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Clinical and Experimental... Sep 2013Gastroparesis is a motility disorder of the stomach causing delay in food emptying from the stomach without any evidence of mechanical obstruction. The majority of cases... (Review)
Review
Gastroparesis is a motility disorder of the stomach causing delay in food emptying from the stomach without any evidence of mechanical obstruction. The majority of cases are idiopathic. Patients need to be diagnosed properly by formal testing, and the evaluation of the severity of the gastroparesis may assist in guiding therapy. Initially, dietary modifications are encouraged, which include frequent and small semisolid-based meals. Promotility medications, like erythromycin, and antiemetics, like prochlorperazine, are offered for symptom relief. In patients who are refractory to pharmacologic treatment, more invasive options, such as intrapyloric botulinum toxin injections, placement of a jejunostomy tube, or implantation of a gastric stimulator, can be considered. Hemin therapy and gastric electric stimulation are emerging treatment options that are still at different stages of research. Regenerative medicine and stem cell-based therapies also hold promise for gastroparesis in the near future.
PubMed: 24039443
DOI: 10.2147/CEG.S50236 -
Daru : Journal of Faculty of Pharmacy,... Sep 2018Fluphenazine and prochlorperazine as phenothiazine-class antipsychotic drugs are widely used to treat schizophrenia, however their use is associated with significant...
PURPOSE
Fluphenazine and prochlorperazine as phenothiazine-class antipsychotic drugs are widely used to treat schizophrenia, however their use is associated with significant side effects such as extrapyramidal symptoms, as well as ocular and skin disorders. Our goal was to determine the effect of fluphenazine and prochlorperazine on cell viability and melanogenesis in lightly pigmented normal human melanocytes.
METHODS
The viability of melanocytes was evaluated by the WST-1 colorimetric assay, while melanin content and tyrosinase activity were tested spectrophotometrically.
RESULTS
It has been shown that both phenothiazines induce the concentration-dependent loss in cell viability. The EC values were calculated to be 6.13 and 0.63 μM for fluphenazine and prochlorperazine, respectively. Fluphenazine in the concentration of 5.0 μM and prochlorperazine in concentrations of 0.5 and 0.75 μM decreased melanin content and tyrosinase activity. The observed inhibition of melanogenesis may be explained by the decrease of enzyme activity.
CONCLUSIONS
The demonstrated changes in melanization process in lightly pigmented cells exposed to fluphenazine and prochlorperazine in vitro suggest a significant role of melanin and melanocytes in the mechanisms of undesirable side effects of these drugs in vivo. Graphical abstract Fluphenazine and prochlorperazine significantly inhibits melanogenesis in lightly pigmented melanocytes HEMn-LP.
Topics: Cell Survival; Cells, Cultured; Fluphenazine; Humans; Melanins; Melanocytes; Monophenol Monooxygenase; Prochlorperazine
PubMed: 30159761
DOI: 10.1007/s40199-018-0206-4 -
British Journal of Anaesthesia Mar 1996This study has compared the incidences of nausea, vomiting and headache after ondansetron 0.06 mg kg-1 i.v., prochlorperazine 0.2 mg kg-1 i.m. and prochlorperazine 0.1... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
This study has compared the incidences of nausea, vomiting and headache after ondansetron 0.06 mg kg-1 i.v., prochlorperazine 0.2 mg kg-1 i.m. and prochlorperazine 0.1 mg kg-1 i.v. given during induction of general anaesthesia to 282 patients undergoing adenotonsillectomy. The cardiovascular effects of the drugs were similar. After operation, nausea per se and vomiting per se occurred with similar frequency, in between 6% and 11% and 11% and 19%, respectively, in each test group. Nausea and vomiting in the same patient was reduced from 29% to 2% by i.v. ondansetron (P < 0.0005) and to 3% by i.m. prochlorperazine (P < 0.0005), and appeared to be less severe in these groups. Headache was most frequent after i.v. ondansetron (35%: P < 0.05), but occurred with similar frequency after i.m. prochlorperazine (32%) and i.v. prochlorperazine (29%).
Topics: Adenoidectomy; Adolescent; Adult; Aged; Antiemetics; Child; Child, Preschool; Double-Blind Method; Female; Humans; Injections, Intramuscular; Injections, Intravenous; Male; Middle Aged; Nausea; Ondansetron; Postoperative Complications; Prochlorperazine; Tonsillectomy; Vomiting
PubMed: 8785149
DOI: 10.1093/bja/76.3.449 -
BMC Neurology Jun 2023Many drugs are prescribed in relieving acute migraine attacks, we aim to compare metoclopramide with other antimigraine drugs. (Meta-Analysis)
Meta-Analysis
The efficacy and safety of metoclopramide in relieving acute migraine attacks compared with other anti-migraine drugs: a systematic review and network meta-analysis of randomized controlled trials.
BACKGROUND
Many drugs are prescribed in relieving acute migraine attacks, we aim to compare metoclopramide with other antimigraine drugs.
METHODS
We searched online databases like PubMed, Cochrane Library, Scopus, and Web of Science till June 2022 for RCTs that compared metoclopramide alone with placebo or active drugs. The main outcomes were the mean change in headache score and complete headache relief. The secondary outcomes were the rescue medications need, side effects, nausea and recurrence rate. We qualitatively reviewed the outcomes. Then, we performed the network meta-analyses (NMAs) when it was possible. which were done by the Frequentist method using the MetaInsight online software.
RESULTS
Sixteen studies were included with a total of 1934 patients: 826 received metoclopramide, 302 received placebo, and 806 received other active drugs. Metoclopramide was effective in reducing headache outcomes even for 24 h. The intravenous route was the most chosen route in the included studies and showed significant positive results regarding headache outcomes; however, the best route whether intramuscular, intravenous, or suppository was not compared in the previous studies. Also, both 10 and 20 mg doses of metoclopramide were effective in improving headache outcomes; however, there was no direct comparison between both doses and the 10 mg dose was the most frequently used dosage. In NMA of headache change after 30 min or 1 h, metoclopramide effect came after granisetron, ketorolac, chlorpromazine, and Dexketoprofen trometamol. Only granisetron's effect was significantly higher than metoclopramide's effect which was only significantly higher than placebo and sumatriptan. In headache-free symptoms, only prochlorperazine was non-significantly higher than metoclopramide which was higher than other medications and showed significantly higher effects only with placebo. In rescue medication, metoclopramide's effect was only non-significantly lower than prochlorperazine and chlorpromazine while its effect was higher than other drugs and showed higher significant effects only than placebo and valproate. In the recurrence rate, studies showed no significant difference between metoclopramide and other drugs. Metoclopramide significantly decreased nausea more than the placebo. Regarding side effects, metoclopramide showed a lower incidence of mild side effects than pethidine and chlorpromazine and showed a higher incidence of mild side effects than placebo, dexamethasone, and ketorolac. The reported extrapyramidal symptoms with metoclopramide were dystonia or akathisia.
CONCLUSION
A dose of 10 mg IV Metoclopramide was effective in relieving migraine attacks with minimal side effects. Compared to other active drugs, it only showed a lower significant effect compared with granisetron regarding headache change while it showed significantly higher effects only with placebo in both rescue medication needs and headache-free symptoms and valproate in only rescue medication need. Also, it significantly decreased headache scores more than placebo and sumatriptan. However, more studies are needed to support our results.
Topics: Humans; Metoclopramide; Sumatriptan; Network Meta-Analysis; Prochlorperazine; Chlorpromazine; Granisetron; Valproic Acid; Ketorolac; Randomized Controlled Trials as Topic; Migraine Disorders; Nausea; Headache
PubMed: 37291500
DOI: 10.1186/s12883-023-03259-7 -
Frontiers in Molecular Biosciences 2023The COVID-19 pandemic caused by SARS-CoV-2 has caused millions of infections and deaths worldwide. Limited treatment options and the threat from emerging variants...
The COVID-19 pandemic caused by SARS-CoV-2 has caused millions of infections and deaths worldwide. Limited treatment options and the threat from emerging variants underline the need for novel and widely accessible therapeutics. G-quadruplexes (G4s) are nucleic acid secondary structures known to affect many cellular processes including viral replication and transcription. We identified heretofore not reported G4s with remarkably low mutation frequency across >5 million SARS-CoV-2 genomes. The G4 structure was targeted using FDA-approved drugs that can bind G4s - Chlorpromazine (CPZ) and Prochlorperazine (PCZ). We found significant inhibition in lung pathology and lung viral load of SARS-CoV-2 challenged hamsters when treated with CPZ or PCZ that was comparable to the widely used antiviral drug Remdesivir. In support, G4 binding, inhibition of reverse transcription from RNA isolated from COVID-infected humans, and attenuated viral replication and infectivity in Vero cell cultures were clear in case of both CPZ and PCZ. Apart from the wide accessibility of CPZ/PCZ, targeting relatively invariant nucleic acid structures poses an attractive strategy against viruses like SARS-CoV-2, which spread fast and accumulate mutations quickly.
PubMed: 37006620
DOI: 10.3389/fmolb.2023.1133123 -
Journal of Dental Anesthesia and Pain... Oct 2021Migraine headaches are the second leading cause of disability worldwide and are responsible for significant morbidity, reduction in the quality of life, and loss of... (Review)
Review
BACKGROUND
Migraine headaches are the second leading cause of disability worldwide and are responsible for significant morbidity, reduction in the quality of life, and loss of productivity on a global scale. The purpose of this systematic review and meta-analysis was to evaluate the efficacy of ketamine on migraines and other primary headache disorders compared to placebo and other active interventions, such as midazolam, metoclopramide/diphenhydramine, and prochlorperazine/diphenhydramine.
METHODS
An electronic search of databases published up to February 2021, including Medline via PubMed, EMBASE, Web of Science, and Cochrane Library, a hand search of the bibliographies of the included studies, as well as literature and systematic reviews found through the search was conducted to identify randomized controlled trials (RCTs) investigating ketamine in the treatment of migraine/headache disorders compared to the placebo. The authors assessed the risk of bias according to the Cochrane Handbook guidelines.
RESULTS
The initial search strategy yielded 398 unduplicated references, which were independently assessed by three review authors. After evaluation, this number was reduced to five RCTs (two unclear risk of bias and three high risk of bias). The total number of patients in all the studies was 193. Due to the high risk of bias, small sample size, heterogeneity of the outcomes reported, and heterogeneity of the comparison groups, the quality of the evidence was very low. One RCT reported that intranasal ketamine was superior to intranasal midazolam in improving the aura attack severity, but not duration, while another reported that intranasal ketamine was not superior to metoclopramide and diphenhydramine in reducing the headache severity. In one trial, subcutaneous ketamine was superior to saline in migraine severity reduction; however, intravenous (I.V.) ketamine was inferior to I.V. prochlorperazine and diphenhydramine in another study.
CONCLUSION
Further double-blind controlled studies are needed to assess the efficacy of ketamine in treating acute and chronic refractory migraines and other primary headaches using intranasal and subcutaneous routes. These studies should include a long-term follow-up and different ketamine dosages in diagnosed patients following international standards for diagnosing headache/migraine.
PubMed: 34703891
DOI: 10.17245/jdapm.2021.21.5.413 -
Ondansetron: recommended antiemetics for patients with acute pancreatitis? a population-based study.Frontiers in Pharmacology 2023Ondansetron administration is a common antemetic of acute pancreatitis therapy in the intensive care unit (ICU), but its actual association with patients' outcomes has...
Ondansetron administration is a common antemetic of acute pancreatitis therapy in the intensive care unit (ICU), but its actual association with patients' outcomes has not been confirmed. The study is aimed to determine whether the multiple outcomes of ICU patients with acute pancreatitis could benefit from ondansetron. 1,030 acute pancreatitis patients diagnosed in 2008-2019 were extracted from the Medical Information Mart for Intensive Care (MIMIC)-IV database as our study cohort. The primary outcome we considered is the 90-day prognosis, and secondary outcomes included in-hospital survival and overall prognosis. In MIMIC-IV, 663 acute pancreatitis patients received ondansetron administration (OND group) during their hospitalization, while 367 patients did not (non-OND group). Patients in the OND group presented better in-hospital, 90-day, and overall survival curves than the non-OND group (log-rank test: in-hospital: < 0.001, 90-day: = 0.002, overall: = 0.009). After including covariates, ondansetron was associated with better survival in patients with multiple outcomes (in-hospital: HR = 0.50, 90-day: HR = 0.63, overall: HR = 0.66), and the optimal dose inflection points were 7.8 mg, 4.9 mg, and 4.6 mg, respectively. The survival benefit of ondansetron was unique and stable in the multivariate analyses after consideration of metoclopramide, diphenhydramine, and prochlorperazine, which may also be used as antiemetics. In ICU acute pancreatitis patients, ondansetron administration was associated with better 90-day outcomes, while results were similar in terms of in-hospital and overall outcomes, and the recommended minimum total dose might be suggested to be 4-8 mg.
PubMed: 37234720
DOI: 10.3389/fphar.2023.1155391 -
Journal of the Advanced Practitioner in... May 2014Case Study Mr. D., a 55-year-old male, presented to the medical oncology service with a diagnosis of stage III adenocarcinoma of the sigmoid colon. He presented 7... (Review)
Review
Case Study Mr. D., a 55-year-old male, presented to the medical oncology service with a diagnosis of stage III adenocarcinoma of the sigmoid colon. He presented 7 weeks post sigmoid colectomy with lymph node resection and was initiated on adjuvant chemotherapy with CAPOX (capecitabine [Xeloda] and oxaliplatin [Eloxatin]). Standard dosing was used: oxaliplatin at 130 mg/m(2) on day 1 and capecitabine at approximately 2,000 mg/m(2)/day (rounded to the nearest 500-mg tablet size) for 14 days on and 7 days off (1 cycle = 21 days). A capped body surface area of 2.4 m2 was used, due to the patient's body habitus. Adverse Effects Mr. D. did not report any complications of therapy during cycle 1, days 1-7, other than grade 1 diarrhea, which was amenable to diphenoxylate/atropine when taken. The next week, he reported significant malaise and fatigue associated with persistent diarrhea occurring every 30 minutes for 5 days. Mr. D. was instructed to go to the emergency room for an immediate evaluation, but he refused. Mr. D. presented to the clinic in poor condition on day 14 of cycle 1. His diarrhea had increased to grade 3 and was not controlled with either loperamide or diphenoxylate/atropine, though he was not taking his medications as directed. He had been instructed to take two 2-mg loperamide tablets after the first loose stool, followed by 1 tablet of diphenoxylate/atropine 2 hours later. He could then alternate this with loperamide every 2 hours as needed, not to exceed 8 tablets of loperamide per day. Instead, he had taken 2 tablets of loperamide after the first loose stool, but either waited 6 hours to take 1 tablet of diphenoxylate/atropine or otherwise chose not to alternate the medications at all despite continued diarrhea, depending on the day. Mr. D.'s timing in taking his supportive medications was inconsistent, and his explanations of this timing were not exact. He also reported persistent grade 3 nausea with vomiting for 5 days, which did not improve with ondansetron and prochlorperazine, though he again did not take these consistently. He was advised to alternate ondansetron and prochlorperazine every 4 hours as needed, but only took one or the other medication approximately 3 times per day. According to Mr. D., his adverse effects initially began on day 9 of cycle 1. He had lost approximately 14 kg (31 lb) during cycle 1. Clinically, he was found to have grade 2 mucositis and grade 1 hand-foot syndrome. At the time of this visit, his absolute neutrophil count was 3,000/ìL, his hemoglobin was 14.4 g/dL, his hematocrit 42.2%, and his platelet count was 139,000/ìL. His kidney function was within the normal range. Mr. D. refused hospitalization despite the primary team's recommendation. He also refused to undergo stool sampling for Clostridium difficile. He was given IV fluids along with adjustments in supportive medications, including a prescription for 10% tincture of opium. He was instructed to use 0.6 mL every 6 hours in addition to alternating loperamide with diphenoxylate/atropine as noted previously. He was advised to rinse his mouth with a baking soda solution for relief of his grade 1 mucositis, and alternation of antiemetics every 4 hours was reiterated. He was to return prior to initiation of cycle 2 for further evaluation. Worsening Symptoms The next day, Mr. D.'s wife called the clinic to report that her husband's diarrhea continued despite the use of tincture of opium and that it was associated with hematochezia. He was also experiencing a worsening of his mucositis, with an associated swelling of the tongue. He was instructed to present to the emergency center, which he did on day 16 of cycle 1. By then, he was found to be febrile at 39.5°C. He was tachycardic, with a heart rate of 126, and he was experiencing significant abdominal pain associated with the diarrhea. The mucositis was worsening, with new odynophagia. At this time, Mr. D.'s absolute neutrophil count had dropped dramatically to 160/ìL, his hemoglobin was 13.1 g/dL, his hematocrit was 39.2%, and his platelet count was 68,000/ìL. He was admitted to the inpatient service and started on empiric antibiotics. His blood cultures remained negative during hospitalization, but stool cultures were positive for C. difficile. His antimicrobial regimen was deescalated to oral vancomycin once his stool volume decreased. He was treated with an institutional compounded mouthwash of diphenhydramine, aluminum/magnesium hydroxide, and viscous lidocaine for the mucositis, which also slowly improved. He was given a dose of growth factor. Neutropenia eventually resolved, with an absolute neutrophil count of 4,820/ìL on the day of discharge. He was discharged 26 days after initiating cycle 1, at which time his myelosuppression and mucositis were also resolved. Throughout his course, he did not report any neurotoxicity. DPD Testing Due to his severe symptoms of neutropenia, mucositis, and diarrhea, Mr. D. was tested for dihydropyrimidine dehydrogenase (DPD) deficiency. Testing confirmed a heterozygous IVS14+IG>A mutation. For this reason, all further adjuvant therapy was withheld, and he was followed on clinical surveillance only.
PubMed: 25089219
DOI: 10.6004/jadpro.2014.5.3.5 -
Biological & Pharmaceutical Bulletin 2019To date, limited drug information is available for the individual optimization of pharmacotherapy. The author attempted multiple evaluations of patient data on factors... (Review)
Review
To date, limited drug information is available for the individual optimization of pharmacotherapy. The author attempted multiple evaluations of patient data on factors related to the pharmacokinetics, drug efficacy, and adverse reactions observed in clinical settings. Through the clinical studies, drug information on the individual optimization of pharmacotherapy needed by health professionals including physicians and pharmacists was identified. Major findings were: 1) Cachectic cancer patients had high plasma concentrations of oxycodone via the reduction of CYP3A activity. The metabolic reduction in cachectic cancer patients was potentially related to the elevated serum level of interleukin-6. 2) Dopamine receptor D (DRD2) genetic mutations and being female led to poor antiemetic efficacy of the treatment of opioid-induced nausea in prochlorperazine-treated patients. The opioid receptor μ1 (OPRM1) wild genotype in addition to being female and having high plasma concentrations of prochlorperazine increased prolactin secretion during oxycodone treatment. 3) Rheumatoid arthritis patients with a genetic mutation of ATP-binding cassette subfamily B member 1 (ABCB1) had high plasma concentrations of tacrolimus and its 13-O-demethylate. The ABCB1 genetic mutation and associated high plasma concentration of tacrolimus decreased kidney function. 4) Chronic inflammation increased the plasma voriconazole concentration via its poor metabolism, whereas it did not alter the plasma itraconazole concentration. Although co-administration of prednisolone did not affect the plasma concentration of triazole antifungals, it weakly increased voriconazole metabolism. 5) In breastfeeding women, the median milk/plasma concentration ratio of amlodipine was 0.85. However, the observed relative infant dose of amlodipine in most patients was less than 10%.
Topics: Drug Therapy; Female; Humans; Male; Precision Medicine; Sex Factors
PubMed: 30713247
DOI: 10.1248/bpb.b18-00766 -
Journal of Pain and Symptom Management Aug 1991Dronabinol (Marinol, Roxane Laboratories, Columbus, OH) and prochlorperazine were tested alone and in combination in a randomized, double-blind, parallel group,... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Dronabinol (Marinol, Roxane Laboratories, Columbus, OH) and prochlorperazine were tested alone and in combination in a randomized, double-blind, parallel group, multicenter study. Patients were randomized to receive either 1) dronabinol 10 mg every 6 hr plus placebo; 2) placebo plus prochlorperazine 10 mg every 6 hr; or 3) dronabinol and prochlorperazine, each 10 mg every 6 hr. Antiemetic treatment was begun 24 hr prior to and continued for 24 hr after the last dose of chemotherapy; all was given orally. Only 29% of patients in group 3 versus 47% in group 1 and 60% in group 2 experienced nausea after chemotherapy. In addition, the median duration per episode and severity of nausea were significantly less with combination therapy. Vomiting occurred after chemotherapy in 41%, 55%, and 35% of patients in groups 1, 2, and 3, respectively. The median duration per episode of vomiting was 1 min in group 3 versus two in group 1 and four in group 2. Side effects, primarily CNS, were more common in group 1 than in group 2; addition of prochlorperazine to dronabinol appeared to decrease the frequency of dysphoric effects seen with the latter agent. The combination was significantly more effective than was either single agent in controlling chemotherapy-induced nausea and vomiting.
Topics: Adult; Aged; Antineoplastic Agents; Double-Blind Method; Dronabinol; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Nausea; Prochlorperazine; Vomiting
PubMed: 1652611
DOI: 10.1016/0885-3924(91)90026-z