Bendroflumethiazide 2.5mg/5ml oral suspension

Thiazide diuretics, widely used in hypertension, cause a variety of adverse reactions, including hyperglycemia, hyperuricemia, and electrolyte abnormalities. In this study, we aimed to identify genetic variants that interact with thiazide-use to increase the risk of these adverse reactions. Using UK Biobank data, we first performed genomewide variance quantitative trait locus (vQTL) analysis of ~ 6.2 million SNPs on 95,493 unrelated hypertensive White British participants (24,313 on self-reported bendroflumethiazide treatment at recruitment) for 2 blood (glucose and urate) and 2 urine (potassium and sodium) biomarkers. Second, we conducted direct gene-environment interaction (GEI) tests on the significant (P -9) vQTLs, included a second UK Biobank cohort comprising 13,647 unrelated hypertensive White British participants (3,478 on thiazides other than bendroflumethiazide) and set significance at P = 0.05 divided by the number of vQTL SNPs tested for GEIs. The vQTL analysis identified eight statistically significant SNPs for blood glucose (5 SNPs) and serum urate (3 SNPs), with none being identified for the urinary biomarkers. Two of the SNPs (1 glucose SNP: CDKAL1 intron rs35612982, GEI P = 6.24 × 10-3; and 1 serum urate SNP: SLC2A9 intron rs938564, GEI P = 4.51 × 10-4) demonstrated significant GEI effects in the first, but not the second, cohort. Both genes are biologically plausible candidates, with the SLC2A9-mediated interaction having been previously reported. In conclusion, we used a two-stage approach to detect two biologically plausible genetic loci that can interact with thiazides to increase the risk of thiazide-associated biochemical abnormalities. Understanding how environmental exposures (including medications such as thiazides) and genetics interact, is an important step toward precision medicine and improved patient outcomes.

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BackgroundBullous pemphigoid (BP) is a serious autoimmune skin disease affecting older people. Given the highly prevalent polypharmacy in older people, identifying drug combinations associated with high BP risk is needed.ObjectivesTo identify drug combinations frequently prescribed for older people prior to BP using association rule mining (ARM) and to estimate their risk of developing BP.MethodsWe conducted a nested case-control study using UK Clinical Practice Research Datalink primary care records (1998-2021). ARM was used to identify the 10 most common drug class or active substance pairs most likely coprescribed (lift) on the same day and within 30 days of one another (sensitivity analysis). Fold change (FC; case-to-control lift ratio) was used to identify combinations with greater lift in cases. Multivariable conditional logistic regression was performed to estimate BP risk following combinations and their constituent drugs.ResultsAmong 16 844 cases and 79 493 controls, the most frequent drug class combinations associated with increased BP risk with greater lift in cases were angiotensin-converting enzyme inhibitors (ACEIs)-statins (FC 1.31; FC in sensitivity analysis 1.18), antiplatelets-statins (1.23; 1.11), proton pump inhibitors (PPIs)-antiplatelets (1.22; 1.14), PPIs-statins (1.22; 1.14) and ACEIs-antiplatelets (1.20; 1.09). Substance combinations with a greater lift in cases included ramipril-simvastatin (FC 1.30), simvastatin-aspirin (1.21), ramipril-aspirin (1.19) and bendroflumethiazide-aspirin (1.16). The results of sensitivity analyses for substances were similar. BP risk following drug combinations was lower than after single drugs.ConclusionsUsing ARM we found that the most frequently prescribed drug combinations associated with increased BP risk were used to treat cardiovascular diseases and hypertension. Patients should be vigilant for skin changes following these drugs rather than avoid them.

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BackgroundElevated blood pressure is a major risk factor for severe medical conditions. Adherence to antihypertensive medication, especially in free-dose combinations, poses a significant challenge. This study aims to develop a novel method for assessing co-exposure to free-dose antihypertensive medications using secondary data sources.MethodsA register-based cohort study was conducted on individuals aged 65 years or older in Denmark who initiated antihypertensive therapy from 1996 to 2016 and followed for 730 days from the index date. A new method was developed to assess co-exposure to antihypertensive medications through redeemed prescriptions, treatment episodes, and overlapping medication events. The method's accuracy was evaluated using a random sample of 400 individuals.ResultsA total of 1,021,819 individuals were included in the study, with a mean age of 68.8 years, and 53.7% were women. The method achieved 100% accuracy in identifying co-exposure periods. During the early stage of the follow-up (0-180 days), 54.1% of individuals were co-exposed to at least two antihypertensive medications, while 37.5% were co-exposed during the late stage of the follow-up period (181-730 days). The most frequent antihypertensive combinations included bendroflumethiazide and potassium with either amlodipine or enalapril in the early (13.2% and 12.5% of patients, respectively) and late stages (16.9% and 15.0% of patients, respectively).ConclusionsThe newly developed method effectively assesses co-exposure to antihypertensive medications, overcoming previous limitations. The findings reveal common co-exposure combinations and evolving trends in antihypertensive medication use among older individuals, reflecting changes in clinical practice and guidelines over two decades.

Abstract licence: CC BY