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Chapter 7

Depressants and Inhalants

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Depressants

A class of drugs that decrease CNS activity

Have a widespread effect in the brain

As a group, also called sedative-hypnotics

Sedatives treat anxiety

Hypnotics treat insomnia

Widely used depressants include:

Alcohol

Benzodiazepines (prescription)

Depressants

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Chloral hydrate

“knockout drops,” “Mickey Finn”

Synthesized in 1832; used clinically in 1870

Induces sleep in less than an hour

Repeated use leads to gastric irritation

Paraldehyde

Synthesized in 1829; used clinically in 1882

Effective with a wide safety margin

Noxious taste and odor

Bromides

Widely used as a sleep agent in patent medicines

Remained in OTC drugs through the 1960s

Accumulates in the body and cause toxic effects

History: Before Barbiturates

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First introduced in 1903

So popular and useful that over 2,500 examples were synthesized

Popular barbiturates included phenobarbital, amobarbital and secobarbital

Grouped based on the time of onset and duration of activity

Short-acting and rapid onset: used to induce sleep and often prescribed in high doses

Long-acting and delayed onset: used to reduce anxiety and often prescribed in low doses

Barbiturates

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Overdose deaths

Intentional and accidental

Caused by respiratory depression

Abuse and dependence

Reinforcing effects of a drug are related to the rapidity of onset of effects

Short-acting drugs are more likely to lead to psychological dependence

Concerns led to search for safer medications

Concerns About Barbiturates

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Widely prescribed beginning in the 1950s

Used as an anxiolytic

Like barbiturates, can produce psychological and physical dependence

Still available as a prescription drug

However, largely replaced by benzodiazepines

Meprobamate

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Other names:

Brand = Quaalude or Sopor

Slang = “ludes” or “sopors”

Despite problems in other countries, drug was introduced in the U.S. (1965)

Package insert read “Addiction potential not established.”

Physicians overprescribed, thinking the drug was a safe alternative to barbiturates

Widely misused and abused

Scheduling history:

1973: Schedule II

1985: Schedule I

Methaqualone

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Image source: National Archives (Image Ch07_04Methaqualone)

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First introduced in 1960:

Chlordiazepoxide (Librium), the first commercially marketed benzodiazepine

Reduces anxiety without inducing sleep

Much larger safety margin than barbiturates

Physical dependence was rare

Overdose was rare (only when combined with other depressants like alcohol)

1970s:

Diazepam (Valium) became the best seller among all prescription drugs

Benzodiazepines

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However, dependence and overdose can occur

Dose level and time course are critical factors

Overdose deaths more likely for drugs sold in higher doses

Psychological dependence more likely with drugs that have a rapid onset of effects

Physical dependence more likely with drugs that have a short duration of action

Are benzodiazepines safer than barbiturates?

More differences among drugs within each class

Fewer differences between these two classes of drugs

Benzodiazepines

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A 1990s version of “Mickey Finn”

Produces profound intoxication when mixed with alcohol

Reportedly used as a “date-rape” drug

Slipped into drinks

1997 change in the formulation causes a distinctive color when dissolved in a drink

However, rohypnol effects are not much different from effects of other CNS depressants

Benzodiazepines: Rohypnol

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“Z-drugs”

Similar to benzodiazepines but with a different chemical structure

Zolpidem (Ambien) became the most widely prescribed hypnotic

Short duration

Rapid onset

Initially thought to be safer than benzodiazepines

Withdrawal symptoms have been reported

Nonbenzodiazepine Hypnotics

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Benzodiazepines and barbiturates

Bind with receptors on GABA receptor complex

Separate binding site for barbiturates and benzodiazepines

Enhances the normally inhibitory effects of GABA

Nonbenzodiazepine hypnotics

Entirely new class of drugs that may selectively bind to different sites on the receptor complex

Mechanism of Action

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Anxiolytics

Sedatives often prescribed to reduce anxiety

Four benzodiazepines are among the top 100 most commonly prescribed medications in the United States

Xanax

Ativan

Klonopin

Valium

Beneficial Uses

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Image source: Ryan McVay/Getty Images (Image Ch07_08Anxiety)

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Sedatives are not appropriate for all anxiety disorders

Example: OCD or specific phobias

Overprescribed?

Most sedatives are not prescribed by psychiatrists

Most patients do not have a clearly defined anxiety disorder or physical ailment

Concerns: Anxiolytics

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Hypnotics (Sleeping Pills)

Sedatives (at large enough doses) decrease sleep onset time

About a third of American adults report trouble sleeping

Beneficial Uses

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Image source: Royalty-Free/Corbis (Image Ch07_09Insomnia)

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Concerns about the nonbenzodiazepine hypnotics include:

Sleepwalking

Sleep-eating

Driving while in a semi-waking state

In 2008, all hypnotic drugs were required to carry a safety label

Zolpidem-related ER visits more than tripled between 2005 and 2010

Concerns: Hypnotics

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Anticonvulsants

Barbiturates and benzodiazepines may be prescribed for seizure disorders (epilepsies)

Other anti-epileptic drugs are preferred but can be used in combination with barbiturates and benzodiazepines

Potential concerns

Tolerance can make it difficult to find a dose that is effective but doesn’t cause excessive drowsiness

Abrupt withdrawal is likely to cause seizures

Beneficial Uses

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Psychological dependence

Especially associated with short-acting sedatives

Physical dependence

Withdrawal syndrome is similar to alcohol and potentially life-threatening

Benzodiazepine withdrawal symptoms:

Common: anxiety, impaired concentration and memory, insomnia, nightmares, muscle cramps, increased sensitivity to touch and light

More severe: delirium tremens, delusions, and convulsions

Cross-dependence occurs among the barbiturates, the benzodiazepines, and alcohol

Dependence Liability

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Behavioral

Alcohol-like intoxication with impaired judgment and coordination

Additive effects if combined with alcohol

Physiological

Respiratory depression

Especially dangerous if combined with alcohol

Acute Toxicity

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Most abuse associated with oral use of legally manufactured products

Two types of typical abusers:

Older adults using prescription drugs who develop tolerance and increase their dosage

Younger people who obtain drugs to get high

may take high doses and/or mix with alcohol

Patterns of Abuse

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Examples of products that contain inhalable solvents

gasoline, glue, paint, lighter fluid, spray cans, nail polish, correction fluid

Effects similar to alcohol and other depressants

Inhalants

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Gaseous Anesthetics

Nitrous oxide, ether

Current and former medical anesthetics

Nitrites

Isoamyl, isobutyl

“Locker room,” “Rush,” “poppers”

Volatile solvents

Petroleum, acetone, toluene

Paint, paint thinner and remover, nail polish remover, correction fluid, glues

Examples of Inhalants

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Nitrous oxide was first used in the early 1800s

“laughing gas”

Still used for light anesthesia

especially by dentists

Used as a propellant for commercial and home whipping-cream dispensers

Gaseous Anesthetics

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Relaxes blood vessels

Increases blood flow and lowers blood pressure

Used as a treatment for cyanide poisoning

With high doses there maybe lightheadedness or faintness

1988 Anti-Drug Abuse Act listed several nitrites as controlled substances

Nitrites

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The modern era of solvent abuse can be traced back to 1959 investigative article

News articles and education programs demonstrated how to abuse volatile solvents

Use may have spread due to increased publicity

In general, abuse tends to occur as localized fads

Most users are very young

6% of 8th-graders reported past year use

3% of 12th-graders reported past year use

Volatile Solvents

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Several solvents have been linked to:

Kidney damage

Brain damage

Peripheral nerve damage

Irritation of the respiratory tract

Severe headache

Death by suffocation

Dangers of Inhaling Solvents

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GHB

Naturally-occurring chemical found in the brain and body

Structurally similar to the inhibitory neurotransmitter GABA

Is a CNS depressant

Behavioral effects similar to alcohol

Schedule I drug

Except for one formulation (Xyrem)

Reduces frequency of cataplexy (narcolepsy symptom)

Gamma Hydroxybutyric Acid

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