-
International Journal of Molecular... Jun 2022Multidrug resistance-associated protein 1 (MRP1, encoded by the gene) may contribute to the clearance of amyloid-beta (Aβ) peptides from the brain into the blood and...
Multidrug resistance-associated protein 1 (MRP1, encoded by the gene) may contribute to the clearance of amyloid-beta (Aβ) peptides from the brain into the blood and stimulation of MRP1 transport activity may be a therapeutic approach to enhance brain Aβ clearance. In this study, we assessed the effect of thiethylperazine, an antiemetic drug which was shown to stimulate MRP1 activity in vitro and to decrease Aβ load in a rapid β-amyloidosis mouse model (APP/PS1-21), on MRP1 transport activity by means of positron emission tomography (PET) imaging with the MRP1 tracer 6-bromo-7-[C]methylpurine. Groups of wild-type, APP/PS1-21 and mice underwent PET scans before and after a 5-day oral treatment period with thiethylperazine (15 mg/kg, once daily). The elimination rate constant of radioactivity () was calculated from time-activity curves in the brain and the lungs as a measure of tissue MRP1 activity. Treatment with thiethylperazine had no significant effect on MRP1 activity in the brain and the lungs of wild-type and APP/PS1-21 mice. This may either be related to a lack of an MRP1-stimulating effect of thiethylperazine in vivo or to other factors, such as substrate-dependent MRP1 stimulation, insufficient target tissue exposure to thiethylperazine or limited sensitivity of the PET tracer to measure MRP1 stimulation.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Brain; Disease Models, Animal; Mice; Mice, Transgenic; Multidrug Resistance-Associated Proteins; Positron-Emission Tomography; Presenilin-1; Thiethylperazine
PubMed: 35742960
DOI: 10.3390/ijms23126514 -
British Journal of Clinical Pharmacology Dec 1976The absorption of effervescent aspirin was studied in three groups of patients during attacks of migraine. The first group received intramuscular thiethylperazine 10 min... (Clinical Trial)
Clinical Trial
The absorption of effervescent aspirin was studied in three groups of patients during attacks of migraine. The first group received intramuscular thiethylperazine 10 min before effervescent aspirin; the second group received intramuscular metoclopramide 10 min before effervescent aspirin; and the third group received effervescent aspirin alone. Where possible each patient was retested when headache-free but under conditions which were otherwise as similar as possible to those during the acute attack. Intramuscular metoclopramide corrected the impairment of drug absorption that occurred during a migraine attack, whereas thiethylperazine did not. In the group of patients treated with thiethylperazine and aspirin, the impairment of absorption did not correlate with the duration of the symptoms, nor with the severity of the headache and nausea. Patients treated with thiethylperazine and aspirin tended to take longer to recover than those patients treated with metoclopramide and aspirin. However, in the thiethylperazine treated group, the time to recover did not correlate with the salicylate level achieved.
Topics: Adult; Antiemetics; Aspirin; Drug Interactions; Drug Therapy, Combination; Female; Humans; Male; Metoclopramide; Middle Aged; Migraine Disorders; Thiethylperazine
PubMed: 22216523
DOI: 10.1111/j.1365-2125.1976.tb00351.x -
Mikrochimica Acta Oct 2023A new voltammetric method is proposed for high sensitive thiethylperazine (THP) determination, using a glassy carbon electrode modified with semi-graphitized carbon...
A new voltammetric method is proposed for high sensitive thiethylperazine (THP) determination, using a glassy carbon electrode modified with semi-graphitized carbon nanofibers/MnO nanocomposite (eCNF/MnO/GC). To the best of our knowledge, this is the first electrochemical assay of THP determination, and the first use of the eCNF/MnO as the electrode modifier. The proposed method using eCNF/MnO/GC is characterized by high repeatability and sensitivity of measurements, with the linearity of THP in the range from 0.05 to 2.2 µmol L. The lowest detection limit achieved on the eCNF/MnO/GC electrode for 30 s of preconcentration was 6.3 nmol L THP in 0.05 mol L acetate buffer of pH 5.6. The proposed method was successfully applied to highly sensitive THP determination in complex matrices, such as tablets and plasma with good recovery (98-103%). The RSD value obtained for THP measurement at a concentration of 0.1 µmol L was 1.3%. Amperometric measurements of THP under the flow injection conditions were also performed to indicate the possibility of its fast and accurate determination (103% and 95% for unmodified and modified electrode, respectively), with the duration of single analysis of approx. 30 s.
PubMed: 37874386
DOI: 10.1007/s00604-023-06025-1 -
BMJ (Clinical Research Ed.) Jul 2001To quantify the antiemetic efficacy and adverse effects of cannabis used for sickness induced by chemotherapy. (Review)
Review
OBJECTIVE
To quantify the antiemetic efficacy and adverse effects of cannabis used for sickness induced by chemotherapy.
DESIGN
Systematic review.
DATA SOURCES
Systematic search (Medline, Embase, Cochrane library, bibliographies), any language, to August 2000.
STUDIES
30 randomised comparisons of cannabis with placebo or antiemetics from which dichotomous data on efficacy and harm were available (1366 patients). Oral nabilone, oral dronabinol (tetrahydrocannabinol), and intramuscular levonantradol were tested. No cannabis was smoked. Follow up lasted 24 hours.
RESULTS
Cannabinoids were more effective antiemetics than prochlorperazine, metoclopramide, chlorpromazine, thiethylperazine, haloperidol, domperidone, or alizapride: relative risk 1.38 (95% confidence interval 1.18 to 1.62), number needed to treat 6 for complete control of nausea; 1.28 (1.08 to 1.51), NNT 8 for complete control of vomiting. Cannabinoids were not more effective in patients receiving very low or very high emetogenic chemotherapy. In crossover trials, patients preferred cannabinoids for future chemotherapy cycles: 2.39 (2.05 to 2.78), NNT 3. Some potentially beneficial side effects occurred more often with cannabinoids: "high" 10.6 (6.86 to 16.5), NNT 3; sedation or drowsiness 1.66 (1.46 to 1.89), NNT 5; euphoria 12.5 (3.00 to 52.1), NNT 7. Harmful side effects also occurred more often with cannabinoids: dizziness 2.97 (2.31 to 3.83), NNT 3; dysphoria or depression 8.06 (3.38 to 19.2), NNT 8; hallucinations 6.10 (2.41 to 15.4), NNT 17; paranoia 8.58 (6.38 to 11.5), NNT 20; and arterial hypotension 2.23 (1.75 to 2.83), NNT 7. Patients given cannabinoids were more likely to withdraw due to side effects 4.67 (3.07 to 7.09), NNT 11.
CONCLUSIONS
In selected patients, the cannabinoids tested in these trials may be useful as mood enhancing adjuvants for controlling chemotherapy related sickness. Potentially serious adverse effects, even when taken short term orally or intramuscularly, are likely to limit their widespread use.
Topics: Antiemetics; Antineoplastic Agents; Cannabinoids; Humans; Nausea; Patient Satisfaction; Randomized Controlled Trials as Topic; Treatment Outcome; Vomiting
PubMed: 11440936
DOI: 10.1136/bmj.323.7303.16 -
Canadian Medical Association Journal Feb 1965A double-blind study of thiethylperazine dimaleate (Torecan) and a placebo, given intramuscularly, was carried out on 40 patients with nausea and/or vomiting due to a...
A double-blind study of thiethylperazine dimaleate (Torecan) and a placebo, given intramuscularly, was carried out on 40 patients with nausea and/or vomiting due to a variety of causes. No effect on these symptoms was noted in five patients who received the drug and in six who received the placebo. Thiethylperazine dimaleate was judged to have a good effect in 14 patients and the placebo in five patients. The placebo had a slight effect in nine patients and the drug in one.
Topics: Biomedical Research; Double-Blind Method; Drug Therapy; Humans; Injections, Intramuscular; Nausea; Pharmacology; Placebos; Thiethylperazine; Vomiting
PubMed: 14261157
DOI: No ID Found -
Basic & Clinical Pharmacology &... Aug 2010The antimicrobial and resistance-reversal activities of seven phenothiazine derivatives were evaluated against vancomycin-sensitive Enterococcus faecalis ATCC 29212,...
The antimicrobial and resistance-reversal activities of seven phenothiazine derivatives were evaluated against vancomycin-sensitive Enterococcus faecalis ATCC 29212, vancomycin resistant E. faecalis ATCC 51299 and ten vancomycin-resistant E. faecium strains originating from human infections. Minimum inhibitory concentrations (MIC) of the compounds were determined by agar dilution method, and synergy between phenothiazines and vancomycin was investigated using Checkerboard (microbroth dilution) technique. We found that all enterococci strains, regardless of their susceptibility to vancomycin, were inhibited by phenothiazines at concentrations varying from 8 to 256 microg/ml, with thiethylperazine being the most potent inhibitory agent. Besides, all the phenothiazines showed partial synergy with vancomycin and could lessen MIC of vancomycin from 512 to 8 microg/ml at their sub-inhibitory concentrations. The highest reduction in MIC was observed with chlorpromazine (32 times); however, thiethylperazine and promethazine stood next (24 times). Although resistance modification was observed at concentrations higher than those that phenothiazines reach in vivo, the potential offered by non-antibiotics justify further animal experiments as well as clinical trials to establish their clinical relevance.
Topics: Anti-Bacterial Agents; Drug Synergism; Drug Therapy, Combination; Enterococcus faecium; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Phenothiazines; Vancomycin; Vancomycin Resistance
PubMed: 20353486
DOI: 10.1111/j.1742-7843.2010.00558.x -
European Journal of Medical Research Apr 2022The SARS-CoV-2 pandemic has become a challenge for the entire healthcare system. Treatment for COVID-19 includes casual and symptomatic management in the acute phase of...
BACKGROUND
The SARS-CoV-2 pandemic has become a challenge for the entire healthcare system. Treatment for COVID-19 includes casual and symptomatic management in the acute phase of the disease and focuses on the treating early complications of the disease. Long-term health consequences of the infection have not yet been fully identified. A special group of patients with comorbidities, including neoplastic disease for whom the interpretation and management of symptoms is a major challenge.
CASE PRESENTATION
In this case report, we present a 73-year-old woman with recently diagnosed gastric adenocarcinoma in whom we diagnosed orthostatic hypotonia in the aftermath of SARS-CoV-2 infection. We administered thiethylperazine maleate 6.5 mg daily. Additionally, we advised the patient to slowly lift from the recumbent position, raise the headboard, take meals in small portions, and increase fluid intake. These pharmacological and nonpharmacological measures resulted in sustained relief of dizziness and nausea.
CONCLUSIONS
The occurrence of orthostatic hypotonia seems a possible late sequela of SARS-CoV-2 infection, and simple measures appeared sufficient to achieve sustained symptom control.
Topics: Aged; COVID-19; Female; Home Care Services; Humans; Muscle Hypotonia; Pandemics; SARS-CoV-2
PubMed: 35488314
DOI: 10.1186/s40001-022-00685-0 -
BMJ (Clinical Research Ed.) Jul 1989To estimate the prevalence of important side effects in patients with malignant disease who were receiving high doses of morphine as part of their palliative treatment.
OBJECTIVE
To estimate the prevalence of important side effects in patients with malignant disease who were receiving high doses of morphine as part of their palliative treatment.
DESIGN
Data on patients were collected over 12 months.
SETTING
Two palliative care units in Western Australia.
PATIENTS
19 Patients with malignant disease who were receiving morphine either subcutaneously or orally as the main analgesic. 10 Patients receiving a total daily dose of morphine of at least 500 mg orally or 250 mg parenterally were enrolled in the study. The other 9 patients were enrolled after an important problem thought to be related to the morphine had been identified. All of the patients were taking drugs to supplement the treatment.
INTERVENTIONS
The dose of morphine or route of administration, or both, was changed in three patients.
MAIN OUTCOME MEASURE
Determination of the prevalence of side effects in the patients. Assessment of the relation of any side effects with the supplemental drugs taken by the patients.
MAIN RESULTS
Plasma morphine and electrolyte concentrations were measured and a full history taken for each patient. Thirteen of the 19 patients had an important side effect; 12 of them had myoclonus and one had hyperalgesia of the skin. Plasma morphine concentrations were similar in patients with and without myoclonus, ranging from 158 to 3465 nmol/l and 39 to 2821 nmol/l respectively. Eight of the patients with side effects were taking an antipsychotic drug concurrently compared with none of those without side effects. A greater proportion of patients with side effects were taking the antinauseant drug thiethylperazine (6/13 v 2/6) and at least one non-steroidal anti-inflammatory drug (10/13 v 2/6), whereas a smaller proportion were taking a glucocorticosteroid (3/13 v 4/6). The estimated prevalence of important side effects in the total population of patients receiving palliative treatment in the two units was 2.7-3.6%.
CONCLUSIONS
Myoclonus as a side effect of treatment with morphine is more likely to occur in patients taking antidepressant or antipsychotic drugs as antiemetics or as adjuvant agents or non-steroidal anti-inflammatory drugs for additional analgesia. If a patient develops myoclonus the best approach may be to change the supplemental treatment.
Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Antiemetics; Antipsychotic Agents; Dose-Response Relationship, Drug; Drug Interactions; Female; Humans; Male; Middle Aged; Morphine; Myoclonus; Neoplasms; Palliative Care
PubMed: 2475196
DOI: 10.1136/bmj.299.6692.150 -
Cases Journal Sep 2009Acute ethanol ingestion can prolong the PR interval, but searching Medline, we have found only one report of Wenckebach-type atrioventricular block in ethanol poisoning....
INTRODUCTION
Acute ethanol ingestion can prolong the PR interval, but searching Medline, we have found only one report of Wenckebach-type atrioventricular block in ethanol poisoning. We present a high-degree atrioventricular block in an ethanol-poisoned patient.
CASE PRESENTATION
A 17-year-old woman with a non-contributory medical history ingested 3dcl of vodka and was found comatose. On arrival she was somnolent with nausea, tympanic temperature 36.0 degrees C, pulse 70 counts/min, blood pressure 90/60 mmHg, respiratory rate 12 counts/min and SpO(2) 96% on room air. Her blood ethanol level was 130 mg/dL; other blood laboratory test results were normal. ECG revealed sinus rhythm, first-degree atrioventricular block with a PR interval of 0.32 seconds and intermittent second- and third-degree atrioventricular blocks with up to 4-second-long pauses that appeared 15-30 seconds after each vomiting. She was given thiethylperazine and vomiting resolved within an hour. ECG 12 hours after admission revealed a first-degree atrioventricular block with a PR interval of 0.24 seconds. One month later Holter monitor showed a sinus rhythm and first-degree atrioventricular block with a PR interval of 0.21 seconds. Vagal maneuvers did not provoke high-degree atrioventricular block. The echocardiogram was normal.
CONCLUSION
Acute ethanol poisoning has the potential to prolong the PR interval in adults with first-degree atrioventricular block and provoke intermittent second- and third-degree atrioventricular blocks, possibly by its direct inhibitory action on the conduction system and increasing parasympathetic tone due to nausea and vomiting.
PubMed: 19918387
DOI: 10.4076/1757-1626-2-8559