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Saudi Pharmaceutical Journal : SPJ :... Jul 2017Patients with mental disorders, such as depression and anxiety, who seek medical care in private psychiatric clinics in Riyadh, Saudi Arabia, have recently expressed...
Patients with mental disorders, such as depression and anxiety, who seek medical care in private psychiatric clinics in Riyadh, Saudi Arabia, have recently expressed concerns to doctors about difficulty in filling psychotropic medications, such as Amitriptyline and Aripiprazole, at retail community pharmacies. The aim of this study was to investigate whether there is a shortage of some commonly prescribed psychotropic medications in retail community pharmacies in Saudi Arabia, and if so, to explore the possible reasons behind the shortage of these medications. The availability of 28 commonly prescribed psychotropic medications was checked in multiple retail community pharmacies in 4 different regions of Saudi Arabia. Further, potential reasons behind the shortage of some psychotropic medications in retail community pharmacies were also explored. Amitriptyline, Amoxapine, Aripiprazole, Bupropion, Buspirone, Duloxetine, Haloperidol, Hydroxyzine, Lithium, Prochlorperazine, Procyclidine, Promethazine, Thioridazine, Trazodone, and Trifluoperazine were unavailable in over half of the 248 community pharmacies surveyed. Four possible reasons behind the shortage of these medications were reported by 31 pharmacists working in different retail community pharmacies' purchasing departments, with a majority (58.06%) reporting the primary reason for a shortage of these medications that they are slow-moving items with low profit margins. The findings of this study should expedite the reform process in both the Ministry of Health and the Saudi Food and Drug Authority (SFDA) to publish and enforce an essential list of medications for retail community pharmacies, which should include the most commonly prescribed psychotropic medications.
PubMed: 28725147
DOI: 10.1016/j.jsps.2016.10.013 -
The Western Journal of Emergency... Apr 2017Headaches represent over three million emergency department (ED) visits per year, comprising 2.4% of all ED visits. There are many proposed methods and clinical... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Headaches represent over three million emergency department (ED) visits per year, comprising 2.4% of all ED visits. There are many proposed methods and clinical guidelines of treating acute headache presentations. However, data on intravenous acetaminophen usage in these settings are lacking. In this study, we sought to determine the efficacy of intravenous (IV) acetaminophen as an adjunct to a standard therapy for the treatment of patients who present to the ED with a chief complaint of "headache."
METHODS
We conducted a single site, randomized, double-blind, placebo-controlled trial investigating the clinical efficacy of IV acetaminophen as an adjunct to a standard therapy with prochlorperazine and diphenhydramine for the treatment of patients who present to the ED with a chief complaint of "headache" or variants thereof. (See below for variants). The primary outcome measure of the efficacy of parenteral acetaminophen as an adjunct treatment for headache in addition to a standard therapy was a threshold two-point reduction in visual analog scale (VAS) pain scores on a 1-10 level at 90 minutes. Secondary outcomes measures included assessment of decreased requirement of "rescue" pain medicines, defined as any analgesic medications outside of diphenhydramine, prochlorperazine and acetaminophen, with particular interest to potential opioid-sparing effects with parenteral acetaminophen. Additional secondary outcome measure included time to disposition from arrival in the ED.
RESULTS
For the acetaminophen group the initial mean pain score was 8.67, for the placebo group 8.61. At 90 minutes pain score was 2.23 for the acetaminophen group and 3.99 for placebo (p<0.01, 95% confidence interval (CI) [0.8%-16%]. Of 45 patients in each group, we observed at least a threshold two-point decrease in pain score 36/45 (80%) with acetaminophen vs. 25/45 (55%) with placebo (p <0.01) 95% CI [5%-41%], number needed to treat (NNT) = 4). Secondary outcome measure did not demonstrate a difference in length of stay (161 minutes for acetaminophen arm and 159 minutes for placebo). However, 17/45 (38%) of patients who received IV acetaminophen required rescue analgesia, opposed to 24/45 (53%) of patients in the placebo group (p=0.13) 95% CI [-5%-34%].
CONCLUSION
IV acetaminophen when used with prochlorperazine and diphenhydramine to treat acute headaches in the ED resulted in statistically significant pain reduction compared with prochlorperazine and diphenhydramine alone as measured by both threshold of lowering VAS pain score by at least two points (NNT = 4) and overall decline in VAS pain score. Further study is required to validate these results.
Topics: Acetaminophen; Administration, Intravenous; Adult; Analgesics; Diphenhydramine; Double-Blind Method; Drug Therapy, Combination; Emergency Service, Hospital; Female; Headache; Humans; Length of Stay; Male; Middle Aged; Pain Measurement; Prochlorperazine; Treatment Outcome; United States; Young Adult
PubMed: 28435487
DOI: 10.5811/westjem.2016.12.29218 -
Frontiers in Cell and Developmental... 2017The growing resistance of leishmaniasis to first-line drugs like antimonials in some regions limits the control of this parasitic disease. The precise mechanisms...
The growing resistance of leishmaniasis to first-line drugs like antimonials in some regions limits the control of this parasitic disease. The precise mechanisms involved in antimony resistance are still subject to debate. The reduction of intracellular Sb accumulation is a common change observed in both laboratory-selected and field isolated resistant strains, but the exact transport pathways involved in antimony resistance have not yet been elucidated. In order to functionally characterize the antimony transport routes responsible for resistance, we performed systematic transport studies of Sb in wild-type and resistant strains of . () and . (. Those include influx and efflux assays and the influence of ABC transporters and metabolism inhibitors: prochlorperazine, probenecid, verapamil, BSO, and sodium azide. The mRNA levels of genes associated with antimony resistance (, and ) were also investigated in addition to intracellular thiol levels. A strong reduction of Sb influx was observed in resistant mutant (LgSbR), but not in (LbSbR). Both mutants showed increased energy-dependent efflux of Sb, when compared to their respective parental strains. In LgSbR, BSO and prochlorperazine inhibited antimony efflux and resistance was associated with increased and mRNA levels, while in LbSbR antimony efflux was inhibited by probenicid and prochlorperazine in absence of resistance-associated gene modulation. Intracellular thiol levels were increased in both Sb-resistant mutants. An energy-dependent Sb efflux pathway sensitive to prochlorperazine was clearly evidenced in both Sb-resistant mutants. In conclusion, the present study allowed the biophysical and pharmacological characterization of energy-dependent Sb efflux pathway apparently independent of MRPA, ABCI4, and ARM58 upregulation, in (Vianna) mutant selected for resistance to Sb. Prochlorperazine has also been identified as an effective chemosensitizer in both Sb resistant mutants, which acts through inhibition of the active efflux of Sb.
PubMed: 28393067
DOI: 10.3389/fcell.2017.00024 -
Genomics & Informatics Sep 2016Zika virus (ZIKV) is a mosquito borne pathogen, belongs to Flaviviridae family having a positive-sense single-stranded RNA genome, currently known for causing large...
Zika virus (ZIKV) is a mosquito borne pathogen, belongs to Flaviviridae family having a positive-sense single-stranded RNA genome, currently known for causing large epidemics in Brazil. Its infection can cause microcephaly, a serious birth defect during pregnancy. The recent outbreak of ZIKV in February 2016 in Brazil realized it as a major health risk, demands an enhanced surveillance and a need to develop novel drugs against ZIKV. Amodiaquine, prochlorperazine, quinacrine, and berberine are few promising drugs approved by Food and Drug Administration against dengue virus which also belong to Flaviviridae family. In this study, we performed molecular docking analysis of these drugs against nonstructural 3 (NS3) protein of ZIKV. The protease activity of NS3 is necessary for viral replication and its prohibition could be considered as a strategy for treatment of ZIKV infection. Amongst these four drugs, berberine has shown highest binding affinity of -5.8 kcal/mol and it is binding around the active site region of the receptor. Based on the properties of berberine, more similar compounds were retrieved from ZINC database and a structure-based virtual screening was carried out by AutoDock Vina in PyRx 0.8. Best 10 novel drug-like compounds were identified and amongst them ZINC53047591 (2-(benzylsulfanyl)-3-cyclohexyl-3H-spiro[benzo[h]quinazoline-5,1'-cyclopentan]-4(6H)-one) was found to interact with NS3 protein with binding energy of -7.1 kcal/mol and formed H-bonds with Ser135 and Asn152 amino acid residues. Observations made in this study may extend an assuring platform for developing anti-viral competitive inhibitors against ZIKV infection.
PubMed: 27729840
DOI: 10.5808/GI.2016.14.3.104 -
BMJ Case Reports Jun 2016We present a case of a man in his late 60s, who had spent 3-4 months of the year in rural Spain, presenting with intermittent hoarseness of voice. He had a background...
We present a case of a man in his late 60s, who had spent 3-4 months of the year in rural Spain, presenting with intermittent hoarseness of voice. He had a background of asthma and bronchiectasis, and was taking inhaled corticosteroids. His dysphonia was initially managed as bronchiectasis with little improvement. Bronchoscopy revealed a cystic lesion on his left vocal fold, and tissue biopsy revealed Leishmania amastigotes. This confirmed a diagnosis of laryngeal leishmaniasis. We propose that this is likely secondary to his inhaled corticosteroid therapy. The infection was treated with a 30-day course of miltefosine, and at most recent follow-up the patient was deemed free from leishmanial infection.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Aged; Antiemetics; Antiprotozoal Agents; Asthma; Bronchoscopy; Dysphonia; Hoarseness; Humans; Laryngeal Diseases; Leishmaniasis; Male; Phosphorylcholine; Prochlorperazine; Spain; Travel; Treatment Outcome; Vocal Cords
PubMed: 27329097
DOI: 10.1136/bcr-2016-215444 -
Cancer Management and Research 2016Chemotherapy-induced nausea and vomiting (CINV) is one of the most common symptoms feared by patients, but may be prevented or lessened with appropriate medications.... (Review)
Review
Chemotherapy-induced nausea and vomiting (CINV) is one of the most common symptoms feared by patients, but may be prevented or lessened with appropriate medications. Several antiemetic options exist to manage CINV. Corticosteroids, serotonin receptor antagonists, and neurokinin receptor antagonists are the classes most commonly used in the prevention of CINV. There are many alternative drug classes utilized for the prevention and management of CINV such as antihistamines, benzodiazepines, anticonvulsants, cannabinoids, and dopamine receptor antagonists. Medications belonging to these classes generally have lower efficacy and are associated with more adverse effects. They are also not as well studied compared to the aforementioned agents. This review will focus on dronabinol, a member of the cannabinoid class, and its role in CINV. Cannabis sativa L. (also known as marijuana) contains naturally occurring delta-9-tetrahydrocannibinol (delta-9-THC). The synthetic version of delta-9-THC is the active ingredient in dronabinol that makes dronabinol an orally active cannabinoid. Evidence for clinical efficacy of dronabinol will be analyzed in this review as monotherapy, in combination with ondansetron, and in combination with prochlorperazine.
PubMed: 27274310
DOI: 10.2147/CMAR.S81425 -
Scientia Pharmaceutica 2016Buccal bioadhesive bilayer tablets of prochlorperazine maleate were designed and formulated by using buccoadhesive polymers such as hydroxypropylmethyl cellulose,...
Enhanced Permeation of an Antiemetic Drug from Buccoadhesive Tablets by Using Bile Salts as Permeation Enhancers: Formulation Characterization, In Vitro, and Ex Vivo Studies.
Buccal bioadhesive bilayer tablets of prochlorperazine maleate were designed and formulated by using buccoadhesive polymers such as hydroxypropylmethyl cellulose, Carbopol 934P, and sodium alginate. Physicochemical characteristics like the uniformity of weight, hardness, thickness, surface pH, drug content, swelling index, microenvironment pH, in vitro drug release, and in vivo buccoadhesion time of the prepared tablets were found to be dependent on the type and composition of the buccoadhesive materials used. The effect of bile salts on the permeation was studied through porcine buccal mucosa and it was found that out of three bile salts incorporated (sodium glycholate, sodium taurocholate, and sodium deoxycholate), sodium glycholate enhanced the permeation rate of prochlorperazine maleate by an enhancement factor of 1.37.
PubMed: 27222611
DOI: 10.3797/scipharm.1505-15 -
Acta Oncologica (Stockholm, Sweden) Jun 2016Delayed nausea and vomiting following administration of carboplatin containing chemotherapy regimen remains a clinically significant problem for patients with cancer... (Observational Study)
Observational Study
BACKGROUND
Delayed nausea and vomiting following administration of carboplatin containing chemotherapy regimen remains a clinically significant problem for patients with cancer despite administration of standard antiemetic prophylaxis comprising of a 5-HT3 antagonist and dexamethasone. We performed a prospective study to define the incidence and risk factors for delayed chemotherapy-induced nausea and vomiting (CINV).
METHODS
Previously untreated patients with newly diagnosed cancer scheduled to receive carboplatin containing chemotherapy (AUC 5 or above), but no prophylactic aprepitant were enrolled in the study. The primary endpoint was the incidence of delayed CINV after Cycle 1 of chemotherapy. Secondary endpoints included the incidence of CINV with the third chemotherapy cycle and gender differences in incidence of CINV. Patients completed the Functional Living Index Emesis (FLIE) questionnaires 24, 48, 72 and 96 hours after receiving chemotherapy. Telephone interviews were conducted 24-48 hours following chemotherapy to assess the severity and need for breakthrough medications for CINV.
RESULTS
Between December 2006 and July 2009, 105 patients were enrolled onto this study. Delayed emesis following Cycle 1 of carboplatin was observed in 30% of patients. Of these, 14.1%, 22.4% and 23.5% of patients described CINV at 48, 72, and 96 hours, respectively. The incidence of delayed CINV following Cycle 3 dropped to 12.8%, 14.6% and 16% of patients at 48, 72 and 96 hours, respectively. No differences were observed in the incidence of CINV between men and women. A total of 20% of patients required use of breakthrough antiemetics with Cycle 1.
CONCLUSIONS
Without prophylactic aprepitant administration, 30% of patients receiving carboplatin containing regimen had moderate to severe delayed CINV.
Topics: Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Female; Humans; Lorazepam; Male; Metoclopramide; Middle Aged; Nausea; Neoplasms; Prochlorperazine; Prospective Studies; Surveys and Questionnaires; Vomiting
PubMed: 27145068
DOI: 10.3109/0284186X.2016.1154603 -
Journal of Pharmaceutical Health Care... 2015Antipsychotics are potent dopamine antagonists used to treat schizophrenia and bipolar disorder. The aim of this study was to evaluate the relationship between...
BACKGROUND
Antipsychotics are potent dopamine antagonists used to treat schizophrenia and bipolar disorder. The aim of this study was to evaluate the relationship between antipsychotic drugs and adverse hyperglycemic events using the FDA Adverse Event Reporting System (FAERS) database. In particular, we focused on adverse hyperglycemic events associated with atypical antipsychotic use, which are major concerns.
FINDINGS
We analyzed reports of adverse hyperglycemic events associated with 26 antipsychotic drugs in the FAERS database from January 2004 to March 2013. The Standardized Medical Dictionary for Regulatory Activities Queries (SMQ) preferred terms (PTs) was used to identify adverse hyperglycemic events. The number of adverse hyperglycemic reports for the top eight antipsychotic drugs, quetiapine, olanzapine, risperidone, aripiprazole, haloperidol, clozapine, prochlorperazine, and chlorpromazine was 12,471 (28.9%), 8,423 (37.9%), 5,968 (27.0%), 4,045 (23.7%), 3,445 (31.5%), 2,614 (14.3%), 1,800 (19.8%), and 1,003 (35.7%), respectively. The reporting ratio increased with co-administration of multiple antipsychotic drugs. For example, adverse hyperglycemic events represented 21.6% of reports for quetiapine monotherapy, 39.9% for two-drug polypharmacy, and 66.3% for three-drug polypharmacy.
CONCLUSION
Antipsychotic drug polypharmacy may influence signal strength, and may be associated with hyperglycemia. After considering the causality restraints of the current analysis, further robust epidemiological studies are recommended.
PubMed: 26819726
DOI: 10.1186/s40780-015-0015-6 -
The Cochrane Database of Systematic... Nov 2015Cannabis has a long history of medicinal use. Cannabis-based medications (cannabinoids) are based on its active element, delta-9-tetrahydrocannabinol (THC), and have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cannabis has a long history of medicinal use. Cannabis-based medications (cannabinoids) are based on its active element, delta-9-tetrahydrocannabinol (THC), and have been approved for medical purposes. Cannabinoids may be a useful therapeutic option for people with chemotherapy-induced nausea and vomiting that respond poorly to commonly used anti-emetic agents (anti-sickness drugs). However, unpleasant adverse effects may limit their widespread use.
OBJECTIVES
To evaluate the effectiveness and tolerability of cannabis-based medications for chemotherapy-induced nausea and vomiting in adults with cancer.
SEARCH METHODS
We identified studies by searching the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and LILACS from inception to January 2015. We also searched reference lists of reviews and included studies. We did not restrict the search by language of publication.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared a cannabis-based medication with either placebo or with a conventional anti-emetic in adults receiving chemotherapy.
DATA COLLECTION AND ANALYSIS
At least two review authors independently conducted eligibility and risk of bias assessment, and extracted data. We grouped studies based on control groups for meta-analyses conducted using random effects. We expressed efficacy and tolerability outcomes as risk ratio (RR) with 95% confidence intervals (CI).
MAIN RESULTS
We included 23 RCTs. Most were of cross-over design, on adults undergoing a variety of chemotherapeutic regimens ranging from moderate to high emetic potential for a variety of cancers. The majority of the studies were at risk of bias due to either lack of allocation concealment or attrition. Trials were conducted between 1975 and 1991. No trials involved comparison with newer anti-emetic drugs such as ondansetron. Comparison with placebo People had more chance of reporting complete absence of vomiting (3 trials; 168 participants; RR 5.7; 95% CI 2.6 to 12.6; low quality evidence) and complete absence of nausea and vomiting (3 trials; 288 participants; RR 2.9; 95% CI 1.8 to 4.7; moderate quality evidence) when they received cannabinoids compared with placebo. The percentage of variability in effect estimates that was due to heterogeneity rather than chance was not important (I(2) = 0% in both analyses).People had more chance of withdrawing due to an adverse event (2 trials; 276 participants; RR 6.9; 95% CI 1.96 to 24; I(2) = 0%; very low quality evidence) and less chance of withdrawing due to lack of efficacy when they received cannabinoids, compared with placebo (1 trial; 228 participants; RR 0.05; 95% CI 0.0 to 0.89; low quality evidence). In addition, people had more chance of 'feeling high' when they received cannabinoids compared with placebo (3 trials; 137 participants; RR 31; 95% CI 6.4 to 152; I(2) = 0%).People reported a preference for cannabinoids rather than placebo (2 trials; 256 participants; RR 4.8; 95% CI 1.7 to 13; low quality evidence). Comparison with other anti-emetics There was no evidence of a difference between cannabinoids and prochlorperazine in the proportion of participants reporting no nausea (5 trials; 258 participants; RR 1.5; 95% CI 0.67 to 3.2; I(2) = 63%; low quality evidence), no vomiting (4 trials; 209 participants; RR 1.11; 95% CI 0.86 to 1.44; I(2) = 0%; moderate quality evidence), or complete absence of nausea and vomiting (4 trials; 414 participants; RR 2.0; 95% CI 0.74 to 5.4; I(2) = 60%; low quality evidence). Sensitivity analysis where the two parallel group trials were pooled after removal of the five cross-over trials showed no difference (RR 1.1; 95% CI 0.70 to 1.7) with no heterogeneity (I(2) = 0%).People had more chance of withdrawing due to an adverse event (5 trials; 664 participants; RR 3.9; 95% CI 1.3 to 12; I(2) = 17%; low quality evidence), due to lack of efficacy (1 trial; 42 participants; RR 3.5; 95% CI 1.4 to 8.9; very low quality evidence) and for any reason (1 trial; 42 participants; RR 3.5; 95% CI 1.4 to 8.9; low quality evidence) when they received cannabinoids compared with prochlorperazine.People had more chance of reporting dizziness (7 trials; 675 participants; RR 2.4; 95% CI 1.8 to 3.1; I(2) = 12%), dysphoria (3 trials; 192 participants; RR 7.2; 95% CI 1.3 to 39; I(2) = 0%), euphoria (2 trials; 280 participants; RR 18; 95% CI 2.4 to 133; I(2) = 0%), 'feeling high' (4 trials; 389 participants; RR 6.2; 95% CI 3.5 to 11; I(2) = 0%) and sedation (8 trials; 947 participants; RR 1.4; 95% CI 1.2 to 1.8; I(2) = 31%), with significantly more participants reporting the incidence of these adverse events with cannabinoids compared with prochlorperazine.People reported a preference for cannabinoids rather than prochlorperazine (7 trials; 695 participants; RR 3.3; 95% CI 2.2 to 4.8; I(2) = 51%; low quality evidence).In comparisons with metoclopramide, domperidone and chlorpromazine, there was weaker evidence, based on fewer trials and participants, for higher incidence of dizziness with cannabinoids.Two trials with 141 participants compared an anti-emetic drug alone with a cannabinoid added to the anti-emetic drug. There was no evidence of differences between groups; however, the majority of the analyses were based on one small trial with few events. Quality of the evidence The trials were generally at low to moderate risk of bias in terms of how they were designed and do not reflect current chemotherapy and anti-emetic treatment regimens. Furthermore, the quality of evidence arising from meta-analyses was graded as low for the majority of the outcomes analysed, indicating that we are not very confident in our ability to say how well the medications worked. Further research is likely to have an important impact on the results.
AUTHORS' CONCLUSIONS
Cannabis-based medications may be useful for treating refractory chemotherapy-induced nausea and vomiting. However, methodological limitations of the trials limit our conclusions and further research reflecting current chemotherapy regimens and newer anti-emetic drugs is likely to modify these conclusions.
Topics: Adult; Antiemetics; Antineoplastic Agents; Cannabinoids; Chlorpromazine; Dizziness; Domperidone; Euphoria; Humans; Metoclopramide; Nausea; Neoplasms; Prochlorperazine; Randomized Controlled Trials as Topic; Vomiting
PubMed: 26561338
DOI: 10.1002/14651858.CD009464.pub2