6 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
7 Effects of barbiturates at increasing doses forebrainhindbrain
10 Which of the following is NOT a term that refers to barbiturates in general? A. idiot pillsB. soft ballsC. pink ladiesD. golf ballsE. goofers
11 Depressants and Inhalants BarbituratesAvoid use with:AlcoholChloramphenicolChlorpromazineCyclophosphamideCyclosporinDigitoxinDoxorubicinAntiepilepticsAntihistaminesNarcotic analgesicsSteroidsAntidepressantsAntihypertensives,Anti-arrhythmics,DoxycyclineMethoxyfluraneMetronidazoleQuinineTheophyllineWarfarinBenzodiazepines
12 Depressants and Inhalants Other sedativesmethaqualone (Quaalude) and chloral hydratemethaqualone proved to have a high potential for abuse and has little clinical usefulness (insomnia) and is now a Schedule I drugchloral hydrate (“Mickey Finn”)insomnia, presurgical, dental sedativepentobarbital + chloral hydrate = Equithesin®
13 Depressants and Inhalants Benzodiazepineschlordiazepoxide (Librium)diazepam (Valium)used prior to surgery anddental procedures for theiranxiolytic and amnesicqualities
14 The Development of Antianxiety Drugs Benzodiazepinesefforts 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 anxietySleep-inducing effects of benzodiazepines especially subject to tolerance
16 The greatest cross-tolerance and cross-dependence develop between __________. A. heroin and amphetaminesB. heroin and LSDC. alcohol and cocaineD. alcohol and barbituratesE. benzodiazines and barbiturates
17 Taken alone, benzodiazepines are very safe drugs Taken alone, benzodiazepines are very safe drugs. However, they can be dangerous when taken in combination with alcohol.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 decadeodorless, colorless and tastelesssynergistic effects with alcoholamnesic propertiesnot approved for any medical use in the U.S.
18 Depressants and Inhalants Contemporary sleep aidszolpidem (Ambien)chemically unrelated to benzodiazepinesbinds to only 1 of 3 benzodiazepine receptor subtypeshas short-lived sedative effectsaddictive, sometimes abused with stimulantseszopiclone (Lunesta)binds to all 3 benzodiazepine receptor subtypeshas sedative effects similar to those of benzodiazepines
19 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).Ambien, Ambien CR(zolpidem tartrate)Butisol sodiumCarbrital (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)
20 Warning issued by Sepracor as part of the FDA approval for Lunesta After taking LUNESTA, you may get up out of bed whilenot being fully awake and do an activity that you do notknow you are doing. The next morning, you may notremember 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 sleepywith LUNESTA. Reported activities include:driving a car ("sleep-driving“) having sexmaking and eating food sleep-walkingtalking on the phoneCall your doctor right away if you find out that you have done any of the above activities after taking LUNESTA.
21 Activities that have been reported to occur while sleeping after taking Lunesta include A. having sexB. driving a carC. shopping naked at the mallD. cooking and eatingE. making phone calls
22 Depressants and Inhalants buspirone (BuSpar)chemically related to benzodiazepinesdoes not act at GABA receptorslittle cross-tolerance with alcohol, other depressantsnot anti-convulsant or muscle relaxantaffinity for 5-HT1A receptors and some DA receptorspharmacological actions complexanxiolytic effects develop slowly (weeks)does not have sedative effectsused for generalized anxiety disorder (GAD)
23 Depressants and Inhalants β-blockersused to treat hypertensionblock sympathetic β-adrenergic receptors of heartuseful for transient treatment for autonomic effectsof anxiety
24 The disadvantage in treating anxiety with buspirone is that __________. A. it shows cross-tolerance with alcoholB. it shows cross-dependence with alcoholC. it has very troublesome side effectsD. there is a long delay before anxiety is relievedE. It is not very useful for GENERALIZED anxiety.
25 Depressants and Inhalants GHB (γ-hydroxybutyrate)“date rape” drug—colorless, odorless, tastelessbinds to GABAB receptor subtype (GABA metabolite)approved by FDA in 2002 for treatment of narcolepsynow a Schedule I drugalso has anabolic (protein-building) effectsCNS and Behavioral effects of GHB:euphoria; dissociation; drowsiness; nausea; headache; disorientation; loss of coordination; memory lossin combination with alcohol, produces unconsciousness
26 Depressants and Inhalants Barbiturates (major tranquilizers)“sleeping pills” and anestheticsOther sedativesmethaqualone and chloral hydrateBenzodiazepines (minor tranquilizers)anxiolyticsContemporary sleep aidsβ-blockersGHB (γ-hydroxybutyrate)“date rape” drug
27 Depressants and Inhalants nitrous oxide (N2O)analgesic, “laughing gas”first investigated in 1798a major recreational drug in the early 1800s“laughing gas parties” in Great Britainsometimes classified as a dissociative substanceN2O is still used recreationally (Whippets)non-toxic, but can result in hypoxia leading to deathnot addictiveclinical application is for routine dental anesthesiacomplex pharmacologyeuphoric effects may be due to NMDA receptor blockade
28 Depressants and Inhalants etherused as a substitute for alcohol during temperance and prohibition movementsused as an anesthetic—first general anestheticdiscontinued as better, safer anesthetics discoveredused as automotive starter fluidreports of ether dependence, but without withdrawaltolerance, craving and complete loss of interestin social contacts and other activities
29 Depressants and Inhalants glues, solvents and propellantseasily obtained, cheap, legal, abuse easily disguisedoften associated with adolescents (11-13 yrs), poormost are very toxiccarcinogenicliver damagedangers of hypoxia, aspiration of vomit, heart failuregenerally do not produce dependence or withdrawalGateway? (He huffed, then he puffed, then he did blow.)