Medication dilemma
Anne Stephenson, Martin Mueller, John Grabinar, Janice Rymer in 100 Cases in General Practice, 2017
A 63-year-old chief executive returns early to his general practitioner for his hypertension review. Since he and his wife had read an article in The Guardian reporting that a ‘drug switch can cut the risk of heart attack by half’ his wife has been asking him to go to the doctor and have his medications changed. The GP responds by looking through the patient's records. The patient initially presented with raised blood pressure 15 years ago. At this time, his untreated blood pressure was around 170/95 mmHg on several occasions; there was no family history of ischaemic heart disease, stroke or diabetes, his body mass index (BMI) was 28, he never smoked and his alcohol intake was 50 units/week. He went to the gym twice a week and had a well-balanced diet. His total fasting cholesterol was 6.1 mmol/L and his HbA1c was normal. At that time, he was not keen to start on medication and so he received lifestyle advice from the practice nurse, who asked him to reduce his alcohol and salt intake, reduce his weight and increase his exercise. At a 6-month review, his blood pressure had not improved and so he agreed to start on atenolol at a dose of 50 mg daily. He responded well to the medication, with no side effects, and his blood pressure dropped to around 145/90 mmHg. At the next review, the doctor added bendroflumethiazide at a dose of 2.5 mg daily and his blood pressure dropped further to 125/80 mmHg. Six-monthly reviews since have documented a consistently well-controlled blood pressure with normal HbA1c while the patient maintains his slightly raised BMI and cholesterol.
Questions and answers
Swati Gupta, Alexandra Marsh, David Dunleavy, Kevin Channer in Cardiology and the Cardiovascular System on the move, 2015
(Bendroflumethiazide) Bendroflumethiazide is a thiazide diuretic commonly used in essential hypertension as a first-line therapy (see Section 10.3 on hypertension). Thiazide diuretics can reduce uric acid excretion, precipitating acute gout in susceptible individuals. It may need to be withdrawn and replaced with another hypertensive. A calcium channel blocker, such as amlodipine, may be a solution and would also be useful for anginal symptoms. Other possible serum abnormalities with thiazide diuretics include hyponatraemia, hypokalaemia, hypercalcaemia and metabolic alkalosis.
Cardiovascular Drugs during Pregnancy
“Bert” Bertis Britt Little in Drugs and Pregnancy, 2022
Among more than 1000 women included in the Collaborative Perinatal Project who received bendroflumethiazide (Naturetin), only 13 received this diuretic in early pregnancy (Heinonen et al., 1977). In a study of diuretics to prevent preeclampsia, no increase in the frequency of malformations or stillbirths was found in the offspring of over 1,000 women who received this diuretic after the first trimester. Among 154 infants born to women who used bendroflumethiazide during the first trimester in the Swedish Birth Defects Registry (Kallen, 2019).
Interactions of antiepileptic drugs with drugs approved for the treatment of indications other than epilepsy
Published in Expert Review of Clinical Pharmacology, 2020
Kinga K. Borowicz-Reutt, Stanisław J. Czuczwar, Marta Rusek
Thiazide (bendroflumethiazide, hydrochlorothiazide), thiazide-like (chlorthalidone, indapamide), and loop (furosemide, bumetanide) diuretics are the most commonly prescribed diuretic agents used to treat hypertension, particularly in patients with heart failure, or at risk of heart failure [147]. Łukawski et al. found that hydrochlorothiazide enhanced the anticonvulsant action carbamazepine but had no impact on the antielectroshock activity of the other AEDs [176]. In addition, hydrochlorothiazide and ethacrynic acid did not have an impact on the anticonvulsant activity of levetiracetam [177]. Indapamide was found to significantly potentiate the anticonvulsant activity of carbamazepine, phenobarbital, and valproate against MES in mice and the interactions with carbamazepine and valproate were apparently pharmacodynamic. As regards phenobarbital, its total brain concentration was raised by indapamide [178]. Most important drug interactions have been shown in Table 1.
Patented therapeutic drug delivery strategies for targeting pulmonary diseases
Published in Expert Opinion on Therapeutic Patents, 2020
Ajay Kumar Thakur, Dinesh Kumar Chellappan, Kamal Dua, Meenu Mehta, Saurabh Satija, Inderbir Singh
Microparticles are defined as solid material that have their sizes ranging from 1 μm to 1000 μm. Microparticles can be prepared by encapsulating, entrapping, or dissolving the active drug within a polymer matrix. These can be employed for targeted delivery, sustained release and controlled release of therapeutic agents in the pulmonary region. Healy et al. investigated excipient-free nanoporous microparticles of bendroflumethiazide. These microparticles were prepared by a spray drying technique, where the drug bendroflumethiazide was prepared in ethanol/water and was dried in a laboratory spray drier. The obtained product was then characterized and delivered to the lungs [56]. Cook et al. reported a method for the pulmonary delivery of sustained released microspheres that were prepared by the spray drying technique. They used nanoparticles of a hydrophilic, ionized drug which was entrapped in hydrophobic microspheres. In this technique, terbutaline sulfate microspheres were successfully developed and delivered to the lungs as a sustained release formulation [57]. Fiore et al. reported the use of polyketal microparticles for pulmonary delivery. In this study, the compatibility of the polyketal microparticles to the lungs was tested, for pulmonary delivery. It was found to be highly biocompatible with the anti-inflammatory property; but, further more investigations were needed at the application level [58]. Tewes et al. prepared steroid/mucokinetic hybrid nanoporous microparticles for pulmonary delivery. Budesonide/ambroxol-HCl-loaded microparticles were developed by the spray drying method. The study reported that hybrid microparticles improved the permeability of budesonide [59].
Was it optimal to drop a diuretic as a first-line choice of drug treatment in the 2020 International Society of Hypertension Guidelines?
Published in Blood Pressure, 2020
Sverre E. Kjeldsen, Krzysztof Narkiewicz, Michel Burnier, Suzanne Oparil
In ASCOT, the diuretic, which was given as the second drug, if needed, in the atenolol + thiazide arm, was severely under-dosed early in the trial, resulting in less effective blood pressure lowering in the beta-adrenergic blocker + diuretic arm compared to the CCB + ACE-inhibitor arm. As a consequence, the study secretary, first author of the current ISH letter, contacted the Nordic leaders and requested higher dosing of bendroflumethiazide in an attempt to minimise the difference in blood pressure between the two arms. This attempt was only partly successful as lower blood pressure in the CCB + ACE-inhibitor arm sustained throughout the length of the ASCOT study [7]. Study leadership did not conclude that the diuretic component of the treatment was inferior [7], but rather that the beta-blocker atenolol was inferior to the CCB amlodipine, leaving ACCOMPLISH [6] as the only trial ever to show a diuretic to be inferior to a CCB when administered in combination with an ACE inhibitor. ACCOMPLISH included a rigid protocol with forced up-titration of blinded study drugs to achieve blood pressure targets [6]. It reached its blood pressure targets in more than 80% of study participants, but required a protocol that differed greatly from how treatment of hypertension is carried out by most health care providers around the world. The ACCOMPLISH findings [6] need to be confirmed in other similarly designed and properly powered outcome trial(s) before concluding that a diuretic is inferior to other drug classes as first or second line treatment. Besides, black patients in sub-Saharan Africa had similar blood pressure responses to amlodipine plus hydrochlorothiazide as they had to amlodipine plus perindopril [8].