Clinical Efficacy of Oral—Transdermal Clonidine Combinations during the Perioperative Period

Segal, Ira S.; Jarvis, D.J.; Duncan, Steven R.; White, Paul F.; Maze, Mervyn

doi:10.1097/00000542-199102000-00005

Cited by 158 publications

(50 citation statements)

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“…The analgesic properties of ␣ 2 AR agonists add to their usefulness in the practice of anesthesiology (2,27,28). We examined the analgesic properties of ␣ 2 AR agonists in attenuating thermally induced pain.…”

Section: Resultsmentioning

confidence: 99%

Substitution of a mutant α _2a -adrenergic receptor via “hit and run” gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo

Lakhlani

MacMillan

Guo

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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310

234

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Norepinephrine contributes to antinociceptive, sedative, and sympatholytic responses in vivo, and ␣ 2 adrenergic receptor (␣ 2 AR) agonists are used clinically to mimic these effects. Lack of subtype-specific agonists has prevented elucidation of the role that each ␣ 2 AR subtype (␣ 2A , ␣ 2B , and ␣ 2C ) plays in these central effects. ␣ 2 -adrenergic receptors (␣ 2 ARs) present in the central nervous system (CNS) respond to norepinephrine (NE) and epinephrine and mediate sympatholytic, sedative-hypnotic, analgesic, anesthetic-sparing, hypotensive, and anxiolytic responses (1). Many of these responses are therapeutically useful and are exploited clinically, for example, during anesthesia and to attenuate the symptoms of opioid withdrawal (2). Three ␣ 2 AR subtypes have been revealed by pharmacological (␣ 2A AR, ␣ 2B AR, and ␣ 2C AR) and molecular cloning (␣ 2a AR, ␣ 2b AR, and ␣ 2c AR) strategies (3), and all couple, via pertussis toxin-sensitive G i ͞G o proteins, to attenuation of adenylyl cyclase, suppression of voltage-gated Ca 2ϩ channels, and activation of inwardly rectifying K ϩ channels (4).Multiple experimental limitations have precluded clarifying the involvement of each ␣ 2 AR subtype in catecholaminemediated physiological responses in the CNS. Subtype-specific ␣ 2 AR agonists and antagonists are not available (5); even when subtype selectivity has been noted in vitro, varying and unknown in vivo bioavailability precludes confident correlation of the administered dose with the amount of drug at the receptor site. Previous studies to explore ␣ 2 AR involvement in various responses have used prazosin to block catecholamine responses mediated by ␣ 1 adrenergic receptors (␣ 1 AR); however, it is now known that the ␣ 2B AR and ␣ 2C AR subtypes also are blocked by prazosin (5), thus confounding the interpretations of these earlier studies. In addition, because ␣ 1 AR can functionally antagonize ␣ 2 AR-mediated responses in some settings, ␣ 2 AR responses in the presence of prazosin (added to block ␣ 1 AR, ␣ 2B AR, and ␣ 2C AR) may reflect the disturbance of the balance between the functionally antagonistic ␣ 2 AR and ␣ 1 AR systems rather than provide insights concerning the role of the ␣ 2A AR subtype. Consequently, we manipulated the mouse genome to provide definitive evidence regarding the role of the ␣ 2A AR subtype in CNS responses.We used the ''hit and run'' targeting variant of homologous recombination (6, 7) to substitute a subtle mutation of the ␣ 2a AR, D79N into the mouse genome as a tool to explore the role of the ␣ 2a AR in vivo (8). The aspartate residue at position 79 (D79) is highly conserved in a topologically identical position in the second transmembrane span in a large subset of G protein-coupled receptors (9). Mutation of this residue has been shown to eliminate allosteric regulation of receptor binding by monovalent cations (10-13) and to perturb receptor-G protein-effector coupling (14-17) in heterologous expression systems. Thus, the animals expressing the D79N ␣ 2a AR provi...

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Section: Resultsmentioning

confidence: 99%

Substitution of a mutant α _2a -adrenergic receptor via “hit and run” gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo

Lakhlani

MacMillan

Guo

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

310

234

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“…In contrast, there are reports of no alfentanil sparing or haemodynamic stability following clonidine premedication [135]. The opioidsparing effect may not be a pure pharmacodynamic effect as clonidine has been reported to increase plasma alfentanil concentration by 60% [136] and dexmedetomidine is known to inhibit alfentanil microsomal liver metabolism [137]. Aho and colleagues [138] reported that the administration of an infusion of dexmedetomidine in patients undergoing abdominal hysterectomy was able to reduce isoflurane requirements by 90%.…”

Section: Anaesthetic Requirementsmentioning

confidence: 99%

Alpha‐2 and imidazoline receptor agonistsTheir pharmacology and therapeutic role

Khan¹,

Ferguson²,

Jones³

1999

Anaesthesia

590

423

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SummaryClonidine has proved to be a clinically useful adjunct in clinical anaesthetic practice as well as in chronic pain therapy because it has both anaesthetic and analgesic-sparing activity. The more selective alpha-2 adrenoceptor agonists, dexmedetomidine and mivazerol, may also have a role in providing haemodynamic stability in patients who are at risk of peri-operative ischaemia. The side-effects of hypotension and bradycardia have limited the routine use of alpha-2 adrenoceptor agonists. Investigations into the molecular pharmacology of alpha-2 adrenoceptors have elucidated their role in the control of wakefulness, blood pressure and antinociception. We discuss the pharmacology of alpha-2 adrenoceptors and their therapeutic role in this review.

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“…Sedation was evaluated by a blinded investigator and was graded by a scale of 1 to 5 (1 -alert; 2 -drowsy but easily aroused by verbal command to an alert state; 3 -sleeping and arousal by verbal command; 4 -sleeping not arousal by verbal stimuli, but arousal to a drowsy state by light tactile stimulation; and 5 -sleeping and difficult to be aroused by tactile stimulation). 12 Energy expenditure and respiratory quotient were measured with a head canopy system (Deltatrac Metabolic Monitor, TM Datex, Helsinki, Finland) which was calibrated before the beginning of the study in each subject. The accuracy of this method is 4 • 2%.…”

Section: Methodsmentioning

confidence: 99%

Oral clonidine premedication decreases energy expenditure in human volunteers

et al. 1997

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Purpose: Clonidine not only stops postoperative shivering and decreases oxygen consumption, but aJso decreases energy expenditure with or without a reduction in shivering during recovery from anaesthesia. It is important to see iF donidine decreases energy expenditure at rest since this may contribute to a postoperative decrease in energy expenditure, The authors tested the hypothesis that oral clonidine decreases energy expenditure at rest, Methods: Twenty healthy male volunteers were randomly assigned to one of two groups. Ten volunteers received oral clonidine approximately 5/ag-kg-' (clonidine group), while the remaining 10 volunteers recek, ed placebo (control group). Blood pressure, heart rate, body temperature at the tympanic membrane, sedation score graded From I (alert) to S (sleeping and difficult to be aroused by tactile stimulation) were measured before and at 30-rain intervals for three hours after administration of clonidine or placebo. IMeasurements of energy expenditure and respiratory quotient were made with a head canopy system at one-minute intervals and averaged over I 5 min before, and at 30, 60, 90, 120, and 180 rain after administration of clonidine or placebo.Results: Sedation score increased from I to 3 (median) after clonidine administration. Energy expenditure decreased From 1452 -+ 225 kcaJ.24hr ~ (mean +-SD) at baseline to 1258 +-175 kcal'24hr j at 180 rain after clonidine administration (P <0.0S). Conclusion:This study suggests that oral clonidine at a dose of 5/4g'kg' decreases energy expenditure at rest.Objectif : En plus de prevenir le fnsson postop&atoire et de diminuer la consommation en oxygene, la donidine diminue ta depense energ~tique au moment du r~veil avec ou sans attenuation du frisson. II est important de savoir si la clonidine diminue la depense energ&ique au repos etant donne que cet effet contribue a une baisse postop&atoire de I'~nergie d~pens~e.M&hodes : Vingt volontaires en bonne sante de sexe masculin ~taient assignes al~atoirement a deux groupes. Dix de ces volontaires recevaient environ 5 pg.kg-' de clonidine (groupe clonidine) alors que les autres recevaient un placebo (groupe contr61e). La pression art&ielle, la frequence cardiaque, la temp&ature corporelle et tympanique, le score de sedation cote sur R&sultats : Le score de sedation a augmente de I r 3 (mediane) apr~.s radministration de la clonidine. La d6pense energetique a diminue de 1452 _+ 225 kcal-24h -~ (moyenne ___ ET)initiaJement, & 1285 + 175 kcal.24h-r 180 rain apres radministration de la clonidine (P <0,05).Conclusion : Cette etude suggere qu'au repos, la clonidine orale 5/ag'kg ~ diminue la depense energetique.

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Clinical Efficacy of Oral—Transdermal Clonidine Combinations during the Perioperative Period

Cited by 158 publications

References 0 publications

Substitution of a mutant α _2a -adrenergic receptor via “hit and run” gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo

Substitution of a mutant α _2a -adrenergic receptor via “hit and run” gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo

Alpha‐2 and imidazoline receptor agonistsTheir pharmacology and therapeutic role

Oral clonidine premedication decreases energy expenditure in human volunteers

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Clinical Efficacy of Oral—Transdermal Clonidine Combinations during the Perioperative Period

Cited by 158 publications

References 0 publications

Substitution of a mutant α 2a -adrenergic receptor via “hit and run” gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo

Substitution of a mutant α 2a -adrenergic receptor via “hit and run” gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo

Alpha‐2 and imidazoline receptor agonistsTheir pharmacology and therapeutic role

Oral clonidine premedication decreases energy expenditure in human volunteers

Contact Info

Product

Resources

About

Substitution of a mutant α _2a -adrenergic receptor via “hit and run” gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo

Substitution of a mutant α _2a -adrenergic receptor via “hit and run” gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo