Kaplan + Sadock's Synopsis of Psychiatry, 11e

29.4  b -Adrenergic Receptor Antagonists

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Table 29.3-2 a 2 -Adrenergic Receptor Agonists Used in Psychiatry a

Usual Child Starting Dosage

Usual Child Dosage Range

Usual Adult Starting Dosage 0.1–0.2 mg, two to four times a day (0.2–0.8 mg/day) 0.1 mg/day every 7 days

Drug

Preparations

Usual Adult Dosage

Clonidine tablets (Catapres)

0.1, 0.2, 0.3 mg

0.05 mg/day

Up to 0.3 mg/day tablets in divided doses

0.3–1.2 mg/day, two to three times a day (1.2 mg/day maximal dosage) 0.1 mg/day patch per week 0.6 mg/day every 7 days

Clonidine

0.1, 0.2, 0.3 mg/day

0.05 mg/day

Up to 0.3 mg/day patch every 5 days (0.5 mg/day every 5 days maximal dosage) 1–2 mg/day at bedtime (3 mg/day maximal dosage)

transdermal system (Catapres-TTS)

Guanfacine (Tenex)

1- and 2-mg tablets

1 mg/day at bedtime

1 mg/day at bedtime

1–2 mg at bedtime (3 mg/day maximal dosage)

a Dosages for medical indications, such as hypertension, vary.

in dose of drug. Prazosin should not be used in nursing mothers or during pregnancy.

Ming X, Gordon E, Kang N, Wagner GC. Use of clonidine in children with autism spectrum disorders. Brain Dev. 2008;30(7):454. Myers SM. The status of pharmacotherapy for autism spectrum disorders. Expert Opin Pharmacother. 2007;8(11):1579. Sallee F, Connor DF, Newcorn JH.A review of the rationale and clinical utilization of 2-adrenoceptor agonists for the treatment of attention-deficit/hyperactivity and related disorders. J Child Adolesc Psychopharmacol. 2013;23(5):308– 319.

Drug Interactions No adverse drug interactions have been reported.

Laboratory Interferences No laboratory interferences have been reported.

▲▲ 29.4 b -Adrenergic Receptor Antagonists

Dosage and Clinical Guidelines The drug is supplied in 1-, 2-, and 5-mg capsules and a nasal spray. The therapeutic dosages most commonly used have ranged from 6 to 15 mg daily given in divided doses. Doses higher than 20 mg do not increase efficacy. When adding a diuretic or other antihypertensive agent, the dose should be reduced to 1 or 2 mg three times a day and retitration then carried out. Concomitant use with a PDE-5 inhibitor can result in additive BP lowering effects and symptomatic hypotension; therefore, PDE-5 inhibitor therapy should be initiated at the lowest dose in patients taking prazosin. Table 29.3-2 provides a summary of a 2 -adrenergic receptor agonists used in psychiatry. R eferences Arnsten AFT, Li B. Neurobiology of executive functions: Catecholamine influ- ences on prefrontal cortical functions. Biol Psychiatry. 2005;57:1377. Biederman J, Melmed RD, Patel A, McBurnett K, Konow J, Lyne A, Scherer N. A randomized, double blind, placebo-controlled study of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder. Pediatrics. 2008;121(1):e73–e84. Boehlein JK, Kinzie JD. Pharmacologic reduction of CNS noradrenergic activity in PTSD: The case for clonidine and prazosin. J Psychiatr Pract. 2007;13:72. Hollander E, Petras JN. a 2 -Adrenergic receptor agonists: Clonidine and guanfa- cine. In: Sadock BJ, Sadock VA, Ruiz P, eds. Kaplan & Sadock’s Comprehen- sive Textbook of Psychiatry. 9 th ed. Vol. 2. Philadelphia: Lippincott Williams & Wilkins; 2009:3004. Karachalios GN, Charalabopoulos A, Papalimneou V, Kiortsis D, Dimicco P. With- drawal syndrome following cessation of antihypertensive drug therapy. Int J Clin Pract. 2005;5:562. Kornfield R, Watson S, Higashi AS, Conti RM, Dusetzina SB, Garfield CF, Dorsey ER, Huskamp HA, Alexander GC. Effects of FDA advisories on the pharma- cologic treatment of ADHD, 2004–2008. Psychiatr Serv. 2013;64(4):339–346. Marsch LA, Bickel WK, Badger GJ, Stothart ME, Quesnel KJ. Comparison on pharmacological treatments for opioid-dependent adolescents: A randomized controlled trial. Arch Gen Psychiatry. 2005;62:1157.

Because of the innervations of many, if not most, periph- eral organs and vasculature by the sympathetic division of the autonomic nervous system, their functions are ultimately controlled, in part, by one of the two major classes of adren- ergic receptors: a -receptors (discussed in Section 29.3) and b -receptors. These receptors are further subdivided based on their action and location, and they are located both peripher- ally and in the central nervous system (CNS). Shortly after being introduced for cardiac indications, propranolol (Inderal) was reported to be useful for agitation, and its use in psychia- try spread rapidly. The five most commonly used b -receptor antagonists in psychiatry are propranolol, nadolol (Corgard), metoprolol (Lopressor, Toprol), pindolol (Visken), and atenolol (Tenormin) (Table 29.4-1). Pharmacologic Actions The b -receptor antagonists differ with regard to lipophilicities, metabolic routes, b -receptor selectivity, and half-lives. The absorption of the b -receptor antagonists from the gastrointes- tinal tract is variable. The agents that are most soluble in lipids (i.e., are lipophilic) are likely to cross the blood–brain barrier and enter the brain; those agents that are least lipophilic are less likely to enter the brain. When CNS effects are desired, a lipo- philic drug may be preferred; when only peripheral effects are desired, a less lipophilic drug may be indicated. Whereas propranolol, nadolol, pindolol, and labetalol (Nor- modyne, Trandate) have essentially equal potency at both the