title: A comparison of dexmedetomidine and placebo on the plasma concentrations of NGF, BDNF, GDNF, and epinephrine during severe alcohol withdrawal.
abstract: Alcohol withdrawal and therapies may affect nerve growth factor (NGF), brain-derived neurotrophic growth factor (BDNF), glial-derived neurotrophic growth factor (GDNF), and epinephrine (EPI). This study evaluated dexmedetomidine (DEX) on NGF, BDNF, GDNF, and EPI in severe alcohol withdrawal and related their plasma concentrations to DEX concentrations. Twenty-four subjects were randomized to DEX 1.2 mcg/kg/hour (high dose [HD]), 0.4 mcg/kg/hour (low dose [LD]), or placebo. Blood was collected at 0 (T0), 48 (T48), and 96-120 (T96) hours after starting the study drug, and concentrations of these transmitters and DEX were determined. Similar NGF suppression occurred at T48 and T96 across all groups. BDNF and GDNF levels increased insignificantly at T48 in the placebo group but steadily declined in both DEX groups, with a trend toward significance in the HD group at T48. EPI concentrations declined significantly in the HD group at T48, only to increase at T96. Median DEX concentrations during the study were insignificantly higher in HD than LD. T0 values of BDNF (r = -0.47, p = 0.02) and GDNF (r = -0.37, p = 0.05) were inversely associated with the need for mechanical ventilation before study enrollment. No other clinical parameter was associated with the plasma concentrations of these transmitters. Daily lorazepam requirements were associated with the severity of withdrawal (r = 0.7, p < 0.0001) and DEX concentrations were inversely related to daily lorazepam requirements (r = -0.33, p = 0.008). DEX utilization suppressed EPI (r = -0.57, p = 0.004). EPI concentrations were associated with BDNF values at T0 (r = 0.55, p = 0.04) and throughout the study (r = 0.25, p = 0.04). In summary, the plasma concentrations of NGF, BDNF, GDNF, and EPI during alcohol withdrawal are variable and the effects of DEX were marginal. DEX administration and higher DEX concentrations attenuated lorazepam administration in the short-term and suppressed EPI.
authors: Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado 80045, USA; University of Colorado Hospital, Aurora, Colorado 80045, USA.
authors: Paul M
authors: PM
authors: Reynolds
authors: Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado 80045, USA.
authors: Scott W
authors: SW
authors: Mueller
authors: Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado 80045, USA. Electronic address: rob.maclaren@ucdenver.edu.
authors: Robert
authors: R
authors: MacLaren
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000627:therapeutic use; D000437:Alcoholism / Q000097:blood* / Q000188:drug therapy; D015415:Biomarkers / Q000097:blood; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D020927:Dexmedetomidine / Q000627:therapeutic use*; D004311:Double-Blind Method; D004837:Epinephrine / Q000097:blood*; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000097:blood*; D006801:Humans; D008297:Male; D020932:Nerve Growth Factor / Q000097:blood*; D015990:Placebo Effect; D012720:Severity of Illness Index; D013375:Substance Withdrawal Syndrome / Q000097:blood* / Q000188:drug therapy
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; C502240:NGF protein, human; D020927:Dexmedetomidine; C579455:BDNF protein, human; D020932:Nerve Growth Factor; D004837:Epinephrine
keywords: Alcohol withdrawal; Brain-derived neurotrophic growth factor; Dexmedetomidine; Epinephrine; Glial cell-derived neurotrophic growth factor; Nerve growth factor