Update on Anxiolytics and Hypnotics Lynn Osako University of California, San Francisco

Chapman University Chapman University Digital Commons Pharmacy Faculty Articles and Research School of Pharmacy 1992 Update on Anxiolytics and Hypnotics Lynn Osako University of California, San Francisco Mary Gutierrez Chapman University, [email protected] Michael Z. Wincor University of Southern California Follow this and additional works at: http://digitalcommons.chapman.edu/pharmacy_articles Recommended Citation Osako L, Gutierrez MA, Wincor M. Update on anxiolytics and hypnotics. Calif Pharmacist. 1992:32-37. This Article is brought to you for free and open access by the School of Pharmacy at Chapman University Digital Commons. It has been accepted for inclusion in Pharmacy Faculty Articles and Research by an authorized administrator of Chapman University Digital Commons. For more information, please contact [email protected]. Update on Anxiolytics and Hypnotics Comments This article was originally published in California Pharmacist in 1992. Copyright California Pharmacists Association This article is available at Chapman University Digital Commons: http://digitalcommons.chapman.edu/pharmacy_articles/488 "' JOURNAL CE------------------------------------------~ • Lynn Osako, Pharm.D, History Mary Gutierrez, Pharm.D. and Michael Wincor, Pharm.D. Agents to produce sleep, called hypnotics, have been around thousands of yeats. Evidence shows that poppy plants were used as the first hypnotics sorne two-thousand yeats ago. The old est hypnotic agent is chloral hydrate. Its popularity waned when the barbiturates came along but has become more popu lar in the last few decades. 1 It is less effective than flurazepam and tolerance toits effects develops rapidly.2 The bromides were introduced in the mid-1800s. Problems with these agents Update on include the ir extremely long half-life of about 12 days, their low therapeutic in dex and irritation to the Gl system.1 anxiolytics and Early in the 20th century, barbitu rates were introduced and quickly be came popular hypnotic agents. These hypnotics agents have numerous adverse reactions such as respiratory depression, nausea and vomiting, circulatory collapse and severe depression of the CNS. Barbitu rates have become associa red with abuse and overdose, and drug withdrawal can also be a serious problem. A chronic user of barbiturates, upon withdrawal, may Goal experience irritability, insomnia and, in serious cases, convulsions and death.1 The goal of this article is to educate pharmacists on the new er anxiolytic and hypnotic agents. Other nonbarbiturate-nonbenzo diazepines indude piperidinediones su ch Objectives as glutethimide and methyprylon, ethchlorvynol, methaqualone and mep After reading this article, the pharmacist shouid be able to: robamate. Ali of these agents have prob lems similar to those of the barbiturates, • Discuss the advantages of the new hypnotics and anxiolytics over specifically physical dependence and 1 3 previous agents. overdose potential. • • Discuss possible adverse effects and drug interactions of the new Benzodiazepines were a major break hypnotics and anxiolytics. through in sedative-hypnotics and have become the most frequently prescribed • Recommend one of the newer agents as an alternative to more conven drugs in the U.S. Their main advantage tionai therapy when appropriate. over previous agents are their higher therapeutic index. T aken alone, these agents rarely cause death and produce 1 3 Provided by an educational grant from little respiratory depression. • Physical dependence has become their major problem, however. 1 Drug therapies of anxiety states are a 32 • CALIFORNIA PHARMACIST • NOVEMBER 1992 JOURNAL CE fairly recent development. Although hypertensive crisis, which can occur epines in itschemical and pharmacologie anxiety states were recognized in the when the patient on an MAOI eats food properties. It was first introduced in 1985 19th cenrury, most therapy revolved rich in tyramine (aged cheese, red wine, in West Germany and is the first drug around psychotherapy.4 A variety of sherry, beer, smoked meats orfish, etc.) developed primarily as an anxiolytic.4 drugs in different pharmacological classes and uses sympathomimetics or stimu are now used to treat the anxiety disor lants. Another disadvantage is that it Pharmacology. Unlike the benzodi ders. Alcohol is commonly used to self takes weeks for a noticeable effect to azepines, buspirone actually increases rreat situational anxiety; however, it is occur.5 noradrenergic activity. Buspirone's never a treatment of choice, 5 and alco mechanism of action is not completely holism has become a complication of lmipramine is the tricyclic amide understood, but it apparently does not many anxiety disorders. z pressant (TCA) most commonly used involve action on the benzodiazepine for treating panic disorder, while other gamma aminobutyric acid-chloride ( BZ 1 When barbiturates came along, they TCAs su ch as desipramine are occasion GABA-Cl) ionophore camp lex. It binds were not only used as hypnotics, but also ally used.5 Like the MAOis, weeks of selectively ta 5-HT lA receptors, and this used to treat anxiety.2 Barbiturates are therapy are required before a response is most likely where the majority of its not, however, specifie anxiolytics and occurs. Their anticholinergic side ef have the disadvantages discussed ear fects are more pronounced than with the Her. MAOls and may cause psychotic reac 2 5 • tions, especially in the elderly. • TCAs Antihistamines are used occasionally can also cause orthostatic hypotension, The major and are especially good for patients with tachycardia and decreased cardiac con 5 6 2 5 a high propensity for drug abuse. • The duction. • T oxicity is another serious disadvantage for ali anticholinergic effects of these agents problem with these patients, and a few the hypnotics and for are their primary disadvantage, espe· week's supply can easily cause death. cîally in the elderly in whom central most of the anxiolytics effects such as confusion and hallucina Benzodiazepines, as mentioned car is their potential for tions may also occur.5 lier, are the most commonly prescribed drugs in the U.S. Anxiery syndromes physical dependence. Beta-adrenergic blocking agents are make up a large percentage of those For those anxiolytics used primarily to alleviate the physical prescriptions, and benzodiazepines can symptoms of stress. These agents are be used in ali different types of anxiety without addictive nonspecific and rarely are helpful in disorders. Their advantages and disad potential, the primary psychiatrie patients.4 Clonidine is also vantages are mentioned above in the used to treat anxiety; however, its side discussion on hypnotics. problems are adverse effects of hypotension, depression and effects and toxicity. fatigue have limited its use.5 The need for newer agents Antipsychotics were used more fre Although the above-mentioned quently for anxiety attacks in the past. agents are effective against anxiety and They are less commonly used for thar insomnia, each has its own problems. anxiolytic activity is produced. 7 These purpose now because of their question The major disadvantage for all the receptors are localized in areas of the able efficacy and the ir high potential for hypnotics and for most of the anxiolytics CNS which may explain its more favor adverse effects su ch as tardive dyskinesia is their potential for physical depen able adverse effect profile versus the and extrapyramidal effects. 4•6 dence. For those anxiolytics without benzodiazepines. Buspirone does not addictive potential, the primary prob share the anticonvulsant and muscle Antidepressants, however, continue lems are adverse effects and toxicity. relaxant properties of the benzodiaz to be used and have shawn efficacy in Therefore, the search goes on for drugs epines and exhibits anxiolytic effects certain anxiety states. In the early 1960s with specifie actions, few side effects, a only.7 monamine oxidase inhibitors (MAOls) high therapeutic index and no addictive were found to be effective for panic potential. Pharmacokinetics. Buspirone is ab disorder.6 Phenelzine is most commonly sorbed rapidly and completely from the used, and studies have proven its effec Buspirone (Buspar®) 01 system. After undergoing first-pass tiveness in panic disorder.5 Side effects metabolism only 4% of the drug reaches include orthostatic hypotension, weight Buspirone is a relatively new drug the systemic circulation.5 The onset of gain, sexual dysfunction, edema and which is unique from the beruodiaz- action of buspirone is considerably de- NOVEMBER 1992 • CALIFORNIA PHARMACIST • 33 JOURNAL CE--------------------------------------------~ layed and occurs sometime during the should be a 10-day washout after MA01 This is probably due to its long onset of first three weeks of therapy; therefore, it use before buspirone therapy is initi action and because buspirone does not cannat be used for short-term or as ated. 8 There have be en reports of eleva alleviate the withdrawal symptoms of needed treatment. The distribution of tions in ALT concentrations with con benzodiazepines. buspirone is not completely known. The comitant buspirone and trazodone use. apparent volume of distribution is about However, this remains unconfirmed in Dosing and administration. 5.3 L/kgJ It is 95% bound to plasma studies. As long as liver function tests Buspirone is only available orally. The proteins,5 mostly to albumin and a 1- are monitored, the manufacturer daims starting dose is 10-15

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