Advantages and disadvantages of alpha2-adrenoceptor agonists for systemic hypertension

Dollery, C. T.

doi:10.1016/0002-9149(88)90456-0

Cited by 21 publications

(6 citation statements)

References 25 publications

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“…Similarly, the clonidine dose used was much higher than clinically prescribed doses, given the fact that higher clonidine doses are associated with a high incidence of adverse effects. 33 Neither treatment caused any mortality. However, it is possible that the adverse effects of both agents when administered concurrently were not tolerated by rats and may account for the 20% mortality in the group that received the combination.…”

Section: Discussionmentioning

confidence: 97%

Alcohol abolishes the hypotensive effect of clonidine in spontaneously hypertensive rats.

Abdel‐Rahman

1994

Hypertension

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This study tested the hypothesis that concurrent ethanol administration attenuates the hypotensive effect of clonidine. Four groups of spontaneously hypertensive rats matched for baseline systolic pressure and body weight were randomly assigned the following treatments: (1) water (control), (2) ethanol, (3) clonidine, and (4) ethanol plus clonidine for 13 weeks. Ethanol was provided in the drinking water as 5% for 1 week, 10% for the next 2 weeks, and 20% from week 4 to 13. Starting from similar baseline systolic blood pressures, the blood pressure of the control group increased 10 to 15 mm Hg over the 13-week treatment period. A similar rise in systolic blood pressure occurred in ethanol-treated rats despite a drastic (40% to 50%, P<.05) reduction in fluid intake. Clonidine (300 p.g/kg per day) caused a smaller and shorter reduction in fluid intake. The fluid intake of the combined treatment group was similar to that of the ethanol group. Either treatment caused a significant and additive reduction in body weight gain. Treatment-related mortality (20%) occurred only in the combined treatment group by the 12th week. Clonidine elicited a slowly developing hypotensive response (P<.05) that started 2 to 3 weeks after treatment was initiated I n a previous study we showed that short-term ethanol administration elicited an immediate reversal of the hypotensive response to clonidine in conscious, unrestrained spontaneously hypertensive rats (SHR).1 This adverse effect of ethanol seems to be targeted against centrally acting hypotensive drugs. In support of this view is the finding that a similar hemodynamic interaction occurs between ethanol and another centrally acting drug, guanabenz.2 The hemodynamic interaction is dose related 2 and involves ethanol doses that are likely to be consumed clinically and lead to blood ethanol concentrations compatible with low to moderate intoxication. Interestingly, in the dose range used in these studies, 2 This latter effect may explain the immediate reversal by ethanol of the hypotensive response of centrally acting drugs that is the consequence of an inhibition of central sympathetic tone. From the Department of Pharmacology, East Carolina University School of Medicine, Greenville, NC.Correspondence to Abdel A. Abdel-Rahman, PhD, Department of Pharmacology, East Carolina University School of Medicine, Greenville, NC 27858.© 1994 American Heart Association, Inc.and lasted throughout the treatment period. Ethanol abolished the hypotensive effect of clonidine and resulted in blood pressure values that were not significantly different from those of the control or the ethanol groups. Blood ethanol concentration was similar in the presence or absence of clonidine (5.5±1.9 versus 6.5 ±3 mmol/L). We investigated whether long-term ethanol administration attenuates the hypotensive response elicited by centrally administered clonidine. The dose-response curve depicting the hypotensive responses to intracisternal clonidine in the ethanol-treated group was significantly shifted upwar...

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Section: Discussionmentioning

confidence: 97%

Alcohol abolishes the hypotensive effect of clonidine in spontaneously hypertensive rats.

Abdel‐Rahman

1994

Hypertension

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“…Clonidine lacks the psychotropic quality of bensodiazepines and will cause a state of sedation more similar to normal tiredness-sleepiness where the patient can easily be awoken to perform various tests (3). A further difference compared with bensodiazepines is that clonidine is frequently described as in fact enhancing memory, especially in the early stages of Alzheimer's disease (74), whereas bensodiazepines impair memory function and even produce amnesia (75,76). In the authors' opinion, further investigations regarding amnesia and premedication are clearly warranted.…”

Section: Amnesia and Effects On Cognition: Midazolam Vs Clonidinementioning

confidence: 99%

Clonidine in paediatric anaesthesia: review of the literature and comparison with benzodiazepines for premedication

Bergendahl

Pa²,

Eksborg

2006

Acta Anaesthesiol Scand

113

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Background: Children undergoing anaesthesia and surgery can experience significant anxiety and distress during the peri‐operative period, but whether routine premedication is necessary is currently debated. Benzodiazepines are the most frequently used drugs as premedication in paediatric anaesthesia. In the US, 50% of young children undergoing surgery receive premedication and midazolam is the most frequently used drug in this context (1). Nishina and coworkers (2) concluded in a review article in 1999 that clonidine, administered via an oral, rectal, or caudal route, is a promising adjunct to anaesthetics and analgesics to enhance quality of peri‐operative management in infants and children. Later publications also support the use of clonidine for premedication (3–6). The aim of this communication is to review the use of clonidine in paediatric anaesthesia and to propose clonidine as a promising alternative to midazolam. Clonidine is associated with a number of beneficial effects in the context ofanaesthesia both in adults and children. Why clonidine is not routinely use in clinical practice despite the massive publication list is to a large extent due to the lack of marketing efforts from the pharmaceutical industry since multiplegeneric preparations are now readily available on most markets. Midazolam is also associated with a number of beneficial effects, but is far from an ideal premedicant in children, especially with regards to the amnesia, confusion and long term behavioural disturbances. Clonidine has contrary to midazolam no effect on respiration. We believe that clonidine is a good alternative to midazolam as premedication in infants and children.

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“…Cardiac output and renal blood fl ow typically go unaffected with drugs in this class [ 12 ]. Also, during exercise, these compounds still reduce peripheral vascular resistance, implying that exercise-related changes in SNS activity are prevented [ 13 ]. Centrally acting agents also reduce plasma renin activity and plasma aldosterone and with long-term treatment, left ventricular hypertrophy will regress [ 14 ].…”

Section: Pharmacodynamicsmentioning

confidence: 99%

Centrally Acting Antihypertensive Agents in the Treatment of Hypertension

Sica

2015

Pathophysiology and Pharmacotherapy of Cardiovascular Disease

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Centrally acting antihypertensive agents stimulate α 2 -adrenergic receptors and/or imidazoline receptors on adrenergic neurons situated within the rostral ventrolateral medulla and in so doing variably reduce sympathetic outfl ow. Centrally acting agents also stimulate peripheral α 2 -receptors, which for the most part is of marginal clinical signifi cance with the medication doses used in clinical practice. Central α-agonists have an extended usage history, starting with α-methyldopa, which has seen its use dramatically decline, in part, because of signifi cant dose-dependent side effects as well as the arrival of more mechanistically attractive classes of antihypertensive medications. Patients with resistant hypertension requiring multidrug therapy, such as those with chronic kidney disease, are commonly responsive to these drugs as are patients with sympathetically mediated forms of hypertension. Perioperative hypertension is typically responsive to clonidine -a clinical circumstance where the anestheticand analgesia-sparing properties of this compound may offer further clinical benefi ts. Clonidine can be used adjunctively with other more traditional therapies in systolic forms of heart failure, particularly when hypertension exists. Sustained-release moxonidine, however, is associated with early mortality and morbidity when used in the patient with heart failure. Escalating doses of drugs in this class often give rise to salt and water retention in which case diuretic therapy becomes a needed adjunctive therapy.

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Advantages and disadvantages of alpha2-adrenoceptor agonists for systemic hypertension

Cited by 21 publications

References 25 publications

Alcohol abolishes the hypotensive effect of clonidine in spontaneously hypertensive rats.

Alcohol abolishes the hypotensive effect of clonidine in spontaneously hypertensive rats.

Clonidine in paediatric anaesthesia: review of the literature and comparison with benzodiazepines for premedication

Centrally Acting Antihypertensive Agents in the Treatment of Hypertension

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