Guanabenz, effect

Inability to gain acceptance on the U.S. market has not discouraged all efforts in this field and three other clinically effective drugs have been studied extensively, namely guanadrel (Upjohn, LVIII), guanabenz (Wyeth, LIX) and guancydine (Lederle LX). 

Guanabenz and guanfacine are centrally active antihypertensive drugs that share the central -adrenoceptor-stimulating effects of clonidine. They do not appear to offer any advantages over clonidine and are rarely used. 

Guanabenz (Wytensin). Guanabenz is used primarily to decrease blood pressure via its effect on alpha-2 receptors in the brainstem. This drug is similar to clonidine in efficacy and clinical use. 

Methyldopa (Aldomet). Methyldopa has been used as an antihypertensive drug for some time, but its mechanism of action is poorly understood. Currently, methyldopa is believed to exert its effects by being converted to alpha-methylnorepinephrine in the body.26 Alpha-methylnorepinephrine is a potent alpha-2 agonist that lowers blood pressure by stimulating inhibitory central adrenergic receptors in a manner similar to clonidine and guanabenz. 

Clinical data on BS-lOO-l l (2)(Sandoz) are now readily available. 2, 25 The compound is as effective an antihypertensive in man as clonidine but ten times less potent. Sedation and dry mouth appeared with the same frequency as with clonidine. The central a-stimulant action of guanabenz (3) in cats appears distinct from that of clonidine in that baroreceptor mechanisms are not involved in the hypotensive response.26 in the clinic, guanabenz (2it-48mg) produced modest blood pressure reduction with sedation as the major side-effect.27... 

Guanabenz is rapidly and completely absorbed from the G1 tract, exerts its effects within 2 hours, has a duration of action of 10 hours, is metabolized in the liver by hydroxy-lation followed by glucuronidation, and 2% of it is excreted unchanged by the hver. 

Guanabenz (Wytensin, others) is a centrally acting tt2 agonist that decreases BP by a mechanism similar to those of clonidine and gnanfacine. Guanabenz has a half-life of 4 to 6 hours and is extensively metabolized by the liver. Dosage adjustment may be necessary in patients with hepatic cirrhosis. The adverse effects caused by guanabenz (e.g., dry mouth and sedation) are similar to those seen with clonidine. 

Nortriptyline may decrease hypotensive effects of centrally acting antihypertensive drugs, such as guanethidine, guanabenz, guanadrel, clonidine, methyldopa, and reser-pine. Concomitant use with disulfiram or ethchlorvynol may cause delirium and tachycardia. 

Apraclonidine Guanfacine Guanabenz Brimonidine a-methyldopa from brain to periphery resulting in decreased PVR and blood pressure Decrease nerve-evoked release of sympathetic transmitters Decrease production of aqueous humor Hypertension To reduce sympathetic response to withdrawal from narcotics, alcohol, and tobacco Glaucoma brimonidine used topically for glaucoma and ocular hypertension Methyldopa is converted in CNS to a-methyl NE, an effective agonist... 

Overall, the frequency of adverse effects produced by guanabenz is similar to that produced by cionidine and the other Q2-adrenergic agonists, but the incidence is lower. As with the other centrally active sympatholytics (e.g., cionidine), abrupt withdrawal of guanabenz may result in rebound hypertension, but the withdrawal syndrome symptoms appear to be less severe. 

III. Clinical presentation. Manifestations of intoxication result from generalized sympathetic depression and include pupillary constriction, lethargy, coma, apnea, bradycardia, hypotension, and hypothermia. Paradoxic hypertension, caused by stimulation of peripheral alpha-1 receptors, may occur with clonidine, oxymetazoline, and tetrahydrozoline (and possibly guanabenz) and is usually transient. The onset of symptoms is usually within 30-60 minutes, although peak effects may occur more than 6-12 hours after ingestion. Full recovery is usual within 24 hours. In an unusual massive overdose, a 28-year-old man who accidentally ingested 100 mg of clonidine powder had a three-phase intoxication over 4 days initial hypertension, followed by hypotension, and then a withdrawal reaction with hypertension. 

Imidazoline-2 receptors are highly distributed on astrocyte mitochondrial membranes (Tesson etal. 1992, Regunathan etal. 1993). In primary cultures of neonatal rat astrocytes, imidazoline drugs, such as idazoxan, guanabenz, guanfacine, BU224, and RS-45041-190, showed protective effects against naphthazarin-induced oxidative cyto-... 

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