcohol withdrawal; life-threatening potential.

  • Chronic Use Side Effects: Includes anxiety, memory loss, insomnia, nightmares, muscle cramps, and severe symptoms after withdrawal.

Causes for Concern for Depressants: Toxicity

  • Behavioral Toxicity: Causes drunken-like intoxication with impaired judgment.

  • Physiological Toxicity: Produces respiratory depression; especially dangerous when combined with alcohol.

Patterns of Abuse of Depressants

  • Two typical abuser demographics:

    1. Older adults increasing dosage due to tolerance.

    2. Younger individuals using drugs recreationally.

Inhalants

Examples of Inhalants

  • Products containing inhalable solvents simulating depressant effects:

    • Gasoline

    • Glue

    • Paint

    • Lighter fluid

    • Spray cans

    • Nail polish remover

    • Liquid Paper

Gaseous Anesthetics

  • Abuse mainly among individuals with access; Nitrous oxide known as “laughing gas,” used for light anesthesia by dentists.

Nitrites

  • Amyl Nitrite:

    • First used for chest pain treatment; relaxes blood vessels; reduces blood pressure briefly with potential lightheadedness.

    • Other nitrites (Butyl, Isopropyl, Isobutyl) cause effects similar to Amyl Nitrite; found in cleaning products.

Volatile Solvents

  • Substances include:

    • Paint, paint thinners, paint removers, nail polish remover, glue, correction fluid.

    • Ingredients: Petroleum, acetone, toluene.

  • Modern era traced back to a 1959 article discussing solvent abuse; localized fads mostly among young users.

    • Usage statistics: 4.7% of eighth-graders, 1.9% of high-school seniors reported use in the past year.

Dangers of Inhaling Solvents

  • Linked to:

    • Kidney damage

    • Brain damage

    • Peripheral nerve damage

    • Respiratory tract irritation

    • Severe headaches

    • Risk of death by suffocation

Gamma Hydroxybutyric Acid (GHB)

  • Naturally occurring in the brain; structurally akin to GABA; a CNS depressant.

  • Behavioral effects resemble alcohol.

  • Scheduled as a Schedule I drug, except for Xyrem, used for narcolepsy symptoms.

Drug Enforcement Administration: Controlled Substances

  • Control schedules indicating potential for abuse and medical use:

    • Schedule I: High abuse potential, no medical use.

    • Schedule II: High abuse potential with severe restrictions on use.

    • Schedule III: Medium abuse potential, some medical use.

    • Schedule IV: Moderate abuse potential, some medical use.

    • Schedule V: Lowest abuse potential, with medical use permitted.