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JAMA Feb 2023Borderline personality disorder (BPD) affects approximately 0.7% to 2.7% of adults in the US. The disorder is associated with considerable social and vocational... (Review)
Review
IMPORTANCE
Borderline personality disorder (BPD) affects approximately 0.7% to 2.7% of adults in the US. The disorder is associated with considerable social and vocational impairments and greater use of medical services.
OBSERVATIONS
Borderline personality disorder is characterized by sudden shifts in identity, interpersonal relationships, and affect, as well as by impulsive behavior, periodic intense anger, feelings of emptiness, suicidal behavior, self-mutilation, transient, stress-related paranoid ideation, and severe dissociative symptoms (eg, experience of unreality of one's self or surroundings). Borderline personality disorder is typically diagnosed by a mental health specialist using semistructured interviews. Most people with BPD have coexisting mental disorders such as mood disorders (ie, major depression or bipolar disorder) (83%), anxiety disorders (85%), or substance use disorders (78%). The etiology of BPD is related to both genetic factors and adverse childhood experiences, such as sexual and physical abuse. Psychotherapy is the treatment of choice for BPD. Psychotherapy such as dialectical behavior therapy and psychodynamic therapy reduce symptom severity more than usual care, with medium effect sizes (standardized mean difference) between -0.60 and -0.65. There is no evidence that any psychoactive medication consistently improves core symptoms of BPD. For discrete and severe comorbid mental disorders, eg, major depression, pharmacotherapy such as the selective serotonin reuptake inhibitors escitalopram, sertraline, or fluoxetine may be prescribed. For short-term treatment of acute crisis in BPD, consisting of suicidal behavior or ideation, extreme anxiety, psychotic episodes, or other extreme behavior likely to endanger a patient or others, crisis management is required, which may include prescription of low-potency antipsychotics (eg, quetiapine) or off-label use of sedative antihistamines (eg, promethazine). These drugs are preferred over benzodiazepines such as diazepam or lorazepam.
CONCLUSIONS AND RELEVANCE
Borderline personality disorder affects approximately 0.7% to 2.7% of adults and is associated with functional impairment and greater use of medical services. Psychotherapy with dialectical behavior therapy and psychodynamic therapy are first-line therapies for BPD, while psychoactive medications do not improve the primary symptoms of BPD.
Topics: Adult; Humans; Borderline Personality Disorder; Psychotic Disorders; Psychotherapy; Depressive Disorder, Major; Mood Disorders
PubMed: 36853245
DOI: 10.1001/jama.2023.0589 -
The Analyst Mar 2023The discovery of novel chiral selectors always fascinates us. This work describes the chiral separation performances of a new chiral selector (kasugamycin, KAS) in...
The discovery of novel chiral selectors always fascinates us. This work describes the chiral separation performances of a new chiral selector (kasugamycin, KAS) in capillary electrophoresis (CE) for six pairs of stereoisomers, including ephedrine and pseudoephedrine, quinine and quinidine, cinchonine and cinchonidine, and amlodipine, promethazine and ofloxacin enantiomers. Kasugamycin, an aminoglycoside antibiotic in agriculture, shows significant biological activity against rice blast with low toxicity. As it turns out, this new chiral selector possesses good CE compatibility and stereoselectivity towards model analytes. In this work, we systematically investigated several separation parameters including kasugamycin concentration, buffer pH, separation voltage and the composition of the buffer solution. A detailed discussion about the chiral recognition mechanism was made based on Statistical Product and Service Solution (SPSS) analysis, NMR experiments (1D and 2D) and molecular modeling. This is the first time that kasugamycin is utilized as a chiral selector in CE, and the development of new chiral selectors from agricultural or veterinary antibiotics deserves more attention.
Topics: Anti-Bacterial Agents; Aminoglycosides; Ofloxacin; Electrophoresis, Capillary; Stereoisomerism; Hydrogen-Ion Concentration
PubMed: 36853240
DOI: 10.1039/d2an01949c -
Histamine H1 receptor antagonist attenuates catecholamine surge and organ injury after severe burns.Frontiers in Endocrinology 2023Severe burns induce a catecholamine surge, causing severe damage to the organism and raising the possibility of multisystem organ failure. Few strategies are generally...
Severe burns induce a catecholamine surge, causing severe damage to the organism and raising the possibility of multisystem organ failure. Few strategies are generally acceptable to reduce catecholamine surge and organ injury post-burn. We have previously shown that histamine can amplify the catecholamine surge. In addition, promethazine, a first-generation histamine H1 receptor antagonist, alleviates catecholamine surge and organ injury after severe burns in rats. However, evidence is lacking on whether promethazine benefits patients after severe burns. Currently, sedation and analgesia (such as midazolam and fentanyl) are commonly required for patients after severe burns. It remains unclear if patients after severe burns derive clinical benefit from histamine H1 receptor antagonists combined with sedation and analgesia. This study investigates the therapeutic effect of promethazine on patients after severe burns. Moreover, we test the therapeutic effect of cetirizine, a second-generation histamine H1 receptor antagonist, combined with sedation and analgesia in rats after severe burns. We find that promethazine-pethidine treatment shows a tendency for a lower level of total bilirubin than midazolam-fentanyl in patients 7-day after severe burn. Our study confirms that cetirizine combined with midazolam and fentanyl reduces catecholamine surge and liver and lung damage after severe burns in rats; the effects are better than midazolam and fentanyl treatment. In summary, for the first time, we suggest that histamine H1 receptor antagonist has the potential clinical value of reducing liver injury in patients after severe burns. In addition, we reveal that cetirizine combined with midazolam and fentanyl may be an ideal strategy for treating severe burns.
Topics: Rats; Animals; Histamine H1 Antagonists; Promethazine; Cetirizine; Midazolam; Pain; Histamine; Fentanyl
PubMed: 36843581
DOI: 10.3389/fendo.2023.1068925 -
Surgical Laparoscopy, Endoscopy &... Jun 2023Postoperative nausea and vomiting (PONV) is one of the most common adverse effects of anesthesia and surgery, resulting in patient discomfort and dissatisfaction. Latest...
PURPOSE
Postoperative nausea and vomiting (PONV) is one of the most common adverse effects of anesthesia and surgery, resulting in patient discomfort and dissatisfaction. Latest research has demonstrated the efficacy of NK-1 receptor antagonists in PONV management and its use in chemotherapy nausea prophylaxis. The authors of this article would like to provide evidence to support the use fosaprepitant, as monotherapy, in postoperative care, replacing a polypharmacological standard of care regimen.
METHODS
This was a retrospective chart review of 400 patients who received standard of care antiemetic regimen or received fosaprepitant (No-Fosaprepitant vs. Fosaprepitant groups, respectively). The primary outcome of this study is to evaluate the impact of fosaprepitant (administered intravenously) on perioperative antiemetic use, treatment cost, and patient satisfaction.
RESULTS
Total PONV medication cost decreased with the replacement of standard of care regimen for fosaprepitant, from 46.47±20.54 United States Dollars in the no-Fosaprepitant group to 25.69±14.84 United States Dollars in the Fosaprepitant group. There was a significant reduction in antiemetic doses between groups; 0.37±0.745 versus 7.61±5.202 for ondansetron ( P =0.001), 92±1.279 versus 2.21±2.399 for promethazine ( P =0.001), 0.25±0.685 versus 1.41±0.577 for scopolamine patch ( P =0.001), and 0.05±0.218 versus 1.14±0.398 for dexamethasone ( P =0.001). Patient satisfaction, measured by a questionnaire, was a 11.6% higher in the Fosaprepitant group.
CONCLUSION
Fosaprepitant is a relevant alternative in preventing and treating PONV in patients who underwent bariatric/metabolic surgical procedures.
Topics: Humans; Antiemetics; Postoperative Nausea and Vomiting; Aprepitant; Patient Satisfaction; Retrospective Studies; Ondansetron; Bariatric Surgery
PubMed: 36821697
DOI: 10.1097/SLE.0000000000001101 -
Contact Dermatitis Jun 2023Photopatch testing has been standardized for diagnosing photoallergic contact dermatitis but is still infrequently used.
BACKGROUND
Photopatch testing has been standardized for diagnosing photoallergic contact dermatitis but is still infrequently used.
OBJECTIVES
To characterize photopatch test (PPT) results and their clinical relevance.
METHODS
We collected retrospective data from patients photopatch tested in our Dermatology Unit (2010-2021), using the European PPT 'baseline' series, other allergens, and patient's own products, when appropriate.
RESULTS
Out of 223 patients, 75 patients (33.6%) were reactive with 124 positive PPT reactions, considered relevant in 56/223 patients (25.1%) and in 72/124 reactions (58.1%). Most reactions were caused by topical drugs (n = 33; 45.8%), such as ketoprofen or promethazine, and 7 (9.8%) by systemic drugs, such as hydrochlorothiazide and fenofibrate. 'Classical' ultraviolet filters were responsible for six positive PPT reactions whereas there was only three relevant PPT to the 'newer' UV filters. Patients' sunscreens/cosmetics or plant extracts caused 10 positive PPT each. Additional patch test reactions were observed, mostly to Tinosorb® M.
CONCLUSION
Contrary to the trend in ACD, most positive PPT reactions were caused by topical drugs, outweighing ultraviolet filters and cosmetics. We stress the low reactivity to the 'newer' UV filters included in the PPT series. PPT was occasionally positive in systemic drug photosensitivity, but overall PPT reactivity was low.
Topics: Humans; Retrospective Studies; Dermatology; Dermatitis, Allergic Contact; Dermatitis, Photoallergic; Allergens; Sunscreening Agents; Patch Tests
PubMed: 36807918
DOI: 10.1111/cod.14297 -
European Journal of Pharmacology Apr 2023The motor activity of the epididymis duct is an essential process for male fertility and it is regulated by hormonal, neuronal and epithelial mechanisms. However,...
The motor activity of the epididymis duct is an essential process for male fertility and it is regulated by hormonal, neuronal and epithelial mechanisms. However, although there is evidence for the presence of histamine in the epididymis, its effects on epididymal motor activity are unknown. This study sought to evaluate the contractile effects of histamine on the rat distal cauda epididymis duct. Segments of the distal cauda epididymis duct from male Wistar rats were isolated and used in isolated organ bath experiments to evaluate the contractile effects of histamine in the absence or presence of antagonists of histamine receptors, α-adrenoceptors and muscarinic acetylcholine receptors. The effects of histamine on noradrenaline induced contractions were also investigated. Histamine was able to induce phasic contractions on rat distal cauda epididymis duct which were prevented by promethazine 10-1000 nM (H receptor antagonist), ranitidine 1-100 μM (H receptor antagonist), atropine 100 nM (muscarinic antagonist), and prazosin 100 nM (α-adrenoceptor antagonist). In addition, histamine was also able to modify noradrenaline-induced contractions possibly via activation of H and H receptors. In conclusion, this study demonstrates that histamine can induce phasic contractions of rat distal cauda epididymis via H receptors and autonomic neurotransmitters. Histamine may also exert modulatory actions on contractions of rat distal cauda epididymis duct induced by adrenergic receptor agonists. Further studies are necessary to unveil the localization of histamine receptors within the epididymal duct and the consequences of manipulation of the histaminergic system on epididymal function and male fertility.
Topics: Rats; Male; Animals; Epididymis; Rats, Wistar; Histamine; Prazosin; Norepinephrine; Receptors, Adrenergic, alpha-1
PubMed: 36804548
DOI: 10.1016/j.ejphar.2023.175603 -
Psychopharmacology Apr 2023Drug combinations are commonly used in pain management, which can produce potent analgesic effects with reduced dosage and adverse effects.
RATIONALE
Drug combinations are commonly used in pain management, which can produce potent analgesic effects with reduced dosage and adverse effects.
OBJECTIVE
This study was designed to evaluate the anti-nociceptive effects and adverse effects of new combinations of flupirtine (a Kv7 potassium channel opener) and antihistamines (promethazine, fexofenadine) on acute and chronic pain in mice, and the possible mechanisms behind the synergistic analgesic effects were preliminarily investigated.
METHODS
In acetic acid writhing test, carrageenan-induced inflammatory pain model, and paclitaxel-induced neuropathic pain model, the interaction indexes (γ) between flupirtine and antihistamines were determined by isobolographic analysis. Furthermore, the Kv7 channel blocker XE991 was used to determine whether the effects of single agents and drug combinations on paclitaxel- and carrageenan-induced mechanical allodynia were mediated by Kv7 channels. Finally, hepatotoxicity markers, liver histopathology, and the rotarod test were used to investigate the adverse effects of drugs in combination doses.
RESULTS
The interaction indexes of flupirtine-promethazine and flupirtine-fexofenadine in all the above three pain models were lower than 1. The analgesic effects of flupirtine (13 mg/kg), promethazine (5 mg/kg), fexofenadine (20 mg/kg), and their combinations were antagonized significantly by XE991 (3 mg/kg). And the adverse effects of flupirtine and antihistamines in combination doses were not significantly different from the vehicle group.
CONCLUSIONS
Flupirtine and antihistamines produced synergistic analgesic effects in all the above pain models. The analgesic effects of antihistamines were partially mediated by Kv7/M channels, and the activation of Kv7/M channels may be partly responsible for the synergistic analgesic effects between flupirtine and antihistamines.
Topics: Mice; Animals; Analgesics; Promethazine; Carrageenan; Aminopyridines; Neuralgia; Histamine Antagonists
PubMed: 36752814
DOI: 10.1007/s00213-023-06329-3 -
Drug Safety Mar 2023Deliberate self-poisoning (DSP) using drugs is the preferred method of suicide at a global level. Its investigation is hampered by limited sample sizes and data...
INTRODUCTION
Deliberate self-poisoning (DSP) using drugs is the preferred method of suicide at a global level. Its investigation is hampered by limited sample sizes and data reliability. We investigate the role of the US FDA Adverse Event Reporting System (FAERS), a consolidated pharmacovigilance database, in outlining DSP habits and toxidromes.
METHODS
We retrieved cases of 'intentional overdose' and 'poisoning deliberate' from the FAERS (January 2004-December 2021). Using descriptive and disproportionality analyses, we estimated temporal trends, potential risk factors, toxidromes, case-fatality rates and lethal doses (LDs) for the most frequently reported drugs.
RESULTS
We retrieved 42,103 DSP cases (17% fatal). Most cases were submitted in winter. Reports of DSP involved younger people, psychiatric conditions, and alcohol use, compared with non-DSP, and fatality was higher in men and older patients. Suspected drugs were mainly antidepressants, analgesics, and antipsychotics. Multiple drug intake was recorded in more than 50% of the reports, especially analgesics, psychotropics, and cardiovascular agents. The most frequently reported drugs were paracetamol, promethazine, amlodipine, quetiapine, and metformin. We estimated LD25 for paracetamol (150 g).
CONCLUSION
Worldwide coverage of the FAERS complements existing knowledge about DSP and may drive tailored prevention measures to timely address the DSP phenomenon and prevent intentional suicides.
Topics: Male; United States; Humans; Suicide; Suicide, Attempted; Suicidal Ideation; Acetaminophen; United States Food and Drug Administration; Reproducibility of Results; Analgesics; Adverse Drug Reaction Reporting Systems
PubMed: 36689131
DOI: 10.1007/s40264-022-01269-x -
Molecules (Basel, Switzerland) Jan 2023Promethazine hydrochloride (PMZ), a potent H1-histamine blocker widely used to prevent motion sickness, dizziness, nausea, and vomiting, has a bitter taste. In the...
Promethazine hydrochloride (PMZ), a potent H1-histamine blocker widely used to prevent motion sickness, dizziness, nausea, and vomiting, has a bitter taste. In the present study, taste masked PMZ nanocapsules (NCs) were prepared using an interfacial polycondensation technique. A one-step approach was used to expedite the synthesis of NCs made from a biocompatible and biodegradable polyamide based on l-arginine. The produced NCs had an average particle size of 193.63 ± 39.1 nm and a zeta potential of −31.7 ± 1.25 mV, indicating their stability. The NCs were characterized using differential scanning calorimetric analysis and X-ray diffraction, as well as transmission electron microscopy that demonstrated the formation of the NCs and the incorporation of PMZ within the polymer. The in vitro release study of the PMZ-loaded NCs displayed a 0.91 ± 0.02% release of PMZ after 10 min using artificial saliva as the dissolution media, indicating excellent taste masked particles. The in vivo study using mice revealed that the amount of fluid consumed by the PMZ-NCs group was significantly higher than that consumed by the free PMZ group (p < 0.05). This study confirmed that NCs using polyamides based on l-arginine and interfacial polycondensation can serve as a good platform for the effective taste masking of bitter actives.
Topics: Mice; Animals; Promethazine; Nanocapsules; Nylons; Taste; Taste Perception; Histamine H1 Antagonists
PubMed: 36677806
DOI: 10.3390/molecules28020748 -
Social Psychiatry and Psychiatric... Oct 2023To describe trends in and characteristics of sedative drug use from 2000 through 2019 in relation to the introduction of central regulations and new drugs.
AIM
To describe trends in and characteristics of sedative drug use from 2000 through 2019 in relation to the introduction of central regulations and new drugs.
METHODS
In this descriptive study, we used individual prescription data on the entire Danish population from the Danish National Prescription Registry to calculate yearly incidence and prevalence of use of benzodiazepines, benzodiazepine-related drugs (Z-drugs), melatonin, olanzapine, low-dose quetiapine, mianserin/mirtazapine, pregabalin, and promethazine from 2000 through 2019. From the Danish National Patient Registry, we obtained data on drug users' psychiatric and somatic comorbidity.
RESULTS
The use of benzodiazepines and Z-drugs declined gradually from 2000 through 2019, whereas the newer alternatives, melatonin, low-dose quetiapine, pregabalin and promethazine, increased in use, while the use of olanzapine and mianserin/mirtazapine was relatively stable. This development was seen in both men and women and across all age groups except for hypnotic benzodiazepines which showed a steep increase in the oldest age group from 2010. For all sedative drugs depression, anxiety, alcohol and misuse disorder, pain and cancer were the most prevalent comorbidities. During our study period, the number of individuals without any of the selected diagnoses increased.
CONCLUSION
In Denmark different central regulations have influenced prescription practice toward more restrictive use of Z-drugs and benzodiazepines, except for hypnotic benzodiazepine prescriptions increased after the introduction of special palliative care. An increase in use of newer sedative drugs, however, indicates that the regulations do not remove the need for sedative drugs in the population.
Topics: Male; Humans; Female; Hypnotics and Sedatives; Pregabalin; Olanzapine; Quetiapine Fumarate; Mirtazapine; Mianserin; Promethazine; Melatonin; Drug Prescriptions; Benzodiazepines; Substance-Related Disorders; Drug Utilization; Denmark
PubMed: 36562827
DOI: 10.1007/s00127-022-02409-5