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Antihypertensive Deprescribing in Older Adults: a Practical Guide
Purpose of ReviewTo summarise evidence on both appropriate and inappropriate antihypertensive drug withdrawal.Recent FindingsDeprescribing should be attempted in the following steps: (1) identify patients with several comorbidities and significant functional decline, i.e. people at higher risk for negative outcomes related to polypharmacy and lower blood pressure; (2) check blood pressure; (3) identify candidate drugs for deprescribing; (4) withdraw medications at 4-week intervals; (5) monitor blood pressure and check for adverse events. Although evidence is accumulating regarding short-term outcomes of antihypertensive deprescribing, long-term effects remain unclear.SummaryThe limited evidence for antihypertensive deprescribing means that it should not be routinely attempted, unless in response to specific adverse events or following discussions between physicians and patients about the uncertain benefits and harms of the treatment.PerspectivesClinical controlled trials are needed to examine the long-term effects of deprescribing in older subjects, especially in those with comorbidities, and significant functional decline.
Journal Article
ACE-Inhibitors in Hypertension: A Historical Perspective and Current Insights
Purpose of ReviewThis review describes the discovery and development of ACE inhibitors as antihypertensive agents, compares their efficacy, tolerability, and safety to ARBs, and highlights the contemporary issues surrounding ACE inhibitor use for HTN.Recent FindingsAngiotensin-converting enzyme (ACE) inhibitors are commonly prescribed medications for the management of hypertension (HTN) and other chronic conditions including heart failure and chronic kidney disease. These agents inhibit ACE, the enzyme that is responsible for converting angiotensin (AT) I to AT II. Inhibiting the synthesis of AT II causes arterial and venous vasodilation, natriuresis, and a decrease in sympathetic activity, resulting in the reduction of blood pressure. ACE inhibitors are first-line therapy in HTN management along with thiazide diuretics, calcium channel blockers, and angiotensin receptor blockers (ARB). Along with inhibiting AT II synthesis, inhibition of ACE causes accumulation of bradykinin, increasing the risk of bradykinin-mediated side effects like angioedema and cough. Since ARBs do not work on ACE in the renin-angiotensin system, the risk of angioedema and cough are lower with ARBs. Recent evidence has also suggested ARBs may have neuroprotective effects compared to other antihypertensives, including ACE inhibitors; however, this warrants further study.Summary Currently, ACE inhibitors and ARBs have an equal class of recommendation for first-line treatment for the management of HTN. Recent evidence has shown ARBs to be just as effective as ACE inhibitors for HTN but with improved tolerability.
Journal Article
Pathophysiology and Current Clinical Management of Preeclampsia
Preeclampsia is characterized by blood pressure greater than 140/90 mmHg in the second half of pregnancy. This disease is a major contributor to preterm and low birth weight babies. The early delivery of the baby, which becomes necessary for maintaining maternal well-being, makes preeclampsia the leading cause for preterm labor and infant mortality and morbidity. Currently, there is no cure for this pregnancy disorder. The current clinical management of PE is hydralazine with labetalol and magnesium sulfate to slow disease progression and prevent maternal seizure, and hopefully prolong the pregnancy. This review will highlight factors implicated in the pathophysiology of preeclampsia and current treatments for the management of this disease.
Journal Article
Oral controlled release formulation design and drug delivery
This book describes the theories, applications, and challenges for different oral controlled release formulations.This book differs from most in its focus on oral controlled release formulation design and process development.
eBook
Dual Endothelin Antagonism with Aprocitentan as a Novel Therapeutic Approach for Resistant Hypertension
Purpose of ReviewResistant hypertension (RH) defined as uncontrolled blood pressure despite the use of a combination of a renin-angiotensin system blocker, a calcium channel blocker, and a diuretic at maximally tolerated doses is associated with a substantially increased risk of cardiovascular and renal events. Despite targeting relevant pathophysiological pathways contributing to elevated blood pressure, approximately 10–15% of hypertensive patients remain above recommended blood pressure targets. Further optimization of blood pressure control is particularly challenging in patient populations who frequently present with RH such as elderly and patients with chronic kidney disease, due to the unfavorable safety profile of the recommended fourth-line therapy with mineralocorticoid receptor antagonists. This review explores the potential role of endothelin antagonists as an alternative fourth-line therapy.Recent FindingsDespite the well-described role of the endothelin pathway in the pathogenesis of hypertension, it is currently not targeted therapeutically. Recently however, main outcome data from the PRECISION study, a randomized placebo-controlled phase 3 trial, in patients with RH on guideline-recommended standardized single-pill background therapy convincingly demonstrated the safety and blood pressure-lowering efficacy of the dual endothelin antagonist Aprocitentan.SummaryFindings from the phase 3 PRECISION study could signify a turning point in the utilization of endothelin receptor antagonists as a standard treatment for patients with RH.
Journal Article
Drug Interactions with Antihypertensives
Purpose of ReviewHypertension is remarkably prevalent, affecting an estimated 1.13 billion people worldwide. It often requires the use of multi-drug regimens and is commonly associated with a myriad of other comorbidities which increase medication use. The pervasive use of antihypertensive medications combined with the presence of polypharmacy in many hypertensive patients results in significant risk of drug interactions. This review will summarize the relevant literature to assist clinicians in mitigating drug interaction risks when prescribing antihypertensives.Recent FindingsPharmacokinetic interactions affect drug disposition in the body and can occur at the steps of absorption, distribution, metabolism, or elimination of involved medications. Data has established the calcium channel blockers, namely, diltiazem and verapamil, as potent inhibitors of CYP3A4, and the majority of significant drug interactions involving antihypertensives are attributable to these two agents. Although less common, pharmacokinetic drug interactions with other antihypertensive classes have also been identified. Pharmacodynamic drug interactions with antihypertensives lead to synergy or antagonism of blood pressure lowering effects and can increase or mitigate adverse effects depending on the agents involved. Knowledge is emerging about drug-induced phenoconversion, a phenomenon whereby a drug interaction results in a drug metabolizing phenotype that is different than that predicted by an individual’s genotype.SummaryAntihypertensive use in patients with comorbidities and polypharmacy increases the likelihood of encountering important drug-drug interactions. Dedicated efforts to better understand the relationship between pharmacokinetic drug interactions and pharmacogenomic information is important to advance efforts related to personalized medicine.
Journal Article
Sexual Dimorphic Interplays Between Gut Microbiota and Antihypertensive Drugs
Purpose of the ReviewThe purpose of this study is to review the current literature regarding gut microbiota in blood pressure regulation and its interactions with antihypertensive drugs and to discuss how sex differences in gut microbiota contribute to sexual dimorphism of hypertension and treatment.Recent FindingsThe significance of gut microbiota in blood pressure regulation and hypertension etiology is growingly recognized. Targeting the dysbiotic microbiota is proposed to be a new therapeutic method. Recently, a few studies demonstrated that the gut microbiota is highly involved in the modulation of the efficacy of antihypertensive drugs, suggesting a novel mechanism by which gut microbiota plays a role in treatment-resistant hypertension. Furthermore, studies on sex differences in gut microbiota, etiology of hypertension, and sex bias in prescription of antihypertensive medications have revealed promising avenues in sexual dimorphism-based precision medicine. However, no scientific questions are ever raised on how sex differences in gut microbiota contribute to the sex specific responses of certain classes of antihypertensive drugs.SummaryGiven the dynamics and complexity among individuals, precision medicine is proposed of great potential. We review current knowledge on the interactions between gut microbiota, hypertension, and antihypertensive drugs with an emphasis on sex as a crucial determinant. We propose that sex differences in gut microbiota be a research focus to advance our understanding of hypertension management.
Journal Article
Inflammation and Hypertension: New Understandings and Potential Therapeutic Targets
Research studying the role of inflammation in hypertension and cardiovascular disease has flourished in recent years; however, the exact mechanisms by which the activated immune cells lead to the development and maintenance of hypertension remain to be elucidated. The objectives of this brief review are to summarize and discuss the most recent findings in the field, with special emphasis on potential therapeutics to treat or prevent hypertension. This review will cover novel immune cell subtypes recently associated to the disease including the novel role of cytokines, toll-like receptors, and inflammasomes in hypertension.
Journal Article
Blood Pressure Effects of SGLT2 Inhibitors: Mechanisms and Clinical Evidence in Different Populations
Purpose of ReviewSodium glucose transporter 2 inhibitors (SGLT2 inhibitors) are increasingly prescribed due to their considerable benefits on clinical outcomes in people with diabetes, heart failure, and chronic kidney disease (CKD). Hypertension is a common comorbidity in each of these disease states, increasing risk of cardiovascular morbidity and mortality. We herein review the effects of SGLT2 inhibitors on blood pressure in different populations, proposed mechanisms of action, and the contribution of blood pressure lowering to end-organ protection.Recent FindingsA recognised effect of SGLT2 inhibitors in recent clinical trials is blood pressure lowering, with multiple postulated mechanisms. This advantageous effect was first identified in populations with type 2 diabetes mellitus, prior to expansion of these trials to broader cohorts.SummaryOn our review, we identified that the blood pressure lowering effect of SGLT2 inhibitors appears to be a dose-independent class-effect, with a magnitude of effect comparable to that seen with a low dose hydrochlorothiazide. There is considerable evidence demonstrating that this effect is observed across populations including those with type 2 diabetes mellitus, chronic kidney disease, and resistant hypertension.
Journal Article