Neuropharmacology: Age-related changes
Hemanshu Prabhakar, Charu Mahajan, Indu Kapoor in Essentials of Geriatric Neuroanesthesia, 2019
Dexmedetomidine quickly produces light sedation by its action in the pontine locus coeruleus where it selectively activates central-alpha-2 receptors, thereby producing sedative effects quickly. Unlike other sedatives, dexmedetomidine does not impair the respiratory drive. Hemodynamically, this medication causes dose-dependent decreases in heart rate and blood pressure that are most pronounced with bolus doses. Although dexmedetomidine has mild analgesic effects and has been shown to be an opioid-sparing agent, it should not be used as monotherapy for analgesia. Since the actions of dexmedetomidine are limited to the locus coeruleus, a noradrenergic nucleus near the 4th ventricle, it has no effects on electrophysiologic tests. Lacking electrophysiologic and respiratory effects, dexmedetomidine has gained much interest in functional neurosurgery and awake procedures (48). In addition, interest is growing for the use of dexmedetomidine as an adjuvant agent during particularly noxious parts of neurosurgical cases rather than increasing doses of the standard anesthetics in response to the patient's increasing heart rate and blood pressure.
Intoxicants
Michael Y. Wang, Andrea L. Strayer, Odette A. Harris, Cathy M. Rosenberg, Praveen V. Mummaneni in Handbook of Neurosurgery, Neurology, and Spinal Medicine for Nurses and Advanced Practice Health Professionals, 2017
Dexmedetomidine. Dexmedetomidine is an α-2 adrenergic receptor agonist, centrally activating, which results in decreased norepinephrine synthesis and therefore less sympathetic nervous system stimulation. A key advantage of dexmedetomidine is the anxiolytic and sympatholysis effects achieved without respiratory depression, making dexmedetomidine appropriate for nonintubated patients. However, dexmedetomidine lacks GABA receptor activity and therefore has no anticonvulsant properties. Dexmedetomidine is appropriate as adjunctive therapy and has been proven to reduce overall benzodiazepine requirements (Schmidt et al., 2016, p. 6). Dexmedetomidine can cause marked bradycardia and hypotension, which are indications for discontinuation of the drug (Ferreira et al., 2015, p. 8).
Paper 5 Answers
James Day, Amy Thomson, Tamsin McAllister, Nawal Bahal in Get Through, 2014
Dexmedetomidine is a sedative medication used in anaesthetics and intensive care. It is unusual as it causes sedation without respiratory depression. Like clonidine, it is an agonist at the a2 adrenergic receptor. It produces a state of rousable sedation where patients can be responsive to verbal commands but then go back to sleep. It is thought that it produces a state more akin to natural sleep than the GABA-ergic hypnotics such as propofol and the benzodiazepines. Dexmedetomidine will cause bradycardia, particularly if given as a large bolus dose. It is therefore given as an infusion but has a slow onset of action where peak effects occur 10 minutes after peak plasma levels. The offset of action is also variable and context-sensitive. It is licensed for use as a sedative in critical care and is also used in general anaesthesia, where it has MAC and opioid sparing effects.
Sublingual dexmedetomidine: repurposing an anesthetic as an anti-agitation agent
Published in Expert Review of Neurotherapeutics, 2023
Justin Faden, Meghan Musselman, Leslie Citrome
Dexmedetomidine has also been demonstrated to prolong the QT interval in a concentration-dependent manner, with a single 120 mcg dose increasing QTcF a mean of 6 msec from baseline and a single 180 mcg dose increasing the mean QTcF by 8 msec. Additional doses have demonstrated further increases in QTcF. This is similar to the prolongation in QT interval observed with injectable ziprasidone or injectable haloperidol, where the mean changes from baseline were 4.6 msec and 6.0 msec after single injections, respectively, and 12.8 msec and 14.7 msec after second injections, respectively[38]. Due to the cardiovascular risks with dexmedetomidine, clinicians are cautioned against using dexmedetomidine in patients with hypotension, orthostatic hypotension, advanced heart block, severe ventricular dysfunction, history of syncope, and in those at risk of torsades de pointes or sudden death due to known QT prolongation, a history of arrhythmia, symptomatic bradycardia, hypomagnesemia, hypokalemia and in those patients receiving medications known to prolong the QT interval. Due to potential additive risk of somnolence, the prescribing information advises that dexmedetomidine should not be used in combination with anesthetics, sedatives, hypnotics, or opioids [26].
Effects of perioperative dexmedetomidine infusion on renal function and microcirculation in kidney transplant recipients: a randomised controlled trial
Published in Annals of Medicine, 2022
Yin-Chin Wang, Ming-Jiuh Wang, Chih-Yuan Lee, Chien-Chia Chen, Ching-Tang Chiu, Anne Chao, Wing-Sum Chan, Meng-Kun Tsai, Yu-Chang Yeh
Dexmedetomidine is a highly selective alpha-2 agonist with sedative and analgesic effects [5]. It modulates inflammation by enhancing parasympathetic tone while reducing sympathetic tone [6,7]. Dexmedetomidine has been reported to confer renal protection effects in patients undergoing coronary artery bypass surgery [8,9]. The protective effects of dexmedetomidine against ischemia-reperfusion injury have been described in many studies [10–12]. Moreover, the sympatholysis effect of dexmedetomidine induced vasodilation [5], and our previous animal study showed that dexmedetomidine prevented alterations of intestinal microcirculation in rats with surgical stress and pain [13]. However, the most common side effects of dexmedetomidine are bradycardia and hypotension. Low cardiac output and low perfusion pressure may deteriorate microcirculation [14,15]. We hypothesised that dexmedetomidine could attenuate the ischemia-reperfusion injuries and preserve transplanted kidneys’ function. In addition, the issue that the effects of dexmedetomidine on perioperative microcirculation were protective or detrimental remained unknown. Thus, this study investigated postoperative renal function and perioperative sublingual microcirculation in patients undergoing kidney transplantation.
Multimodal analgesia in neurosurgery: a narrative review
Published in Postgraduate Medicine, 2022
Caterina Aurilio, Maria Caterina Pace, Pasquale Sansone, Luca Gregorio Giaccari, Francesco Coppolino, Vincenzo Pota, Manlio Barbarisi
Dexmedetomidine is a new α2 -receptor agonists that has the property as anesthetic sparing that allow a reduction in the amount of inhaled anesthetics and opioids needs, resulting in a more rapid recovery with fewer side effects. In the central nervous system (CNS), dexmedetomidine acts through the release of catecholamines in nerve endings and by reducing the sympathetic nervous system activation [24]. It was also found that the direct action on α2 receptors in monoaminergic neurons and dendrites in the brain inhibits the secretion of catecholamines [25]. Both these studies concluded that dexmedetomidine could reduce neuronal damage by inhibiting neurotransmitter release, which may improve ischemic perfusion and metabolic disorders [26]. Furthermore, these researches brought the interest in the use of dexmedetomidine as analgesic in the postoperative craniotomy surgery and as part of multimodal analgesia. The interest for dexmedetomidine in intracranial and postoperative surgery is based not only on analgesia and a cooperative sedation but also on a better hemodynamic stability, on reducing respiratory depression, intracranial pressure, and the risk of post-operative bleeding for its sympatholytic mechanisms. In two studies including 128 patients, dexmedetomidine was used in the similar way with an infusion of up to 0.5µgr/kg/hr or placebo intraoperatively to evaluate post-craniotomy pain. Dexmedetomidine lead to a reduction in pain score up to 24 h postoperatively with a less 27,28].
Related Knowledge Centers
- Delirium
- Tracheal Intubation
- Clonidine
- Schizophrenia
- Bipolar Disorder
- Medication
- Sympatholytic
- Agonist
- Alpha-2 Adrenergic Receptor
- Mechanical Ventilation