Nursing Pharmacology Chapter 12:  Anxiolytics and Sedative-Hypnotics

• α-2  receptors agonists:

  • Preoperatively, clonidine (Catapres) an α-2 adrenergic receptor agonist, causes sedation and reduces autonomic nervous system reflects responses.  

    • These responses may include those secondary to catecholamine release in general and hypertension and tachycardia in particular. 

  • Centrally-acting agents, such as clonidine (Catapres), reduce sympathetic autonomic outflow by acting mainly at α-2 presynaptic receptor sites. {note that α₂ receptors have been found and extra-synaptic and postsynaptic sites as well} 

  • Presynaptic stimulation decreases transmitter release.

     

    • Inhibition of norepinephrine release by presynaptic α₂ receptor activation

      Physiology of the α2-adrenoceptor agonists receptor. Adapted from dexmedetomidine.com

• Clonidine (Catapres):  an appropriate oral dosage for preoperative medication should produce sedation and reduced autonomic nervous system reflects responses.

  • Preoperatively, appropriate oral clonidine may reduce preoperative myocardial ischemia in patients who likely have coronary vascular disease

  • Clonidine (Catapres) also may be used for patients not only with uncontrolled hypertension but also have the need for urgent surgery.  

    •  However, significant impairment of autonomic function, in particular attenuation of sympathetic responses, may mask hidden volume loss and delay compensation for the unrecognized hypovolemic state

• ⁵Dexmedetomidine (Precedex) is a more specific/potent alpha-2 receptor agonist compared clonidine (Catapres).   

  • Dexmedetomidine (Precedex) exhibits both central and peripheral actions.

    • Anxiolytic, analgesic, sedative, and sympatholytic characteristics have been attributed to dexmedetomidine (Precedex).  These characteristics are considered beneficial in the perioperative  stressful setting. 

  • Dexmedetomidine (Precedex) has been thus far ONLY been approved by the FDA for use in short-term sedation of intensive care patients (May 2000, Abbott Laboratories); http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021038s017lbl.pdf ; updated safety information (10/2010) http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm233675.htm .

  • Dexmedetomidine (Precedex), like clonidine (Catapres), enhances the anesthetic effect of intravenous and volatile agents as well as those used for regional block.  

    • Dexmedetomidine (Precedex) appears to reduce by about 20%-30% the amount of thiopental (Pentothal) required for induction.

• Side Effects for α₂ receptor agonists include bradycardia and dry mouth.

References

• ¹Preoperative Medication in Basis of Anesthesia, 4th Edition, Stoelting, R.K. and Miller, R., p 119- 130, 2000) 

• Hobbs, W.R, Rall, T.W., and Verdoorn, T.A., Hypnotics and Sedatives; Ethanol In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc., 1996, pp. 364-367.

• ³Sno E. White The Preoperative Visit and Premedication in Clinical Anesthesia Practice pp.  576-583 (Robert Kirby & Nikolaus Gravenstein, eds) W.B.  Saunders Co., Philadelphia, 1994

• ⁴John R. Moyers and Carla M. Vincent Preoperative Medication in Clinical Anethesia, 4th edition (Paul G. Barash, Bruce. F. Cullen, Robert K. Stoelting, eds) Lippincott Williams & Wilkins, Philadelphia, PA, 2001

• ⁵Gertler, R., Brown, H. C, Mitchell, D.H and Silvius, E.N Dexmedetomidine (Precedex): a novel sedative-analgesic agent, BUMC Proceedings 2001; 14:13-21.