-
British Journal of Clinical Pharmacology May 2024We report on investigations exploring the P2X3-receptor antagonist filapixant's effect on taste perception and cough-reflex sensitivity and describe its...
Pharmacodynamics, pharmacokinetics and CYP3A4 interaction potential of the selective P2X3 receptor antagonist filapixant: A randomized multiple ascending-dose study in healthy young men.
AIMS
We report on investigations exploring the P2X3-receptor antagonist filapixant's effect on taste perception and cough-reflex sensitivity and describe its pharmacokinetics, including its CYP3A4-interaction potential.
METHODS
In a randomized, placebo-controlled, double-blind study, 3 × 12 healthy men (18-45 years) were assigned (3:1) to filapixant (20, 80 or 250 mg by mouth) or placebo twice daily over 2 weeks. A single dose of midazolam (1 mg), a CYP3A4 substrate, was administered with and without filapixant. Assessments included a taste-strips test, a taste questionnaire, cough challenge with adenosine triphosphate, adverse event reports and standard safety assessments.
RESULTS
Taste disturbances were observed mainly in the 250-mg group: six of nine participants (67%) in this group reported hypo- or dysgeusia in the questionnaire; eight participants (89%) reported taste-related adverse events. Five participants (56%) had a decrease in overall taste-strips-test scores ≥2 points (point estimate -1.1 points, 90% confidence interval [-3.3; 1.1]). Cough counts increased with adenosine triphosphate concentration but without major differences between treatments. Filapixant exposure increased proportionally to dose. Co-administration of filapixant had no clinically relevant effect on midazolam pharmacokinetics. Area under the concentration-time curve ratios and 90% confidence intervals were within 80-125%. No serious or severe adverse events were reported.
CONCLUSIONS
Overall, filapixant was safe and well tolerated, apart from mild, transient taste disturbances. Such disturbances occurred more frequently than expected based on (in vitro) receptor-selectivity data, suggesting that other factors than P2X3:P2X2/3 selectivity might also play an important role in this context. The cough-challenge test showed no clear treatment effect. Filapixant has no clinically relevant CYP3A4 interaction potential.
PubMed: 38775025
DOI: 10.1111/bcp.16091 -
Cureus Apr 2024We use vernakalant, an intravenous anti-arrhythmic, to cardiovert paroxysmal atrial fibrillation (AF) into sinus rhythm. It is a relatively atrium-selective,...
BACKGROUND
We use vernakalant, an intravenous anti-arrhythmic, to cardiovert paroxysmal atrial fibrillation (AF) into sinus rhythm. It is a relatively atrium-selective, early-activating potassium and frequency-dependent sodium channel blocker with a half-life of 2 to 3 hours. Due to concerns regarding its safety profile, it is not Food and Drug Administration (FDA)-approved.
OBJECTIVE
This study aims to assess the efficacy of intravenous vernakalant in cardioversion of paroxysmal AF and the safety of its use.
METHODS
Patients with paroxysmal AF who presented to the American University of Beirut Medical Center (AUBMC) between 2015 and 2020 and received vernakalant for cardioversion were included. Patients did not receive vernakalant if they had any of the following: QTc > 440 ms, heart rate < 50 bpm, acute coronary syndrome within the last 30 days, second- and third-degree atrioventricular (AV) block in the absence of a pacemaker, severe aortic stenosis (AS), use of intravenous antiarrhythmics (class I and class III) within four hours of vernakalant infusion, systolic blood pressure <100 mmHg, and heart failure (New York Heart Association (NYHA) III or NYHA IV class). The primary endpoint is conversion to sinus rhythm for at least one minute within 90 minutes of the start of the vernakalant infusion. The secondary endpoint included the presence of these side effects: bradycardia, QTc prolongation, AV block, ventricular arrhythmias, hypotension, taste alteration/dysgeusia, sneezing, nausea, vomiting, paresthesia, cardiogenic shock, or death.
RESULTS
The study included 23 patients with paroxysmal AF (15 men, mean age 54 ± 14 years). Fourteen patients (61%) cardioverted to sinus rhythm within 90 minutes of the start of the Vernakalant infusion. Seven patients (30%) reverted to sinus rhythm within 15 minutes after the first infusion. After treatment with vernakalant, four patients (17%) developed sinus bradycardia, and four patients (17%) developed first-degree AV block. No patient had a QTc greater than 460 ms. None of the patients experienced sinus pauses, high-grade AV block, ventricular arrhythmias, hypotension, dysgeusia, sneezing, nausea, vomiting, paresthesia, cardiogenic shock, or death.
CONCLUSION
Vernakalant had 61% efficacy in the rapid cardioversion of paroxysmal AF to sinus rhythm, was well tolerated, and had a low rate of adverse events in our study population.
PubMed: 38770450
DOI: 10.7759/cureus.58616 -
MedRxiv : the Preprint Server For... May 2024Many of those infected with COVID-19 experience long-term disability due to persistent symptoms known as Long-COVID, which include ongoing respiratory issues, loss of...
BACKGROUND
Many of those infected with COVID-19 experience long-term disability due to persistent symptoms known as Long-COVID, which include ongoing respiratory issues, loss of taste and smell, and impaired daily functioning.
RESEARCH QUESTION
This study aims to better understand the chronology of long-COVID symptoms.
STUDY DESIGN AND METHODS
We prospectively enrolled 403 adults from the University of Iowa long-COVID clinic (June 2020 to February 2022). Participants provided symptom data during acute illness, symptom progression, and other clinical characteristics. Patients in this registry received a survey containing questions including current symptoms and status since long-COVID diagnosis (sliding status scale, PHQ2, GAD2, MMRC). Those >12 months since acute-COVID diagnosis had chart review done to track their symptomology.
RESULTS
Of 403 participants contacted, 129 (32%) responded. The mean age (in years) was 50.17 +/-14.28, with 31.8% male and 68.2% female. Severity of acute covid treatment was stratified by treatment in the outpatient (70.5%), inpatient (16.3%), or ICU (13.2%) settings. 51.2% reported subjective improvement (sliding scale scores of 67-100) since long-COVID onset. Ages 18-29 reported significantly higher subjective status scores. Subjective status scores were unaffected by severity. 102 respondents were >12 months from their initial COVID-19 diagnosis and were tracked for longitudinal symptom persistence. All symptoms tracked had variance (mean fraction 0.58, range 0.34-0.75) in the reported symptoms at the time of long-COVID presentation when compared with patient survey report. 48 reported persistent dyspnea, 23 (48%) had resolved it at time of survey. For fatigue, 44 had persistence, 12 (27%) resolved.
INTERPRETATION
Overall, 51.2% respondents improved since their long-COVID began. Pulmonary symptoms were more persistent than neuromuscular symptoms (anosmia, dysgeusia, myalgias). Gender, time since acute COVID infection, and its severity didn't affect subjective status or symptoms. This study highlights recall bias that may be prevalent in other long-COVID research reliant on participant memory.
PubMed: 38746213
DOI: 10.1101/2024.04.30.24306497 -
Clinical NeuropharmacologyEvaluate the safety and efficacy of zavegepant (BHV-3500), a recently approved nasal spray containing a third-generation calcitonin gene-related peptide receptor... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Evaluate the safety and efficacy of zavegepant (BHV-3500), a recently approved nasal spray containing a third-generation calcitonin gene-related peptide receptor antagonist, for treating acute migraine attacks.
METHODS
A comprehensive search was conducted across various databases up to 06/26/2023 to identify relevant randomized clinical trials (RCTs) on zavegepant's efficacy and safety in treatment of acute migraine attacks. Primary outcome: freedom from pain at 2 hours postdose. Safety outcomes were evaluated based on adverse events (AEs), with zavegepant 10 mg and placebo groups compared for incidence of AEs.
RESULTS
Two RCTs, involving 2061 participants (1014 receiving zavegepant and 1047 receiving placebo), were quantitatively analyzed. An additional trial was included for qualitative synthesis. Zavegepant 10 mg exhibited a significantly higher likelihood of achieving freedom from pain at 2 hours postdose compared with the placebo group (risk ratio [RR] 1.54, 95% confidence interval [CI] 1.28 to 1.84). It also showed superior relief from the most bothersome symptoms at 2 hours postdose compared with placebo (RR 1.26, 95% CI 1.13 to 1.42). However, the zavegepant 10 mg group experienced a higher incidence of AEs compared with placebo (RR 1.78, 95% CI 1.5 to 2.12), with dysgeusia being the most reported AE (RR 4.18, 95% CI 3.05 to 5.72).
CONCLUSION
Zavegepant 10 mg is more effective than placebo in treating acute migraine attacks, providing compelling evidence of its efficacy in relieving migraine pain and most bothersome associated symptoms. Further trials are necessary to confirm its efficacy, tolerability, and safety in diverse clinic-based settings with varied patient populations.
Topics: Migraine Disorders; Humans; Randomized Controlled Trials as Topic; Calcitonin Gene-Related Peptide Receptor Antagonists; Treatment Outcome
PubMed: 38743600
DOI: 10.1097/WNF.0000000000000588 -
Photobiomodulation, Photomedicine, and... May 2024
PubMed: 38739455
DOI: 10.1089/photob.2024.0040 -
Cancers Apr 2024Despite a better understanding of the mechanisms causing cancer cachexia (CC) and development of promising pharmacologic and supportive care interventions, CC persists... (Review)
Review
Despite a better understanding of the mechanisms causing cancer cachexia (CC) and development of promising pharmacologic and supportive care interventions, CC persists as an underdiagnosed and undertreated condition. CC contributes to fatigue, poor quality of life, functional impairment, increases treatment related toxicity, and reduces survival. The core elements of CC such as weight loss and poor appetite should be identified early. Currently, addressing contributing conditions (hypothyroidism, hypogonadism, and adrenal insufficiency), managing nutrition impact symptoms leading to decreased oral intake (nausea, constipation, dysgeusia, stomatitis, mucositis, pain, fatigue, depressed mood, or anxiety), and the addition of pharmacologic agents when appropriate (progesterone analog, corticosteroids, and olanzapine) is recommended. In Japan, the clinical practice has changed based on the availability of Anamorelin, a ghrelin receptor agonist that improved lean body mass, weight, and appetite-related quality of life (QoL) compared to a placebo, in phase III trials. Other promising therapeutic agents currently in trials include Espindolol, a non-selective β blocker and a monoclonal antibody to GDF-15. In the future, a single therapeutic agent or perhaps multiple medications targeting the various mechanisms of CC may prove to be an effective strategy. Ideally, these medications should be incorporated into a multimodal interdisciplinary approach that includes exercise and nutrition.
PubMed: 38730648
DOI: 10.3390/cancers16091696 -
Journal of Renal Nutrition : the... May 2024Dysgeusia is a common altered taste perception in chronic kidney disease patients. The study aims to identify available treatments for educating, screening, and... (Review)
Review
Dysgeusia is a common altered taste perception in chronic kidney disease patients. The study aims to identify available treatments for educating, screening, and clinically managing dysgeusia in this population. A scoping review was conducted following the protocol of Arksey and O'Malley, incorporating the Joanna Briggs Institute methodology, and adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. Among the 424 identified records, 13 studies were included. Screening methodologies, educational strategies, particularly a hospital-based program focusing on salt reduction, showed a significant improvement in dysgeusia (P < .001). The identified clinical treatments exclusively included oral zinc supplementation, with dosages ranging from 50 to 220 mg, reporting heterogeneous results not consistent across different studies. The personalized management of dysgeusia associated with chronic kidney disease is crucial, requiring targeted education and treatment protocols to prevent and address nutritional complications such as malnutrition.
PubMed: 38729584
DOI: 10.1053/j.jrn.2024.04.005 -
International Journal of Clinical... May 2024Although patients with advanced pancreatic cancer (PC) often experience dysgeusia with zinc deficiency during chemotherapy, data on zinc supplementation for dysgeusia...
BACKGROUND
Although patients with advanced pancreatic cancer (PC) often experience dysgeusia with zinc deficiency during chemotherapy, data on zinc supplementation for dysgeusia and its effects on nutritional status are scarce. We aimed to examine the efficacy of zinc supplementation in patients with advanced PC.
METHODS
Thirty-three patients with unresectable PC who presented with dysgeusia and zinc deficiency during chemotherapy and received zinc acetate hydrate between January 2018 and December 2022 were included. We evaluated the changes in serum zinc levels and the improvement in dysgeusia. Among the 26 patients who received zinc supplementation for 12 weeks, we also compared patient characteristics and changes in serum zinc and albumin levels between patients who showed improvement in dysgeusia (effective group) and those who did not (non-effective group).
RESULTS
The serum zinc level increased significantly after zinc supplementation (median: 60 µg/dL at baseline, 99.5 µg/dL at 4 weeks, 101 µg/dL at 8 weeks and 101 µg/dL at 12 weeks). The rate of improvement in dysgeusia increased over time (18.2% at 4 weeks, 33.3% at 8 weeks, and 42.4% at 12 weeks). Comparing the effective group and non-effective group revealed that while the median serum albumin level of the effective group did not change, the non-effective group showed a significant decrease from baseline to 12 weeks (3.2 g/dL to 3.0 g/dL, p = 0.03).
CONCLUSION
Zinc supplementation significantly increased serum zinc levels, improving dysgeusia. Zinc supplementation might also contribute to maintaining nutritional status in patients with unresectable PC.
PubMed: 38724773
DOI: 10.1007/s10147-024-02544-w -
Photobiomodulation, Photomedicine, and... Jun 2024
Topics: Humans; COVID-19; Dysgeusia; Low-Level Light Therapy; SARS-CoV-2
PubMed: 38722111
DOI: 10.1089/pho.2024.0040 -
Cureus Apr 2024This study aimed to evaluate alterations in taste and smell perceptions among non-head and neck cancer patients receiving chemotherapy, aiming to identify factors...
OBJECTIVE
This study aimed to evaluate alterations in taste and smell perceptions among non-head and neck cancer patients receiving chemotherapy, aiming to identify factors influencing these changes.
METHODS
A cohort of 70 non-head and neck cancer patients undergoing one to four cycles or more than four cycles, over a six-month period, from oncology outpatient clinics was recruited. Participants completed structured taste and smell questionnaires with assistance from interviewers. Demographic data, recurrence history, chemotherapy cycles, drug regimens, and taste and smell perceptions were analyzed using descriptive statistics and chi-square tests.
RESULTS
The mean age of participants was 46.5 years, with a predominance of females (81.4%) and breast cancer cases (42.9%). Taste changes were more prevalent (62.9%) than smell changes (32.9%) post chemotherapy, particularly among those on combination drug regimens. Salty taste alterations were the most common (30.0%), followed by sweet taste (22.9%) and sour/bitter tastes (14.3%). Moreover, 38.57% of patients reported experiencing dysgeusia, while 30% noted the occurrence of parosmia post chemotherapy.
CONCLUSION
Chemotherapy-induced alterations in taste and smell significantly impact the quality of life and nutritional status of cancer patients. Despite often being overlooked, these changes warrant increased attention in oncological practice to inform treatment decisions and enhance symptom management, particularly in palliative care settings. Further research is needed to explore the implications of chemosensory alterations on patient outcomes and treatment strategies.
PubMed: 38721225
DOI: 10.7759/cureus.57787