Alpha-adrenergic Agonist Research Articles

A randomised trial to assess the impact of midodrine on early mobilisation after elective primary hip replacement surgery.

Early mobilisation following elective total hip arthroplasty (THA) facilitates quicker rehabilitation, and reduces complications and hospital length of stay. Reasons for delayed mobilisation are multifactorial, but the most common cause is orthostatic intolerance. Midodrine, an oral alpha-1 agonist, is used off-label for perioperative hypotension. However, there are few randomised trials assessing its use in the perioperative setting to improve patient outcomes. The aim of the study was to determine whether midodrine improves early mobilisation following primary THA, and whether this relates to reduced orthostatic intolerance. This prospective, triple-blinded, multicentre study involved 42 patients randomised to either placebo or 20 mg midodrine, 2 h before physiotherapy, on Day 1 postoperatively. The inclusion criteria were adults undergoing elective unilateral THA under spinal anaesthesia. The primary endpoint was the ability to walk 5 m with physiotherapists. Secondary endpoints included the incidence of orthostatic intolerance and hypotension. A preplanned interim analysis showed no statistical difference in ability to mobilise 5 m (78.26% vs 78.95%, P = 1.0). There was no statistically significant difference in the incidence of orthostatic intolerance between the groups 17.4% vs 31.6% (P = 0.45). Pre-emptive use of midodrine did not improve patient mobilisation the morning after elective primary THA and had no significant effect on the incidence of orthostatic hypotension.

Neuroprotection of retinal ganglion cells by agonism of the beta but not the alpha oestrogen receptor in the axotomized retina of male and female mice.

To compare the course of retinal ganglion cell (RGC) loss following optic nerve crush (ONC) in male and female mice and to assess the neuroprotective potential of intravitreally administered oestrogen receptor alpha (ERα) or beta (ERβ) agonists. Optic nerve crush was performed on the left optic nerve of male and female C57BL/6 mice. RGC loss was evaluated at 3-21 days post-lesion. ERα and ERβ agonists (PPT and DPN, respectively) were injected either immediately after ONC with retinas analysed at 5 days or immediately post-ONC and again at 9 days, with retinas analysed at 21 days post-lesion. Intact retinas served as controls. The total population of Brn3a+RGCs was quantified in retinal flat mounts. To assess the retinal expression of ERα and ERβ, immunodetection was performed on cross sections, and the percentage of RGCs expressing each receptor was determined in flat mounts. Retinal ganglion cell loss in both sexes followed two distinct linear phases: A rapid phase up to 9 days post-lesion, followed by a slower phase. However, the onset of RGC loss was earlier in males than in females. Both ERα and ERβ were expressed in all retinal layers and by the majority of RGCs. While ERα agonism did not confer RGC protection, ERβ agonism was neuroprotective during the second phase of axotomy-induced RGC loss. Preclinical results may be influenced by pooling data from male and female mice. The neuroprotective effects of ERβ during the second phase of RGC loss, likely linked to neuroinflammation, suggest potential therapeutic applications for chronic conditions such as glaucoma.

Medicare Part D Glaucoma Drug Prescribing Patterns by Ophthalmologists from 2018 to 2022.

Background: Glaucoma is a chronic, progressive disease of visual loss and blindness that is often managed pharmacologically. The objective of this study was to evaluate glaucoma drug prescribing trends by ophthalmologists in the United States from 2018 to 2022. Methods: Data on ophthalmologist prescribers were abstracted from Medicare Part D Prescriber Public Use Files to identify the total number of claims for each drug. Drugs were classified by type (generic or brand-name) and by drug class (carbonic anhydrase inhibitors, alpha-2 agonists, beta-blockers, prostaglandin analogs, rho kinase inhibitors, parasympathomimetic drugs, and mixed-mechanism drugs). The types of drugs prescribed were compared longitudinally. Results: Forty glaucoma drugs were prescribed under Medicare Part D from July 1st, 2018, to June 30th, 2022. A dip in total claims and claims by drug class was observed from 2018-2019 to 2019-2020. This was followed by increases to the greater number of claims in 2021-2022. Prostaglandin analogues were the most frequently prescribed class, and the most commonly prescribed drugs were latanoprost, timolol, and the dorzolamide/timolol combination. The majority of claims consisted of generics, and this value increased longitudinally as well. The most rapidly growing class prescribed by physicians was rho kinase inhibitors. Conclusion: Longitudinal differences in Medicare Part D glaucoma drug claims may reflect changing practice patterns and preferences among providers. An increasing number of claims annually, with the exception of the COVID-19 pandemic onset, reflects the growing prevalence of glaucoma. The utilization of new glaucoma agents, such as rho kinase inhibitors, is rapidly increasing as a new therapeutic option.

A randomized controlled interventional study for analgesic effects of intrathecal versus intravenous dexmedetomidine on subarachnoid anesthesia with hyperbaric bupivacaine

Background: Various pharmacologic agents such as opioids, benzodiazepines, ketamine, and alpha2 adrenergic agonists are commonly used to increase the duration of subarachnoid block. Alpha2 agonists have analgesia and sedative properties when used as adjuvant in regional anesthesia. Stable hemodynamics and decreased oxygen requirement due to enhanced sympathoadrenal stability make them very useful adjuvants. Aims and Objectives: To evaluate the effects of intrathecal versus intravenous (IV) dexmedetomidine on the block, characteristics, and sedation in patients receiving subarachnoid block with hyperbaric bupivacaine. Materials and Methods: In this prospective, randomized controlled, double-blind study total of 90 patients with the American Society of Anesthesiologists grade I and II were randomly allocated into three groups: Group A (n=30) received IV 20 mL 0.9% NaCl over 10 min followed by intrathecal 2.4 mL 0.5% hyperbaric bupivacaine+0.2 mL normal saline, group B (n=30) received IV 20 mL 0.9% NaCl over 10 min followed by intrathecal 2.4 mL 0.5% hyperbaric bupivacaine+0.2 mL (5 mcg) dexmedetomidine, and group C (n=30) received IV dexmedetomidine 1 mcg/kg in 20 mL 0.9% NaCl over 10 min followed by intrathecal 2.4 mL 0.5% hyperbaric bupivacaine+0.2 mL normal saline. Results: The mean time for two-segment regression in group A was 100.57±4.24 min, in group B it was 193.3±7.07 min, and in group C was 170.23±3.53 min. The duration of sensory and motor block was prolonged in groups B and C. The Visual analog scale scores were comparatively higher in group A than in groups B and C. The Sedation score in group C was significantly higher as compared to groups A and B. Conclusion: Both intrathecal and IV dexmedetomidine prolong the effect of intrathecal hyperbaric bupivacaine, improves post-operative analgesia, and provides arousable sedation without causing hemodynamic instability.

Efficacy of 5 µg and 10 µg Dexmedetomidine as Adjuvants to 3 mL 0.5% Hyperbaric Bupivacaine in Pelvic and Lower Limb Orthopaedic Surgeries: A Randomised Clinical Study

Introduction: Low-dose bupivacaine used in spinal anaesthesia results in speedy recovery. For lower limb orthopaedic surgeries, to provide sufficient anaesthesia and prolong postoperative analgesia in a less cumbersome way, author can add potent adjuvants like dexmedetomidine (an alpha-2 adrenergic receptor agonist) in effective and safer doses intrathecally. Aim: To compare the effects of intrathecal 5 µg dexmedetomidine versus 10 µg dexmedetomidine as adjuvants to 3 mL of 0.5% hyperbaric bupivacaine in pelvic and lower limb orthopaedic surgeries. Materials and Methods: This randomised clinical and singleblind study study was conducted at the Operation Theatre (OT) complex of Dheeraj Hospital, SBKS, and MIRC, Sumandeep Vidyapeeth, Vadodara, Gujarat, India in the Department of Anaesthesia over a period of 18 months, from September 2022 to March 2024 and total of 82 patients scheduled for lower limb and pelvic orthopaedic surgery who were to receive spinal anaesthesia were divided into Group D1 and D2. Group D1 (n=41) received 3 mL of bupivacaine (0.5% heavy) with 5 µg dexmedetomidine, totaling 3.1 mL, while group D2 (n=41) received 3 mL of bupivacaine (0.5% heavy) with 10 µg dexmedetomidine, also totaling 3.1 mL intrathecally. The onset and duration of sensory and motor blockade, as well as the duration of analgesia, were noted, along with the monitoring of haemodynamic parameters and any side effects. All observed data were analysed using statistical tests such as the unpaired t-test and Chi-square test. A p-value <0.05 was considered statistically significant. Results: Demographic data were comparable in both groups and were non significant (p-value >0.05). The onset of sensory block was earlier in group D2 (2.01±0.12 min) than in group D1 (2.87±0.36 min) (p-value <0.05). The onset of motor block was also earlier in group D2 (2.63±0.26 min) compared to group D1 (3.36±0.43 min). The duration of sensory block was longer in group D2 (457.46±32.85 min) than in group D1 (318.02±32.27 min). The duration of motor block was also longer in group D2 (396.17±36.13 min) than in group D1 (257.37±25.02 min) (p-value <0.05). The duration of analgesia and the time until the need for the first rescue analgesia was significantly longer in group D2 (364.29±43.64 min) compared to group D1 (219.51±23.39 min). Conclusion: Intrathecal bupivacaine with dexmedetomidine at a dose of 10 µg results in an earlier onset and longer duration of sensory and motor block compared to a dose of 5 µg. The duration of postoperative analgesia was longer, and the time until the need for the first rescue analgesia was extended with the 10 µg dosage. No significant side effects were observed in either group.

Semen Collection by Urethral Catheterization After Pharmacological Induction With Dexmedetomidine and Methadone in Ferrets.

The evaluation of fertility in stud animals is crucial across all species. Various semen collection techniques have been described in the literature, depending on the practitioner's expertise, available equipment and the species being examined. These techniques include the use of an artificial vagina, electroejaculation, urethral catheterization and the administration of alpha-2 adrenergic agonists to induce penile erection and ejaculation. Since 1965, several studies have explored semen collection methods in ferrets. Chang etal. initially performed post-mortem collection from the epididymis and vas deferens, while in 1970, Shump etal. successfully utilised electroejaculation. More recently, reproductive specialists have reported improved semen collection results through urethral catheterization following the administration of alpha-2 adrenergic agonists. The first successful application of this technique in felids was documented in 2008 by Zambelli etal. using medetomidine. In 2017, Pisu etal. employed a similar protocol, combining dexmedetomidine and methadone. In ferrets, urethral catheterization was first described in 2020, using a combination of ketamine, midazolam, and dexmedetomidine. The goal of this study was to present an alternative protocol for semen collection in ferrets, utilising dexmedetomidine and methadone to induce ejaculation.

Effects of Adding Tizanidine on Stimulants in Treatment of ADHD: A Randomized, Double-Blind, Placebo-Controlled Trial

Background: Attention deficit hyperactivity disorder (ADHD) is defined as a neurodevelopmental disorder and is one of the most common psychiatric disorders in children and adolescents. Various treatments have been recommended to manage this disorder, including stimulants and non-stimulants. Stimulants are the first-line treatment strategy for ADHD; however, approximately 30% of patients exhibit drug resistance or sensitivity to these medications. Consequently, other drug groups, such as Alpha2 agonists, are used in such cases. Clonidine and guanfacine are Food and Drug Administration (FDA)-approved drugs for the treatment of ADHD, and they belong to this group. Tizanidine is an Alpha2 agonist that has not yet been studied for this disorder. Objectives: Due to the lack of information and studies in this area, the purpose of this study is to investigate the effects of adding tizanidine to stimulants in the treatment of ADHD. Methods: This research was a double-blind, placebo-controlled, randomized trial conducted in outpatient units and admission wards of university hospitals. Forty patients aged 6 to 18 years, with at least one month of unsuccessful treatment of ADHD with lisdexamfetamine (Vyvanse), participated in the study. The participants received either Vyvanse and tizanidine (group 1, n = 20) or Vyvanse alone (group 2, n = 19) for an 8-week period. Symptom severity improvement was assessed using the CONNERS' Parent Rating Scale-48 (CPRS-48) and the Swanson, Nolan, and Pelham Rating Scale (SNAP-IV). Safety measurements were assessed using pulse rate, blood pressure, and electrocardiogram (ECG) changes during the study period. Results: During the 8-week follow-up, SNAP-IV measures did not change significantly in either of the two groups. A significant within-group change was observed only in the conduct domain of CPRS-48 (P < 0.05). Conclusions: Adding tizanidine is not effective in the treatment of ADHD but demonstrates sufficient safety for use in the pediatric age group.

Associations between dementia and exposure to topical glaucoma medications.

Some studies have suggested that glaucoma may be associated with neurodegeneration and a higher risk of dementia. To evaluate whether exposure to different categories of topical glaucoma medications is associated with differential dementia risks in people with glaucoma. We used data from Adult Changes in Thought, a population-based, prospective cohort study that follows cognitively normal older adults from Kaiser Permanente Washington (KPWA) until Alzheimer's disease (AD) and related dementia development. We included participants with a diagnosis of glaucoma, KPWA pharmacy records of filling topical glaucoma medication (alpha-adrenergic agonists [AAA], beta-adrenergic antagonists, miotics, carbonic anhydrase inhibitors [CAI], and prostaglandins) and at least 10 years of pharmacy records. Eight-year sliding windows were derived for each medication class by computing days on each medication starting 10 years earlier and excluding the most recent 2 years. Cox regression used all 5 classes of medication simultaneously to predict AD and all-cause dementia. We included 521 participants (mean age 78 [range 65-96], 62% female) with APOE genotype data. Beta-adrenergic antagonists were the most frequently prescribed (n = 431) followed by prostaglandins (351), AAA (239), CAI (162), and miotics (142). Adjusting for time-varying exposure to other glaucoma medications, APOE, demographics, and smoking, each year of use of alpha-adrenergic agonists in an 8-year window was associated with a higher risk of developing dementia (HR = 1.33, 95% CI = 1.03-1.72). Among older adults with treated glaucoma, exposure to alpha-adrenergic agonists appears to be associated with risk for developing all-cause dementia.

COMPARISON OF TWO DIFFERENT DOSES OF TABLET CLONIDINE (100MCG AND 150MCG) GIVEN 90 MIN PRIOR TO SURGERY TO ATTENUATE HAEMODYNAMIC CHANGES DURING ENDOTRACHEAL INTUBATION

Objective: Endotracheal intubation can elicit significant haemodynamic responses, posing risks for patients with cardiovascular conditions. Clonidine, an alpha-2 adrenergic agonist, is used to mitigate these responses, but the optimal dosing is uncertain. This study compares the efficacy and safety of two doses of oral clonidine, 100 μg and 150 μg, administered 90 min before surgery. Methods: Sixty patients aged 18–55 y, classified as ASA physical status I or II and scheduled for elective lower abdominal surgeries, were randomly assigned to two groups. Group A received 100 μg of oral clonidine, and Group B received 150 μg. Haemodynamic parameters-heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP)-were recorded at baseline, during induction, immediately after intubation, and at intervals up to 15 min post-intubation. Side effects and the need for rescue analgesia were also assessed. Results: Group A demonstrated significantly lower SBP and HR at induction and during the immediate post-intubation period compared to Group B (p < 0.05). No significant differences were observed in DBP and MAP at most time points. The incidence of hypotension was higher in Group B but not statistically significant. Group B required significantly less rescue analgesia postoperatively (p < 0.001). Conclusion: A 100 μg dose of oral clonidine is more effective in attenuating haemodynamic responses during endotracheal intubation compared to a 150 μg dose. While the higher dose offers improved postoperative analgesia, it does not enhance haemodynamic stability and may increase the risk of hypotension.

A Review of Treatment Methods and Available Therapies for Individuals with ADHD

This review explores treatment approaches and therapies for Attention Deficit Hyperactivity Disorder (ADHD), a neurodevelopmental condition affecting adults, with symptoms often persisting from childhood into adulthood. The research examines the efficacy, tolerability, and accessibility of pharmacological and psychosocial interventions. ADHD management necessitates a multimodal approach combining medications, behavioral therapies, and educational interventions tailored to individual needs. The analysis focuses on stimulant and non-stimulant medications, including methylphenidate, amphetamines, atomoxetine, and alpha-2 agonists, with regional variations in treatment guidelines. Stimulants, primarily methylphenidate and amphetamine formulations, demonstrate robust efficacy in symptom reduction for patients. Non-stimulant options like atomoxetine are recommended for patients with contraindications to stimulants. Emerging formulations, such as extended-release medications, address tolerance and adherence challenges. Psychosocial interventions, particularly cognitive behavioral therapy (CBT), complement pharmacological treatments by targeting organizational skills, emotional regulation, and comorbidities like anxiety and depression. Evidence suggests that combined approaches improve long-term functional outcomes, such as academic performance and interpersonal relationships. Despite advances, gaps in treatment access and the need for individualized care remain significant challenges. This review underscores the importance of ongoing research to optimize ADHD management strategies and ensure equitable access to effective therapies worldwide.

Intranasal Administration of the Combination of Dextro-Ketamine and Dexmedetomidine for Treatment of Diabetic Neuropathic Pain in Rats.

Diabetes mellitus (DM) has become a public health problem, which is associated with high morbidity and mortality, due to the chronic complications, such as diabetic neuropathy. Current recommendations for the treatment of neuropathic pain achieve a reduction of 30% in only 30% of cases. Therefore, it is necessary to identify new therapeutic approaches to improve the quality of life of diabetic patients. This work evaluated the antinociceptive effect of intranasal administration of the combination of dextro-ketamine (keta), a non-competitive glutamatergic receptor antagonist, and dexmedetomidine (DEX), a selective alpha2-adrenergic agonist, in rats with neuropathic pain induced by streptozotocin-DM. The thermal hyperalgesia and mechanical allodynia observed in DM model are reduced with the intranasal administration of the combination of keta and DEX (200 + 0.10 μg/kg) after 3 days of treatment. The antinociceptive action could be due to reduction of Ca2+ influx with lower glutamate release and reduced excitability through the activation of alpha2-adrenergic receptors by DEX and reduction of NMDA receptor activation by glutamate with lower excitability due to the antagonism produced by keta. DM induced increased expression of glial fibrillary acid protein (GFAP) and tumor necrosis factor-alpha (TNF-alpha) detected by immunohistochemistry, indicating greater astrocyte activity and intense inflammatory response. Intranasal administration for 10 days of the combination of low doses of keta and DEX promoted an intense decrease in the expression of both GFAP and TNF-alpha, indicating lower activation of astrocytes in the spinal cord and reduced production and release of TNF-alpha, favoring the reduction of inflammation. Intranasal administration of low doses of keta with DEX could be a new therapeutic approach to reduce neuropathic pain and consequently improve the quality of life of diabetic patients.

Effect of phenylephrine infusion on postpartum blood loss after cesarean delivery: a placebo-controlled, randomized clinical trial.

Preclinical studies have documented the role of alpha-adrenergic agonists in myometrial contraction. Phenylephrine is frequently used to prevent and treat post-spinal hypotension during cesarean delivery. We hypothesized phenylephrine would reduce postpartum blood loss due to alpha-1 receptor-mediated uterine and vascular smooth muscle contraction. This translational study aimed to evaluate the role of phenylephrine in reducing postpartum blood loss due to alpha-1 receptor mediated uterine and vascular smooth muscle contraction. This was a prospective, randomized, placebo-controlled, blinded, pilot, clinical trial. Low-risk parturients undergoing cesarean delivery under spinal anesthesia were recruited in this study. The women were randomized to receive phenylephrine or placebo (normal saline) infusion. Each mL of phenylephrine contained 60 micrograms. The study drug began simultaneously with the start of spinal anesthesia, and was stopped at the end of surgery. The infusion rate was started at 50 mcg/min and was titrated to maintain the systolic blood pressure between 80% and 120 % of baseline. The primary outcome measure was postpartum blood loss till 24 hours postpartum, and it was assessed using a surgical swab weighing technique added to suction canister blood contents. The secondary outcomes were incidence of hypertension, hypotension, Apgar score, cord blood gas analysis and neonatal intensive care unit admission (NICU) admission. One hundred six women received study drugs and were eligible for final analysis. The demographic data, obstetric profiles, and medications were comparable. In the phenylephrine group, the mean postpartum blood loss (median [interquartile range]) was significantly lower ([420 {349-502} vs 494 {397-600} mL; p=.009]). Additionally, a significantly lower number of women had >500 mL of blood loss in the phenylephrine group (26.4% vs 47.1%; p=.02). Furthermore, more women in the control arm needed blood transfusion (37.7% vs 16.9%; p=.01). Six women each had bradycardia and hypertension in the phenylephrine group. NICU admission, Apgar score, and umbilical artery PH were comparable. Continuous phenylephrine infusion led to a statistically significant but clinically inconsequential reduction in postpartum blood loss in low-risk parturients undergoing cesarean delivery under spinal anesthesia.

Intrauterine growth restriction does not lead to pronounced changes in the regulation of arterial contractile responses in rats in the early postnatal period

Intrauterine growth retardation (IUGR) is one of the most common pathologies of pregnancy. As a result of this pathology, the functioning of many systems, including the cardiovascular system, is disrupted. In adult animals who have suffered IUGR, the contribution of procontractile mechanisms regulating vascular tone (for example, the Rho-kinase signaling pathway) increases, and the contribution of anticontractile mechanisms (for example, endothelial NO), on the contrary, decreases, which can lead to vasospasm and impaired blood supply to organs. Since NO and Rho-kinase have a pronounced vasomotor role in early postnatal ontogenesis, the purpose of this work was to assess the influence of IUGR on the contribution of these mechanisms to the regulation of arterial contractile responses in early postnatal ontogenesis. IUGR was modeled by limiting the amount of food consumed by females (by 50%) from the 11th day of pregnancy until birth. In offspring aged 11 - 12 days, the reactions of the isolated saphenous artery were studied in isometric mode, and the content of mRNA and proteins of interest in this artery was also assessed. IUGR did not lead to a change in the reactivity of the arteries of the offspring to the α1-adrenergic receptor agonist methoxamine. The increase in contractile responses to methoxamine in the presence of the NO-synthase inhibitor L-NNA, as well as the expression levels of eNOS (mRNA and protein) and arginase-2 (mRNA) were not changed in the arteries of IUGR rats, while the sensitivity of the arteries to the exogenous NO donor DEA /NO was higher in IUGR compared to control rat pups. Despite the relatively low content of RhoA and Rho-kinase II proteins in the arterial tissue of rat pups from the IUGR group, the decrease in contractile responses under the influence of the Rho-kinase inhibitor Y27632 was equally pronounced in the arteries of rat pups from two experimental groups. Thus, IUGR, caused by maternal nutritional restriction during pregnancy, does not lead to pronounced changes in the regulation of systemic vascular tone in the early postnatal period.

Competitive Antagonism of Xylazine on α7 Nicotinic Acetylcholine Receptors and Reversal by Curcuminoids.

Co-use of xylazine with opioids is a major health threat in the United States. However, a critical knowledge gap exists in the understanding of xylazine-induced pharmacological and pathological impact. Xylazine is mostly known as an agonist of α2-adrenergic receptors (α2-ARs), but its deleterious effects on humans cannot be fully reversed by the α2-AR antagonists, suggesting the possibility that xylazine targets receptors other than α2-ARs. Here, we report the discovery of α7 nicotinic acetylcholine receptors (α7 nAChRs) as targets of xylazine. In Xenopus oocytes expressing α7 nAChRs, xylazine competitively antagonizes channel currents elicited by the agonist acetylcholine. In PC12 cells, xylazine suppresses choline-stimulated intracellular calcium ([Ca2+]in) transients that are mediated by endogenously expressed α7 nAChRs. Furthermore, we find that curcuminoids, ivermectin, and the α7-specific positive allosteric modulator PNU120596 can effectively offset the xylazine inhibition of α7 nAChRs. Considering the prominent role of α7 nAChRs in the cholinergic anti-inflammatory pathway and wide expression in the human body, our findings present a potential new strategy to reverse xylazine-caused damage using curcuminoids or repurposing ivermectin. This α7 nAChR-focused strategy may offer an immediate deployment that is likely effective in improving xylazine-related treatment outcomes.

Clonidine Oral Suspension (Onyda XR) for ADHD

The FDA has approved Onyda XR (Tris), an extended-release (ER) oral suspension formulation of the alpha2-adrenergic agonist clonidine, for use as monotherapy or as an adjunct to stimulant therapy for treatment of attention-deficit/hyperactivity disorder (ADHD) in children ≥6 years old. Clonidine ER tablets have been available for years for treatment of ADHD in children 6-17 years old.

A contemporary review of the management strategies for sickle cell disease related ischaemic and stuttering priapism.

Sickle cell disease is one of the most common autosomal recessive genetic disorders with 23% and over 70% of men with this condition, experiencing episodes of ischaemic priapism and stuttering priapism, respectively, with potentially severe consequences. The effective prevention of sickle cell disease induced ischaemic priapism and stuttering priapism requires a multidisciplinary and multimodal approach. A search of the English literature was performed utilising Pubmed® and Google Scholar to identify publications on contemporary and novel treatment options, with their associated treatment outcomes if available, that are utilised to prevent stuttering priapism episodes and hence a fulminant ischaemic priapism. This narrative review focuses on three main aspects which include firstly, patient education and lifestyle modifications. Secondly, strategies aimed at preventing stuttering priapism episodes with traditional treatments such as alpha-adrenergic agonists and hormone manipulation strategies among others. Finally, we review treatments utilised to treat the underlying sickle cell disease with contemporary options such as hydroxyurea to more novel therapies such as crizanlizumab and voxelotor. The role of potentially curative techniques such as gene therapy and stem cell transplantation are also reviewed and summarised.

Dexmedetomidine Improves Learning Functions in Male Rats Modeling Cognitive Impairment by Modulating the BDNF/TrkB/CREB Signaling Pathway.

Dexmedetomidine (DEX) is a selective alpha-2 adrenergic receptor agonist with sedative and anxiolytic properties. Increasing evidence reports that DEX has a neuroprotective effect. In this study, we investigated the potential effects of DEX on learning and memory functions in rats with experimental cognitive impairment. In the study, 21 adult male rats were used. The rats were divided into three groups, namely control, Scopolamine (SCOP) and SCOP + DEX. Cognitive impairment was induced with 1 mg/kg SCOP daily for 21 days. DEX was administered at a dose of 10 µg/kg between days 14 and 21 of the experiment. Following the injections, a spatial memory test was performed with a Morris Water Maze (MWM). At the end of the experiment, the hippocampus was dissected. The brain-derived neurotrophic factor (BDNF), acetylcholine (ACh) and acetylcholinesterase (AChE) levels were determined by ELISA. The tropomyosin receptor kinase B (TrkB) and Cyclic AMP-Response Element-Binding Protein (CREB) levels were measured by immunohistochemistry. DEX treatment improved the learning performance of rats compared to SCOP for 5 days. However, it did not significantly change memory performance. DEX increased the BDNF and ACh levels in the hippocampus while decreasing the AChE levels. Similarly, DEX treatment significantly increased CREB phosphorylation. No significant difference was observed between the TrkB receptor levels of the groups. This study demonstrated that the role of DEX in reducing SCOP-induced cognitive impairment is partially mediated by the increase in BDNF/TrkB/CREB signaling pathway activity.

Development and Preliminary Testing of the Withdrawal Assessment Tool-Alpha 2 Agonist: An Assessment Instrument for Monitoring Iatrogenic Withdrawal Symptoms in Children Receiving an Alpha-2 Agonist.

To develop and conduct preliminary testing of the Withdrawal Assessment Tool-Alpha 2 Agonist (WAT-A2A) to monitor dexmedetomidine and clonidine withdrawal symptoms in acutely ill children. Three-phase instrument development study. Phase 1: retrospective chart review of symptoms exhibited by children with documented dexmedetomidine withdrawal; phase 2: WAT-A2A instrument construction based on phase 1 data; and phase 3: prospective testing of the WAT-A2A in children weaning from alpha 2 agonists (A2As). Academic free-standing children's hospital. Acutely ill children weaning from at least 5 days of dexmedetomidine. Excluded were children concurrently weaning other sedatives. None. Phase 1: In 83 of 303 children weaning from at least 5 days of dexmedetomidine who had clinician documentation and were managed for A2A withdrawal, 88% ( n = 72) exhibited at least a 20% increase in heart rate (HR), 83% ( n = 69) exhibited agitation or change in usual state behavior, 46% ( n = 38) exhibited at least a 20% increase in diastolic blood pressure (DBP), and when documented, 56% (27/48) exhibited tremors during their A2A withdrawal episode. Phase 2: The WAT-A2A was constructed, based on phase 1 data, and includes four items: HR, state behavior, DBP, and tremors. Phase 3: The WAT-A2A was tested and performed well in 82 children weaning from A2A. The total WAT-A2A score correlated with clinician subjective assessment of A2A withdrawal (Spearman correlation = 0.5; p < 0.001). Inter-rater agreement, comparing paired ratings of prospectively collected WAT-A2A data, indicated moderate inter-rater reliability. Acutely ill children receiving sedation with an A2A for more than 5 days may develop physiologic dependence, requiring gradual dosing reductions. While further psychometric testing is advised, the WAT-A2A provides an objective instrument to help clinicians quantify dexmedetomidine withdrawal symptoms in acutely ill children may facilitate A2A weaning and limit unnecessary variation in practice.

Nonopioid medications for managing opioid withdrawal in acute care settings: A scoping review.

There are hospitalized patients with chronic opioid use who will experience signs and symptoms of opioid withdrawal who were not on medications for opioid use disorder (OUD) prior to admission, do not want to start or are unable to start medications for OUD during admission, and want to limit or avoid the use of opioids. The purpose of this scoping review was to assess the potential effectiveness and safety of using non-opioid agents for managing acute opioid withdrawal in acute care settings. PubMed (inception to 2024), Embase (inception to 2024), and Cochrane Library (inception to 2024) were the databases evaluated for the literature search. Bibliographies of full-text articles were reviewed for additional relevant papers. Twenty-eight studies evaluating nonopioid agents for managing acute opioid withdrawal were identified in the literature search. The agents could be divided into 4 broad mechanistic categories: α-adrenergic receptor agonists, N-methyl-d-aspartate (NMDA) antagonists, gamma-aminobutyric acid (GABA) modulators, and serotonergic agents. Of these drug classes, the available literature suggests the α-adrenergic receptor agonists clonidine and lofexidine have the best evidence of efficacy as alternative agents for acute opioid withdrawal, although the majority of studies comparing such agents to opioids for opioid withdrawal were conducted well before the rise in synthetic opioid overdose deaths and have other methodologic issues that limit firm conclusions concerning efficacy and, particularly, safety. For the nonopioid alternative agents that have been studied for acute opioid withdrawal, there is more evidence supporting the efficacy of α-adrenergic receptor agonists as opposed to NMDA antagonists, GABA modulators, or sertonergic agents; however, more research is needed regarding the efficacy and safety of nonopioid alternatives for acute opioid withdrawal in order to better guide clinical decision-making.

Utility of high-dose clonidine in managing pediatric dystonia: A case series in a multi-ethnic Asian population

Background: Dystonia is a debilitating movement disorder. Clonidine, an alpha-2 agonist, is reported to be beneficial for pediatric dystonia. The use of high-dose clonidine remains poorly documented. We aimed to describe our experience with high-dose clonidine. Methods: Dystonia-Severity-Action- Plan (DSAP) is used to evaluate the severity of dystonia. Results: The clinical information of five children, seen at KK Hospital between 2019 and 2023, on high-dose clonidine were reviewed and reported. High-dose clonidine was effective in the management of severe exacerbations of dystonia, with an improvement in DSAP scoring. Clonidine may be administered enterally, intravenously, and through the transdermal route. The median dose reported was 2 mcg/kg/h, with doses up to 6 mcg/ kg/h. Adverse effects reported were dose-dependent and include bradycardia, hypotension, sedation, and application site reaction. Conclusion: High-dose clonidine is effective in improving severe dystonia in our multi-ethnic Asian population, and well tolerated. Our experience complements the existing data and suggest that high- dose clonidine can be considered in the management of pediatric dystonia and status dystonicus.