EDITORIAL

a ₂-Adrenergic agonists: current status

a_2-Adrenergic agonists have potentially useful properties in anesthesia and intensive care including ¹: anti-hypertensive effect, analgesia, sedation, minimum alveolar concentration (MAC) decrease of inhalational anesthetics and postoperative shivering reduction.

Anti-hypertensive effects of clonidine, the a_2-adrenergic agonists prototype, is due to the sympatholysis resulting from the inhibition of locus ceruleus (brainstem nucleus related to noradrenergic activity) as well as of norepinephrine release at the neuroeffector ². In fact, the dose-response curve is not so simple: while clonidine decreases noradrenergic activity in low doses (which are used in hypertension control), it exacerbates such activity in high doses by activating a_2-B-adrenergic receptors located in smooth muscle cells of resistance vessels. Anyway, hypotension and bradycardia (or tachycardia decrease) may result from the use of clonidine in anesthesia and intensive care.

Analgesia seems to be related to the effect on spinal cord posterior horn where clonidine causes an increase in acetylcholine release ³. The simultaneous administration of neostigmine maximizes the analgesic effect of a_2-adrenergic agonists ⁴.

Sedation is a consequence of the effect of such drugs on the brainstem locus ceruleus and presents an interesting characteristic: although apparently at deep sedation shown by bispectral index (BIS), the individual may be completely awaken by an external stimulus (auditory, for example) with no impairment in his psychomotor abilities ⁵. This is seldom obtained with other drugs used for sedation and may be a clear advantage, for example, in Intensive Care sedated patients, who may be asked to cooperate with the physiotherapist, going back to sleep again when left alone after the procedure ⁶. It is worth stressing also that dexmetomidine, the newest a_2-adrenergic agonist approved for clinical use, significantly decreases propofol requirement for a given sedation level, allowing the patient to be easily awaken and return to sleep as needed ⁷.

The effect of clonidine in decreasing inhalational agents MAC has been well studied and raises the possibility of interactions with Central Nervous System supraspinal depressants ^8,9.

Intravenous clonidine prevents postoperative shivering in patients submitted to both general and epidural anesthesia ^1,10,11. The mechanism is still to be better explained.

For what has been described above, especially the analgesic and sedative effects, a_2-adrenergic agonists have already become part of anesthesiologists and intensivists therapeutic arsenal. Dexmedetomidine is highly specific for the a₂ receptor with an a₂/a₁ specificity ratio seven times higher than that of clonidine; on the other hand, its plasma elimination half-life is approximately 2 hours, much lower than the one of clonidine, which is more than 8 hours ^12,13. Such properties, added to a moderate and more predictable decrease in blood pressure and heart rate, make dexmedetomidine a promising agent for optimizing sedation and analgesia management.

José Roberto Nociti, M.D.

Address: Rua Stélio Machado Loureiro, 21

Alto da Boa Vista

ZIP: 14025-470 City: Ribeirão Preto, Brazil

REFERENCES

01. Kamibayashi T, Maze M - Clinical uses of a₂-adrenegic agonists. Anesthesiology, 2000; 93:1345-1349.

02. McCallum JB, Boban N, Hogan Q et al - The mechanism of a₂-adrenergic inhibition of sympathetic ganglionic transmission. Anesth Analg, 1998;87:503-510.

03. Klimscha W, Tong C, Eisenach JC - Intrathecal a₂-adrenergic agonists stimulate acetylcholine and norepinephrine release from the spinal cord dorsal horn in sheep. An in vivo microdialysis study. Anesthesiology, 1997; 87:110-116.

04. Bouaziz H, Hewitt C, Eisenach JC - Subarachnoid neostigmine potentiation of alpha 2-adrenergic agonist analgesia. Dexmedetomidine versus clonidine. Reg Anesth, 1995;20:121-127.

05. Hall JE, Uhrich TD, Ebert TJ - The sedative analgesic and cognitive effects of clonidine infusions in humans. Br J Anaesth, 2001;86:5-11.

06. Jones MEP, Maze M - Can we characterize the central nervous system actions of a₂-adrenergic agonists? Br J Anaesth, 2001;86:1-3.

07. Hall JE, Uhrich TD, Barney JA et al - Sedative, amnesic, and analgesic properties of small-dose dexmedetomidine infusions. Anesth Analg, 2000;90:699-705.

08. Bloor BC, Flack WE - Reduction in halothane anesthetic requirements by clonidine, an alpha-adrenergic agonist. Anest Analg, 1982;61:741-745.

09. Ghignone M, Calvillo O, Quintin L - Anesthesia and hypertension: the effect of clonidine on perioperative hemodynamics and isoflurane requirements. Anesthesiology, 1987;67:3-10.

10. Buggy D, Higgins P, O’Donovan F - Clonidine at induction reduces shivering after general anaesthesia. Can J Anaesth, 1997;44:263-267.

11. Horn EP, Standl T, Sessler DI et al - Physostigmine prevents postanesthetic shivering as does meperidine or clonidine. Anesthesiology, 1998;88:108-113.

12. Dick JB , Shafer SL - Dexmedetomidine pharmacokinetics and pharmacodynamics. Anaesth Pharm Review, 1993;1:238-245.

13. Hayashi Y, Maze M - Alpha 2-adrenoreceptor agonists and anaesthesia. Br J Anaesth, 1993;71:108-118.

Publication Dates

• Publication in this collection
  21 Mar 2011
• Date of issue
  2001