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Current Issues in Molecular Biology Jun 2023Skeletal muscle disuse leads to pathological muscle activity as well as to slow-to-fast fiber-type transformation. Fast-type fibers are more fatigable than slow-type, so...
Skeletal muscle disuse leads to pathological muscle activity as well as to slow-to-fast fiber-type transformation. Fast-type fibers are more fatigable than slow-type, so this transformation leads to a decline in muscle function. Prochlorperazine injections previously were shown to attenuate autonomous rat soleus muscle electrical activity under unloading conditions. In this study, we found that prochlorperazine blocks slow-to-fast fiber-type transformation in disused skeletal muscles of rats, possibly through affecting calcium and ROS-related signaling.
PubMed: 37504270
DOI: 10.3390/cimb45070354 -
Frontiers in Neurology 2021Polypharmacy in abortive medications is often inevitable for patients with refractory headaches. We seek to enumerate an exhaustive list of headaches abortive...
Polypharmacy in abortive medications is often inevitable for patients with refractory headaches. We seek to enumerate an exhaustive list of headaches abortive medications that are without drug-drug interactions. We updated a list of acute medications based on the widely used Jefferson Headache Manual with novel abortive medications including ubrogepant, lasmiditan, and rimegepant. Opioids and barbiturate-containing products are excluded. From this resultant list of medications, we then conducted an exhaustive search of all pair-wise interactions via DrugBank's API. Using this interaction list, we filtered all possible two, three, and four drug combinations of abortive medications. The list of medications was then reapplied to DrugBank to verify the lack of known drug-drug interactions. There are 192 medication combinations that do not contain any drug-drug interactions. Most common elements in these combinations are ubrogepant, prochlorperazine, followed by tizanidine. There are 67 three-drug combinations that do not contain interactions. Only two of the four-drug combinations do not yield some form of drug-drug interactions. This list of headaches abortive medications without drug-drug interactions is a useful tool for clinicians seeking to more effectively manage refractory headaches by implementing a rational polypharmacy.
PubMed: 33679591
DOI: 10.3389/fneur.2021.632830 -
The American Journal on Addictions Jul 2020Highly potent synthetic opioids (HPSO) are increasingly responsible for opioid overdose deaths in the United States.
BACKGROUND AND OBJECTIVES
Highly potent synthetic opioids (HPSO) are increasingly responsible for opioid overdose deaths in the United States.
METHODS
In an open-label, uncontrolled trial to test the feasibility of extended-release buprenorphine (BXR) injection treatment of heroin-using individuals with opioid use disorder testing positive for HPSO, participants were enrolled and began an induction with sublingual BXR (n = 5). During the induction, ancillary medications (clonidine, clonazepam, zolpidem, and prochlorperazine) were provided for breakthrough opioid withdrawal symptoms.
RESULTS
Two participants received the BXR injection on the second day of the induction and three participants on the third day.
DISCUSSION AND CONCLUSION
All five participants were retained at least 1-month postinduction.
SCIENTIFIC SIGNIFICANCE
It may be feasible to provide BXR treatment to HPSO-positive heroin users rapidly to achieve clinical stabilization. (Am J Addict 2020;00:00-00).
Topics: Adult; Buprenorphine; Delayed-Action Preparations; Female; Heroin Dependence; Humans; Induction Chemotherapy; Injections; Male; Middle Aged; Narcotic Antagonists; Psychotropic Drugs; Substance Withdrawal Syndrome; Treatment Outcome
PubMed: 32167629
DOI: 10.1111/ajad.13018 -
BioPsychoSocial Medicine 2020Akathisia is a rather common extrapyramidal side effect of antipsychotic drugs and antidepressants, often resulting in severe discomfort for patients. However, due to...
BACKGROUND
Akathisia is a rather common extrapyramidal side effect of antipsychotic drugs and antidepressants, often resulting in severe discomfort for patients. However, due to the diversity of symptoms, it is often overlooked. We hereby report a case with akathisia that mainly appeared in an amputated leg.
CASE PRESENTATIONS
A 60-year-old woman, who had undergone external hemipelvectomy for a recurrent soft tissue sarcoma, was referred to the Department of Psycho-Oncology due to worsening anxiety and restlessness. She was not unconscious or disoriented. Her chief complains included restlessness, an itching sensation in the area corresponding to the amputated left leg, and a feeling as if the lost left leg were raising itself. Detailed examination revealed that she had been administered 10 mg per day of oral prochlorperazine maleate for nausea induced by the oxycodone that had been prescribed to control post-operative pain. Akathisia was suspected and prochlorperazine maleate treatment was discontinued. All the symptoms were alleviated on the next day, and disappeared in 3 days. Eventually, she was diagnosed with akathisia.
CONCLUSIONS
This case indicates that the symptoms associated with akathisia can occur in an amputated extremity. Considering two previous reports of "phantom dyskinesia", extrapyramidal syndromes may result in unusual presentations if occurring in an amputated extremity. Not only should the use of antipsychotic drugs and antidepressants be carefully considered, but also closer observation of psychological symptoms is required after prescription of these drugs because the clinical presentation of akathisia can be various and confusing due to modifications caused by other factors as in this case.
PubMed: 32165917
DOI: 10.1186/s13030-020-00178-8 -
Nanomedicine : Nanotechnology, Biology,... Feb 2024Anti-cancer monoclonal antibodies often fail to provide therapeutic benefit in receptor-positive patients due to rapid endocytosis of antibody-bound cell surface...
A PEGylated liposomal formulation of prochlorperazine that limits brain exposure but retains dynamin II activity: A potential adjuvant therapy for cancer patients receiving chemotherapeutic mAbs.
Anti-cancer monoclonal antibodies often fail to provide therapeutic benefit in receptor-positive patients due to rapid endocytosis of antibody-bound cell surface receptors. High dose co-administration of prochlorperazine (PCZ) inhibits endocytosis and sensitises tumours to mAbs by inhibiting dynamin II but can also introduce neurological side effects. We examined the potential to use PEGylated liposomal formulations of PCZ (LPCZ) to retain the anti-cancer effects of PCZ, but limit brain uptake. Uncharged liposomes showed complete drug encapsulation and pH-dependent drug release, but cationic liposomes showed limited drug encapsulation and lacked pH-dependent drug release. Uncharged LPCZ showed comparable inhibition of EGFR internalisation to free PCZ in KJD cells. After IV administration to rats, LPCZ reduced the plasma clearance and brain uptake of PCZ compared to IV PCZ. The results suggest that LPCZ may offer some benefit over PCZ as an adjunct therapy in cancer patients receiving mAb treatment.
Topics: Humans; Rats; Animals; Prochlorperazine; Dynamin II; Liposomes; Neoplasms; Antineoplastic Agents; Antibodies, Monoclonal; Brain; Polyethylene Glycols
PubMed: 38199450
DOI: 10.1016/j.nano.2024.102733 -
CEN Case Reports Apr 2024Carcinoid syndrome is caused by the release of serotonin and other substances, which commonly occurs due to liver metastasis of neuroendocrine tumors. It rarely occurs...
Carcinoid syndrome is caused by the release of serotonin and other substances, which commonly occurs due to liver metastasis of neuroendocrine tumors. It rarely occurs due to liver metastasis of neuroendocrine carcinoma. We report the case of a patient with liver metastasis of neuroendocrine carcinoma who suffered from acute abdominal pain and diarrhea triggered by hemodialysis. Various differential diagnoses were considered, but we concluded these symptoms to be probably caused by exacerbation of carcinoid syndrome, as the serum 5HIAA level was markedly elevated, and a drug with anti-serotonin activity was effective. Prochlorperazine maleate, which has anti-serotonin activity, was effective for these symptoms, and the patient was able to continue maintenance hemodialysis, which contributed to his quality of life and prognosis. We speculated the mechanism of carcinoid exacerbation was that substances such as serotonin had entered the systemic circulation via the increased extrahepatic shunt of the portal venous blood flow, entering the inferior vena cava and that this condition had been triggered by hemodialysis via the same mechanism as portal systemic encephalopathy.
Topics: Humans; Prochlorperazine; Serotonin; Quality of Life; Carcinoid Tumor; Renal Dialysis; Carcinoma, Neuroendocrine; Liver Neoplasms
PubMed: 37606883
DOI: 10.1007/s13730-023-00814-6 -
Cureus Nov 2019This study presents the case of a man who developed a temporary and asymptomatic blue tongue. The dyschromia occurred following topical contact with gelato that...
This study presents the case of a man who developed a temporary and asymptomatic blue tongue. The dyschromia occurred following topical contact with gelato that contained Food, Drug, and Cosmetic (FD&C) blue dye no. 1. The etiology of a blue tongue is either congenital (in individuals with blue rubber bleb nevus syndrome) or acquired. Acquired blue dyschromia of the tongue results from either endogenous conditions or exogenous agents. The endogenous conditions include not only benign (angioleiomyoma, hemangioma, melanocytic macule, and varicosities) and malignant (ovarian carcinoma) tumors but also reactive lesions (intravascular papillary endothelial hyperplasia and mucocele) and systemic disorders (argyria, cyanosis, methemoglobinemia, primary adrenal insufficiency, and thrombocytosis). Exposure to the exogenous agents can either be systemic (ingestion of medications such as haloperidol, metoclopramide, minocycline, prochlorperazine, and risperidone), traumatic (tattoo resulting from the implantation of dental amalgam), or topical (contact with FD&C blue dye no. 1). Clinical clues to the topical exogenous etiology in the reported individual included not only the fact that the dyschromia spared both the lateral aspects and the tip of the tongue but also the observation that the blue color focally appeared on his upper lip.
PubMed: 31890441
DOI: 10.7759/cureus.6243 -
Tidsskrift For Den Norske Laegeforening... Nov 2019It is generally agreed that prescribing of antipsychotic drugs to older patients should be reduced, but figures for the prescribing of these drugs to older patients...
BACKGROUND
It is generally agreed that prescribing of antipsychotic drugs to older patients should be reduced, but figures for the prescribing of these drugs to older patients living at home in Norway are not available. The study aimed to investigate developments in prescribing of antipsychotic drugs among older patients living at home from 2006 to 2018, and whether there were differences in prescribing rates between the age groups 65-74 years, 75-84 years and 85 years or older.
MATERIAL AND METHOD
Data were retrieved from the Norwegian Prescription Database. All persons aged 65 years or older who were dispensed at least one antipsychotic drug in 2006, 2010, 2014 and 2018 were included, and gender-specific prevalence for the ten most widely used antipsychotic drugs was calculated.
RESULTS
The proportion of patients aged 65 or older who were prescribed antipsychotic drugs in the period decreased for both sexes. For the age group 65-74 years, an increase was found from 2014 to 2018. There was a clear decrease in the prescribing rate for prochlorperazine and levomepromazine, whereas prescriptions for quetiapine increased.
INTERPRETATION
Attention should be paid to the increase in prescribing of antipsychotic drugs for the youngest age group of older patients (65-74 years) in the last four years, along with the increase in prescribing of quetiapine for older patients.
Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Drug Prescriptions; Drug Utilization; Female; Humans; Independent Living; Male; Norway; Prevalence; Registries
PubMed: 31686488
DOI: 10.4045/tidsskr.19.0233 -
Headache Mar 2020There has been a rise in urgent care centers throughout the country over the past 10 years, leading to an increase in patients accessing medical care in these...
OBJECTIVE
There has been a rise in urgent care centers throughout the country over the past 10 years, leading to an increase in patients accessing medical care in these locations. These centers advertise an alternative to the Emergency Department (ED) for the evaluation and treatment of urgent medical conditions. The goal of this analysis was to examine the use of urgent care visits for migraine within 2 urgent care centers within a large academic medical system in New York City. We examined the trends in management and treatment of migraine in these urgent care settings, as well as prescriptions and instructions given to this patient population upon discharge. We paid particular attention to whether the medications administered and prescribed on discharge were those recommended by American Headache Society migraine management guidelines.
METHODS
We conducted a retrospective chart review of patients with migraine diagnoses at 2 different urgent care locations within 1 large urban medical center. We determined baseline patient demographics, previous migraine characteristics, frequencies of reasons for urgent care visits as well as various medications administered, medications prescribed on discharge, and characteristics of patient outcomes post-discharge.
RESULTS
Of the 78 patients who visited urgent care with a migraine diagnosis, 20 (25.6%) had a known primary care provider within the urgent care centers' healthcare system. More than three-fourths of all patients (78.2%) had a self-reported history of either recurrent headache or migraine prior to the urgent care visit. Of those with a documented frequency of prior headaches, 94.1% (32/34) had episodic migraine and 79.4% (27/34) experienced at most 1-2 headache days per month. Of those presenting to the urgent care during an episode of migraine, 12.3% (9/73) were given intravenous metoclopramide and none were given subcutaneous sumatriptan or intravenous prochlorperazine. Of those with reported nausea or vomiting with their migraine, 46.2% (18/39) received an anti-emetic at the visit and 33.3% (13/39) were given an anti-emetic prescription. Only 11.1% (6/54) of patients who did not have a record of previous triptan use were given a triptan prescription at the urgent care visit.
CONCLUSIONS
The majority of patients in our study who sought medical treatment for migraine in these 2 urgent care centers were not established patients within the urgent care centers' healthcare system. While 93.6% (73/78) of patients were experiencing current pain upon presentation to the urgent care centers, only 12.3% (9/73) received administration of the medications with the highest level of evidence by the American Headache Society (Level B) for acute migraine treatment in an ED. In addition, the majority of patients with a migraine history presenting to the urgent care setting were not given triptans or anti-emetic prescriptions upon discharge from their urgent care visit. Having these migraine-specific prescriptions may improve self-treatment at home should a migraine attack recur.
Topics: Academic Medical Centers; Adolescent; Adult; Antiemetics; Drug Prescriptions; Emergency Service, Hospital; Female; Guideline Adherence; Humans; Male; Metoclopramide; Migraine Disorders; New York City; Practice Guidelines as Topic; Retrospective Studies; Tryptamines; Young Adult
PubMed: 31802490
DOI: 10.1111/head.13717 -
Trials Jul 2020PRIMARY OBJECTIVE: To determine whether chemoprophylaxis with hydroxychloroquine versus placebo increases time to contracting coronavirus disease 2019 (COVID-19) in...
ChemoPROphyLaxIs with hydroxychloroquine For covId-19 infeCtious disease (PROLIFIC) to prevent covid-19 infection in frontline healthcare workers: A structured summary of a study protocol for a randomised controlled trial.
OBJECTIVES
PRIMARY OBJECTIVE: To determine whether chemoprophylaxis with hydroxychloroquine versus placebo increases time to contracting coronavirus disease 2019 (COVID-19) in frontline healthcare workers.
SECONDARY OBJECTIVES
1) To determine whether chemoprophylaxis with daily versus weekly dosing of hydroxychloroquine increases time to contracting COVID-19 disease in frontline healthcare workers. 2) To compare the number of COVID-19 cases between each trial arm on the basis of positive tests (as per current clinical testing methods and/or serology) 3) To compare the percentage of COVID-19 positive individuals with current testing methods versus serologically-proven COVID-19 in each trial arm 4) To compare COVID-19 disease severity in each trial arm 5) To compare recovery time from COVID-19 infection in each trial arm EXPLORATORY OBJECTIVES: 1) To determine compliance (as measured by trough pharmacokinetic hydroxychloroquine levels) on COVID-19 positive tests 2) To determine if genetic factors determine susceptibility to COVID-19 disease or response to treatment 3) To determine if blood group determines susceptibility to COVID-19 disease 4) To compare serum biomarkers of COVID-19 disease in each arm TRIAL DESIGN: Double-blind, multi-centre, 2-arm (3:3:2 ratio) randomised placebo-controlled trial PARTICIPANTS: National Health Service (NHS) workers who have direct patient contact delivering care to patients with COVID-19. Participants in the trial will be recruited from a number of NHS hospitals directly caring for patients with COVID-19.
INCLUSION CRITERIA
To be included in the trial the participant MUST: 1) Have given written informed consent to participate 2) Be aged 18 years to 70 years 3) Not previously have been diagnosed with COVID-19 4) Work in a high-risk secondary or tertiary healthcare setting (hospitals accepting COVID-19 patients) with direct patient-facing care EXCLUSION CRITERIA: The presence of any of the following will mean participants are ineligible: 1) Known COVID-19 positive test at baseline (if available) 2) Symptomatic for possible COVID-19 at baseline 3) Known hypersensitivity reaction to hydroxychloroquine, chloroquine or 4-aminoquinolines 4) Known retinal disease 5) Known porphyria 6) Known chronic kidney disease (CKD; eGFR<30ml/min) 7) Known epilepsy 8) Known heart failure or conduction problems 9) Known significant liver disease (Gilbert's syndrome is permitted) 10) Known glucose-6-phosphate dehydrogenase (G6PD) deficiency 11) Currently taking any of the following contraindicated medications: Digoxin, Chloroquine, Halofantrine, Amiodarone, Moxifloxacin, Cyclosporin, Mefloquine, Praziquantel, Ciprofloxacin, Clarithromycin, Prochlorperazine, Fluconazole 12) Currently taking hydroxychloroquine or having a clinical indication for taking hydroxychloroquine 13) Currently breastfeeding 14) Unable to be followed-up during the trial 15) Current or future involvement in the active treatment phase of other interventional research studies (excluding observational/non-interventional studies) before study follow-up visit 16) Not able to use or have access to a modern phone device/web-based technology 17) Any other clinical reason which may preclude entry in the opinion of the investigator INTERVENTION AND COMPARATOR: Interventions being evaluated are: A) Daily hydroxychloroquine or B) Weekly hydroxychloroquine or C) Placebo The maximum treatment period is approximately 13 weeks per participant. Hydroxychloroquine-identical matched placebo tablets will ensure that all participants are taking the same number and dosing regimen of tablets across the three trial arms. There is no variation in the dose of hydroxychloroquine by weight. The dosing regimen for the three arms of the study (A, B, C) are described in further detail below. Arm A: Active Hydroxychloroquine (- daily dosing and placebo-matched hydroxychloroquine - weekly dosing). Form: Tablets Route: Oral. Dose and Frequency: Active hydroxychloroquine: Days 1-2: Loading phase - 400mg (2 x 200mg tablets) taken twice a day for 2 days Days 3 onwards: Maintenance Phase - 200mg (1 x 200mg tablet) taken once daily, every day for 90 days (~3 months) Matched Placebo hydroxychloroquine: Days 3 onwards: Maintenance Phase - 2 tablets taken once a week on the same day each week (every 7 day) for 90 days (~3 months) Arm B: Active Hydroxychloroquine (- weekly dosing and placebo matched hydroxychloroquine - daily dosing.) Form: Tablets Route: Oral. Dose and Frequency: Active hydroxychloroquine: Days 1-2: Loading Phase - 400mg (2 x 200mg tablets) taken twice daily for 2 days Days 3 onwards: Maintenance Phase - 400mg (2 x 200mg tablets) taken once a week on the same day each week (every 7 day) for 90 days (~3 months) Matched Placebo hydroxychloroquine: Days 3 onwards: Maintenance Phase - 1 tablet taken once daily for 90 days (~3 months) Arm C: Matched placebo Hydroxychloroquine (- daily dosing and matched placebo hydroxychloroquine - weekly dosing.) Form: Table. Route: Oral. Frequency: Matched placebo hydroxychloroquine - daily dosing: Days 1-2: Loading Phase - 2 tablets taken twice daily for 2 days Days 3 onwards: Maintenance Phase - 1 tablet taken once daily for 90 days (~3 months) Matched placebo hydroxychloroquine - weekly dosing: Days 3 onwards: Maintenance Phase - 2 tablets taken once a week on the same day each week (every 7th day) for 90 days (~3 months) A schematic of the dosing schedule can be found in the full study protocol (Additional File 1).
MAIN OUTCOMES
Time to diagnosis of positive COVID-19 disease (defined by record of date of symptoms onset and confirmed by laboratory test) RANDOMISATION: Participants will be randomised to either hydroxychloroquine dosed daily with weekly placebo, HCQ dosed weekly with daily placebo, or placebo dosed daily and weekly. Randomisation will be in a 3:3:2 ratio [hydroxychloroquine-(daily), hydroxychloroquine-(weekly), placebo], using stratified block randomisation. Random block sizes will be used, and stratification will be by study site.
BLINDING (MASKING)
Participants and trial investigators consenting participants, delivering trial assessments and procedures will be blinded to intervention.
NUMBERS TO BE RANDOMISED (SAMPLE SIZE)
A sufficient number of participants will be enrolled so that approximately 1000 participants in total will have data suitable for the primary statistical analysis. It is anticipated that approximately 1,200 participants will need to be enrolled in total, to allow for a 20% dropout over the period of the trial. This would result in approximately 450:450:300 participants randomised to hydroxychloroquine daily, hydroxychloroquine weekly+daily matched placebo or matched-placebo daily and weekly.
TRIAL STATUS
V 1.0, 7 April 2020 EU Clinical Trials Register EudraCT Number: 2020-001331-26 Date of registration: 14 April 2020 Trial registered before first participant enrolment. Trial site is Cambridge University Hospitals NHS Foundation Trust. Recruitment started on 11 May 2020. It is anticipated that the trial will run for 12 months. The recruitment end date cannot yet be accurately predicted.
FULL PROTOCOL
The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).
Topics: Adolescent; Adult; Aged; Antiviral Agents; Betacoronavirus; COVID-19; COVID-19 Testing; Chemoprevention; Clinical Laboratory Techniques; Coronavirus Infections; Drug Administration Schedule; England; Female; Health Personnel; Host-Pathogen Interactions; Humans; Hydroxychloroquine; Male; Medication Adherence; Middle Aged; Occupational Health; Pandemics; Pneumonia, Viral; Protective Factors; Randomized Controlled Trials as Topic; Remission Induction; Risk Assessment; Risk Factors; SARS-CoV-2; Severity of Illness Index; Time Factors; Treatment Outcome; Young Adult; COVID-19 Drug Treatment
PubMed: 32616067
DOI: 10.1186/s13063-020-04543-4