Barbiturates (major tranquilizers) A major disadvantage of barbiturates is the potential of a lethal overdose, particularly when the barbiturate is combined with other depressants such as alcohol. In addition, barbiturate withdrawal symptoms are very severe and require careful medical attention. Barbiturates of very limited usefulness as sleeping agents because the “sleep” produced is more akin to unconsciousness than normal sleep. there are also undesirable “hangovers” in the short term addictive and result in alcohol-like withdrawal symptoms in the long term
Effects of barbiturates at increasing doses forebrain hindbrain
Which of the following is NOT a term that refers to barbiturates in general? A. idiot pills B. soft balls C. pink ladies D. golf balls E. goofers
Depressants and Inhalants Other sedatives methaqualone (Quaalude) and chloral hydrate methaqualone proved to have a high potential for abuse and has little clinical usefulness (insomnia) and is now a Schedule I drug chloral hydrate (“Mickey Finn”) insomnia, presurgical, dental sedative pentobarbital + chloral hydrate = Equithesin® Depressants
Depressants and Inhalants Benzodiazepines Depressants chlordiazepoxide (Librium) diazepam (Valium) used prior to surgery and dental procedures for their anxiolytic and amnesic qualities
The Development of Antianxiety Drugs efforts in the 1950s focused on developing an anxiolytic that was not a general depressant (sedative). Meprobamate (Miltown) was the first in 1955 for this purpose, although its effects resulted more from its sedative properties than from its ability to relieve anxiety. Librium (1960) and Valium (1963) (benzodiazepines) were the first to selectively reduce anxiety Sleep-inducing effects of benzodiazepines especially subject to tolerance Benzodiazepines
The greatest cross-tolerance and cross- dependence develop between __________. A. heroin and amphetamines B. heroin and LSD C. alcohol and cocaine D. alcohol and barbiturates E. benzodiazines and barbiturates
Social problems related to benzodiazepine drugs during the 1970s centered on the widespread misuse of the drug. Prescriptions were written too frequently and for excessive dosages. flunitrazepam (Rohypnol; “roofies”) emerged as a date rape drug in the last decade odorless, colorless and tasteless synergistic effects with alcohol amnesic properties not approved for any medical use in the U.S. Taken alone, benzodiazepines are very safe drugs. However, they can be dangerous when taken in combination with alcohol.
Depressants and Inhalants Depressants Contemporary sleep aids zolpidem (Ambien) chemically unrelated to benzodiazepines binds to only 1 of 3 benzodiazepine receptor subtypes has short-lived sedative effects addictive, sometimes abused with stimulants eszopiclone (Lunesta) chemically unrelated to benzodiazepines binds to all 3 benzodiazepine receptor subtypes has sedative effects similar to those of benzodiazepines
Ambien, Ambien CR(zolpidem tartrate) Butisol sodium Carbrital (pentobarbital and carbromal) Dalmane (flurazepam hydrochloride) Doral (quazepam) Halcion (triazolam) Lunesta (eszopiclone) Placidyl (ethchlorvynol) Prosom (estazolam) Restoril (temazepam) Rozerem (ramelteon) Seconal (secobarbital sodium) Sonata (zaleplon) FDA’s list of sedative-hypnotics (sleep aids) that carry a risk of sleep- driving, defined as driving while not fully awake and with no memory of the event (blackout driving).
After taking LUNESTA, you may get up out of bed while not being fully awake and do an activity that you do not know you are doing. The next morning, you may not remember that you did anything during the night. You have a higher chance for doing these activities if you drink alcohol or take other medicines that make you sleepy with LUNESTA. Reported activities include: driving a car ("sleep-driving“)having sex making and eating food sleep-walking talking on the phone Call your doctor right away if you find out that you have done any of the above activities after taking LUNESTA. Warning issued by Sepracor as part of the FDA approval for Lunesta
Activities that have been reported to occur while sleeping after taking Lunesta include A. having sex B. driving a car C. shopping naked at the mall D. cooking and eating E. making phone calls
Depressants and Inhalants Depressants buspirone (BuSpar) chemically related to benzodiazepines does not act at GABA receptors little cross-tolerance with alcohol, other depressants not anti-convulsant or muscle relaxant affinity for 5-HT 1A receptors and some DA receptors pharmacological actions complex anxiolytic effects develop slowly (weeks) does not have sedative effects used for generalized anxiety disorder (GAD)
Depressants and Inhalants Depressants β-blockers used to treat hypertension block sympathetic β-adrenergic receptors of heart useful for transient treatment for autonomic effects of anxiety
The disadvantage in treating anxiety with buspirone is that __________. A. it shows cross-tolerance with alcohol B. it shows cross-dependence with alcohol C. it has very troublesome side effects D. there is a long delay before anxiety is relieved E. It is not very useful for GENERALIZED anxiety.
Depressants and Inhalants Depressants GHB (γ-hydroxybutyrate) “date rape” drug—colorless, odorless, tasteless binds to GABA B receptor subtype (GABA metabolite) approved by FDA in 2002 for treatment of narcolepsy now a Schedule I drug also has anabolic (protein-building) effects CNS and Behavioral effects of GHB: euphoria; dissociation; drowsiness; nausea; headache; disorientation; loss of coordination; memory loss in combination with alcohol, produces unconsciousness
Depressants and Inhalants Barbiturates (major tranquilizers) “sleeping pills” and anesthetics Benzodiazepines (minor tranquilizers) anxiolytics Other sedatives methaqualone and chloral hydrate Depressants Contemporary sleep aids GHB (γ-hydroxybutyrate) “date rape” drug β-blockers
Depressants and Inhalants Inhalants N 2 O is still used recreationally (Whippets) non-toxic, but can result in hypoxia leading to death not addictive clinical application is for routine dental anesthesia complex pharmacology euphoric effects may be due to NMDA receptor blockade nitrous oxide (N 2 O) analgesic, “laughing gas” first investigated in 1798 a major recreational drug in the early 1800s “laughing gas parties” in Great Britain sometimes classified as a dissociative substance
Depressants and Inhalants Inhalants ether used as a substitute for alcohol during temperance and prohibition movements used as an anesthetic—first general anesthetic discontinued as better, safer anesthetics discovered used as automotive starter fluid reports of ether dependence, but without withdrawal tolerance, craving and complete loss of interest in social contacts and other activities
Depressants and Inhalants Inhalants glues, solvents and propellants easily obtained, cheap, legal, abuse easily disguised often associated with adolescents (11-13 yrs), poor most are very toxic carcinogenic liver damage dangers of hypoxia, aspiration of vomit, heart failure generally do not produce dependence or withdrawal Gateway? (He huffed, then he puffed, then he did blow.)