Dexmedetomidine as a Novel Countermeasure for Cocaine-Induced Central Sympathoexcitation in Cocaine-Addicted Humans

Cocaine-induced acute hypertension is mediated largely by increased central sympathetic nerve activity. We hypothesized that dexmedetomidine, a central sympatholytic, reverses cocaine-induced increases in sympathetic nerve activity, mean arterial pressure (MAP), and heart rate (HR) in cocaine-addict...

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Bibliographic Details
Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 2013-02, Vol.61 (2), p.388-394
Main Authors: Kontak, Andrew C, Victor, Ronald G, Vongpatanasin, Wanpen
Format: Article
Language:English
Subjects:
Adrenergic alpha-2 Receptor Agonists - pharmacology
Adrenergic alpha-2 Receptor Agonists - therapeutic use
Adult
Arterial hypertension. Arterial hypotension
Biological and medical sciences
Blood and lymphatic vessels
Blood Pressure - drug effects
Cardiology. Vascular system
Cocaine-Related Disorders - complications
Dexmedetomidine - pharmacology
Dexmedetomidine - therapeutic use
Dose-Response Relationship, Drug
Experimental diseases
Female
Heart Rate - drug effects
Humans
Hypertension - drug therapy
Hypertension - etiology
Male
Medical sciences
Middle Aged
Skin - blood supply
Skin - drug effects
Sympathetic Nervous System - drug effects
Treatment Outcome
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Summary:Cocaine-induced acute hypertension is mediated largely by increased central sympathetic nerve activity. We hypothesized that dexmedetomidine, a central sympatholytic, reverses cocaine-induced increases in sympathetic nerve activity, mean arterial pressure (MAP), and heart rate (HR) in cocaine-addicted subjects. First, we conducted a dose-finding study in 15 nontreatment-seeking cocaine-addicted subjects and 12 cocaine-naive healthy controls to find doses of intravenous dexmedetomidine that lower MAP and HR in the absence of acute-cocaine challenge. We then conducted a placebo-controlled treatment trial in 26 cocaine-addicted subjects to determine whether dexmedetomidine reverses MAP and HR increases after intranasal cocaine (3 mg/kg). Skin sympathetic nerve activity (measured in the second protocol) and skin vascular resistance (measured in both protocols) served as indices of cocaine-sensitive central sympathoexcitation. In doses up to 0.6 µg/kg IV, dexmedetomidine alone caused comparable dose-dependent decreases in blood pressure in cases and controls but a 1.0 µg/kg dose was required to lower HR. In cocaine-addicted subjects, low-dose dexmedetomidine (0.4 µg/kg; n=14) abolished cocaine-induced increases in skin sympathetic nerve activity (156±26 versus −15±22%, cocaine/placebo versus cocaine/dexmedetomidine; P
ISSN:0194-911X
1524-4563
DOI:10.1161/HYPERTENSIONAHA.112.203554