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1.
Comput Math Methods Med ; 2021: 3822450, 2021.
Article in English | MEDLINE | ID: mdl-34938353

ABSTRACT

Brachial plexus block commonly used in finger replantation has the advantages of simple operation, small side effects, and stable circulation, but it has inherent problems such as imperfect block range, slow onset of anesthesia, and short maintenance time of anesthesia. In order to explore the reliable clinical anesthesia effect, this paper uses experimental investigation methods to study the effect of dexmedetomidine in clinical surgery of replantation of severed fingers. Moreover, this paper uses comparative test methods, uses statistical methods to process test data, and uses intuitive methods to display test results. Finally, this paper verifies the reliability of dexmedetomidine in replantation of severed finger through comparative analysis and verifies that the anesthesia method proposed in this paper has certain user satisfaction through parameter survey.


Subject(s)
Amputation, Traumatic/surgery , Brachial Plexus Block/methods , Dexmedetomidine/administration & dosage , Finger Injuries/surgery , Fingers/surgery , Replantation/methods , Adrenergic alpha-2 Receptor Agonists/administration & dosage , Anesthesia, Local/methods , Anesthetics, Local/administration & dosage , Computational Biology , Humans
2.
Medicine (Baltimore) ; 100(34): e27064, 2021 Aug 27.
Article in English | MEDLINE | ID: mdl-34449500

ABSTRACT

BACKGROUND: Dexmedetomidine (Dexm), a selective alpha-2 adrenoceptor agonist, and dexamethasone (Dexa), a very potent and highly selective glucocorticoid, have both been proven effectively to prolong the duration of local anesthetics (LA) in regional anesthesia. However, data comparing the efficacy of Dexm and Dexa as perineural adjuvants are inconsistent. Therefore, this systematic review and meta-analysis of randomized and quasi-randomized controlled trials (RCTs) was conducted to compare the effects of Dexm and Dexa when used as LA adjuvants on peripheral nerve block (PNB). METHODS: We systematically searched PubMed, Cochrane Library, EMBASE, Web of Science, and ScienceDirect databases up to October, 2020. The primary outcome was the duration of analgesia. Secondary outcomes included incidence of rescue analgesia, cumulative opioid consumption, time required for onset of sensory and motor blockades, duration of sensory and motor blockades, incidence of postoperative nausea and vomiting (PONV), and side effect-associated outcomes (e.g., bradycardia, sedation, hypotension, rates of infection, and neurological complications). The study was registered on PROSPERO, number CRD42020188796. RESULTS: After screening of full-text relevant articles, 13 RCTs that met the inclusion criteria were retrieved for this systematic review. It was revealed that perineural Dexm provided equivalent analgesic duration to perineural Dexa. Besides, the intake of Dexm increased the incidence of rescue analgesia in limbs surgery, as well as the cumulative opioid consumption, and decreased the time required for onset of sensory and motor blockades for long-acting LA (all P < .05). Other analysis revealed insignificant difference between the 2 groups in terms of the incidence of PONV (P > .05). Additionally, 2 studies demonstrated that Dexm possesses more sedative properties than Dexa (P < .05). CONCLUSIONS: This meta-analysis indicated that the analgesic duration of Dexm and Dexa as LA adjuvants in PNB is the same. Meanwhile, the effects of perineural Dexm and Dexa on some secondary outcomes, including the incidence of rescue analgesia, cumulative opioid consumption, and time required for onset of sensory and motor blockades, are associated with the surgical site and type of LA.


Subject(s)
Adrenergic alpha-2 Receptor Agonists/therapeutic use , Anesthesia, Local/methods , Dexamethasone/therapeutic use , Dexmedetomidine/therapeutic use , Glucocorticoids/therapeutic use , Nerve Block/methods , Adjuvants, Anesthesia , Adrenergic alpha-2 Receptor Agonists/administration & dosage , Dexamethasone/administration & dosage , Dexmedetomidine/administration & dosage , Glucocorticoids/administration & dosage , Humans , Peripheral Nerves , Randomized Controlled Trials as Topic
3.
Int J Mol Sci ; 22(8)2021 Apr 16.
Article in English | MEDLINE | ID: mdl-33923533

ABSTRACT

It has been established that the selective α2A adrenoceptor agonist guanfacine reduces hyperactivity and improves cognitive impairment in patients with attention-deficit/hyperactivity disorder (ADHD). The major mechanisms of guanfacine are considered to involve the activation of the postsynaptic α2A adrenoceptor of glutamatergic pyramidal neurons in the frontal cortex, but the effects of chronic guanfacine administration on catecholaminergic and glutamatergic transmissions associated with the orbitofrontal cortex (OFC) are yet to be clarified. The actions of guanfacine on catecholaminergic transmission, the effects of acutely local and systemically chronic (for 7 days) administrations of guanfacine on catecholamine release in pathways from the locus coeruleus (LC) to OFC, the ventral tegmental area (VTA) and reticular thalamic-nucleus (RTN), from VTA to OFC, from RTN to the mediodorsal thalamic-nucleus (MDTN), and from MDTN to OFC were determined using multi-probe microdialysis with ultra-high performance liquid chromatography. Additionally, the effects of chronic guanfacine administration on the expression of the α2A adrenoceptor in the plasma membrane fraction of OFC, VTA and LC were examined using a capillary immunoblotting system. The acute local administration of therapeutically relevant concentrations of guanfacine into the LC decreased norepinephrine release in the OFC, VTA and RTN without affecting dopamine release in the OFC. Systemically, chronic administration of therapeutically relevant doses of guanfacine for 14 days increased the basal release of norepinephrine in the OFC, VTA, RTN, and dopamine release in the OFC via the downregulation of the α2A adrenoceptor in the LC, OFC and VTA. Furthermore, systemically, chronic guanfacine administration did not affect intrathalamic GABAergic transmission, but it phasically enhanced thalamocortical glutamatergic transmission. The present study demonstrated the dual actions of guanfacine on catecholaminergic transmission-acute attenuation of noradrenergic transmission and chronic enhancement of noradrenergic transmission and thalamocortical glutamatergic transmission. These dual actions of guanfacine probably contribute to the clinical effects of guanfacine against ADHD.


Subject(s)
Adrenergic alpha-2 Receptor Agonists/pharmacology , Attention Deficit Disorder with Hyperactivity/drug therapy , Guanfacine/pharmacology , Prefrontal Cortex/drug effects , Synaptic Transmission/drug effects , Thalamus/drug effects , Adrenergic alpha-2 Receptor Agonists/administration & dosage , Adrenergic alpha-2 Receptor Agonists/therapeutic use , Animals , Dopamine/metabolism , Glutamic Acid/metabolism , Guanfacine/administration & dosage , Guanfacine/therapeutic use , Male , Norepinephrine/metabolism , Prefrontal Cortex/metabolism , Prefrontal Cortex/physiopathology , Rats , Rats, Sprague-Dawley , Receptors, Adrenergic, alpha-2/genetics , Receptors, Adrenergic, alpha-2/metabolism , Thalamus/metabolism , Thalamus/physiopathology , gamma-Aminobutyric Acid/metabolism
4.
J Glaucoma ; 29(10): 846-850, 2020 10.
Article in English | MEDLINE | ID: mdl-32740512

ABSTRACT

PRECIS: Preoperative intravenous (IV) dexmedetomidine produced a 33% reduction in intraocular pressure (IOP) within 15 minutes of administration in patients with glaucoma. PURPOSE: To evaluate the effect of preoperative IV dexmedetomidine on IOP in adult patients undergoing glaucoma surgery under local anesthesia. METHODS: In a prospective interventional case series, 12 patients with uncontrolled IOP (IOP>24 mm Hg in both the eyes) with the systemic status of American Society of Anesthesiologists (ASA) classification I-II, received IV dexmedetomidine 0.6 µg/kg 30 minutes preoperatively. The IOP of the nonsurgical eye (measured with Perkins tonometer), the heart rate (HR), and blood pressure (BP) were recorded 5 minutes prior, 15 minutes and 2 hours after IV dexmedetomidine administration, and were compared using analysis of variance and Tukey honestly significant difference tests. RESULTS: There were 4 women and 8 men with a mean age (±SD) of 60.6±10.4 years. The mean number of antiglaucoma medications was 4.3±1.3. The mean pre-dexmedetomidine IOP was 31.5±5.6 mm Hg. At 15 minutes post-dexmedetomidine administration, the mean and percentage drop in IOP were 10.2±3.2 mm Hg (P=0.001) and 33%±11%, respectively. The mean and percentage drop in systolic BP were 18±20 mm Hg (P=0.01) and 12%±14%, and drop in diastolic BP were 6.5±10 mm Hg (P=0.05) and 7%±11%, respectively. The mean and percentage drop in HR were 2±0.6 bpm (P=0.48) and 2%±13%, respectively. None of the subjects experienced any medication-related adverse effects. At 2 hours, the mean and percentage drop in IOP were 5.3±3 mm Hg and 17%±11%, respectively. CONCLUSION: In the small sample of (ASA I-II) patients studied, preoperative dexmedetomidine produced a significant drop in IOP (33%) within 15 minutes of IV administration in patients with glaucoma that was reversing at 2 hours, with a good safety profile.


Subject(s)
Adrenergic alpha-2 Receptor Agonists/administration & dosage , Dexmedetomidine/administration & dosage , Filtering Surgery , Glaucoma/surgery , Intraocular Pressure/drug effects , Administration, Intravenous , Adult , Aged , Anesthesia, Local , Blood Pressure/drug effects , Female , Heart Rate/drug effects , Humans , Male , Middle Aged , Ocular Hypertension , Pilot Projects , Prospective Studies , Tonometry, Ocular
6.
Best Pract Res Clin Anaesthesiol ; 33(4): 415-423, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31791560

ABSTRACT

Adjuvants are medications that work synergistically with local anesthetics to help enhance the duration and quality of analgesia in regional techniques. Regional anesthesia has become more prevalent as evidence continues to show efficacy, enhancement of patient care, increased patient satisfaction, and improved patient safety. Practitioners in the perioperative setting need to not only be familiar with regional techniques but also the medications used for them. Some examples of adjuvant medications for regional techniques include dexamethasone, alpha 2 agonists such as clonidine and dexmedetomidine, midazolam, buprenorphine, NMDA antagonists, including ketamine and magnesium, neostigmine, sodium bicarbonate, epinephrine, and non-steroidal anti-inflammatory drugs. The aim of the present investigation, therefore, is to provide a comprehensive review of the most commonly used non-opioid adjuvants in clinical practice today. Regional adjuvants can improve patient safety, increase patient satisfaction, and enhance clinical efficacy. Future studies and best practice techniques can facilitate standardization of regional anesthesia adjuvant dosing when providing nerve blocks in clinical practice.


Subject(s)
Anesthesia, Conduction/methods , Anesthetics, Local/administration & dosage , Nerve Block/methods , Pain, Postoperative/prevention & control , Adrenergic alpha-2 Receptor Agonists/administration & dosage , Analgesics, Opioid/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Drug Synergism , Drug Therapy, Combination , Humans , Ketamine/administration & dosage
7.
Am J Vet Res ; 80(9): 868-877, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31449445

ABSTRACT

OBJECTIVE: To determine the effects of 3 α2-adrenergic receptor agonists (α2-ARAs), alone or in combination with butorphanol tartrate, on objective measurements of lameness in horses. ANIMALS: 17 adult polo horses with naturally occurring forelimb or hind limb lameness (or both). PROCEDURES: In a crossover design, each horse received each protocol (saline [0.09% NaCl] solution [2 mL, IV] or xylazine hydrochloride [0.33 mg/kg, IV], detomidine hydrochloride [0.007 mg/kg, IV], or romifidine hydrochloride [0.033 mg/kg, IV] alone or in combination with butorphanol [0.007 mg/kg, IV]) in random order, with a washout period (≥ 7 days) between protocols. Horses were assessed immediately prior to (baseline) and 10, 15, 20, 30, and 40 minutes after administration of each protocol for degree of sedation, mechanical nociceptive threshold (MNT), and objective lameness measurements. RESULTS: Compared with baseline values, sedation scores and MNTs were significantly higher at all evaluated time points following administration of all sedation protocols except xylazine alone; following administration of xylazine alone, sedation scores and MNTs were significantly higher at ≤ 30 minutes and ≤ 20 minutes, respectively. Significant differences in objective forelimb lameness measurements were noted after administration of the 3 α2-ARA-butorphanol combinations. Most significant differences in objective measurements of hind limb lameness were detected after administration of detomidine or romifidine, alone or in combination with butorphanol. CONCLUSIONS AND CLINICAL RELEVANCE: In the study horses, xylazine alone had the least impact on objective lameness measurements. The administration of α2-ARAs, particularly detomidine or romifidine, alone or in combination with butorphanol, resulted in small but significant effects on objective lameness measurements.


Subject(s)
Adrenergic alpha-2 Receptor Agonists/therapeutic use , Butorphanol/therapeutic use , Imidazoles/therapeutic use , Lameness, Animal/drug therapy , Xylazine/therapeutic use , Adrenergic alpha-2 Receptor Agonists/administration & dosage , Animals , Cross-Over Studies , Drug Therapy, Combination , Female , Forelimb/drug effects , Gait/drug effects , Horses , Imidazoles/administration & dosage , Male , Random Allocation
8.
Indian J Ophthalmol ; 67(5): 636-640, 2019 05.
Article in English | MEDLINE | ID: mdl-31007226

ABSTRACT

Purpose: We conducted a prospective, randomized study to evaluate the efficacy of dexmedetomidine as an additive to peribulbar block for vitreoretinal surgery in terms of onset time of block, hemodynamic stability profile, patient comfort, and surgeon satisfaction. Methods: One hundred patients of American Society of Anesthesiologists grade 1 and 2 scheduled for vitreoretinal surgery were randomly assigned into two groups: control group (n = 50) received lignocaine bupivacaine block, and Dex group (n = 50) received lignocaine bupivacaine plus 20 µg dexmedetomidine peribulbar block. Information regarding time for onset of block, hemodynamic data, visual analog scale for pain, sedation levels, total duration of surgery, and surgeon satisfaction levels were collected. Results: All the demographic characteristics including age, gender, American Society of Anesthesiologists grade, onset of anesthesia, and duration of surgery were comparable in both groups. At the baseline, there was no statistically significant difference in heart rate, mean arterial pressure, diastolic blood pressure, and respiratory rate between the two groups, with a difference noted in systolic blood pressure at the baseline. There was significant difference noted in the systolic blood pressure and mean arterial pressure at different time intervals with a decreasing trend as time progressed. The mean sedation score was significantly higher in the Dex group than that in the control group. The surgeon satisfaction was higher in the Dex group than that in the control group. Conclusion: Dexmedetomidine is a useful and safe drug in combination with lignocaine bupivacaine in peribulbar for vitreoretinal surgery as it maintains hemodynamic stability and provides sedation, which enables full cooperation and potentially better operating conditions.


Subject(s)
Anesthesia, Local/methods , Dexmedetomidine/administration & dosage , Nerve Block/methods , Pain, Postoperative/prevention & control , Vitreoretinal Surgery/methods , Adolescent , Adrenergic alpha-2 Receptor Agonists/administration & dosage , Adult , Aged , Anesthetics, Local/administration & dosage , Bupivacaine/administration & dosage , Case-Control Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pain Measurement , Pain, Postoperative/diagnosis , Prospective Studies , Retinal Diseases/surgery , Time Factors , Young Adult
9.
J Cosmet Laser Ther ; 21(4): 225-227, 2019.
Article in English | MEDLINE | ID: mdl-30235041

ABSTRACT

Postinflammatory hyperpigmentation (PIH) and erythema are the most common adverse effects associated with laser treatment, particularly in dark-skinned individuals. Several methods have been used to prevent or minimize these adverse effects; however, to date, no definitive precautions/strategies are known to prevent post-laser PIH and erythema. We investigated whether the topical application of the α-adrenergic receptor agonist brimonidine could reduce laser treatment-related complications such as erythema and PIH.


Subject(s)
Adrenergic alpha-2 Receptor Agonists/administration & dosage , Brimonidine Tartrate/administration & dosage , Erythema/prevention & control , Hyperpigmentation/prevention & control , Low-Level Light Therapy , Administration, Topical , Adolescent , Erythema/etiology , Humans , Hyperpigmentation/etiology , Male , Middle Aged , Tattooing/adverse effects
10.
BMC Anesthesiol ; 18(1): 136, 2018 09 27.
Article in English | MEDLINE | ID: mdl-30261833

ABSTRACT

BACKGROUND: To examine the response to an α2receptor agonist used as a sedative for patients using long-term selective α1 blockers. METHODS: Sixty-nine consecutive patients undergoing transurethral prostate resection or holmium laser resection of the prostateunder spinal anesthesia were divided into two groups; group N (n = 37), which did not receive α1 blockers, and group T (n = 32), which was administered tamsulosin for at least 1 month before the study. Bispectral index scores, Modified Observer's Assessment of Alertness/Sedation scale scores, heart rate, and mean blood pressure were obtained under sedation using dexmedetomidine for 30 min during surgery. RESULTS: The only significant difference found between the groups were mean bloodpressure 15 min after the first loading dose injection of dexmedetomidine. Differencesbetween both groupswere noted at 15 min(group T: 100.2 ± 12.9 mmHg; group N: 90.0 ± 17.5 mmHg; P = 0.08), 20 min (group T: 99.8 ± 12.3 mmHg; group N: 87.4 ± 15.0 mmHg; P < 0.00), 25 min (group T: 99.3 ± 13.4 mmHg; group N: 85.4 ± 13.8 mmHg; P < 0.00), and 30 min (group T: 98.8 ± 13.1 mmHg; group N: 84.5 ± 13.5 mmHg; P < 0.00). CONCLUSIONS: The use of α2 agonists is appropriate during surgery for benign prostatic hyperplasia patients using tamsulosin, and there is no need to alter the dose. Alertness with anesthesia involving α2 agents was maintained for patients using long-term tamsulosin and patients who did not use tamsulosin. TRIAL REGISTRATION: The study was retrospectively registered with the Clinical Research Informational Service ( KCT0002967 , July 2, 2018).


Subject(s)
Adrenergic alpha-1 Receptor Antagonists/administration & dosage , Adrenergic alpha-2 Receptor Agonists/administration & dosage , Anesthetics/administration & dosage , Lasers, Solid-State/therapeutic use , Prostatic Hyperplasia/surgery , Transurethral Resection of Prostate/methods , Aged , Female , Holmium , Humans , Intraoperative Care/methods , Lasers, Solid-State/adverse effects , Male , Middle Aged , Pilot Projects , Prospective Studies , Prostate/pathology , Prostate/surgery , Prostatic Hyperplasia/diagnosis , Prostatic Hyperplasia/drug therapy , Transurethral Resection of Prostate/adverse effects , Treatment Outcome
11.
Anesth Prog ; 64(4): 221-225, 2017.
Article in English | MEDLINE | ID: mdl-29200366

ABSTRACT

Hypertensive patients receiving nonselective ß-adrenergic antagonists are vulnerable to hypertension and bradycardia when injected with dental local anesthetic formulations containing epinephrine. Dexmedetomidine (DEX), an α2-adrenergic agonist, has been reported to prolong and enhance the local anesthetic effects of lidocaine. The cardiovascular effects of the DEX-lidocaine combination have not yet been investigated in the presence of nonselective ß-adrenergic antagonists. Therefore, we assessed the cardiovascular effects of the DEX-lidocaine combination in spontaneously hypertensive rats (SHR) treated with a nonselective ß-adrenergic antagonist (propranolol). We injected propranolol-treated rats with various concentrations of DEX alone, 100 µg/kg epinephrine alone, or 5 µg/kg DEX combined with 2% lidocaine and measured their blood pressure (BP) and heart rates (HR) to assess the cardiovascular effects. The BP of propranolol-treated SHR was significantly increased by treatment with 100 µg/kg epinephrine alone. The BP and HR of propranolol-treated SHR were not significantly changed by treatment with low concentrations of DEX, but they were significantly decreased by treatment with a high concentration of DEX (50 µg/kg). Moreover, there was no significant difference in the BP and HR of propranolol-treated SHR after the injection of a combination of 5 µg/kg DEX and 2% lidocaine. Thus, the DEX-lidocaine combination may be an acceptable addition to dental local anesthetic solutions from a cardiovascular standpoint for hypertensive patients receiving nonselective ß-adrenergic antagonists.


Subject(s)
Anesthesia, Dental/methods , Dexmedetomidine/administration & dosage , Hypertension/complications , Lidocaine/administration & dosage , Adrenergic alpha-2 Receptor Agonists/administration & dosage , Adrenergic alpha-2 Receptor Agonists/adverse effects , Adrenergic beta-Antagonists/administration & dosage , Adrenergic beta-Antagonists/pharmacology , Anesthesia, Dental/adverse effects , Anesthesia, Local/adverse effects , Anesthesia, Local/methods , Anesthetics, Local/administration & dosage , Anesthetics, Local/adverse effects , Animals , Blood Pressure/drug effects , Bradycardia/etiology , Dexmedetomidine/adverse effects , Drug Therapy, Combination , Epinephrine/administration & dosage , Epinephrine/pharmacology , Heart Rate/drug effects , Humans , Lidocaine/adverse effects , Propranolol/administration & dosage , Propranolol/pharmacology , Rats , Rats, Inbred SHR
12.
Mol Med Rep ; 14(4): 3237-42, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27498747

ABSTRACT

Tolerance to hypoxia can be induced by reducing oxygen consumption. Dexmedetomidine (DEX) decreases locomotor activity and induces bradycardia and hypothermia in mice. The present study examined the hypothesis that DEX improves hypoxia tolerance in mice. Adult mice received an intraperitoneal injection of 1, 5, 10, 20, 40, 80, 160 or 320 µg/kg DEX, 20 mg/kg propranolol or saline. Acute hypoxic conditions were induced by placing the mice in a limited enclosed container with soda lime. Core body temperature (CBT) and heart rate (HR) were measured prior to and 30 min after drug administration. Survival time was monitored in the sealed container. Survival times (mean ± standard deviation) of mice in the saline, 1, 5, 10, 20, 40, 80, 160 and 320 µg/kg DEX, and the 20 mg/kg propranolol groups were 22.4±1.1, 23.4±1.1, 26.0±0.9, 36.9±5.2, 42.4±2.9, 43.2±2.3, 58.2±4.2, 80.5±4.0, 79.2±6.0, and 38.2±2.8 min, respectively. Pretreatment with propranolol and 10, 20, 40, 80, 160 or 320 µg/kg DEX, but not 1 or 5 µg/kg, significantly prolonged survival time compared with saline­injected mice (P<0.05 or P<0.01). CBT and HR decreased in a similar manner. The correlation coefficients between survival time and CBT, and survival time and HR were ­0.802 and ­0.726, respectively. Thus, DEX dose­dependently enhances hypoxia tolerance in mice. In conclusion, it is suggested that DEX may be used in clinical practice as a novel protective agent for organs and tissues during hypoxic injury.


Subject(s)
Adrenergic alpha-2 Receptor Agonists/therapeutic use , Dexmedetomidine/therapeutic use , Heart Rate/drug effects , Hypnotics and Sedatives/therapeutic use , Hypoxia/drug therapy , Adrenergic alpha-2 Receptor Agonists/administration & dosage , Animals , Dexmedetomidine/administration & dosage , Heart/drug effects , Heart/physiopathology , Hypnotics and Sedatives/administration & dosage , Hypoxia/physiopathology , Male , Mice
14.
BMC Anesthesiol ; 15: 17, 2015 Jan 27.
Article in English | MEDLINE | ID: mdl-25971886

ABSTRACT

BACKGROUND: Dexmedetomidine (DMT), a highly selective α2-adrenoceptor agonist, has been used safely as a sedative in patients under regional anesthesia. The purpose of this study was to determine the 50% effective dose (ED50) of single-dose DMT to induce adequate light sedation in elderly patients in comparison with younger patients undergoing transurethral resection of the prostate (TURP) with spinal anesthesia. METHODS: Forty-two male patients were recruited. The young age group (Group Y) included patients 45 to 64 years old and the old age group (Group O) included patients 65 to 78 years old. After the spinal anesthesia was performed, a pre-calculated dose of DMT was administered for 10 min. The Observer's Assessment of Alertness/Sedation (OAA/S) scale, bispectral index score (BIS) were assessed then at 2-min intervals for 20 min. A modified Dixon's up-and-down method was used to determine the ED50 of the drug for light sedation (OAA/S score 3/4). In the recovery room, regression times of the motor and sensory blocks were recorded. RESULTS: The ED50 of DMT was 0.25 (95% C.I. 0.15-0.35) µg/kg in Group O and 0.35 (95% C.I. 0.35-0.45) µg/kg in Group Y (p = 0.002). The ED95 was 33% lower in Group O compare with Group Y (0.38 (95% C.I. 0.29-0.39) µg/kg vs. 0.57 (95% C.I. 0.49-0.59) µg/kg). The regression time of sensory block was longer in Group O than in Group Y (109.0 ± 40.2 min vs. 80.0 ± 31.6 min) (p = 0.014). CONCLUSION: The single-dose of DMT for light sedation was lower by 21% in Group O compare with Group Y underwent TURP with spinal anesthesia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01665586. Registered July 31, 2012.


Subject(s)
Adrenergic alpha-2 Receptor Agonists/administration & dosage , Dexmedetomidine/administration & dosage , Hypnotics and Sedatives/administration & dosage , Transurethral Resection of Prostate/methods , Adult , Age Factors , Aged , Anesthesia, Spinal/methods , Dose-Response Relationship, Drug , Drug Administration Schedule , Hemodynamics/drug effects , Humans , Male , Middle Aged
15.
J Med Food ; 17(10): 1079-85, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25055183

ABSTRACT

Platonia insignis Mart. (Clusiaceae) is a medicinal plant from the Brazilian Amazon region. The present study evaluated the biological potential of the ethanol extract (Pi-EtOH) and ethyl acetate fraction (Pi-EtOAc) of the P. insignis fruit shells on the cardiovascular system of rats. Pi-EtOH or Pi-EtOAc (12.5, 25, and 50 mg/kg) was administered intravenously in normotensive rats (260-300 g), and the mean arterial pressure and the heart rate were monitored. The Pi-EtOH induced hypotension (-11.56±0.89, -7.43±0.85, and -17.56±1.97 mmHg) followed by bradycardia in two highest doses (-8.89±3.62 and -15.79±1.83 beats/min) and Pi-EtOAc, at the same doses, induced hypotension (-11.2±1.03, -14.48±1.13, -29.89±2.67 mmHg) more intensively, followed by tachycardia at the dose 12.5 and 25 mg/kg (15.64±2.06, 19.31±1.92 beats/min) and bradycardia at a dose of 50 mg/kg (-9.98±7.33 beats/min). The hypotensive response from Pi-EtOAc was not attenuated when used in the pretreatment with L-NAME, verapamil, propranolol, and hexamethonium. However, when using yohimbine, the hypotensive effect was inhibited (-4.42±1.28 (P<.05), -3.29±0.99 (P<.05), 2.06±1.18 mmHg (P<.05); Student's t-test). Hence, the Pi-EtOAc seems to act similarly to the α2-adrenergic agonist in this hypotensive effect.


Subject(s)
Adrenergic alpha-2 Receptor Agonists/administration & dosage , Antihypertensive Agents/administration & dosage , Clusiaceae/chemistry , Hypertension/drug therapy , Plant Extracts/administration & dosage , Receptors, Adrenergic, alpha-2/metabolism , Animals , Blood Pressure/drug effects , Heart Rate/drug effects , Humans , Hypertension/genetics , Hypertension/metabolism , Hypertension/physiopathology , Male , Rats , Rats, Wistar , Receptors, Adrenergic, alpha-2/genetics
16.
J Oral Maxillofac Surg ; 72(3): 474-80, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24268964

ABSTRACT

PURPOSE: The combination of α2-adrenoceptor agonists, such as dexmedetomidine (DEX) and clonidine, with local anesthetics has been found to extend the duration of peripheral nerve blocks, probably owing to the resultant local vasoconstriction in the peripheral nerves. However, because the clear elucidation of the effect of DEX requires examination of the local anesthetic effect with DEX alone and the combination of various concentrations of DEX with local anesthetics, we evaluated the local anesthetic effect of various concentrations of DEX alone and with a local anesthetic. MATERIALS AND METHODS: The present study assessed the tail-flick (TF) latencies after injection of the appropriate drug in male Sprague-Dawley rats, using an epidural model that allowed constant pain stimulation intensity, dispersion of the anesthetic, and a precise injection site and dose. Lidocaine alone, lidocaine with 2.5-ppm DEX, lidocaine with 5.0-ppm DEX, lidocaine with 7.5-ppm DEX, and DEX alone were administered at the predetermined dose. The TF latency changes over time were compared using repeated measures analysis of variance (ANOVA). Comparisons among the groups were analyzed using ANOVA followed by a post hoc Dunnett's multiple comparison test or Tukey's multiple comparison test. RESULTS: The addition of DEX to lidocaine increased the TF latency and dose-dependently prolonged its duration as follows: 0-ppm DEX, 20 minutes; 2.5-ppm, 40 minutes; 5.0-ppm, 40 minutes; and 7.5-ppm, 50 minutes. DEX alone did not change the TF latency. CONCLUSIONS: Our results have demonstrated that DEX dose-dependently enhances the local anesthetic action of lidocaine in a rat TF model.


Subject(s)
Adjuvants, Anesthesia/administration & dosage , Adrenergic alpha-2 Receptor Agonists/administration & dosage , Anesthesia, Dental/methods , Anesthesia, Local/methods , Anesthetics, Local/administration & dosage , Dexmedetomidine/administration & dosage , Lidocaine/administration & dosage , Animals , Dose-Response Relationship, Drug , Injections, Epidural , Male , Rats , Rats, Sprague-Dawley
17.
Eur J Pharmacol ; 724: 16-23, 2014 Feb 05.
Article in English | MEDLINE | ID: mdl-24374198

ABSTRACT

Intrathecal application of α2 noradrenergic receptor agonists effectively alleviates the pathological pain induced by peripheral tissue injury. However, the spinal antinociceptive mechanisms of α2 noradrenergic receptors remain to be characterized. The present study performed immunohistochemistry and western blot to elucidate the signaling pathway initiated by α2 noradrenergic receptors in spinal dorsal horn of mice, and identified calcium/calmodulin-dependent protein kinase II (CaMKII) as an important target for noradrenergic suppression of inflammatory pain. Our data showed that intraplantar injection of Complete Freund's Adjuvant (CFA) substantially enhanced CaMKII autophosphorylation at Threonine 286, which could be abolished by intrathecal administration of α2 noradrenergic receptor agonist clonidine. Gi protein-coupled α2 noradrenergic receptor might inhibit cAMP-dependent protein kinase (PKA) to disturb CaMKII signaling. We found that pharmacological activation of PKA in intact mice also enhanced spinal CaMKII autophosphorylation level, which was completely antagonized by clonidine. Moreover, direct PKA inhibition in CFA-injected mice mimicked the suppressive effect of α2 noradrenergic receptors on CaMKII. PKA inhibition has been shown to downregulate CaMKII by enhancing protein phosphatase activity. Consistent with this notion, spinal treatment with protein phosphatase inhibitor okadaic acid ruled out clonidine-mediated CaMKII dephosphorylation in CFA-injected mice. Through PKA/protein phosphatase/CaMKII pathway, clonidine noticeably decreased CFA-evoked phosphorylation of N-methyl-d-aspartate subtype glutamate receptor GluN1 and GluN2B subunit as well as α-amino-3-hydroxy-5-methylisoxazole-4-propionic Acid subtype glutamate receptor GluA1 subunit. These data suggested that interference with CaMKII signaling might represent an important mechanism underlying noradrenergic suppression of inflammatory pain.


Subject(s)
Adrenergic alpha-2 Receptor Agonists/pharmacology , Calcium-Calmodulin-Dependent Protein Kinase Type 2/antagonists & inhibitors , Clonidine/pharmacology , Inflammation/metabolism , Pain/metabolism , Adrenergic alpha-2 Receptor Agonists/administration & dosage , Animals , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Clonidine/administration & dosage , Freund's Adjuvant , Inflammation/chemically induced , Injections, Spinal , Male , Mice , Pain/chemically induced , Posterior Horn Cells/drug effects , Posterior Horn Cells/metabolism , Receptors, AMPA/antagonists & inhibitors , Receptors, AMPA/metabolism , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Receptors, N-Methyl-D-Aspartate/metabolism , Signal Transduction
18.
Biol Pharm Bull ; 36(6): 959-65, 2013.
Article in English | MEDLINE | ID: mdl-23727917

ABSTRACT

Low-dose bupivacaine can limit the spinal block level with minimal hemodynamic effects and yield a rapid recovery, but sometimes it may not provide adequate anesthesia for surgery. Dexmedetomidine, a selective α2-adrenoreceptor agonist, was shown to be a potent antinociceptive agent when given intrathecally in animals and humans. The purpose of this study was to evaluate the adjuvant effects of intrathecal dexmedetomidine in elderly patients undergoing transurethral prostate surgery with low-dose bupivacaine spinal anesthesia. Fifty-four patients undergoing transurethral prostate surgery were randomized into two groups receiving either dexmedetomidine 3 µg (n=27) or normal saline (n=27) intrathecally with 6 mg of 0.5% hyperbaric bupivacaine. The characteristics of the spinal block and postoperative analgesic effects were evaluated. The peak block level was similar for the two groups. However, the dexmedetomidine group demonstrated a faster onset time to the peak block and longer duration of spinal block than the saline group (p<0.01). The motor block scales at the time of peak sensory block and regression of 2-sensory dermatomes were higher in the dexmedetomidine group than in the saline group (p<0.001). There was less analgesic request and the time to the first analgesic request was longer in the dexmedetomidine group than in the saline group (each 487, 345 min, p<0.05). Dexmedetomidine 3 µg when added to intrathecal bupivacaine 6 mg produced fast onset and a prolonged duration of sensory block and postoperative analgesia in elderly patients for transurethral surgery. However, recovery of motor block could be delayed in dexmedetomidine-added patients.


Subject(s)
Adjuvants, Pharmaceutic/administration & dosage , Adrenergic alpha-2 Receptor Agonists/administration & dosage , Analgesics, Non-Narcotic/administration & dosage , Anesthetics, Local/administration & dosage , Bupivacaine/administration & dosage , Dexmedetomidine/administration & dosage , Aged , Anesthesia, Spinal , Double-Blind Method , Hemodynamics/drug effects , Humans , Injections, Spinal , Male , Middle Aged , Transurethral Resection of Prostate
19.
Fundam Clin Pharmacol ; 27(1): 104-12, 2013 Feb.
Article in English | MEDLINE | ID: mdl-21793900

ABSTRACT

Previous work has shown that intraperitoneal administration of riparin III (ripIII) reduces immobility time in the forced swimming test (FST), which suggests potential antidepressant activity. As the mechanism of action is not completely understood, this study is aimed at investigating the antidepressant-like action of ripIII. Following intraperitoneal administration of ripIII at doses of 25 and 50 mg/kg, there were decreases in the immobility time in the FST and tail suspension test without accompanying changes in ambulation (data not shown). The pretreatment of mice with sulpiride (50 mg/kg, i.p.), prazosin (1 mg/kg, i.p.), yohimbine (1 mg/kg, i.p.), and p-chlorophenylalanine (PCPA, 100 mg/kg, i.p. for, four consecutive days) significantly prevented the anti-immobility effect of ripIII in the FST. On the other hand, the anti-immobility effect of ripIII (50 mg/kg, v.o.) was not altered by pretreatment of mice with SCH23390 (15 µg/kg, i.p.) Furthermore, ripIII potentiated the sleeping latency and sleeping time of the pentobarbital-induced sleeping time test and also potentiated apomorphine (16 mg/kg, i.p.)-induced hypothermia in mice. In conclusion, the present study provides evidence that the antidepressant-like effect of ripIII is dependent on its interaction with the serotonergic, noradrenergic (α1- and α2- receptors), and dopaminergic (dopamine D2 receptors) systems.


Subject(s)
Antidepressive Agents/therapeutic use , Benzamides/therapeutic use , Brain/drug effects , Depression/drug therapy , Neurons/drug effects , Tyramine/analogs & derivatives , Administration, Oral , Adrenergic alpha-1 Receptor Agonists/administration & dosage , Adrenergic alpha-1 Receptor Agonists/therapeutic use , Adrenergic alpha-2 Receptor Agonists/administration & dosage , Adrenergic alpha-2 Receptor Agonists/therapeutic use , Animals , Antidepressive Agents/administration & dosage , Behavior, Animal/drug effects , Benzamides/administration & dosage , Brain/metabolism , Brazil , Depression/metabolism , Dopamine Agonists/administration & dosage , Dopamine Agonists/therapeutic use , Ethnopharmacology , Fruit/chemistry , Fruit/growth & development , Guyana , Lauraceae/chemistry , Lauraceae/growth & development , Male , Mice , Neurons/metabolism , Receptors, Dopamine D2/agonists , Receptors, Dopamine D2/metabolism , Serotonin Receptor Agonists/administration & dosage , Serotonin Receptor Agonists/therapeutic use , Tyramine/administration & dosage , Tyramine/therapeutic use
20.
Can Vet J ; 53(2): 193-5, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22851784

ABSTRACT

The prophylactic antiemetic effect of 3 dosages of promethazine injected into cats 1 h before administration of xylazine was compared with that of a saline solution. Prior treatment with 2 and 4 mg/kg of promethazine significantly reduced the frequency of emetic episodes. Promethazine may be used as a prophylactic antiemetic in cats treated with xylazine.


Subject(s)
Adrenergic alpha-2 Receptor Agonists/administration & dosage , Antiemetics/therapeutic use , Cat Diseases/prevention & control , Promethazine/therapeutic use , Vomiting/veterinary , Xylazine/administration & dosage , Adrenergic alpha-2 Receptor Agonists/adverse effects , Animals , Cats , Dose-Response Relationship, Drug , Female , Male , Vomiting/prevention & control , Xylazine/adverse effects
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