Comparison of Adrenaline and Dexmedetomidine in Improving the Cutaneous Analgesia of Mexiletine in Response to Skin Pinpricks in Rats

Pharmacology ◽  
2020 ◽  
Vol 105 (11-12) ◽  
pp. 662-668
Author(s):  
Mingming Han ◽  
Fang Kang ◽  
Chengwei Yang ◽  
Ziyou Liu ◽  
Ting Wang ◽  
...  
Keyword(s):  
Experimental Research ◽  
Local Anesthetics ◽  
Analgesic Effect ◽  
Sensory Block ◽  
Mechanisms Of Action ◽  
High Dose ◽  
Low Doses ◽  
Subcutaneous Injections ◽  
Injection Dose ◽  
The Difference

<b><i>Background:</i></b> Adrenaline (Adr) and dexmedetomidine (Dex) are commonly used adjuvants of local anesthetics; however, the difference in the improvement of analgesia of local anesthetics between the 2 adjuvants remains unclear. <b><i>Objective:</i></b> The objective of this experimental research was to evaluate the cutaneous analgesic effect of mexiletine (Mex) by coadministration with Dex or Adr. <b><i>Methods:</i></b> The effect of a nociceptive block was assessed based on the inhibition of the cutaneous trunci muscle reflex in response to skin pinpricks in rats. The analgesic activity of Mex alone and Mex coadministered with Dex or Adr was evaluated after subcutaneous injections. Subcutaneous injections of drugs or combinations include Mex 0.6, 1.8, and 6.0 μmol; Adr 13.66 nmol; Dex 1.05600 nmol; saline; and Mex 1.8 and 6.0 μmol, respectively, combined with Dex 0.01056, 0.10560, and 1.05600 nmol or Adr 0.55, 2.73, and 13.66 nmol, with each injection dose of 0.6 mL. <b><i>Results:</i></b> Subcutaneous injections of Mex elicited dose-related cutaneous analgesia. Compared with Mex (1.8 μmol), adding Dex or Adr to Mex (1.8 μmol) solutions for skin nociceptive block potentiated and prolonged the action. Mex (6.0 μmol) combined with Dex or Adr extended the duration of cutaneous analgesia when compared with Mex (6.0 μmol) alone. A high dose of Adr is more effective with Mex 1.8 μmol than that of Dex, whereas medium and low doses were less effective. Mex 6.0 μmol combined with any dose of Adr is superior to that of Dex. <b><i>Conclusions:</i></b> Both Dex and Adr improve the sensory block and enhance the nociceptive block duration of Mex. But in most cases, Adr is superior to Dex. It may be that different mechanisms of action of the 2 adjuvants lead to the differences.

scholarly journals A comparative study of serotonin and norepinephrine as adjuncts to improve cutaneous antinociception of mexiletine in response to skin pinpricks in rats

2021 ◽  
Vol 35 ◽  
pp. 205873842110161
Author(s):  
Mingming Han ◽  
Fang Kang ◽  
Chengwei Yang ◽  
Mingyu Zhai ◽  
Kesong Zheng ◽  
...  
Keyword(s):  
Comparative Study ◽  
Local Anesthetics ◽  
Subcutaneous Injection ◽  
Sensory Block ◽  
Subcutaneous Injections ◽  
Injection Dose ◽  
The Difference

As adrenaline, serotonin and norepinephrine are two other vasoconstrictors and both of which have been proved to increase the quality and duration of local anesthetics when added as adjuvants. However, the difference in the improvement of the nociception of local anesthetics between the two adjuvants remains unclear. The purpose of this study was to assess the cutaneous nociception of mexiletine by coadministration with serotonin and norepinephrine. Subcutaneous injection of drugs or combinations includes mexiletine 0.6, 1.8, 6.0 μmol, serotonin 1.6500 μmol, noradrenaline 0.8895 nmol, saline, mexiletine 1.8 and 6.0 μmol, respectively combined with serotonin 0.4125, 0.8250, 1.6500 μmol and noradrenaline 0.0356, 0.1779, 0.8895 nmol, with each injection dose of 0.6 ml. The nociception of mexiletine alone and mexiletine coadministered with serotonin and norepinephrine was assessed after subcutaneous injection. Subcutaneous injections of mexiletine elicited dose-related cutaneous antinociception ( P < 0.05, 0.01, or 0.001). Compared with mexiletine (1.8 μmol), adding norepinephrine (except for lowest dose) and serotonin to mexiletine (1.8 μmol) solutions for skin nociceptive block potentiated and prolonged the action ( P < 0.01 or 0.001). Mexiletine (6.0 μmol) combined with norepinephrine and serotonin extended the duration of cutaneous antinociception when compared with mexiletine (6.0 μmol) alone ( P < 0.05, 0.01, or 0.001). Both serotonin and norepinephrine improve the sensory block and enhances the nociceptive block duration of mexiletine, and serotonin is superior to that of norepinephrine.

scholarly journals Selecting the ideal adjuvant to improve neuraxial and regional analgesia: A narrative review

2020 ◽  
Vol 24 (6) ◽  
Author(s):  
Dmytriiev Dmytro ◽  
Nazarchuk Oleksandr ◽  
Dmytriiev Kostiantyn ◽  
Lysak Evgenii ◽  
Zaletska Olesya
Keyword(s):  
Local Anesthetics ◽  
Sensory Block ◽  
Narrative Review ◽  
Regional Analgesia ◽  
Effect Duration ◽  
The Difference ◽  
Time To Onset ◽  
Crucial Part ◽  
Better Than ◽  
The Ideal

Introduction: The aim of this review was to systematize known facts about the effects of adjuvants to local anesthetics for neuraxial and regional analgesia in order to determine the adjuvant with the best effect among all others. More precisely to consider the time to onset, the strength of the effect, duration of the motor and sensory block and some additional effects such as ‘marker of intravascular injection’, safety and toxicity profile. We aimed to find an ideal adjuvant which has all these properties to a good degree. Methodology: For this narrative review we searched the information in Medline, PubMed, Scopus, and Embase databases. 105 articles were identified regarding the topic, published since 1989 to 2020. Data from 105 articles about adjuvants to local anesthetics was analyzed and synthesized in this review. Results: Regional methods of analgesia are becoming a crucial part of anesthesiologists’ practice and the knowledge about adjuvants is developing alongside with it, so there are more and more studies devoted to it. All of them try to find the “ideal” adjuvant, having sufficient necessary effects, but we think that due to the difference in various classes of adjuvants, some may be better than others. However, use of combination of adjuvants is not desirable at all times. Conclusion: A variety of adjuvants to local anesthetics are available now, yet the data about most of them remains inconclusive, so more studies are required to found out the best adjuvants with the most desirable profile and the least adverse effects Key words: Local anesthetic; Adjuvants; Pain management; Regional anesthesia. Citation: Dmytro D, Oleksandr N, Kostiantyn D, Evgenii L, Olesya Z. Selecting the ideal adjuvant to improve neuraxial and regional analgesia: A narrative review. Anaesth. pain intensive care 2020;24(6):---; DOI: 10.35975/apic.v24i6.1209 Received: 24 March 2020, Reviewed: 23 April, 25 June 2020, Revised: 18 October 2020, Accepted: 27 October 2020

PLASMA CORTICOSTEROID LEVELS AND ADRENAL ASCORBIC ACID AFTER INTRAVENOUS CORTICOTROPHIN INJECTIONS AND »STRESSFUL« STIMULI IN THE RAT

1962 ◽  
Vol 39 (4) ◽  
pp. 527-538 ◽  
Author(s):  
Pavo Hedner ◽  
Claus Rerup
Keyword(s):  
Ascorbic Acid ◽  
Abdominal Surgery ◽  
Response Curve ◽  
Significant Rise ◽  
Blocking Effect ◽  
High Dose ◽  
Ascorbic Acid Concentration ◽  
Unilateral Adrenalectomy ◽  
Subcutaneous Injections ◽  
Hypophysectomized Rats

ABSTRACT Measurements of plasma corticosteroid levels and adrenal ascorbic acid concentration in steroid blocked and hypophysectomized rats were performed. It was found that prednisolone and dexamethasone were effective in blocking endogenous corticotrophin release within 3–4 hours after subcutaneous injection. These agents also prevented completely the normally occurring rise in plasma corticoid levels after exposure of the rats to ether. Abdominal surgery (unilateral adrenalectomy) resulted in a slight but significant rise in plasma corticoid levels in spite of dexamethasone blockade. The values of adrenal ascorbic acid were not affected significantly. The blocking effect of two daily subcutaneous injections of a high dose of dexamethasone persisted for about one week after the last injection. The sensitivity of the plasma corticoid response was essentially the same in hypophysectomized and dexamethasone blocked rats. The lower part of the log dose response curve was found to be clearly non-linear in the plasma corticoid method following intravenous corticotrophin injection. As a consequence the dose level in quantitative assays of intravenously injected corticotrophin are, in our hands, of the same order as in the adrenal ascorbic acid depletion method.

EFFECT OF LOCALLY IMPLANTED OESTROGEN ON THE RESPONSE OF THE RAT'S LACTATING MAMMARY GLAND TO OXYTOCIN

1973 ◽  
Vol 73 (4) ◽  
pp. 700-712 ◽  
Author(s):  
J. D. Bruce ◽  
X. Cofre ◽  
V. D. Ramirez
Keyword(s):  
Mammary Gland ◽  
Mammary Glands ◽  
Myoepithelial Cells ◽  
Recording System ◽  
Saline Infusion ◽  
High Dose ◽  
Low Doses ◽  
Milk Ejection ◽  
Lactating Mammary Gland ◽  
Small Rise

ABSTRACT On the day following delivery (day 1 of lactation) one abdominal mammary gland was implanted with oestrogen and the contralateral gland received an empty needle. At 2, 5 or 10 days of lactation the rats were anaesthetized with pentobarbital and the nipples of both abdominal glands were cannulated and their pressures recorded by means of transducers coupled to an amplifier and recording system. The normal mammary glands of 5-day lactating rats responded to very low doses of oxytocin (Syntocinon®, Sandoz) (5× 10−8 mU) with a rhythmic elevation in pressure. However, saline infusion also evoked a small rise in intra-mammary pressure. Earlier (2 days) and later (10 days) in lactation the responses were smaller. Oestrogen decreases significantly the milk ejection response to oxytocin, and the effect was maximal at day 10 of lactation. Histological observations confirmed the diminished reaction of the gland to oxytocin, since the milk was retained in the alveoli of rats bearing a mammary-oestrogen implant. A paradoxical rise in pressure was detected in normal as well as in oestrogen-implanted glands when the lowest dose of oxytocin was injected in lactating rats which had previously received a high dose of oxytocin (50 mU or 500 mU). These results reinforce the hypothesis that oestrogen alters the milk ejection response to oxytocin and that the mechanism is probably related to changes in the contractility of the myoepithelial cells.

Dexamethasone-Chemical Structure and Mechanisms of Action in Prophylaxis of Postoperative Side Effects

2019 ◽  
Vol 70 (3) ◽  
pp. 843-847 ◽  
Author(s):  
Oana Roxana Ciobotaru ◽  
Mary-Nicoleta Lupu ◽  
Laura Rebegea ◽  
Octavian Catalin Ciobotaru ◽  
Oana Monica Duca ◽  
...  
Keyword(s):  
Wound Healing ◽  
Side Effects ◽  
Length Of Stay ◽  
Hospital Admission ◽  
Postoperative Period ◽  
Analgesic Effect ◽  
Chemical Structure ◽  
Mechanisms Of Action ◽  
Good Recovery ◽  
Synthetic Glucocorticoid

Dexamethasone is a synthetic glucocorticoid used for its anti-inflammatory and analgesic effect. In addition to these therapeutic indications, it is also recommended for nausea and vomiting treatment which may occur during the postoperative period, with impact on postoperative evolution, regarding the evolution of wound healing and length of stay (LOS), with a reflection on the costs of hospital admission. Therefore, their prevention is very important for both patients� comfort and a good recovery.

scholarly journals Effects of Dexmedetomidine as an Analgesic Adjuvant for Surgery of Femur Fracture: A Systematic Review and Meta-Analysis

Pharmacology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Shan Deng ◽  
Yonghao Yu
Keyword(s):  
Femur Fracture ◽  
Meta Analysis ◽  
Sensory Block ◽  
Cochrane Library ◽  
Rescue Analgesia ◽  
Block Level ◽  
Block Time ◽  
Sedation Scores ◽  
The Difference ◽  
The Cochrane Library

Patients who undergo surgery of femur fracture suffer the excruciating pain. Dexmedetomidine (DEX) is a unique α2-adrenergic receptor agonist with sedative and analgesic properties, whose efficacy and safety are still unclear for surgery of femur fracture. Randomized controlled trials comparing the effects of addition of DEX to general or local anesthesia in surgery of femur fracture were searched from MEDLINE, EMBASE, and the Cochrane Library database. Patients who received DEX infusion had a significant longer time to rescue analgesia compared with those without DEX coadministration. DEX treatment seemed to reduce the visual analog score; however, the significance did not reach any statistical difference. DEX as an analgesic adjuvant did not reduce the onset of sensory block time, shorten the time to achieve maximum sensory block level, and provide a longer duration of sensory block. The difference in mean sedation scores between 2 groups was not statistically significant. As for adverse effects, DEX therapy significantly increased the rate of hypotension. In conclusion, dexmedetomidine as a local anesthetic adjuvant in femur fracture surgery had a longer duration of rescue analgesia. However, the incidence of hypotension was markedly increased in these patients. It was worth noting that the evidence was of low to moderate quality.

Perspectives of physicians on medical acupuncture in Lebanon: a preliminary study

2020 ◽  
pp. 096452842096883
Author(s):  
Fadila Bassem Naji ◽  
Kamal Wahab ◽  
Ghassan Hamadeh ◽  
Sani Hlais
Keyword(s):  
Integrative Medicine ◽  
Online Survey ◽  
Response Rate ◽  
Mechanisms Of Action ◽  
Medical Curricula ◽  
Chinese Acupuncture ◽  
The Future ◽  
Preliminary Study ◽  
Medical Acupuncture ◽  
The Difference

Objectives: There are no regulations governing the practice of acupuncture in Lebanon as it is not yet registered as a profession. To our knowledge, no studies have ever been conducted in Lebanon regarding the practice of acupuncture. The purpose of this preliminary study was to explore the knowledge of Lebanese physicians about acupuncture, with the intent of conducting larger scale studies and developing strategies aimed at refining this knowledge in the future, and the ultimate goal of setting guidelines for acupuncture practice in Lebanon. Methods: An online survey looking into physicians’ knowledge of acupuncture, its mechanisms of action, effectiveness, indications and safety, and physicians’ understanding of its concepts, was circulated to 4651 physicians registered in the Lebanese orders of physicians. Results: One hundred forty-nine physicians (3.2%) completed the survey. Most study respondents stated that they were unaware of the difference between traditional Chinese acupuncture (TCA) and Western medical acupuncture (WMA). Overall, 30% of respondents had personally used and/or referred patients for acupuncture. Physicians who had personally tried acupuncture were more likely to refer patients for acupuncture (p < 0.001). Those who know the difference between WMA and TCA were more likely to have tried or referred for acupuncture (p = 0.004). 72% believed that acupuncture and other integrative medicine modules should be introduced in medical curricula in Lebanon. Conclusion: Interest in acupuncture among physicians in Lebanon appears to be limited, based on the low response rate. Among respondents, physicians who had tried or referred patients for acupuncture appeared to be more well informed about different acupuncture styles.

scholarly journals Busulfan plus melphalan versus melphalan alone conditioning regimen after bortezomib based triplet induction chemotherapy for patients with newly diagnosed multiple myeloma

2021 ◽  
Vol 12 ◽  
pp. 204062072110129
Author(s):  
Songyi Park ◽  
Dong-Yeop Shin ◽  
Junshik Hong ◽  
Inho Kim ◽  
Youngil Koh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Chemotherapy ◽  
Statistical Significance ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
High Dose ◽  
Newly Diagnosed ◽  
Cell Engraftment ◽  
The Difference ◽  
High Dose Melphalan

Background: High dose melphalan (HDMEL) is considered the standard conditioning regimen for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients. Recent studies showed superiority of busulfan plus melphalan (BUMEL) compared to HDMEL as a conditioning regimen. We compared the efficacy of HDMEL and BUMEL in newly diagnosed Asian MM patients, who are often underrepresented. Methods: This is a single-center, retrospective study including MM patients who underwent ASCT after bortezomib-thalidomide-dexamethasone (VTD) triplet induction chemotherapy between January 2015 and August 2019. Result: In the end, 79 patients in the HDMEL group were compared to 31 patients in the BUMEL group. There were no differences between the two groups with regards to sex, age at ASCT, risk group, and stage. The HDMEL group showed better response to pre-transplant VTD compared to BUMEL, but after ASCT the BUMEL group showed better overall response. In terms of progression-free survival (PFS), although BUMEL showed trends towards better PFS regardless of pre-transplant status and age, the difference did not reach statistical significance. The BUMEL group more often experienced mucositis related to chemotherapy, but there was no difference between the two groups with regards to hospitalization days, cell engraftment, and infection rates. Conclusion: BUMEL conditioning deserves attention as the alternative option to HDMEL for newly diagnosed MM patients, even in the era of triplet induction chemotherapy. Specifically, patients achieving very good partial response (VGPR) or better response with triplet induction chemotherapy might benefit the most from BUMEL conditioning. Tailored conditioning regimen, based on patient’s response to induction chemotherapy and co-morbidities, can lead to better treatment outcomes.

scholarly journals Enlarged glycemic variability in sulfonylurea-treated well-controlled type 2 diabetics identified using continuous glucose monitoring

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fumi Uemura ◽  
Yosuke Okada ◽  
Keiichi Torimoto ◽  
Yoshiya Tanaka
Keyword(s):  
Glucose Level ◽  
Continuous Glucose Monitoring ◽  
Glucose Monitoring ◽  
Glycemic Variability ◽  
High Dose ◽  
Type 2 Diabetics ◽  
Time In Range ◽  
The Difference ◽  
Glycated Hemoglobin Level

AbstractTime in range (TIR) is an index of glycemic control obtained from continuous glucose monitoring (CGM). The aim was to compare the glycemic variability of treatment with sulfonylureas (SUs) in type 2 diabetes mellitus (T2DM) with well-controlled glucose level (TIR > 70%). The study subjects were 123 patients selected T2DM who underwent CGM more than 24 h on admission without changing treatment. The primary endpoint was the difference in glycemic variability, while the secondary endpoint was the difference in time below range < 54 mg/dL; TBR < 54, between the SU (n = 63) and non-SU (n = 60) groups. The standard deviation, percentage coefficient of variation (%CV), and maximum glucose level were higher in the SU group than in the non-SU group, and TBR < 54 was longer in the high-dose SU patients. SU treatment was identified as a significant factor that affected %CV (β: 2.678, p = 0.034). High-dose SU use contributed to prolonged TBR < 54 (β: 0.487, p = 0.028). Our study identified enlarged glycemic variability in sulfonylurea-treated well-controlled T2DM patients and high-dose SU use was associated with TBR < 54. The results highlight the need for careful adjustment of the SU dose, irrespective of glycated hemoglobin level or TIR value.

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