Antihypertensive therapy: special focus on drug interactions

Today, the lifetime risk of patients aged 55 – 65 years to receive antihypertensive drugs approaches 60%. Yet, recent trials suggest that hypertension is not adequately controlled in the majority of patients. The prevalence of hypertension increases with advancing age, as does the prevalence of comorbid conditions and the total number of medications taken. Multi-drug therapy, advancing age and comorbid conditions are also key risk factors for adverse drug reactions and drug interactions. In this review, the authors evaluate the most frequently used antihypertensive drugs (diuretics, β-adrenergic blockers, angiotensin-converting enzyme inhibitors, calcium channel blockers, angiotensin II receptor Type 1 blockers and α-adrenergic blockers) with special reference to pharmacodynamic and pharmacokinetic drug interactions. As the spectrum of drugs prescribed is constantly changing, safety yesterday does not imply safety today and safety today does not imply safety tomorrow. Furthermore, therapeutic efficacy should not be neglected over concerns regarding drug interactions. Many patients are at risk of clinically relevant drug interactions involving antihypertensive drugs but, presently, even more patients may be at risk of suffering from the consequences of their inadequately treated hypertension. In this respect, the authors discuss controversial viewpoints on the overall clinical relevance of drug interactions occurring at the level of cytochrome P450 metabolism.     

Drug interactions with angiotensin receptor blockers

Many patients with high blood pressure receive multiple medications for hypertension and other conditions, placing them at risk for adverse drug interactions. Additionally, as the prevalence of hypertension increases with age, factors like greater frailty, comorbidity of the elderly requiring polypharmacy, and reduced hepatic and renal clearance rates for the elimination of drugs increase the likelihood of drug interactions. Angiotensin receptor blockers (ARBs) are the most recent class of agents for the treatment of hypertension. Due to a favourable side effect profile, this class of drugs deserves increased attention. This article reviews drug interactions of ARBs and suggests measures for reducing the risk of adverse events when drugs are co-administered. MEDLINE, EMBASE, Cochrane library, and CINAHL were searched. Reported and likely clinical relevant interactions of ARBs with concomitantly given drugs are summarised in Table 2 and 3. Compared to other classes of antihypertensive agents, the ARBs appear to have a low potential for drug interactions; however, interactions with this class occur and variations within the class have been detected, mainly due to different affinities for cytochrome P450 isoenzymes.     

常用降压药物的相互作用

高血压是心脑血管疾病的主要危险因素之一,安全和有效的控制血压是降低心脑血管疾病风险必不可少的措施。本文简单介绍了常用的5种降压药物（利尿剂、钙拮抗剂、β肾上腺素受体阻滞剂、血管紧张素转换酶抑制剂、血管紧张素Ⅱ受体阻滞剂）联合应用的原则,重点介绍这5种降压药物联合应用时可能产生的药物相互作用,以及与其它非降压药物联合应用时可能产生的药物相互作用。旨在引起临床关注联合治疗中药物的相互作用和对用药安全产生的影响。     

Hypertension management and control in primary care: a study of 20 practices in 14 states

STUDY OBJECTIVE: To describe the management and control of hypertension in primary care practice. DESIGN: Retrospective medical record review. SETTING: Twenty primary care practices in 14 states. PATIENTS: Thirteen thousand forty-seven patients with hypertension. MEASUREMENTS AND MAIN RESULTS: Diagnoses, drugs prescribed, and blood pressure readings were extracted from the electronic medical record at each practice in the study. For patients with hypertension and comorbid diagnoses, the most recent blood pressure and antihypertensive drugs prescribed were determined. Analyses assessed the blood pressure control rates and the association between control and demographic variables, frequency of visits to the practice site, and pharmacologic treatment patterns. Among the 20 practices in the study, 13,047 patients had received a diagnosis of hypertension and their blood pressures had been measured within the previous 12 months. One third of the patients had comorbid coronary heart disease, diabetes mellitus, heart failure, and/or renal insufficiency. The most recent blood pressure reading was below 140/90 in half the patients. Control was associated with age 60 years or younger, female sex, more than one visit to the practice, more than one comorbidity, and type of practice (p<0.01, logistic regression). Wide variability was noted among practices in the use of multiagent antihypertensive therapy, and in antihypertensive therapy by drug class. Among patients without comorbidity treated with one drug, systolic blood pressure did not differ significantly by drug class. Diastolic blood pressure was slightly lower in patients prescribed thiazide diuretics than in those prescribed angiotensin receptor blockers (p=0.03, analysis of covariance). CONCLUSION: Blood pressure control in primary care practice can be much better than reports usually indicate. Good control in this study was not due to specific drug choice, but instead may have been due to regular monitoring of blood pressure and motivation of the practice to improve patient care.     

Drug interactions with angiotensin receptor blockers: a comparison with other antihypertensives.

The ever-increasing introduction of new therapeutic agents means that the potential for drug interactions is likely to escalate. Numerous different classes of drugs are currently used to treat hypertension. The angiotensin receptor blockers offer one of the newest approaches to the management of patients with high blood pressure. Compared with other classes of antihypertensive agents, the angiotensin receptor blockers appear overall to have a low potential for drug interactions, but variations within the class have been detected. Losartan and irbesartan have a greater affinity for cytochrome p450 (CYP) isoenzymes and, thus, are more likely to be implicated in drug interactions. There is pharmacokinetic evidence to suggest that such interactions could have a clinical impact. Candesartan cilexetil, valsartan and eprosartan have variable but generally modest affinity and telmisartan has no affinity for any of the CYP isoenzymes. In vitro studies and pharmacokinetic/pharmacodynamic evaluation can provide evidence for some interactions, but only a relatively small number of drug combinations are usually studied in this way. The absence of any pharmacokinetic evidence of drug interaction, however, should not lead to complacency. Patients should be made aware of possible interactions, especially involving the concurrent use of over-the-counter products, and it may be prudent for all patients receiving antihypertensive treatment to be monitored for possible drug interactions at their regular check-ups. The physician can help by prescribing agents with a low potential for interaction, such as angiotensin receptor blockers.     

33 398例次肾移植术后高血压患者降血压药物利用分析

目的 分析2015-2018年全国5个城市肾移植术后高血压患者特征及降血压药物使用情况,为临床合理用药提供参考.方法 基于《医院处方分析合作项目》随机抽取的多中心处方大数据,采用世界卫生组织(WHO)推荐的药物利用分析方法,对降血压药物的使用情况进行分析.结果 抽取5个城市共40家三级医院(不含军队医院)共计33 39...     

Hypertension control in the elderly with amlodipine

Treatment of hypertension in the elderly reduces the incidence of cardiovascular events. Some classes of antihypertensive drugs, including long-acting dihydropyridine calcium channel blockers such as amlodipine, can be prescribed in the presence of comorbid conditions. The results of clinical trials support the use of long-acting dihydropyridine calcium channel blockers in the elderly; amlodipine has been shown to be effective and well tolerated in the elderly population.     

Patterns in the drug treatment of hypertension in Auckland, 1982-7

This paper examines the pattern of drug treatment of hypertension in Auckland in the period 1982 to 1987 using data from a representative sample of the adult population interviewed in 1982 and followed up in 1987. In 1982 the age standardised prevalence of antihypertensive treatment for people aged 40-64 years was 12.2% (95%Cl 10.4, 14.0) and in 1987 it was 10.2% (95%Cl 8.5, 11.8). Over the five year period of this study, 6% of the sample untreated in 1982 began treatment with antihypertensive medication, while 24% of those on drugs in 1982 had stopped treatment by 1987. The most common medications used in both 1982 and 1987 for hypertension were diuretics and beta blockers. Over the five year period diuretic use fell and beta blocker use remained constant. In 1982 3% of hypertensives were taking a calcium antagonist but in 1987 13% were on these drugs and a further 13% were using ACE inhibitors. This study suggests that the prevalence of drug treatment for hypertension has plateaued in New Zealand; coincidentally there is a trend towards use of more expensive drugs.     

药物治疗顽固性高血压的研究进展

在高血压患者中,有15％～20％属于顽固性高血压。顽固性高血压具有更高的心血管事件的风险,给患者造成的危害也更严重。临床治疗顽固性高血压,需要结合患者的自身情况,选择不同的降压药联合用药。目前较为常用方案为血管紧张素转换酶抑制剂（或血管紧张素II受体阻滞剂）、钙拮抗剂和噻嗪类利尿剂3种药物组合,或由扩血管药、减慢心率药和利尿剂组合。本文综述了治疗顽固性高血压的联合用药方案和药物选择等方面的研究进展,为更好地治疗该病提供借鉴。     

Changing Trends in Antihypertensive Therapy in Two New England Communities During the 1980s

The prevalence rates and correlates of antihypertensive drug use among individuals with hypertension were determined using data derived from five biennial population-based surveys conducted between 1981 and 1990 in two New England communities. Point prevalence estimates were determined for nine categories of antihypertensive agents at five time points, and were analyzed by age and sex using multiple logistic regression. In the first cross-sectional survey, the prevalence of use per 1000 individuals with hypertension was 235.4 for diuretics, 57.1 for β-blockers, 65.5 for combination products, 29.2 for central α-agonists, 2.8 for peripheral α-antagonists, and 8.4 each for adrenergic blockers and direct vasodilators. The prevalence rates for calcium channel blockers and angiotensin-converting enzyme inhibitors increased sharply between the third and fourth survey cycles. Significant age- and sex-related differences in antihypertensive use were detected.     

Calcium channel blockers and treatment of hypertension

Over the past years, research efforts have been focused on the pathophysiologic role of calcium ions, and the implication for the potential role of calcium channel blockers in the management of essential hypertension. Numerous studies have shown that nifedipine and verapamil are effective antihypertensive agents, initial experience with diltiazem is also encouraging. The magnitude of blood pressure reduction with these drugs is related to the pre-treatment blood pressure. In refractory hypertension, combination with other antihypertensive agents provide additive effect. In the elderly population and in patients with ischemic heart disease, supraventricular arrhythmia, bronchospastic disease, peripheral vascular disease or diabetes mellitus, the calcium channel blockers offer potential advantages over other antihypertensive agents. Experimental studies also suggest that these drugs may reverse ventricular hypertrophy. When long-term safety with these drugs is documented from well-controlled clinical trials, the calcium channel blockers may be our first line of therapy for the management of hypertension.     

Challenges in the pharmacological treatment of geriatric asthma

Asthma in older populations is characterized by frequent comorbid conditions, which increase the risk of side effects and of detrimental interactions between respiratory and non-respiratory drugs. These observations lead to the need to manage asthma in older populations by applying a multidimensional assessment and a multidisciplinary treatment; therefore, we favor the use of the ‘geriatric’ term to define asthma in the elderly. Geriatric asthma is a complex disease, which may not necessarily imply that it is also complicated, although the two conditions may often coexist. On this basis, the switch from an organ-driven management to the holistic approach may be the key factor to attain optimal control of the disease in this age range. The current review discusses the age-related factors affecting asthma treatment in the oldest individuals, such as the comorbid conditions, and age-related changes of metabolism and excretion that can impair the efficacy and safety of drugs.     

Hypertension Control in the Elderly with Amlodipine

Summary

Treatment of hypertension in the elderly reduces the incidence of cardiovascular events. Some classes of antihypertensive drugs, including long-acting dihydropyridine calcium channel blockers such as amlodipine, can be prescribed in the presence of comorbid conditions. The results of clinical trials support the use of long-acting dihydropyridine calcium channel blockers in the elderly; amlodipine has been shown to be effective and well tolerated in the elderly population.     

Patterns of antihypertensive medication use in hemodialysis patients.

PURPOSE: Patterns of antihypertensive drug use in patients undergoing long-term hemodialysis therapy were studied. METHODS: Patients attending seven outpatient hemodialysis units in Ohio were eligible for the study if they had been receiving the treatment for at least three months. Demographic and clinical data were obtained from patient interviews and computerized databases, and blood pressure (BP) measurements were obtained before dialysis. Labeled names and dosages of antihypertensive drugs were recorded from containers the patients brought with them. Patients were asked to describe their adherence to the medications, their ability to afford the drugs, and their knowledge and beliefs about hypertension. Physical impairments in taking medication were also evaluated. RESULTS: The frequency of hypertension was 89% in the 270 participants. Antihypertensive drugs were prescribed for 76% of the patients; 25% required three or more drugs. Hypertensive patients who were not receiving antihypertensive drugs (14%) had significantly higher BP than patients who were. Calcium-channel blockers were prescribed for 60% of patients, angiotensin-converting-enzyme inhibitors for 33%, and beta-blockers for 34%. Eighty-three percent said the cost of drugs was never a problem, and 23% said they sometimes forgot to take their medication. Almost all patients said they would not stop taking antihypertensive drugs if they were feeling better and agreed that monitoring BP was important. Twenty-two percent could not read the warning on a standard tablet container, and 12% could not remove one tablet from the container. CONCLUSION: Multidrug antihypertensive therapy was common among hemodialysis patients and was associated with significantly lower BP; calcium-channel blockers were the most frequently prescribed agents. Most patients said they could afford drugs and reported good adherence to antihypertensive drug therapy.     

Antihypertensive therapy in the geriatric patient. I: A review of the role of calcium channel blockers

Animal and clinical studies have demonstrated the efficacy of calcium channel blockers in reducing blood pressure, especially in older patients whose hypertension is characterized by increased peripheral vascular resistance. Their chemical heterogeneity, which permits targeted therapy, as well as their minimal side effects, drug interactions, and clinical utility in numerous pathophysiologic states common to the elderly, enhance the suitability of calcium channel blockers in treating mild to moderate hypertension in this subgroup. This is particularly relevant for those patients who have concomitant conditions, such as diabetes, chronic obstructive pulmonary disease, or peripheral vascular disease, and for whom many of the more traditional antihypertensive drugs are either contraindicated or might cause a worsening of the disease.     

Discontinuation of antihypertensive drugs due to adverse events: a systematic review and meta-analysis.

We conducted a systematic review of randomized, controlled, monotherapy trials since 1990 of oral antihypertensive agents in patients with essential hypertension. Our objective was to quantify the frequency of discontinuation of antihypertensive agents due to adverse events from a meta-analysis of the studies. A total of 190 studies met inclusion criteria. The highest frequency of discontinuations due to adverse events (DAEs) occurred with calcium channel blockers (6.7%) and alpha-adrenergic blockers (6.0%); the lowest with diuretics and angiotensin receptor blockers (each 3.1%). Only in calcium channel blocker studies was the frequency of DAEs greater in treated patients than in patients receiving placebo, but the difference was not significant. This systematic review suggests that the frequency of DAEs in monotherapy antihypertensive trials varies across drug classes and should be considered when choosing drugs for patients with essential hypertension.     

Effects of antihypertensive drug treatment on the risk of dementia and cognitive impairment

Dementia is a common and serious health problem that affects 33 million persons globally. With the increase in life expectancy, the prevalence of dementia is expected to reach 81.1 million persons by 2040. Dementia impairs quality of life and is associated with profound disease burden, morbidity, and mortality in both patients and caregivers. Therefore, identifying measures to prevent dementia is a research priority. Midlife hypertension has increased the risk of dementia in large prospective cohort studies. Researchers have investigated the blood pressure-lowering effects of antihypertensive drugs on the incidence of dementia. Although prospective cohort studies have shown that use of antihypertensive drugs was associated with a reduced rate of cognitive impairment and dementia, these studies were not placebo controlled. Four randomized, placebo-controlled studies-the Systolic Hypertension in Europe (Syst-Eur) study, Study on Cognition and Prognosis in the Elderly (SCOPE), Systolic Hypertension in the Elderly Program (SHEP), and Perindopril Protection Against Recurrent Stroke Study (PROGRESS)-investigated the effects of antihypertensive agents on the incidence of dementia. The Syst-Eur study found that active treatment with nitrendipine, enalapril, and/or hydrochlorothiazide reduced the rate of dementia by 50% compared with placebo (p=0.05). The PROGRESS study showed that active treatment with perindopril and indapamide was associated with reduced cognitive decline compared with placebo (risk ratio 19%, p=0.01). In contrast, the SCOPE study (candesartan or hydrochlorothiazide vs placebo) and the SHEP trial (chlorthalidone, atenolol, or reserpine vs placebo) found no significant difference between the active treatment and placebo groups on the incidence of dementia. Some researchers have suggested that certain antihypertensive drug classes, such as angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, diuretics, and calcium channel blockers, may offer benefit in reducing dementia risk in addition to their blood pressure-lowering effect. Further prospective randomized studies comparing different antihypertensive classes are needed to provide more evidence regarding the effects of antihypertensive drugs on dementia risk and to determine whether certain antihypertensive classes provide greater benefits than others.     

Avoiding drug interactions

(1) Drug interactions potentiate or oppose the therapeutic or adverse effects of one or more co-administered drugs. (2) There are two mechanisms: pharmacodynamic interactions occur between drugs that have similar actions or adverse effects. The shared effect can potentiate or antagonise the actions of a physiological system such as clotting, or the parasympathetic nervous system. Pharmacokinetic interactions alter the metabolism of the relevant drug(s). (3) The clinical consequences of drug interactions are very variable. Most interactions with serious consequences involve either high risk drugs or high risk patients (such as older people). (4) The risk of interactions increases with the number of drugs taken, and with advancing age. (5) Some patients are at an increased risk of drug interactions because they have pathology that alters drug metabolism, such as renal failure, liver failure or malnutrition. Other patients are at risk because of the type and number of drugs they need (this is particularly true for patients with heart disease, HIV infection, epilepsy, tuberculosis and migraine). (6) In practice, patients must be questioned thoroughly about all the drugs they are taking, whether or not they have been prescribed.     

我院门诊2012年口服降压药应用分析

目的:了解我院门诊2012年口服降压药的临床应用情况,为临床合理用药及药品管理提供有效依据。方法:采用限定日剂量、用药频度,对我院2012年门诊降压药应用情况进行统计、分析。结果:从随机抽查的处方中发现,60岁以上的老年患者发病率较高,占67.14%;使用降压药品种30个,处方频率排前3位的降压药分别为钙拮抗药(CCB)、血管紧张素转化酶抑制剂(ACEI)和血管紧张素Ⅱ受体阻滞药(ARB);降压药用药频度排前3位的分别是苯磺酸氨氯地平片、缬沙坦胶囊和厄贝沙坦片;治疗以CCB+ARB联用为主。结论:我院降压药应用基本合理,符合《中国高血压防治指南》,联合治疗策略值得推广。