Another 5 drugs guanfacine hydrochloride, nifedipine, prazosin hydrochloride, terazosin hydrochloride, and valsartan are not produced in a form that would allow the use of lower dosages.

These disparities occurred with some of the most prescribed antihypertensive drugs, such as amlodipine besylate, atenolol, bisoprolol fumarate, diltiazem hydrochloride, lisinopril, losartan potassium, metoprolol, propranolol hydrochloride, and ramipril.

Even when the JNC VI and PDR agree on the initial doses of 17 drugs, even lower doses of these drugs might be effective. For example, the American Hospital Formulary Service recommends an initial enalapril dose of 2. The range of manufactured doses varies considerably among antihypertensive drugs.

The most common dosage ranges are 4- and 8-fold. Individual variation in drug response due to differences in age, weight, sex, ethnic background, state of health, concomitant medication use, and genetic polymorphisms in drug metabolism is a long-accepted pharmacological principle.

Therefore, drugs offering wider ranges of dosages that allow maximum flexibility in titrating treatment may be generally preferable.

Because of the importance of avoiding ADEs at the beginning of treatment, the JNC VI cautions physicians against trying to bring mild-to-moderate hypertension under control too quickly: "Therapy for most patients uncomplicated hypertension, stages 1 and 2 should begin with the lowest dosage.

to prevent adverse effects of too great or too abrupt a reduction in blood pressure. Thus, initial interventions are usually aimed at lifestyle modifications such as weight loss, stress reduction, exercise, dietary changes, reduction of alcohol use, and cessation of smoking.

Medication interventions are usually considered secondary, because lifestyle changes alone represent major interventions and adjustments for many patients and can have substantial impact on blood pressure. MacConnachie and Maclean 12 link compliance directly to dosage: "Therefore, any measure [that] reduces the dosage requirement of an antihypertensive while maintaining therapeutic efficacy, or otherwise limits the possibility of commonly encountered ADEs, will encourage good patient compliance and so improve long-term control of hypertension.

First-dose reactions are ADEs that occur with the initial dose of a drug or when the dosage is increased. First-dose reactions have been described with the use of α-receptor blockers, 16 calcium channel blockers, 16 ACE inhibitors, 30 , 31 and β-blockers, 32 but clinical experience suggests that first-dose reactions may occur with any antihypertensive drug.

First-dose reactions due to antihypertensive drugs are frequently dose related and may result from an abrupt lowering of blood pressure, causing postural hypotension, dizziness, syncope, headaches, lethargy, or other symptoms.

First-dose reactivity explains why a large proportion of ADEs due to antihypertensive drugs occur at the beginning of treatment 9 and may indicate that some patients are sensitive to the pharmacological effects of the standard initial doses of antihypertensive drugs that physicians are prescribing.

Hypertension is most prevalent among people older than 60 years, 1 , 33 , 34 and treatment can be especially challenging because of altered pharmacokinetics eg, reduced liver and kidney function, and increased receptor sensitivity , which can produce even greater extremes in individual drug response than in younger adults.

These ADEs in older patients are typically dose related 38 , 39 and are the leading cause of older patients' discontinuing antihypertensive therapy.

For these reasons, some experts recommend that older patients, especially those who are frail, ill, or taking other medications, should be prescribed initial doses that are lower than those for younger adults. Some of these are drugs for which the JNC VI recommends lower initial doses not only for seniors, but for all patients.

Moreover, the pharmacokinetic data of some drugs suggest the appropriateness of lower doses for seniors. For example, the plasma levels of acebutolol and bisoprolol are doubled in seniors compared with young adults, 16 yet the PDR -recommended initial doses are the same.

With other drugs eg, nifedipine and diltiazem , the PDR lacks pharmacological data on the response of older patients, so the physician's ability to make educated judgments about dosage is limited. With some drugs, physicians wanting to use half doses are stymied because the pills do not facilitate this capsules or irregular or coated tablets.

Hypertension is the most common indication for visits to US physicians, 40 and it is a leading cardiovascular risk factor. Low-dose therapy allows patients time to adjust psychologically to the fact they have hypertension and to begin making lifestyle changes recommended by the physician—no small undertaking for most patients.

Some patients experience distress about having hypertension and possibly requiring lifelong drug therapy, and they develop anxiety symptoms that may be mistaken for ADEs, which may lead to skipping doses or quitting treatment.

Drug therapy commencing with minimal doses is generally more acceptable to patients, allays fears about unpleasant side effects, and minimizes possible confusion between drug-related ADEs vs anxiety-related symptoms or coincidental factors.

The danger in commencing treatment with the lowest recommended doses is, of course, undermedication, which also is a problem in antihypertensive management today. The stepwise approach to treating hypertension presupposes that proper titration will lead to higher doses in some patients or to the addition of 1 or 2 more antihypertensive drugs, when necessary.

The "start low, go slow" approach, which is intended to minimize dose-related ADEs that hinder compliance, is effective if proper follow-up and dosage titration are provided.

Some patients experience first-dose reactions when their dosages are increased. Smaller dosage increases, which may require splitting pills, may sometimes prevent this complication. Drugs produced as scored pills in wide ranges of doses provide the most dosage flexibility.

Overall, optimal antihypertensive pharmacotherapy in mild-to-moderate hypertension is most often accomplished when initiated at the lowest effective doses, to maximize compliance by minimizing ADEs. To provide optimal therapy, physicians must have a readily available source of current information that defines the very lowest effective doses of antihypertensive drugs.

The PDR , which was initiated 54 years ago as a promotional device, is now the leading source of drug information among physicians, mainly because of its easy-to-use format and excellent indexes, and because it is distributed free to physicians each year. However, the information in the PDR consists mainly of the limited prerelease data that the manufacturer and the Food and Drug Administration deemed necessary for the safe and effective use of medications at the time of their approvals.

This information may not be adequate for making therapeutic decisions in the much wider range of patients seen in clinical practice compared with patients undergoing evaluation in prerelease studies.

Ray et al 43 have stated: "Although these studies generally ensure that a drug is efficacious and does not cause unacceptable harm, pre-marketing studies often fail to provide much of the information needed to make therapeutic decisions. Thus, the point of this article is not that the producers of the PDR are failing to fulfill an expected responsibility, but rather that a situation has developed in which there is no readily available source where physicians can obtain current information about the best methods of initiating antihypertensive drug therapy.

This situation requires solutions. Because of the wide popularity of the PDR , the ideal solution might be to establish mechanisms by which the information in the PDR can be kept current to reflect the evolving standards of care and the full range of proven effective drug dosages.

If such mechanisms cannot be established, then perhaps the free dissemination of the PDR should be discouraged, and an alternative, objective source of accurate, current information should be created in its place.

The findings of this article raise many questions. What initial doses of antihypertensive drugs are physicians actually prescribing? Studies have shown that the recommendations of the JNC VI have had little impact on the types of antihypertensive drugs that physicians prescribe, 44 , 45 but this has not been examined in regard to doses.

Furthermore, the implementation of optimal pharmacotherapeutic methods ultimately depends on physicians. If physicians were better informed about the JNC VI— recommended initial doses of antihypertensive drugs, would they alter their methods?

What would best motivate them to do so? What would motivate drug manufacturers to define the lowest, safest doses of new drugs in their prerelease research, to provide pills that allow for flexible dosing, to provide rational guidelines for older patients, and to reverse the trend that seems apparent in drug advertising toward 1-size-fits-all and other simplistic methods of dosing?

With a perennial high incidence of ADEs, most of which are dose related, and with well-defined problems with ADEs and compliance in treating hypertensive patients, these questions need to be answered and solutions need to be found and implemented.

The optimal pharmacotherapy of hypertension depends on the availability of information on the full range of effective dosages of antihypertensive drugs. This includes effective dosages that may be lower than those recommended by drug manufacturers. The PDR is the most used source of drug information among physicians, and it is heavily relied on by hospital staff who may lack the clinical experience to know that PDR dosage recommendations are general guidelines based on limited prerelease research, not on hard and fast rules of optimal therapeutics.

Moreover, although experts generally suggest reduced initial doses for older patients, the PDR does not recommend such reductions for old or even very old patients with 37 of 45 drugs. If the JNC VI recommendations, which represent prerelease and postrelease data, are considered the state of the art, mechanisms need to be implemented by which these recommendations are incorporated into the PDR and the corresponding package inserts, where physicians are most likely to see and use them.

If such mechanisms cannot be established for the PDR , another source of current, readily available drug information should be created so that physicians' methods will keep pace with evolving standards of optimal pharmacotherapy for patients with hypertension.

Corresponding author: Jay S. Cohen, MD, Del Mar Heights Rd, , Del Mar, CA e-mail: jacohen uscd. full text icon Full Text. Download PDF Top of Article Abstract Compliance with antihypertensive treatment Adverse drug events and compliance Materials and methods Results Comment Conclusions Article Information References.

Table 1. View Large Download. Range of Dosages Provided by the Manufacturers of 45 Commonly Prescribed Antihypertensive Drugs. Not Available, The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure.

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Postgrad Med. Because some clinical trials included sitting BP and supine or standing BP measurements, we decided to use all studies based on sitting or supine BP measurements, and excluded any reports that were based on standing measurements of BP.

This decision was based on an empirical finding in HyperGEN where sitting BP was more highly correlated with supine than with standing BP eg, the correlation of the mean sitting with mean supine systolic BP was 0.

The efficacy reported in Tables 1 2 3 to 4 , and in Tables A2 to A8 in Appendix A , represents the reductions in sitting or supine BP as compared to the placebo effect or baseline before the treatment. Weighted average effects of antihypertensives as monodrug therapy by ethnicity for sitting or supine BP.

Lists the class or group of antihypertensive medications along with an Appendix table in parentheses that provides the details of individual clinical trials. For example, see Table A2 in the Appendix A for ACE inhibitors. Dosage effects of antihypertensives as monodrug therapy by ethnicity for sitting or supine BP.

No clinical trials were reviewed in African Americans for α-blockers and loop diuretics with relative high dosage. Abbreviations as in Table 1.

Weighted average effects of antihypertensives as monodrug therapy by ethnicity for sitting BP only. Weighted effect of the second medication in combination drug therapy for sitting and supine BP. More clinical trials were included for all ethnicities because they used mixed populations that could not be categorized into either African Americans or non-African Americans.

No literature of not containing diuretic combinations was summarized for African Americans. Tables A2 through A7 in Appendix A summarize results from clinical trials on the effects of antihypertensive medications as monodrug therapy with commonly used dosage.

A total of 10, participants were involved in these studies, with ages from 18 to 86 years, with diagnosis of mild-to-moderate hypertension. The clinical trials were mostly double-blinded, randomized, with the duration of the treatment varying from 1 week to 3 years. The weighted average effects of monodrug therapy were calculated in two different ways separately by ethnicity, which are shown in Tables 1 2 to 3 : one includes clinical trials using sitting or supine BP Table 1 , whereas the other Table was based on clinical trials using only sitting BP measurements Table 2.

More trials were available when using sitting or supine BP measurements. As seen in Tables 1 and 2 , the two types of average effects were similar. When calcium channel blockers were divided into two groups, as dihydropyradine and non-dihydropyradine, the same pattern of the weighted average effects was shown across ethnicities.

However, there was only one clinical trial in the literature reporting on the loop diuretics in African Americans, which included just 16 participants. Because most of the clinical trials on loop diuretics used supine BP measurement, this group of medications was not listed in Table 2.

When the dose was increased, the BP responses to the antihpertensives improved, including ACE, calcium channel blockers, thiazide and thiazide-like diuretics, and loop diuretics Table 3.

The overall responses did not improve with increased doses of α 1 -blockers and β-blockers. We also noted that, as doses of medications increased, the racial difference in BP responses decreased for ACE and calcium channel blockers but increased for β-blockers and thiazides.

The relatively limited number of clinical trials on combination drug therapy of different classes with different mechanisms of action are reported in Table A8 in Appendix A.

We pooled several types of combination drug therapy together, including ACE inhibitors and calcium channel blockers, diuretics and ACE inhibitors, α 1 -blockers and calcium channel blockers, and diuretics and angiotensin II antagonist.

When the components of the combination drug therapy used the same dosages as in the corresponding monotherapies, the combination drug therapy was generally more effective than either of the monotherapies for systolic and diastolic BP.

Most of them had less than additive effects, although some showed synergistic effects on treatment of hypertension.

The medication with higher effect on BP from monodrug therapy trials in the combination was considered as the first medication, and the one with lower effect as the second one. The weighted average effect of the second medication was calculated from 28 reported clinical trials with a total sample size of participants Table 4.

To correct the measured sitting or supine BPs in whites taking ACE inhibitor and a thiazide diuretic, for example, the net effect of the combination drug therapy can be estimated as follows without considering dosage:.

For diastolic BP, the first drug is ACE inhibitor with an effect of The goals of treatment for hypertension are to optimally control high BP and to reduce associated cardiovascular and renal morbidity and mortality. These estimates may be used to impute the original unmedicated BPs of participants using antihypertensive therapy.

We recognize the limitations of using group averages to predict individual responses, but prediction of individual measurements does not appear to be feasible. A meta-analysis of clinical trials on the efficacy of antihypertensive medications was performed by Law et al.

They concluded that the BP-lowering effects of these classes of medications were similar, with an average reduction of 9. However, there were clear differences between African Americans and non-African Americans.

For example, β-blockers were shown to be less effective than thiazide diuretics in African American patients. Hypertensive African Americans are considered to exhibit higher plasma volumes, reflected in lower plasma renin activities, than hypertensive whites.

The effects estimated by combining the races should be used for loop diuretics because of the small race-specific sample sizes for loop diuretics. Law et al 13 concluded that the effects of combination medications were additive. However, based on our review of the clinical trials, combination medications were found to be less effective than the sum of the two medication effects.

In addition, the combination medications responded better than either medication used alone. For instance, the combination of ACE inhibitor and thiazide diuretic was shown to have advantages over the two monodrug therapies Table A8.

The ACE inhibitors block the counter-regulatory increase in the angiotensin II triggered by diuretic therapy; conversely, thiazide diuretics may stimulate the renin-angiotensin system and enhance the antihypertensive action of ACE inhibitors.

For purposes of imputing the original untreated BP, in combination drug therapy, the effect of the first medication can be used in the same way as monodrug therapy, and the effect of the second medication should be adjusted with the percent effects shown in Table 4.

We suggest that ethnic-specific percentages may be used for non-African Americans, whereas the overall percentages should be used for African Americans due to small samples available. The process of imputing original untreated BP measurements for subjects under antihypertensive medications is a complicated process.

Our study has some potential limitations. We assumed that these trials used the most commonly recommended doses. Third, poor adherence to antihypertensive therapy is always a major therapeutic problem leading to the lack of adequate control in large sections of patients with hypertension.

Therefore the efficacy obtained from the clinical trials may be higher than that in the general hypertensive population under treatment. In summary, our study provides a summary of the effects on BP of different antihypertensive medications used in controlled clinical trials.

The imputed BPs can be used in epidemiologic and genetic analyses in which a more precise estimation of the phenotype is required to improve the power of the study.

Prediction of pretreatment BP in individuals on antihypertensive medications is useful for epidemiologic and genetic analysis. For individuals on combination drug therapy, the measured BPs may be corrected by first adding the monodrug therapy effect of the first medication with the highest effect, plus the weighted average effect of the second medication.

As a general case, the overall weighted average of medication effects can be used to correct the effects of the medications not belonging to the classes we focused here.

Supplement S1. We are thankful to the study participants and the Primary Centers and Investigators of HyperGEN:. University of Utah Network Coordinating Center, Field Center, and Molecular Genetics Lab : Steven C. Hunt, PhD Network Director and Field Center P.

Leppert, PhD Molecular Genetics P. Weiss, PhD; Paul N. Hopkins, MD, MSPH; Hilary Coon, PhD; Roger R. Williams, MD late ; Janet Hood. Boston University Field Center : R. Curtis Ellison, MD P. Myers, PhD; Luc Djoussé, MD, DSc; Yuqing Zhang, MD; Jemma B.

Wilk, DSc; Greta Lee Splansky, MS. University of Alabama Field Center : Albert Oberman, MD, MPH P. Lewis, MD, MSPH; Michael T.

Weaver, PhD; Phillip Johnson; Susan Walker; Christie Oden. University of Minnesota Field Center and Biochemistry Lab : Donna K.

Arnett, PhD Field Center P. Eckfeldt, MD, PhD Biochemistry Lab P. Pankow, PhD; Michael B. Miller, PhD; Anthony A. Killeen, MD, PhD; Kim Weis, MPH; Greg Rynders; Catherine Leiendecker-Foster, MS; Gregory Feitl; Barbara Lux; Jean Bucksa.

University of North Carolina Field Center : Gerardo Heiss, MD, PhD P. I ; Barry I. Freedman, MD; Kari E. North, PhD; Kathryn Rose, PhD; Amy Haire. Washington University Data Coordinating Center : D. Rao, PhD P. Province, PhD; Aldi T.

Kraja, PhD; Ingrid B. Borecki, PhD; Charles Gu, PhD; Treva Rice, PhD; Mary Feitosa, PhD; Jun Wu, MD; Karen L. Schwander, MS; Derek Morgan; Stephen Mandel; Shiping Wang MS; Brandon Pierce; Tracy Mades. National Heart, Lung and Blood Institute: Susan E.

Old, PhD; Cashell Jaquish, PhD; Dina Paltoo, PhD. Detailed results from individual clinical trials were summarized into seven tables, numbered as Tables A2 to A7 for monodrug therapy and A8 for combination drug therapy. Table A2 shows information on ACE inhibitors lowering BP effects.

Reviewed were 36 trials spread over 22 studies with participants. Medications reported were benazepril, captopril, enalapril, lisinopril, perindopril, ramipril, spirapril, and trandolapril. These medications had a lowering systolic BP effect that ranged from 5 to 25 mm Hg, and from 2 to 18 mm Hg for diastolic BP.

There was a high correlation between the same medication effect on lowering systolic and diastolic BP. Table A3 summarized reports on medication effects of α 1 -blockers, including doxazosin, prazosin, and terazosin. The decrease of BP with using this class of antihypertensives ranged from 7.

For β 1 -blockers, 18 trials from 14 clinical studies with patients were reviewed Table A4 for the antihypertensive effects of atenolol, bisoprolol, acebutolol, celiprolol, betaxolol, and metoprolol.

The lowering effects observed were from 7. For calcium channel blockers, nifedipine, verapamil, isradipine, diltiazem, amlodipine, felodipine, and nicardipine were used in 33 clinical trials exploring the medication-lowering BP effects Table A5.

The reduction in systolic BP ranged from 5. For thiazide and loop diuretics, hydrochlorothiazide and furosemide were commonly used in clinical trials Tables A6 and A7. Based on the clinical trials, systolic BP decreased from 5. Supplementary data associated with this article can be found, in the online version, at doi: Joint National Committee The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure.

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Blood Pressure Toolkit. Home Health Topics High Blood Pressure Changes You Can Make to Manage High Blood Pressure Types of Medications. Prescription blood pressure drugs come in many classes. Classes of blood pressure medications Some of the major types of commonly prescribed cardiovascular medications are provided here.

However, this information does not signify a recommendation or endorsement from the American Heart Association. It's important to discuss all of the drugs you take with your health care professional and understand their desired effects and possible side effects. Never stop taking a medication and never change your dose or frequency without first consulting your doctor.

If you have an illness, you may wish to discuss your medications with your health care professional. If you have been prescribed blood pressure medication, consult your health care professional prior to conception if you are considering pregnancy or if there is a chance you could become pregnant.

If you discover that you are pregnant consult your health care professional as soon as possible to determine the safest medication for you at this time. The classes of blood pressure medications include: Diuretics Beta-blockers ACE inhibitors Angiotensin II receptor blockers Calcium channel blockers Alpha blockers Alpha-2 receptor agonists Combined alpha and beta-blockers Vasodilators Diuretics Diuretics help the body get rid of excess sodium salt and water and help control blood pressure.

Symptoms such as weakness, leg cramps or being tired may result. Eating foods containing potassium may help prevent significant potassium loss. If your health care professional recommends it, you could prevent potassium loss by taking a liquid or tablet that has potassium along with the diuretic.

People who take diuretics have increased risk of developing gout as a side effect. This isn't common and can be managed by other treatment.

People with diabetes may find that diuretic drugs increase their blood sugar level. A change in medication, diet, insulin or oral anti-diabetic dosage corrects this in most cases. Impotence may occur. Beta-blockers Beta-blockers reduce the heart rate, the heart's workload and the heart's output of blood, which lowers blood pressure.

Angiotensin-converting enzyme inhibitors ACE inhibitors Angiotensin is a chemical that causes the arteries to become narrow, especially in the kidneys but also throughout the body.

If you're taking an ACE inhibitor or an ARB and think you might be pregnant, see your health care professional immediately. These drugs have been shown to be dangerous to both mother and baby during pregnancy. They can cause low blood pressure, severe kidney failure, excess blood potassium hyperkalemia , fetal malformation and even death of the newborn.

Angiotensin II receptor blockers ARBs These drugs block the effects of angiotensin, a chemical that causes the arteries to become narrow. Medications that act directly on the renin-angiotensin system can cause injury or even death to a developing fetus.

When pregnancy is detected, consult your health care professional as soon as possible. Calcium channel blockers This drug prevents calcium from entering the muscle cells of the heart and arteries.

Usually none of these symptoms are severe, and most will go away after a few weeks of treatment. This drug isn't usually used by itself. Minoxidil is a potent drug that's usually used only in resistant cases of severe high blood pressure.

It may cause fluid retention marked weight gain or excessive hair growth. reported that patients who perceived adverse effects from their antihypertensive medications were 1. One Palestinian study also reported a 4. Even though none of the study participants in the current study discontinued their antihypertensive medications, a three-fold increase in the rates of non-adherence were observed.

In a systematic review of qualitative studies, tiredness, urinary frequency, ankle swelling, lethargy, and impotence were mentioned as troublesome adverse effects [ 33 ] while tiredness, muscle pain, and poor sleep were associated with poor adherence in the current study. On the other hand, patients who reported to have regular physical exercise were more likely to be adherent to their antihypertensive medications.

Better knowledge about the disease and its management could contribute to better adherence by these patients. Efforts that focus on improving the knowledge and awareness of patients is crucial for optimal treatment outcomes especially in patients with diseases such as hypertension.

Hypertensive patients do not usually present with symptoms but can ultimately experience serious cardiovascular consequences.

Forgetfulness was the most commonly mentioned reason for poor adherence to antihypertensive medications. This has been reported in other studies [ 24 , 28 , 29 , 32 ]. Fasting has been reported as the second most common cause of poor adherence.

HCT, enalapril, and amlodipine were the most commonly prescribed medications. While it is believed that there might be differences in the adverse effect profiles of different antihypertensive medications, no difference was observed in the level of adherence among patients different antihypertensive medications.

On the other hand, hypertensive patients usually present with other chronic conditions for which they receive other medications. This increases the pill burden and complexity of regimens and has been attributed to poor adherence.

In the current study, While this decreased the rate of adherence to antihypertensive medications upon univariate analysis, it failed to independently predict adherence upon multivariate analysis.

Just below half of the study participants The complexity of medication regimens including the number of antihypertensive medications was associated with poor adherence [ 28 , 29 ].

However, the number of medications was not found to be statistically significant in predicting adherence in the current study. Despite this, promoting the use of fixed-dose combination antihypertensive medications FDC may improve medication adherence.

Several studies reported advantages of FDC in terms of reducing adverse effects and simplifying regimens and thereby improving adherence [ 36 ]. However, availability of these FDC is also another issue in the current set up. On the other hand, selecting antihypertensive medications with better safety profile can help improve medication adherence.

Studies reported that Angiotensin II Receptor Blockers ARBs have similar, if not better, safety profile than other antihypertensive classes and can improve medication adherence in hypertensive patients [ 26 , 29 , 36 ].

None of the study participants in the current study received ARBs and the use of these medications might be hindered by availability and affordability issues.

ACEIs are better tolerated than most other antihypertensive medications; hence, they could be preferably used in the absence of ARBs [ 26 ]. Adherence to antihypertensive medications should be stressed as it is associated with poor outcomes. This necessitates efforts to improve medication adherence.

One effort could be involving pharmacists in direct patient care as it has been demonstrated that pharmacist-led interventions improve antihypertensive medication adherence and BP control [ 37 ]. Interpretation of the findings of this study should be in light of the following limitations.

This is a single-center cross-sectional study with small sample size and hence generalization to other settings should be done with caution. It is also impossible to differentiate whether the adverse effects were due to the antihypertensive medications or other medications the patients were taking.

Statistically significant associations were identified among antihypertensive medications and a number of ADRs. As one might expect from its pharmacologic action, hydrochlorothiazide was associated with a six-fold increase in the number of patients experiencing frequent urination.

As reported from clinical trials [ 38 , 39 ], enalapril use was associated with cough. Other ADRs include cold hands or feet with furosemide and atenolol and swollen feet or legs with CCBs amlodipine and nifedipine and atenolol. In addition, furosemide was associated with nausea, constipation, palpitation, and skin rash.

Adverse effect significantly contributes to antihypertensive medication non-adherence in hypertensive patients. However, patients who thought that their symptoms were due to the antihypertensive medications they were taking tend to be non-adherent.

Patients should be counseled about adverse effects common to their antihypertensive medications and should be directly involved in the decision process.

Studies with prospective study designs should be done in the future to help better understand the association between adverse effects and non-adherence. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al.

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Breeze E, Rake EC, Donoghue MD, Fletcher AE. Comparison of quality of life and cough on eprosartan and enalapril in people with moderate hypertension. Download references. We would like to acknowledge the school of pharmacy for supporting us during conducting this study.