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Biomedicines Jul 2023Patients with chronic obstructive pulmonary disease (COPD) are prone to developing arterial hypertension, and many patients are treated with the calcium channel blocker...
Patients with chronic obstructive pulmonary disease (COPD) are prone to developing arterial hypertension, and many patients are treated with the calcium channel blocker amlodipine. However, it remains unclear whether using this drug potentially affects the risk of acute severe exacerbations (AECOPD) and all-cause mortality in these patients. The data were collected from Danish national registries, containing complete information on health, prescriptions, hospital admissions, and outpatient clinic visits. The COPD patients ( = 48,488) were matched via propensity score on known predictors of the primary outcome in an active comparator design. One group was exposed to amlodipine treatment, and the other was exposed to bendroflumethiazide, since both of these drugs are considered to be the first choice for the treatment of arterial hypertension according to Danish guidelines. The use of amlodipine was associated with a reduced risk of death from all causes at the 1-year follow-up (hazard ratio 0.69, 95% confidence interval: 0.62-0.76) compared with the use of bendroflumethiazide in the matched patients. No difference in the risk of severe AECOPD was found. In the COPD patients, amlodipine use was associated with a lower risk of death from all causes compared with the use of bendroflumethiazide. Amlodipine seems to be a safe first choice for the treatment of arterial hypertension in COPD patients.
PubMed: 37509614
DOI: 10.3390/biomedicines11071974 -
Therapeutic Drug Monitoring Apr 2020Therapeutic drug monitoring of antihypertensive drugs is being increasingly used to optimize treatment and to assess nonadherence. Separator gels are often used in blood...
BACKGROUND
Therapeutic drug monitoring of antihypertensive drugs is being increasingly used to optimize treatment and to assess nonadherence. Separator gels are often used in blood collection tubes to facilitate serum or plasma separation from other blood constituents before analyses. Drug adsorption into the separator gel presents a possible pre-analytical cause of falsely low concentrations or false negative results.
METHODS
Drug-free blood from blood donors was spiked with therapeutic concentrations of 21 antihypertensive drugs, transferred to serum tubes with and without separator gel (Vacuette gel plastic tubes and plain serum plastic tubes, respectively), and centrifuged. Serum was collected immediately after centrifugation and after 24 and 72 hours of room temperature storage, samples were analyzed in triplicates using liquid chromatography-mass spectrometry.
RESULTS
Serum samples collected immediately after centrifugation or 24 hours later, had the same drug concentrations in the gel and nongel tubes. After 72 hours of room temperature storage, verapamil and lercanidipine serum concentrations were 43% and 29%, respectively, lower in gel tubes than nongel tubes. Canrenone, diltiazem, and bendroflumethiazide showed between 10% and 20% concentration loss in gel tubes, compared with nongel tubes, with the 2 latter observed as unstable also in nongel tubes.
CONCLUSIONS
Except for verapamil, lercanidipine, and canrenone, which showed substantial concentration loss in gel tubes, gel tubes may be used for therapeutic drug monitoring purposes for the most commonly used antihypertensive drugs. Transferring serum to gel-free containers immediately after centrifugation minimizes concentration loss; however, bendroflumethiazide and diltiazem are generally unstable at room temperature.
Topics: Antihypertensive Agents; Blood Specimen Collection; Chromatography, Liquid; Drug Monitoring; Gels; Humans
PubMed: 31609885
DOI: 10.1097/FTD.0000000000000708 -
Journal of Pharmaceutical and... Sep 2022We developed three ultra-high pressure liquid chromatography coupled to mass spectrometry detection (UHPLC-MS/MS) methods to quantify 25 antihypertensive drugs in serum...
We developed three ultra-high pressure liquid chromatography coupled to mass spectrometry detection (UHPLC-MS/MS) methods to quantify 25 antihypertensive drugs in serum samples. Patient-reported drug lists were collected, and drug concentrations were analysed in samples from 547 patients, half with uncontrolled hypertension, and all treated with ≥ 2 antihypertensive drugs. For sample preparation, serum was mixed with deuterated internal standards and acetonitrile and precipitated. Aliquots of the supernatant were injected on UHPLC-MSMS with a C18 reversed phase column. The mobile phase was 0.1 % HCOOH (formic acid) in water and 0.1 % HCOOH in acetonitrile (except in methanol for spironolactone/canrenone) at a flow rate of 0.4 mL/min. The calibrators and internal controls were prepared in Autonorm™. The calibration ranges were wide, and the models were linear or quadratic with squared correlation coefficients ≥ 0.97. The limits of detection and quantification, specificity, carry-over, and matrix effects were acceptable. The accuracy of the internal controls was in the range 85-121 %, and the intermediate precision for all drugs was 4-28 %. The patient-reported antihypertensive drug use and the detected serum drug concentrations were in accordance with that most frequently prescribed nationally. The percent non-detectable level was 5-10 % for bendroflumethiazide, doxazosin, nifedipine, and ramipril. Often the drug dose chosen was lower than the recommended maximum daily dose. We report the maximum (C) and minimum (C) drug concentrations after drug intake. The inter-individual pharmacokinetic variability at C was 18-fold for hydrochlorothiazide, 22-fold for losartan carboxyl acid, 26-fold for amlodipine, 44-fold for candesartan, and 50-fold for valsartan. Our methods are suitable for measuring antihypertensive drugs in patient serum for therapy control.
Topics: Acetonitriles; Antihypertensive Agents; Chromatography, High Pressure Liquid; Humans; Hypertension; Tandem Mass Spectrometry
PubMed: 35803015
DOI: 10.1016/j.jpba.2022.114908 -
British Medical Journal Mar 1964
Topics: Abnormalities, Drug-Induced; Anemia; Anemia, Hemolytic; Bendroflumethiazide; Chlorothiazide; Female; Fetal Diseases; Hemolysis; Humans; Infant, Newborn; Infant, Newborn, Diseases; Pre-Eclampsia; Pregnancy; Thiazides; Toxicology
PubMed: 14096472
DOI: 10.1136/bmj.1.5384.696-b -
British Medical Journal Jan 1970
Topics: Bendroflumethiazide; Calcium; Calcium Metabolism Disorders; Humans; Hypokalemia; Phosphates
PubMed: 5413948
DOI: 10.1136/bmj.1.5688.110 -
British Journal of Clinical Pharmacology Sep 19941. Central effects of the diuretic, bendrofluazide (2.5, 5 and 10 mg) were studied in 12 healthy volunteers. Two placebos and an active control drug, oxazepam (15 mg),... (Clinical Trial)
Clinical Trial Comparative Study
1. Central effects of the diuretic, bendrofluazide (2.5, 5 and 10 mg) were studied in 12 healthy volunteers. Two placebos and an active control drug, oxazepam (15 mg), were included. Single doses were administered double-blind at 10.00 h. The effects of drugs on performance and subjective feelings were assessed before and from 1.5-2.5 and 3.5-4.5 h after ingestion, and recording of the electrical activity of the brain (EEG) and body sway carried out. 2. Performance was assessed using digit symbol substitution, continuous attention, letter cancellation, choice reaction time, finger tapping, immediate and short-term memory, together with critical flicker fusion and two flash fusion. Subjects assessed their mood and well-being on a series of 12 visual analogue scales. The EEG was recorded with eyes open while the subjects carried out a mental arithmetic task, and with eyes closed, when they were required to relax. Body sway was recorded with eyes open and with eyes closed. 3. Bendrofluazide (10 mg) increased the number of errors at letter cancellation and reduced the rate of finger tapping (P < 0.05), while oxazepam increased the number of errors and reduced accuracy at continuous attention (P < 0.01), and increased the number of involuntary rest pauses during tapping (P < 0.05). 4. There were no effects of drugs on subjective assessment of mood. 5. No changes in the electrical activity of the brain were observed with bendrofluazide. In recordings with eyes open, oxazepam reduced delta (0.5-3 Hz), theta (3.5-7 Hz) and alpha 2 (10.5-13 Hz) while increasing beta 1 (13.5-21 Hz) activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adult; Analysis of Variance; Bendroflumethiazide; Central Nervous System; Chromatography, High Pressure Liquid; Double-Blind Method; Electroencephalography; Humans; Male; Oxazepam; Psychomotor Performance
PubMed: 7826827
DOI: 10.1111/j.1365-2125.1994.tb04349.x -
Therapeutic Advances in Cardiovascular... 2022Management of high blood pressure (BP) typically requires adherence to medication regimes. However, it is known that the COVID-19 pandemic both interrupted access to...
Impact of the COVID-19 pandemic on cardiovascular heart disease medication use: time-series analysis of England's prescription data during the COVID-19 pandemic (January 2019 to October 2020).
BACKGROUND
Management of high blood pressure (BP) typically requires adherence to medication regimes. However, it is known that the COVID-19 pandemic both interrupted access to some routine prescriptions and changed some patient health behaviours.
AIM
This study, therefore, retrospectively investigated prescription reimbursement of cardiovascular (CVD) medicines as a proxy measure for patient adherence and access to medicines during the pandemic.
METHODS
A cohort study of all primary care patients in England prescribed CVD medicines. The exposure was to the global pandemic. Prescriptions were compared before and after the pandemic's onset. Statistical variation was the outcome of interest.
RESULTS
Descriptive statistics show changes to monthly prescriptions, with wide confidence intervals indicating varying underlying practice. Analysis of variance reveals statistically significant differences for bendroflumethiazide, potassium-sparing diuretics, nicorandil, ezetimibe, ivabradine, ranolazine, colesevelam and midodrine. After the pandemic began (March-October 2020), negative parameters are observed for ACE inhibitors, beta-blockers, calcium channel blockers, statins, antiplatelet, antithrombotics, ARBs, loop diuretics, doxazosin, bendroflumethiazide, nitrates and indapamide, indicating decelerating monthly prescription items (statistically significant declines of calcium channel blockers, antithrombotic, adrenoreceptor blockers and diuretics) of CVD medicines within the general population. Many data points are not statistically significant, but fluctuations remain clinically important for the large population of patients taking these medications.
CONCLUSION
A concerning decline in uptake of CVD therapies for chronic heart disease was observed. Accessible screening and treatment alongside financial relief on prescription levies are needed. A video abstract is (4 min 51 s) available: https://bit.ly/39gvEHi.
Topics: Humans; Pandemics; COVID-19; Angiotensin-Converting Enzyme Inhibitors; Bendroflumethiazide; Retrospective Studies; Cohort Studies; Angiotensin Receptor Antagonists; Cardiovascular Agents; Cardiovascular Diseases; Heart Diseases; Diuretics; Drug Prescriptions
PubMed: 36420815
DOI: 10.1177/17539447221137170 -
British Medical Journal (Clinical... Jul 1985
Comparative Study
Topics: Bendroflumethiazide; Cerebrovascular Disorders; Coronary Disease; Female; Humans; Hypertension; Male; Propranolol; Sex Factors
PubMed: 3926098
DOI: 10.1136/bmj.291.6488.89 -
Endocrinology, Diabetes & Metabolism... Oct 2019Although pheochromocytoma classically presents with headaches, palpitations and paroxysmal hypertension, atypical presentations such as cardiomyopathy, stroke and...
SUMMARY
Although pheochromocytoma classically presents with headaches, palpitations and paroxysmal hypertension, atypical presentations such as cardiomyopathy, stroke and subarachnoid haemorrhage have been infrequently documented. We present in this case report, an uncommon presentation of pheochromocytoma with myocardial infarction with normal coronary arteries (MINOCA). A 79-year-old woman presented with central crushing chest pain radiating to left arm associated with headache, palpitations, sweating and difficulty in breathing. For 2 years, she experienced brief episodes of headache, tinnitus, dizziness, palpitations, and sweating that spontaneously resolved. Clinical examination was unremarkable except for high blood pressure (210/105 mmHg). Her electrocardiogram showed T wave inversions from V1 to V6 and elevated troponins (774 ng/L at baseline and 932 ng/L 3 h from baseline (normal <16 ng/L) in keeping with a diagnosis of non-ST elevated myocardial infarction. Coronary angiography showed normal coronary arteries. Patient was hence treated as myocardial infarction with normal coronaries (MINOCA). Despite appropriate treatment for MINOCA, she continued to experience episodic headaches, palpitations, dizziness and erratic blood pressures (particularly severe hypertension shortly after beta-blocker administration). Further investigations revealed raised urine noradrenaline of 4724 nmol/24 h (<554 nmol/24 h) and urine adrenaline of 92863 nmol/24 h (<77 nmol/24 h). Computerised tomography demonstrated a well-defined rounded mass in right adrenal gland morphological of pheochromocytoma. She underwent laparoscopic right adrenalectomy with histology confirming pheochromocytoma. This case highlights the importance of thorough investigation for the underlying cause for MINOCA. In patients with unexplained erratic blood pressure control, pheochromocytoma should be considered as a differential diagnosis.
LEARNING POINTS
Pheochromocytoma is rare tumour that often presents with non-specific symptoms. It is important to investigate underlying cause of MINOCA. Thorough history is the key to diagnosis.
PubMed: 31634865
DOI: 10.1530/EDM-19-0089 -
PloS One 2012Plant activators are agrochemicals that activate the plant immune system, thereby enhancing disease resistance. Due to their prophylactic and durable effects on a wide...
Plant activators are agrochemicals that activate the plant immune system, thereby enhancing disease resistance. Due to their prophylactic and durable effects on a wide spectrum of diseases, plant activators can provide synergistic crop protection when used in combination with traditional pest controls. Although plant activators have achieved great success in wet-rice farming practices in Asia, their use is still limited. To isolate novel plant activators applicable to other crops, we screened a chemical library using a method that can selectively identify immune-priming compounds. Here, we report the isolation and characterization of three diuretics, bumetanide, bendroflumethiazide and clopamide, as immune-priming compounds. These drugs upregulate the immunity-related cell death of Arabidopsis suspension-cultured cells induced with an avirulent strain of Pseudomonas syringae pv. tomato in a concentration-dependent manner. The application of these compounds to Arabidopsis plants confers disease resistance to not only the avirulent but also a virulent strain of the pathogen. Unlike salicylic acid, an endogenous phytohormone that governs disease resistance in response to biotrophic pathogens, the three diuretic compounds analyzed here do not induce PR1 or inhibit plant growth, showing potential as lead compounds in a practical application.
Topics: Arabidopsis; Arabidopsis Proteins; Bendroflumethiazide; Bumetanide; Cell Death; Cells, Cultured; Clopamide; Disease Resistance; Diuretics; Dose-Response Relationship, Drug; Gene Expression Regulation, Plant; Host-Pathogen Interactions; Molecular Structure; Plant Diseases; Plant Immunity; Pseudomonas syringae; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factors
PubMed: 23144763
DOI: 10.1371/journal.pone.0048443