Depressants & Inhalants
(Ch. 8)

These prescription drugs all have a widespread effect in the brain that can be summed up as decreased neural activity. The behavioral effects are very similar to the effects of alcohol. At low doses these drugs might be prescribed for daytime use to reduce anxiety (as a sedative). At higher doses many of these same drugs are prescribed as sleeping pills (hypnotics). This grouip of prescription drugs is often referred to as sedative-hypnotics, part of a larger group of substances considered to be CNS depressants.

* the most widely used depressant is alcohol
* the most widely used prescribed types of sedative-hypnotics fall into the chemical grouping called the benzodiapezines, which in
   the past 30 years have replaced the barbiturates.

  1. Nonbarbiturates have a longer history than barbiturates but are less frequently used today
  2. The names of barbiturates always end with the letters "al"
  3. Barbiturates are grouped on the basis of the duration of their activity: short-acting, intermediate-acting, or long-acting (refer to Table 8.1 on page 167 of your textbook).
    1. In general, the drugs that are the most lipid-soluble are the ones that have both the shortest time of onset (i.e., they are absorbed and enter the brain rapidly) and the shortest duration of action (i.e., they leave the brain quickly and tend to be more rapidly metabolized).
    2. Sedatives are usually low dose of a long-acting barbiturate (like phenobarbital); and sleeping pills are usually of higher dose of a short-acting drug (such as amobarbital or secobarbital).
  4. Tolerance, psychological and physical dependence, and fatal overdose are possible drawbacks to barbiturates.
    1. Barbiturates are one of the classes of drugs that stimulate the activity of microsomal enzymes of the liver. Some of the tolerance that develops is the result of an INCREASED rate of deactivation caused by this stimulation.
    2. They depress respiration and, in large doses or in combination with alcohol, can completely stop one's breathing.
  5. Mechanism of Action: GABA (gamma amino butyric acid) receptor complex, which includes a barbiturate binding site and a benzodiazepine receptor. When these chemicals bind to their receptor respective receptor site, they enhance the normally inhibitory effects of of GABA on its receptors.
  2. Because of concerns of addiction liability and the danger of overdose, new sedative or hypnotic agents were accepted and utilized.
  1. Meprobamate, released in 1955, was the first modern antianxiety agent, was a revolutionary drug
  2. Benzodiazepines replaced meprobamate and were considered a safer substitute than barbiturates. Chlordiazepoxide (Librium) and Diazapam (Valium).
    1. In looking at the differences between barbiturates and so-called safer drugs (like benzodiazapines), we have learned that it is the dose and the time course of individual drugs that make the difference. A drug that has a rapid onset of action will be more likely to produce psychological dependence than a slow-acting drug. Physical dependence occurs when the drug leaves the system more rapidly than the body can adapt. - one way to reduce the severity of withdrawal symptoms is to reduce the dose of a drug slowly over time. Drugs with a shorter duration of action leave the system quickly and are much more likely to produce withdrawal symptoms than longer-acting drugs. There might be a greater difference among the bartiturates and among the benzodiazepines than there are between the two classes.
    2. Rohypnol (flunitrazipam) a benzodiazepine sold as a hypnotic in many countries but NOT the U.S.
  3. Methaqualone appeared in the late 1950ís and early 1960ís and was incorrectly viewed as safe, nonbarbiturate sleeping pill. Methaqqualone causes the same kind of motor incoordination as alcohol and the barbiturates.
  1. Reducing anxiety, not curing neurotic behavior, is the one primary purpose of these drugs. Most psychiatrists refer to the benzodiazepines as antiantiety agents (anxiolytics). For a typical general practitioner, about half of the patients have NO treatable physical ailment.
  2. Because of the possibility of tolerance, dependency, rebound insomnia, and hangover effects, the use of hypnotic drugs has decreased - they are usually taken for only a few nights at a time.
  3. Barbiturates and benzodiazepines are often used for the control of epileptic seizures
  1. Short-acting barbiturates are more likely to lead to dependency than benzodiazepines are
  2. Withdrawal syndrome can occur with any of the sedative-hypnotic drugs
  3. Withdrawal can be life threatening
  4. These drugs impair judgement and coordination
  5. Violence induced by barbiturates has been reported (especially when used with alcohol)
  6. Respiration rate is affected (respiration is depressed), sometimes to the point of respiratory failure
  7. Abuse usually occurs by an older person using these drugs for a long time for sedation or sleeping; or by a young person using these drugs to get high (using sleeping pills from home, etc.)
  2. High-dose exposure to these fumes makes users intoxicated, often slurring their speech and causing them to have trouble walking
  3. Because so many different sovents are involved, it is impossible to characterize the potential harm produced by abuse, except to say that several solvents have been linked to kidney damage, brain damage and peripheral nerve damage and many produce irritation to the respiratory tract and result in severe headaches. However, several users of various inhalants have suffocated as a result of this activity.
  1. Gaseous anesthetics, e.g., nitrous oxide, chloroform, ether, etc.
  2. Nitrates, e.g., isoamyl nitrite, butyl nitrite, etc.
  3. Volatile solvents, e.g., petroleum distillates, acetone, toluene, etc.
  4. Aerosols, e.g., nitrous oxide, butane, propane, etc.
  5. Use of inhalants is increasing