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Psychology 321 - Substance Abuse - Lecture Outline
Depressants, Sedatives & Inhalants - Notes
Overview of Topics
Depressants, Sedatives & Inhalants
Overall history of depressants, sedatives & inhalants Tolerance, Dependence, and Adverse Effects Pharmacokinetics of Barbiturates and Benzodiazepines Pharmacodynamics of Barbiturates and Benzodiazepines Psychology 321 - Substance Abuse - Lecture Outline
Depressants, Sedatives & Inhalants - Notes
With the exception of alcohol, depressant drugs were discovered or developed in response to medical needs to sedate or anesthesize patients.
Synthesized by Joseph Priestly and Humphrey Davy in 1776.
Intoxicating effects were immediately noted, and people would pay a fee to experience the effects. A dentist, Horace Wells attended a demonstration and noticed that one of the staggering participants cut himself and did not seem to feel the pain.
1845, Dr. Horace Wells, a Boston dentist failed to show its anesthetic effects in front of a group of physicians at Massachusetts General Hospital. He had not experimented enough with the drug to establish effective doses. The patient woke up during the surgical procedure Psychology 321 - Substance Abuse - Lecture Outline
Depressants, Sedatives & Inhalants - Notes
William Morton, another Boston dentist, knew of Well’s failed attempt.
Ether was already known as an intoxicant, so Morton experimented with it, established effective doses, and demonstrated its anesthetic effects during surgery at Massachusetts General Hospital, in1846, a year after Everyone was ready and waiting , including the strong men to hold down the struggling patient, but Mortondid not appear. Fifteen minutes passed, and the surgeon, becoming impatient, took his scalpel and turningto the gallery said, “As Dr. Morton has not arrived I presume he is otherwise engaged.” While the audiencesmiled and the patient cringed, the surgeon turned tho make his incision. Just then Morton entered . [thesurgeon] said, “Well, sir, your patient is ready.” Surrounded by a silent and unsympathetic audience,Morton went quietly to work. After a few minutes of ether inhalation, the patient was unconscious,whereupon Morton looked up and said, “”Dr. Warren, your patient is ready.” The operation was begun. The patient showed no sign of pain, yet he was alive and breathing. The strong men were not needed. When the operation was completed. Dr. Warren turned to the astonished audience and made the famousstatement “Gentlemen, this is no humbug” (pp 258-259).
Cooperman and Wollman (1980) Psychology 321 - Substance Abuse - Lecture Outline
Depressants, Sedatives & Inhalants - Notes
Barbiturates
Synthesized in 1862 in the Bayer labs in Germany from components of urine.
Some say the name Barbiturates originated from a woman named ‘Barbara’ who donated urine (Barbara’s urates?). Others say the discovery took place on St.
Classed by chemical structure, there have been over 2000 related substances developed from the parent barbital. Traditionally all brand and generic names for Barbiturates end with the suffix - “al”.
The effects of these related substances are similar, differing mainly in their First marketed as Veronal in 1903, the use of barbiturates increased until the early 1960's when diazepam was introduced, then use quickly decreased. Psychology 321 - Substance Abuse - Lecture Outline
Depressants, Sedatives & Inhalants - Notes
Barbiturates - Continued
At moderate doses they induce a drunken state.
Like ETOH, they induce loss of motor control, staggering gait, and slurred speech.
At higher doses, they sedate and induce sleep.
Higher doses produce surgical anesthesia.
Coma and death result from higher doses, usually from respiratory arrest.
Short-acting barbiturates are used as anesthetics.
Longer-acting barbiturates are used to treat epilepsy.
Psychology 321 - Substance Abuse - Lecture Outline
Depressants, Sedatives & Inhalants - Notes
Barbiturates - Continued
Tolerance, Dependence, and Adverse Effects Tolerance with an associated withdrawal syndrome develops very quickly to the barbiturates. This is the main reason that they are not used medically for their anxiolytic and sedative properties today.
Mild DTS, shakes, insomnia rebound, REM rebound DTS with an increased risk of convulsions and seizures Low therapeutic index and high risk of overdose.
Barbiturates exert a euphoric effect similar to alcohol and became a significant recreational drug in the 1950s and 1960s.
Accidental overdose is relatively common.
Accidental overdose occurs much more frequently when Barbiturates are taken with Alcohol or other depressants because one often potentiates the Psychology 321 - Substance Abuse - Lecture Outline
Depressants, Sedatives & Inhalants - Notes
Nonbarbiturate Depressants
Several nonbarbiturate sedatives were developed and introduced in the 1950s and 1960s as possible alternatives to the Barbiturates.
Quaalude was first thought to be safer than most Barbiturates, it turned out to be quite toxic at high doses, with a quickly developed tolerance, and withdrawal similar to Alcohol and Barbiturates. Moreover, it produces a highly reinforcing drunkenness which made it a very popular drug of abuse in the 1970s.
Eventually, Quaalude was made a Schedule I drug and is not currently available in the US Other nonbarbiturates have similar properties and problems as the barbiturates.
Their high abuse potential and limited medical use, result in rare use.
Psychology 321 - Substance Abuse - Lecture Outline
Depressants, Sedatives & Inhalants - Notes
Benzodiazepines
Developed to treat severe anxiety (anti-anxiety or anxiolytic) and as a sleep aid (sedative) Freud considered anxiety, part of normal psychological functioning.
However, when severe anxiety interferes with daily functioning, people seek Autonomic hyperactivity (sweating,, pounding heart) Apprehensive expectation (fear, rumination) Vigilance (hyperstartle, impatience, insomnia) Most often managed with benzodiazepines (anxiolytics, tranquilizers).
Less often but more effectively treated with behavior therapy.
Psychology 321 - Substance Abuse - Lecture Outline
Depressants, Sedatives & Inhalants - Notes
Benzodiazepines - Continued
Developed in the Roche Labs in the late 1950s.
Animal testing showed sedative, anticonvulsant, and muscle-relaxant effects similar to those of the Barbiturates.
In addition, it showed a ‘taming’ effect in monkeys (anti-anxiety?).
Even better, it showed a low toxicity with a LD50 difficult to achieve.
Librium (chlordiazepoxide) first marketed in 1960.
Today benzodiazepines are consistently in the top ten most prescribed drugs in the Longer-acting benzodiazepines are used to manage anxiety at low doses that do Shorter-acting benzodiazepines that are metabolized before morning are used as Used in management of withdrawal from ETOH.
Used in milder cases of seizure disorders for anticonvulsant properties.
Used as an anesthesia in dental surgery.
Psychology 321 - Substance Abuse - Lecture Outline
Depressants, Sedatives & Inhalants - Notes
Benzodiazepines - Continued
Functional tolerance develops relatively slowly to benzodiazepines compared to barbiturates, and it tends to develop only at higher doses.
Cross-tolerance to other depressants develops.
An abstinence syndrome is associated with cessation of chronic benzodiazepine use similar to withdrawal from other depressants.
However, withdrawal from benzodiazepines tends to have a delayed onset (2-3 days), and may last a fairly long time (several weeks).
Anterograde Amnesia is often seen with the use of Benzodiazepines. This is similar to the blackouts experienced by the effects of alcohol.
All of the drugs used to treat anxiety disorders cause side effects of some sort. Thus, the search for saferanti-anxiety drugs has been a major goal of psychopharmacology. Recently a new drug was brought to themarket by Bristol-Myers called “BuSpar” (generic name, Buspirone). Buspirones’s chemical structure andactivity are very different from any of the traditional anxiolytic drugs but, in spite of the differences, itappears to relieve anxiety symptoms much like the benzodiazepines. No withdrawal symptoms have beenreported following chronic use of buspirone, and it is considered to have a very low abuse potential. Forexample, animals will not self-administer buspirone, and humans report no intoxication or euphoria aftertaking it. Virtually no sedation or motor impairment has been shown during buspirone treatment , and itdoes not produce synergistic effects with alcohol or other depressant drugs. Buspirone seems to relieveanxiety without producing any of the undesirable side effects of the other anxiolytic drugs. Buspirone is anew drug and more research is needed to determine whether it really works as well as the benzodiazepines,and whether it may produce side effects that have yet to be determined. We still do not know exactly whatis responsible for buspirones’ anxiolytic actions. BuSpar appears to affect the serotonin neurotransmittersystem, and unlike benzodiazepines does not show direct action on the GABA system. Regardless of howBuSpar works, the increase in prescriptions for it suggests that we are entering a new era in the treatment ofanxiety disorders.
Psychology 321 - Substance Abuse - Lecture Outline
Depressants, Sedatives & Inhalants - Notes
Pharmacokinetics of Barbiturates and Benzodiazepines
Usually taken orally, but may be administered intravenously.
Mostly eliminated by the bladder in urine.
Pharmacodynamics of Barbiturates and Benzodiazepines
Benzodiazepines and barbiturates work by stimulating the GABA - the major inhibitory - neurotransmitter system. However, they work at two independent Current thought is that benzodiazepines mimick a naturally occurring neural transmitter that mediates fear and anxiety.
The discovery of a drug (FG7142) that are antagonists at the benzodiazepine receptor site, blocks the effects of benzodiazepines and exerts opposite effects of its own (called an inverse agonist) appears to support the evidence for the mechanism of action for benzodiazepines.
When given to animals and three humans, FG7142 produced convulsions, The different benzodiazepines basically vary in duration of effect which Psychology 321 - Substance Abuse - Lecture Outline
Depressants, Sedatives & Inhalants - Notes
Inhalants
A mixed bag of substances that have the route of administration and the fact that they Some are used medically such as nitrous oxide and halothane as anesthetics.
The nitrite inhalants - Amyl, Butyl, and Isopropyl Nitrite - dilate cerebral blood vessels, producing a brief period of euphoria and dizziness.
Amyl also dilates coronary arteries, and was once prescribed to patients suffering from angina in the form of ampules that were crushed and inhaled All of the different Nitrites are often sold over the counter or through mail-order sources, for the putative use of room deodorizers, under brand names like “Rush” and “Locker Room” (they smell like dirty socks). Nitrites are often marketed to the gay community in particular, but also to heterosexuals, to prolong and intensify sexual activities.
Nitrites have been shown to produce side effects such as headaches, tachycardia, eye problems, and rare sudden deaths.
Psychology 321 - Substance Abuse - Lecture Outline
Depressants, Sedatives & Inhalants - Notes
Inhalants - Continued
However, most inhalant use is in the form of solvents glues and solvents such as gas (auto fuel), acetone (nail polish remover), butane (lighter fluid) and spray paint (propane) Solvent use is predominantly by children and chronic homeless substance abusers and is of epidemic proportions in third world nations.
Inhaling glue and/or solvents is one of the faster methods (short of blunt trauma)

Source: http://www.ucs.louisiana.edu/~deg8396/classes/psy321/depress.pdf

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