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Journal of Pharmacological Sciences Jun 2019Antipsychotics are often the first-line treatment for behavioral and psychological symptoms of dementia. However, the potential anticholinergic effects of antipsychotics...
Antipsychotics are often the first-line treatment for behavioral and psychological symptoms of dementia. However, the potential anticholinergic effects of antipsychotics could counteract the therapeutic effects of cholinesterase inhibitors used to treat dementia. We investigated the inhibitory effects of 26 antipsychotics on [N-Methyl-H]scopolamine specific binding in mouse cerebral cortex. At 10 M, chlorpromazine, levomepromazine, prochlorperazine, timiperone, zotepine, pimozide, blonanserin, olanzapine, quetiapine, and clozapine inhibited [N-Methyl-H]scopolamine binding by > 45%. Furthermore, the pK values of chlorpromazine, levomepromazine, zotepine, olanzapine, and clozapine overlapped with their clinically achievable blood concentrations. Therefore, the anticholinergic properties of these antipsychotics could attenuate the effects of cholinesterase inhibitors.
Topics: Animals; Antipsychotic Agents; Cerebral Cortex; Chlorpromazine; Cholinergic Antagonists; Cholinesterase Inhibitors; Depression, Chemical; Drug Interactions; Male; Methotrimeprazine; Mice, Inbred Strains; Prochlorperazine; Protein Binding; Receptors, Muscarinic; Scopolamine
PubMed: 31178327
DOI: 10.1016/j.jphs.2019.05.006 -
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 -
Sao Paulo Medical Journal = Revista... 2018The therapeutic effects of cannabinoid compounds have been the center of many investigations. This study provides a synthesis on all Cochrane systematic reviews (SRs)...
BACKGROUND
The therapeutic effects of cannabinoid compounds have been the center of many investigations. This study provides a synthesis on all Cochrane systematic reviews (SRs) that assessed the use of cannabinoids as a therapeutic approach.
DESIGN AND SETTING
Review of SRs, conducted in the Discipline of Evidence-Based Medicine, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP).
METHODS
A broad search was conducted in the Cochrane Database of Systematic Reviews to retrieve any Cochrane SRs that assessed the efficacy and safety of cannabinoids as a therapeutic approach. The results and key characteristics of all reviews included were summarized and discussed.
RESULTS
Eight SRs were included. They assessed the use of cannabinoids for the following types of conditions: neurological (two SRs), psychiatric (two SRs), rheumatological (one SR), infectious (one SR) and oncological (two SRs). There was moderate-quality evidence showing that the use of cannabinoids reduced nausea and vomiting among adults, compared with placebo. Additionally, there was moderate-quality evidence showing that there was no difference between cannabinoids and prochlorperazine regarding the number of participants who reported vomiting, in this same population.
CONCLUSIONS
This review identified eight Cochrane systematic reviews that provided evidence of unknown to moderate quality regarding the use of cannabinoids as a therapeutic intervention. Further studies are still imperative for solid conclusions to be reached regarding practical recommendations.
Topics: Cannabinoids; Dementia; Epilepsy; Evidence-Based Medicine; Fibromyalgia; HIV Infections; Humans; Nausea; Schizophrenia; Systematic Reviews as Topic; Tourette Syndrome; Vomiting
PubMed: 30365598
DOI: 10.1590/1516-3180.2018.0313210818 -
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 -
Antimicrobial Agents and Chemotherapy Sep 2018Chloroquine-resistant (CQR) vivax malaria has emerged as a threat to the malaria elimination agenda. The objective of this study was to assess if a combination of...
Chloroquine-resistant (CQR) vivax malaria has emerged as a threat to the malaria elimination agenda. The objective of this study was to assess if a combination of chloroquine (CQ) and prochlorperazine was able to reverse CQ resistance of the AMRU-1 strain from Papua New Guinea in infected monkeys. For this purpose, in two independent experimental drug efficacy trials, a total of 18 monkeys infected with blood obtained from donor animals were randomly assigned to treatment and control groups and orally administered CQ at 10 mg/kg or prochlorperazine at 20 mg/kg, alone or in combination, for five consecutive days. Reversal of CQR was achieved in animals that received the drug combination, whereas neither drug alone produced cures. This same drug combination reverses CQR in and could be an alternative for treatment in humans with chloroquine-resistant infections.
Topics: Animals; Antimalarials; Chloroquine; Drug Resistance; Female; Haplorhini; Malaria, Falciparum; Malaria, Vivax; Male; Papua New Guinea; Plasmodium falciparum; Plasmodium vivax
PubMed: 29941642
DOI: 10.1128/AAC.00582-18 -
Cureus Apr 2018The objective of this literature review is to evaluate the efficacy of opioids for the treatment of headaches, particularly migraines, in the emergency department (ED).... (Review)
Review
The objective of this literature review is to evaluate the efficacy of opioids for the treatment of headaches, particularly migraines, in the emergency department (ED). Despite safer alternatives, opiates are routinely used as an abortive treatment for migraine headaches. The studies reviewed demonstrate that opiates are less effective in terminating acute headaches and result in prolonged ED visits. Dopamine receptor antagonists, such as metoclopramide and prochlorperazine, were the most efficacious in terminating migraines in the studies examined.
PubMed: 29881652
DOI: 10.7759/cureus.2439 -
Acta Neurologica Taiwanica Jun 2017In 2015, the American Headache Society (AHS) amended the treatment guideline of acute migraine based on evidence-based medicine (EBM) that all triptans in any form of...
In 2015, the American Headache Society (AHS) amended the treatment guideline of acute migraine based on evidence-based medicine (EBM) that all triptans in any form of preparations, acetaminophen, and non-steroid anti-inflammation drugs-NSAID (aspirin, diclofenac, ibuprofen, naproxen), sumatriptan/naproxen, combined acetaminophen/aspirin/caffeine are considered effective (Level A). Previously effective drugs as prochlorperazine, and dihydroergotamine-DHE (excluded inhaled form) were downrated to probable effective (Level B). Taiwan Headache Society published its treatment guideline for acute migraine attack in 2007. It should be updated based on the new available evidence. The Treatment Guideline Subcommittee of Taiwan Headache Society reviewed the recent trials, evaluated the grade of evidence, and appraised the clinical efficacy to reach a new consensus. We also referred to the guidelines from United States, Europe, Canada and other countries to make this one meets our needs and feasible. Acute medications currently available in Taiwan can be categorized into "migraine-specific"and"migraine-nonspecific" groups. Migraine-specific triptans and migraine-nonspecific nonsteroidal antiinflammatory drugs (NSAIDs) have the best levels of evidence, and are recommended as the first-line medications for acute migraine attacks. The administration should follow the concept of "stratified care". For mild to moderate migraine attacks, oral NSAIDs are the first choice; with oral aspirin, combination analgesics, intravenous/intramuscular NSAIDs as alternatives. For moderate to severe attacks, oral or nasal spray triptans and ergotamine/caffeine compounds are recommended and should be administered in the early stage of migraine attacks. Antiemetics can be used as supplement to alleviate nausea and vomiting. Notably, a combination of a triptan and a NSAID yielded a better efficacy compared with either therapy alone. Parenteral steroid and fluid supply are the first choice in treatment of status migrainosus. Acetaminophen is suitable for mild to moderate migraine attacks and remains the first choice for children and pregnant women. Opiates are not recommended for acute migraine treatment at the present time because of serious adverse events. To prevent medication-overuse headache, the use of acute treatment should be limited to a maximum of ten days a month.
Topics: Acute Disease; Anti-Inflammatory Agents, Non-Steroidal; Humans; Migraine Disorders; Practice Guidelines as Topic; Tryptamines
PubMed: 29250761
DOI: No ID Found -
Neurology Nov 2017To determine outcomes among patients with migraine in the emergency department (ED) who receive IV hydromorphone vs IV prochlorperazine + diphenhydramine. (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVE
To determine outcomes among patients with migraine in the emergency department (ED) who receive IV hydromorphone vs IV prochlorperazine + diphenhydramine.
METHODS
This study was conducted in 2 EDs in New York City. Patients who met international criteria for migraine were eligible for participation if they had not used an opioid within the previous month. Clinicians, participants, investigators, and research personnel were blinded to treatment. Patients were randomized in blocks of 4. Participants received hydromorphone 1 mg or prochlorperazine 10 mg + diphenhydramine 25 mg. Diphenhydramine was administered to prevent akathisia, a common side effect of IV prochlorperazine. The primary outcome was sustained headache relief, defined as achieving a headache level of mild or none within 2 hours of medication administration and maintaining that level for 48 hours without the requirement of rescue medication. A planned interim analysis was conducted once 48-hour data were available for 120 patients.
RESULTS
The trial was halted by the data monitoring committee after 127 patients had been enrolled. The primary outcome was achieved in the prochlorperazine arm by 37 of 62 (60%) participants and in the hydromorphone arm by 20 of 64 (31%) participants (difference 28%, 95% confidence interval 12-45, number needed to treat 4, 95% confidence interval 2-9).
CONCLUSIONS
IV hydromorphone is substantially less effective than IV prochlorperazine for the treatment of acute migraine in the ED and should not be used as first-line therapy.
CLINICALTRIALSGOV IDENTIFIER
NCT02389829.
CLASSIFICATION OF EVIDENCE
This study provides Class I evidence that for patients in the ED with migraine, IV prochlorperazine + diphenhydramine is superior to IV hydromorphone.
Topics: Acute Disease; Administration, Intravenous; Adult; Analgesics, Opioid; Diphenhydramine; Dopamine Antagonists; Double-Blind Method; Drug Therapy, Combination; Emergency Service, Hospital; Female; Follow-Up Studies; Humans; Hydromorphone; Hypnotics and Sedatives; Male; Middle Aged; Migraine Disorders; Outcome Assessment, Health Care; Prochlorperazine
PubMed: 29046364
DOI: 10.1212/WNL.0000000000004642 -
The Oncologist Mar 2018Although opioid-induced nausea and vomiting (OINV) often result in analgesic undertreatment in patients with cancer, no randomized controlled trials have evaluated the... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy of Prophylactic Treatment for Oxycodone-Induced Nausea and Vomiting Among Patients with Cancer Pain (POINT): A Randomized, Placebo-Controlled, Double-Blind Trial.
BACKGROUND
Although opioid-induced nausea and vomiting (OINV) often result in analgesic undertreatment in patients with cancer, no randomized controlled trials have evaluated the efficacy of prophylactic antiemetics for preventing OINV. We conducted this randomized, placebo-controlled, double-blind trial to evaluate the efficacy and safety of prophylactic treatment with prochlorperazine for preventing OINV.
MATERIALS AND METHODS
Cancer patients who started to receive oral oxycodone were randomly assigned in a 1:1 ratio to receive either prochlorperazine 5 mg or placebo prophylactically, given three times daily for 5 days. The primary endpoint was the proportion of patients who had a complete response (CR) during the 120 hours of oxycodone treatment. CR was defined as no emetic episode and no use of rescue medication for nausea and vomiting during 5 days. Key secondary endpoints were the proportion of patients with emetic episodes, proportion of patients with moderate or severe nausea, quality of life, and proportion of treatment withdrawal.
RESULTS
From November 2013 through February 2016, a total of 120 patients were assigned to receive prochlorperazine ( = 60) or placebo ( = 60). There was no significant difference in CR rates (69.5% vs. 63.3%; = .47) or any secondary endpoint between the groups. Patients who received prochlorperazine were more likely to experience severe somnolence ( = .048).
CONCLUSION
Routine use of prochlorperazine as a prophylactic antiemetic at the initiation of treatment with opioids is not recommended. Further research is needed to evaluate whether other antiemetics would be effective in preventing OINV in specific patient populations.
IMPLICATIONS FOR PRACTICE
Prophylactic prochlorperazine seems to be ineffective in preventing opioid-induced nausea and vomiting (OINV) and may cause adverse events such as somnolence. Routine use of prophylactic prochlorperazine at the initiation of treatment with opioids is not recommended. Further research is needed to evaluate whether other antiemetics would be effective in preventing OINV in specific patient populations.
Topics: Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Antiemetics; Cancer Pain; Double-Blind Method; Female; Humans; Male; Middle Aged; Nausea; Oxycodone; Prochlorperazine; Treatment Failure; Vomiting
PubMed: 29038236
DOI: 10.1634/theoncologist.2017-0225