title: Role of α2-agonists in the treatment of acute alcohol withdrawal.
abstract: OBJECTIVE
  To evaluate literature reporting on the role of norepinephrine in alcohol withdrawal and to determine the safety and efficacy of α(2)-agonists in reducing symptoms of this severe condition.
  
  
  METHODS
  Articles evaluating the efficacy and safety of the α(2)-agonists clonidine and dexmedetomidine were identified from an English-language MEDLINE search (1966-December 2010). Key words included alcohol withdrawal, delirium tremens, clonidine, dexmedetomidine, α(2)-agonist, norepinephrine, and sympathetic overdrive.
  
  
  METHODS
  Studies that focused on the safety and efficacy of clonidine and dexmedetomidine in both animals and humans were selected.
  
  
  RESULTS
  The noradrenergic system, specifically sympathetic overdrive during alcohol withdrawal, may play an important role in withdrawal symptom development. Symptoms of sympathetic overdrive include anxiety, agitation, elevated blood pressure, tachycardia, and tremor. Therefore, α(2)-agonists, which decrease norepinephine release, may have a role in reducing alcohol withdrawal symptoms. The majority of controlled animal and human studies evaluated clonidine, but the most recent literature is from case reports on dexmedetomidine. The literature reviewed here demonstrate that these 2 α(2)-agonists safely and effectively reduce symptoms of sympathetic overdrive and concomitant medication use. Dexmedetomidine may offer an advantage over current sedative medications used in the intensive care unit, such as not requiring intubation with its use, and therefore further study is needed to fully elicit its benefit in alcohol withdrawal.
  
  
  CONCLUSIONS
  Clonidine and dexmedetomidine may provide additional benefit in managing alcohol withdrawal by offering a different mechanism of action for targeting withdrawal symptoms. Based on literature reviewed here, the primary role for clonidine and dexmedetomidine is as adjunctive treatment to benzodiazepines, the standard of care in alcohol withdrawal.
authors.affiliation: Campbell University School of Pharmacy and Health Sciences, Durham, NC, USA. Andrew.Muzyk@duke.edu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Muzyk
authors.forename: Jill A
authors.initials: JA
authors.lastname: Fowler
authors.forename: Daryn K
authors.initials: DK
authors.lastname: Norwood
authors.forename: Allison
authors.initials: A
authors.lastname: Chilipko
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000009:adverse effects / Q000494:pharmacology*; D020927:Dexmedetomidine / Q000009:adverse effects / Q000494:pharmacology*; D000431:Ethanol / Q000009:adverse effects*; D006801:Humans; D009638:Norepinephrine / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000431:Ethanol; D020927:Dexmedetomidine; D003000:Clonidine; D009638:Norepinephrine