-
European Journal of Psychotraumatology 2024Clonidine is a centrally acting anti-adrenergic agent that may have applications in post-traumatic stress disorder (PTSD), particularly for sleep. In this systematic... (Review)
Review
Clonidine is a centrally acting anti-adrenergic agent that may have applications in post-traumatic stress disorder (PTSD), particularly for sleep. In this systematic review, we aimed to summarize the effect of clonidine on sleep quality and duration, nightmares, and PTSD symptom severity in adults with PTSD. PubMed (Medline), Embase, PsycINFO, CINAHL, and clinicaltrials.gov were searched up to April 2023. Studies on clonidine use in adult PTSD patients reporting data on the effect on sleep, nightmares, and PTSD symptoms were included. A narrative summary and a meta-analysis of the study findings are presented. Ten reports, accounting for = 569 patients with PTSD (145 on clonidine and 436 controls), were included in the final selection. There were four case reports, four observational studies, one non-blind clinical trial, and one crossover randomized controlled trial (RCT). Median clonidine dose was 0.15 mg/day (range: 0.1-0.5 mg/day). Median follow-up time was 31 days (range: 3 days to 19 months). The quality of the evidence was rated from very low to low. There was marked between-study heterogeneity and low power in the individual studies, but many reported improved sleep quality, nightmare reduction, and improvement of PTSD symptoms for patients treated with clonidine. Meta-analysis was only possible for two studies reporting the effect of clonidine on nightmares, and showed no difference from the comparator (i.e. prazosin or terazosin) (odds ratio: 1.16; 95% confidence interval: 0.66 to 2.05), potentially pointing towards non-inferiority between these medications. Future research, such as well-powered RCTs, is needed to identify the efficacy in the lower dose range and the most suitable treatment group, and to obtain good evidence on the effects of clonidine in the treatment of sleep disorders related to PTSD.
Topics: Clonidine; Humans; Stress Disorders, Post-Traumatic; Dreams; Sleep Quality; Adrenergic alpha-2 Receptor Agonists
PubMed: 38941125
DOI: 10.1080/20008066.2024.2366049 -
Progress in Neuro-psychopharmacology &... Jun 2024Substance dependence represents a pervasive global concern within the realm of public health. Presently, it is delineated as a persistent and recurrent neurological... (Review)
Review
Substance dependence represents a pervasive global concern within the realm of public health. Presently, it is delineated as a persistent and recurrent neurological disorder stemming from drug-triggered neuroadaptations in the brain's reward circuitry. Despite the availability of various therapeutic modalities, there has been a steady escalation in the mortality rate attributed to drug overdoses. Substantial endeavors have been directed towards the exploration of innovative interventions aimed at mitigating cravings and drug-induced repetitive behaviors. Within this review, we encapsulate the most auspicious contemporary treatment methodologies, accentuating meta-analyses of efficacious pharmacological and non-pharmacological approaches: including gabapentin, topiramate, prazosin, physical exercise regimens, and cerebral stimulation techniques.
PubMed: 38908501
DOI: 10.1016/j.pnpbp.2024.111070 -
Seminars in Oncology Nursing Jun 2024Duloxetine, the only American Society of Clinical Oncology (ASCO) treatment recommended for chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors, is not...
OBJECTIVES
Duloxetine, the only American Society of Clinical Oncology (ASCO) treatment recommended for chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors, is not effective for 40% of survivors. This study examined the ability of a duloxetine-prazosin combination to prevent the development of allodynia and hyperalgesia in a rat model of oxaliplatin-induced peripheral neuropathy (OPIN).
METHODS
Female (n = 24) and male (n = 41) rats were started on duloxetine (15 mg), prazosin (2 mg), or a duloxetine-prazosin combination one week prior to administration of the chemotherapy drug, oxaliplatin, and continued the duloxetine-prazosin combination for 32 days. Behavioral testing for mechanical allodynia and mechanical hyperalgesia was done with selected von Frey filaments over the course of the study.
RESULTS
Overall percent paw withdrawal for rats that received the duloxetine-prazosin combination was significantly lower in female (p < .001 for both conditions) and male (p = .029 for allodynia; p < .001 for hyperalgesia) than those that received water. No significant posttreatment differences were found for allodynia or hyperalgesia between rats treated with duloxetine and rats that received the duloxetine-prazosin combination in either sex.
CONCLUSIONS
These finding provide preliminary evidence that a duloxetine-prazosin combination can prevent the posttreatment development of allodynia and hyperalgesia in both male and female rats; however, the results suggest that the duloxetine-prazosin combination is no more efficacious than duloxetine alone in preventing chronic OIPN.
IMPLICATIONS FOR NURSING PRACTICE
The profession of nursing is built on clinical practice supported by scientific research. The current study addressed the clinical practice problem of prevention and management of painful OIPN, which is a priority area in oncology nursing.
PubMed: 38897856
DOI: 10.1016/j.soncn.2024.151686 -
Neurology Jul 2024Terazosin, doxazosin, and alfuzosin (Tz/Dz/Az) are α-1 adrenergic receptor antagonists that also bind to and activate a key adenosine triphosphate (ATP)-producing...
BACKGROUND AND OBJECTIVES
Terazosin, doxazosin, and alfuzosin (Tz/Dz/Az) are α-1 adrenergic receptor antagonists that also bind to and activate a key adenosine triphosphate (ATP)-producing enzyme in glycolysis. It is hypothesized that the increase in energy availability in the brain may slow or prevent neurodegeneration, potentially by reducing the accumulation of alpha-synuclein. Recent work has suggested a potentially neuroprotective effect of the use of Tz/Dz/Az in Parkinson disease in both animal and human studies. We investigated the neuroprotective effects of Tz/Dz/Az in a closely related disease, dementia with Lewy bodies (DLB).
METHODS
We used a new-user active comparator design in the Merative Marketscan database to identify men with no history of DLB who were newly started on Tz/Dz/Az or 2 comparator medications. Our comparator medications were other drugs commonly used to treat benign prostatic hyperplasia that do not increase ATP: the α-1 adrenergic receptor antagonist tamsulosin or 5α-reductase inhibitor (5ARI). We matched the cohorts on propensity scores and duration of follow-up. We followed up the matched cohorts forward to estimate the hazard of developing DLB using Cox proportional hazards regression.
RESULTS
Men who were newly started on Tz/Dz/Az had a lower hazard of developing DLB than matched men taking tamsulosin (n = 242,716, 728,256 person-years, hazard ratio [HR] 0.60, 95% CI 0.50-0.71) or 5ARI (n = 130,872, 399,316 person-years, HR 0.73, 95% CI 0.57-0.93). while the hazard in men taking tamsulosin was similar to that of men taking 5ARI (n = 159,596, 482,280 person-years, HR 1.17, 95% CI 0.96-1.42). These results were robust to several sensitivity analyses.
DISCUSSION
We find an association in men who are taking Tz/Dz/Az and a lower hazard of DLB compared with similar men taking other medications. When combined with the literature of Tz/Dz/Az on Parkinson disease, our findings suggest that glycolysis-enhancing drugs may be broadly protective in neurodegenerative synucleinopathies. A future randomized trial is required to assess these associations for causality.
CLASSIFICATION OF EVIDENCE
This study provides Class III evidence that Tz/Dz/Az use reduces the rate of developing DLB in adult men.
Topics: Humans; Male; Doxazosin; Aged; Prazosin; Lewy Body Disease; Adrenergic alpha-1 Receptor Antagonists; Quinazolines; Aged, 80 and over; Tamsulosin; Prostatic Hyperplasia; Neuroprotective Agents; Middle Aged; Cohort Studies
PubMed: 38896813
DOI: 10.1212/WNL.0000000000209570 -
Scientific Reports Jun 2024Binge drinking (BD) contributes strongly to the harms of alcohol use disorder. Most rodent models do not result in binge-level blood alcohol concentrations (BACs), and...
Binge drinking (BD) contributes strongly to the harms of alcohol use disorder. Most rodent models do not result in binge-level blood alcohol concentrations (BACs), and to better understand individual and sex differences in neurobiological mechanisms related to BD, the use of outbred rat strains would be valuable. Here, we developed a novel BD model where after 3+ months of intermittent access to 20% alcohol Wistar rats drank, twice a week, with two 5-min intake (what we called Two-shot) separated by a 10-min break. Our findings showed during Two-Shot that most animals reached ≥ 80 mg% BAC levels (when briefly food-restricted). However, when increasing alcohol concentrations from 20 to 30%, 40%, or 50%, rats titrated to similar intake levels, suggesting rapid sensing of alcohol effects even when front-loading. Two-Shot drinking was reduced in both sexes by naltrexone (1 mg/kg), validating intake suppression by a clinical therapeutic agent for human problem drinking. Further, both propranolol (β-adrenergic receptor antagonist) and prazosin (α1-adrenergic receptor antagonist) reduced female but not male BD at the lower dose. Thus, our results provide a novel model for BD in outbred rats and suggest that female binging is more sensitive to adrenergic modulation than males, perhaps providing a novel sex-related therapy.
Topics: Animals; Female; Binge Drinking; Male; Rats; Disease Models, Animal; Rats, Wistar; Ethanol; Adrenergic Antagonists; Naltrexone; Propranolol; Sex Factors; Alcohol Drinking
PubMed: 38890353
DOI: 10.1038/s41598-024-64565-9 -
The Journal of the Association of... Apr 2024The isometric handgrip (IHG) test is commonly used to detect sympathetic autonomic dysfunction. Tamsulosin, approved for the management of symptomatic benign prostatic... (Observational Study)
Observational Study
Effect of α-blockers on Handgrip Test Response of Diastolic Blood Pressure in Hypertensive, Benign Hypertrophy of Prostate Patients in a Therapeutics Clinic, Kolkata: A Cross-sectional Study.
BACKGROUND
The isometric handgrip (IHG) test is commonly used to detect sympathetic autonomic dysfunction. Tamsulosin, approved for the management of symptomatic benign prostatic hyperplasia (BPH), acts as an antagonist for α1-adrenergic receptors (α1-AR), whereas prazosin, an α receptor blocker, being less selective than tamsulosin, is used as an antihypertensive agent clinically. Our objective was to investigate if there is a distinction in blood pressure (BP) increase during IHG exercise between individuals with essential hypertension taking tamsulosin compared to those taking prazosin.
MATERIALS AND METHODS
A cross-sectional observational study was performed on 50 subjects receiving tablet prazosin and 47 subjects receiving tamsulosin, who were asked to undergo an IHG test. Pre- and posttest BP was recorded for both the groups, and the difference in diastolic BP (DBP) (delta DBP) was compared between the groups and to their respective baseline values.
RESULTS
Post-IHG test, mean DBP was found to be 93.98 ± 9.13 mm Hg in the prazosin group and 101.00 ± 12.05 mm Hg in the tamsulosin group, respectively. The change of delta DBP in the tamsulosin group was significant, but the prazosin group showed an insignificant rise in DBP.
CONCLUSION
Prazosin, being less selective than tamsulosin in terms of α1 receptor antagonism, showed suppression of BP during IHG. Tamsulosin demonstrates high selectivity for prostatic receptors while showing minimal affinity for vascular receptors. As a result, its impact on BP is expected to be minimal.
Topics: Humans; Male; Cross-Sectional Studies; Prostatic Hyperplasia; Prazosin; Tamsulosin; Middle Aged; Adrenergic alpha-1 Receptor Antagonists; Blood Pressure; Hypertension; Hand Strength; Aged; Antihypertensive Agents; India
PubMed: 38881078
DOI: 10.59556/japi.72.0501 -
Research Square May 2024Binge drinking (BD) contributes strongly to the harms of alcohol use disorder. Most rodent models do not result in binge-level blood alcohol concentrations (BACs), and...
Binge drinking (BD) contributes strongly to the harms of alcohol use disorder. Most rodent models do not result in binge-level blood alcohol concentrations (BACs), and to better understand individual and sex differences in neurobiological mechanisms related to BD, the use of outbred rat strains would be valuable. Here, we developed a novel BD model where after 3+ months of intermittent access to 20% alcohol Wistar rats drank, twice a week, with two 5-minute intake (what we called Two-shot) separated by a 10-minute break. Our findings showed during Two-Shot that most animals reached ≥ 80mg% BAC levels (when briefly food-restricted). However, when increasing alcohol concentrations from 20% to 30%, 40%, or 50%, rats titrated to similar intake levels, suggesting rapid sensing of alcohol effects even when front-loading. Two-Shot drinking was reduced in both sexes by naltrexone (1mg/kg), validating intake suppression by a clinical therapeutic agent. Further, both propranolol (β adrenergic receptor antagonist) and prazosin (α1 adrenergic receptor antagonist) reduced female but not male BD at the lower dose. Thus, our results provide a novel model for BD in outbred rats and suggest that female binging is more sensitive to adrenergic modulation than males, perhaps providing a novel sex-related therapy.
PubMed: 38853968
DOI: 10.21203/rs.3.rs-4402198/v1 -
Cellular Physiology and Biochemistry :... May 2024Adrenaline quickly inhibits the release of histamine from mast cells. Besides β2-adrenergic receptors, several in vitro studies also indicate the involvement of...
BACKGROUND/AIMS
Adrenaline quickly inhibits the release of histamine from mast cells. Besides β2-adrenergic receptors, several in vitro studies also indicate the involvement of α-adrenergic receptors in the process of exocytosis. Since exocytosis in mast cells can be detected electrophysiologically by the changes in the membrane capacitance (Cm), its continuous monitoring in the presence of drugs would determine their mast cell-stabilizing properties.
METHODS
Employing the whole-cell patch-clamp technique in rat peritoneal mast cells, we examined the effects of adrenaline on the degranulation of mast cells and the increase in the Cm during exocytosis. We also examined the degranulation of mast cells in the presence or absence of α-adrenergic receptor agonists or antagonists.
RESULTS
Adrenaline dose-dependently suppressed the GTP-γ-S-induced increase in the Cm and inhibited the degranulation from mast cells, which was almost completely erased in the presence of butoxamine, a β2-adrenergic receptor antagonist. Among α-adrenergic receptor agonists or antagonists, high dose prazosin, a selective α1-adrenergic receptor antagonist, significantly reduced the ratio of degranulating mast cells and suppressed the increase in the Cm. Additionally, prazosin augmented the inhibitory effects of adrenaline on the degranulation of mast cells.
CONCLUSION
This study provided electrophysiological evidence for the first time that adrenaline dose-dependently inhibited the process of exocytosis, confirming its usefulness as a potent mast cell-stabilizer. The pharmacological blockade of α1-adrenergic receptor by prazosin synergistically potentiated such mast cell-stabilizing property of adrenaline, which is primarily mediated by β2-adrenergic receptors.
Topics: Animals; Mast Cells; Epinephrine; Rats; Prazosin; Cell Degranulation; Male; Exocytosis; Patch-Clamp Techniques; Adrenergic alpha-1 Receptor Antagonists; Rats, Wistar
PubMed: 38852193
DOI: 10.33594/000000703 -
Current Drug Safety May 2024Serotonin syndrome is a potentially life-threatening condition that can occur as a result of the therapeutic use of serotonergic medications or drug interaction. In this...
INTRODUCTION
Serotonin syndrome is a potentially life-threatening condition that can occur as a result of the therapeutic use of serotonergic medications or drug interaction. In this study, we describe two cases of serotonin syndrome-associated hypertensive crisis following linezolid use.
CASE PRESENTATION
The first patient was a 52-year-old female who was admitted due to a diabetic foot infection and pneumonia associated with a decreased consciousness level. Serotonin syndrome occurred 24 hours after starting the linezolid use. Resistant hypertension was the main hemodynamic finding. It could not be controlled with amlodipine, valsartan, prazosin, and nitroglycerin infusion. Resistant hypertension and other symptoms of serotonin syndrome were resolved about 48 hours after discontinuation of linezolid use. The second case was a man with a history of kidney transplant, diabetes, and hypertension. He was admitted to the ICU due to severe COVID-19 broad-spectrum antibiotics [linezolid, cefepime], and remdesivir was initiated. Following intubation, continuous infusion of fentanyl was used for sedation. Within 24 hours after fentanyl and linezolid initiation, severe agitation, eye clonus, hyperreflexia, hypertension [160-186 /90-110 mmHg], and tachycardia [>100/min] were noted. With the possible diagnosis of serotonin syndrome, fentanyl was discontinued, and morphine was initiated. The patient's symptoms improved 48 hours after discontinuation of fentanyl.
CONCLUSION
Both of the patients had a history of controlled hypertension. However, serotonin syndrome occurred following the use of linezolid and concomitant/recent use of serotonergic agents. A thorough evaluation of the patient's medical history and current situation can help clinicians prevent this syndrome in critically ill patients.
PubMed: 38847376
DOI: 10.2174/0115748863299100240507052341 -
The Mental Health Clinician Jun 2024Posttraumatic stress disorder (PTSD) in children and adolescents has a high prevalence of accompanying sleep disturbances. Currently, pediatric treatment of PTSD-related...
INTRODUCTION
Posttraumatic stress disorder (PTSD) in children and adolescents has a high prevalence of accompanying sleep disturbances. Currently, pediatric treatment of PTSD-related nightmares is extrapolated from adult studies. This study aims to determine the effectiveness and safety of clonidine and guanfacine compared with prazosin for the treatment of PTSD-related nightmares.
METHODS
This was a retrospective, single-center, medical record review of patients 5 to 17 years old admitted to an inpatient psychiatric unit from January 2015 to September 2021. Patients with a new initiation of an alpha-2 agonist (clonidine or guanfacine) or an alpha-1 antagonist (prazosin) with a diagnosis of PTSD, other trauma- or stressor-related disorder or unspecified anxiety disorder were included. The primary endpoint was the percentage of patients with a decrease in the frequency of nightmares.
RESULTS
A total of 59 patients were included in the study: 37 in the alpha-2 agonist group and 22 in the alpha-1 antagonist group. There was no statistically significant difference in reduction of nightmares with both groups having a high percentage of patients showing response (alpha-2 agonist: 91.9%, alpha-1 antagonist: 86.4%). Time to decrease in nightmares was comparable between groups with a relatively quick onset. Within the alpha-2 agonist group, clonidine (1.59 ± 1.06 days) compared with guanfacine (3.18 ± 1.74 days) had a statistically significant faster time to reduction in nightmares ( = .005).
DISCUSSION
Both pharmacologic classes of medications were effective treatment options for pediatric PTSD-associated nightmares with a low incidence of adverse effects. There was a quick time to onset seen with all agents.
PubMed: 38835814
DOI: 10.9740/mhc.2024.06.199