- CONDITION CENTERS
After completing this continuing education article, the pharmacist should be able to:
Elevated blood pressure (BP) is a leading cause of morbidity and mortality in the United States and worldwide. Control of BP to accepted goals leads to reductions in the development of the adverse cardiovascular (CV) complications of hypertension.1,2 In addition to lifestyle changes, pharmacologic therapy is a mainstay of treatment for elevated BP.
According to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), thiazide diuretics are the preferred first-line agents for patients with uncomplicated hypertension.2 The JNC 7 also recognizes beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II (AT II) receptor antagonists, and calcium channel blockers as valid first-line agents, as several studies support the CV risk reductions seen with the use of each of these classes. In addition, the side-effect profiles of these drug classes are less than those of other antihypertensive drug classes.
The benefit of these agents, however, can be attenuated by many factors (Table 1).2 Reasons for the lack of BP control can be grouped together under the headings of medication use and adherence. There are a multitude of reasons for medication nonadherence, including the cost of medications, lack of understanding of the response, and plain forgetfulness. In addition, the development or potential development of side effects or drug interactions, as well as lack of patient knowledge, often results in less than acceptable BP control and an increased risk of complications.
Pharmacists are in an optimal position to improve BP in their hypertensive patients through better medication use. Too often, however, pharmacists rely on information that is less than complete to guide their decisionmaking process. In particular, pharmacists often overlook the pharmacologic rationale behind a medication's mechanism of action, drug interactions, and side-effect profile, as well as the rationale to continue therapy. In the process, their interventions become less effective.
This article highlights a common question encountered for each of the first-line drug therapies for the treatment of hypertension and details the pharmacologic basis for the clinical interpretations. We think that a stronger understanding of these mechanisms will allow pharmacists to be more successful in making recommendations for drug therapy and in counseling patients, thereby improving compliance, drug use, and the achievement of therapeutic goals. Case-scenario questions are integrated throughout the article to illustrate the main objectives.
Case Scenario 1
You are about to fill a prescription for hydrochlorothiazide 25 mg qd for a patient with known symptomatic benign prostatic hypertrophy (BPH; on finasteride for 2 months). The patient has a medical history only of hypertension and BPH. Given this scenario, what would you do?
This scenario sounds like a typical one that is encountered often. Clearly, this prescription should be reconsidered. How can a patient who already has urination complaints cope with the diuresis from treatment with hydrochlorothiazide? To answer this question, one must first understand the mechanism of the antihypertensive effect of thiazide diuretics.
The antihypertensive properties of the thiazide diuretics are complex and involve not only their natriuretic effects, but also their direct effects on the vasculature. The prevailing mechanism by which the thiazide diuretics lower BP changes over time. Each of the phases is characterized by distinct changes that highlight the pharmacologic complexity of this class of agents.
During the acute phase (1-2 weeks) of administration, the thiazide diuretics lower BP primarily through their diuretic effects. In the tubules of the kidneys, these agents prevent the reabsorption of sodium and chloride ions in the distal convoluted tubule, thus increasing renal sodium and water excretion. This increase in sodium and water excretion causes a reduction in extracellular fluid volume, leading to a decrease in cardiac preload and a subsequent decline in cardiac output.
After several weeks of thiazide therapy, a noticeable decline in diuresis occurs. The loss of thiazide-induced diuresis is the defining event in the subacute phase of treatment, and it is most likely due to the phenomenon known as diuretic braking. Diuretic braking is a process by which the body slowly adapts to and resists the diuretic effects of these agents by (1) increasing the activity of the sympathetic nervous system, (2) increasing the activity of the renin-angiotensin system, and (3) increasing the release of antidiuretic hormone. Despite the reduction in diuresis during the subacute phase of treatment, the BP-lowering effects of these agents remain. Although this fact may seem counterintuitive, the decline in BP is most likely due to a developing reduction in peripheral vascular resistance.
During the chronic phase of treatment, the diuretic effects of these agents remain impaired, cardiac preload and cardiac output return to pretreatment levels, and peripheral vascular resistance continues to be reduced. The persisting BP-lowering effects during chronic administration of thiazide diuretics appear to be due primarily to the vascular effects of these agents. The exact mechanism by which the thiazide diuretics cause vascular relaxation is not entirely clear. It appears, however, that these agents can change the electrical charge distribution across smooth muscle cell membranes, resulting in relaxation.3
Thiazide diuretics are underutilized by practitioners despite their clear benefit in patients with hypertension. Many reasons for this underutilization have been hypothesized, which include the potential adverse effects this drug class may cause. It is therefore important for pharmacists to be aware of these side effects, their incidence, and their clinical relevance. Pharmacists often rely on tertiary sources of information to counsel patients. Among the most frequently used references is the USP DI, Volume II: Advice for the Patient, which recommends instructing patients that "thiazide diuretics are used to help reduce the amount of water in the body by increasing the flow of urine."4 All available evidence supports only a minor and transient diuresis with thiazide diuretic use. Furthermore, evidence from large randomized controlled trials indicate that patients' quality of life improves with the use of thiazide diuretics.5 Therefore, if one considers the pharmacology of the product, one should inform the patient that some slight increased urination may occur, but it usually is minimal, and the effects should occur for only a short period of time (1-2 weeks). The pharmacist also should inform the patient of the known BP-lowering effects of the drug so that the patient may better understand what the "water pill" actually is accomplishing.
Case 1 Discussion
The answer to Case Scenario 1 is (c). The relevance of diuresis during thiazide diuretic therapy is supported by the pharmacology of the drug's effect on BP, and the lack of large and sustained diuresis. Therefore, the use of this drug class in patients with urinary difficulties should not be discouraged or avoided, but rather encouraged. Also, it is probable that the thiazide diuretic will at some point in time be described to the patient as a "water pill." Rather than avoiding this terminology, the pharmacist should inform the patient of its minimal and temporary effect on urine output. In addition, the pharmacist should convey in a patient-friendly manner the primary mechanism of the drug's antihypertensive effect, which, as described above, is a decrease in peripheral vascular resistance (in patient terms, "a reduction in resistance to blood flow"). This step will help patients to better classify the drug they are taking and make them less prone to discontinue the drug in anticipation of side effects.
Switching to an alpha-blocker to help with BPH and hypertension is a possible consideration. Yet, evidence from the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) indicates increased development of CV events in patients treated with doxazosin versus those treated with chlorthalidone, and therefore alpha-blockers are no longer recommended as firstline antihypertensive agents.6
Case Scenario 2
FR is a 65-year-old woman who has a history of coronary artery disease (CAD), peripheral vascular disease, congestive heart failure (CHF; ejection fraction = 35%), hyperlipidemia, hypertension, and diabetes mellitus. Her physician writes a prescription for lisinopril 5 mg qd for the first time. All available laboratory test results are within normal limits (serum creatinine = 1.4). She also is taking aspirin 325 mg qd, metoprolol succinate 50 mg qd, and glyburide 5 mg qd. What should be done for FR and why?
The concomitant use of ACE inhibitors and aspirin is common. Often pharmacists treat patients with hypertension who develop CV such as coronary heart disease or a cerebral vascular accident. The results of recent clinical trials suggest that the benefits of ACEinhibitor therapy in a patient with CHF may be negated by the concomitant use of aspirin.7 This interaction has been described for some time, and it is detailed by the theoretical pharmacologic interaction between the 2 products.8 Particularly, there is evidenc to suggest that aspirin actually can impair or reverse the vasodilatory effects of the ACE inhibitor.
The therapeutic benefits of ACE inhibitors are due to their ability to inhibit ACE. This enzyme has multiple substrates and is responsible for the production and metabolism of the important vasoactive peptides, AT II and bradykinin (Figure 1). AT II is a potent vasoactive peptide. It elevates BP through direct arterial vasoconstriction and by stimulating aldosterone release from the adrenal glands, causing renal sodium and water retention. Blood volume increases, leading to an increase in cardiac preload and eventually to an increase in BP.
ACE also is responsible for the metabolism of the vasodilatory peptide, bradykinin. The mechanisms through which bradykinin stimulates arterial relaxation are diverse and not completely understood. By acting on the endothelial layer of blood vessels, bradykinin can stimulate the release of a number of compounds thought to cause relaxation of arteries, including nitric oxide (NO) prostacyclins and a yet uncharacterized substance referred to as the endothelial-derived hyperpolarizing factor (EDHF).9-13 The augmentation of bradykinin levels by ACE inhibitors is thought to be a major part of the therapeutic actions of these drugs.
Pharmacologically, aspirin may have the ability to inhibit bradykinin-induced vasodilation. Bradykinin can produce arterial vasodilation by promoting the production and release of vasodilatory prostaglandins from the endothelial layer of blood vessels. The production of prostaglandins is dependent on the enzyme cyclooxygenase, which is the target for aspirin. Despite this potential interaction, it is clear that bradykinin can cause vasodilation through other prostaglandinindependent mechanisms (Figure 1). Furthermore, scientific studies have demonstrated that the contributions of NO, prostaglandins, and EDHF to bradykinin-induced vasodilation may not be the same in different species and may vary in arterial tissue derived from specific anatomical regions.14,15 With these studies in mind, it is clear that (1) even if prostaglandin synthesis is inhibited by aspirin, bradykinin can reduce peripheral vascular resistance through NO and EDHF release; (2) the importance of bradykinininduced prostaglandin release as a vasodilatory agent may be limited to arteries from specific anatomical regions of the body; and (3) in patients with other comorbid conditions such as CHF, the therapeutic benefits of ACE inhibitors are not limited to their vasodilatory effects. Their renal protective effects and their ability to inhibit cardiac remodeling may be equally important.
Two studies most recently describe the clinical evidence affecting the ACE inhibitor?Caspirin interaction.16,17 Both studies are in heart failure patients. This is an important distinction, because the use of these products is common in other comorbid conditions when patients are not suffering from heart failure. In particular, the benefits of combined therapy are well-established for patients status post myocardial infarction.18 Evidence from the trials in heart failure patients are contradictory. In the prospective-design trial, there was no difference in the development of events between heart failure patients treated with an ACE inhibitor alone and those treated with an ACE inhibitor and aspirin.17 In the retrospective trial, aspirin doses >325 mg qd were associated with increased death, but no difference was seen between heart failure patients treated with ACE inhibitors alone and those treated with ACE inhibitors and aspirin at doses ??160 mg qd.16
Appropriate concomitant use of ACE inhibitors and aspirin could be achieved by using doses of aspirin that are high enough to inhibit platelet activation but too low to inhibit cyclooxygenase. Based on the dose of aspirin to inhibit prostaglandin synthesis, the lack of identified clinical interaction at doses ??160 mg qd, and the known benefits of aspirin even at low dosages for most CV disorders, it appears logical to recommend lowdose (81 mg) aspirin in combination with ACE inhibitors until further evidence supports doing otherwise. The dosing may be separated, but there is no evidence to date to support this separation as an effective way of minimizing this potential interaction. In practice, this separation is likely to induce more adherence concerns and lack of therapeutic goal achievement.
Lastly, ACE inhibitors and AT II receptor blockers often are used interchangeably in heart failure because of their similar effects on AT II and their comparable clinical benefit. AT II receptor blockers, however, do not have any known inhibitory effect on the breakdown of bradykinin. Assuming that increased bradykinin levels are in part responsible for the improved efficacy of ACE inhibitors in the treatment of CHF, then a clear outcome benefit should be seen in ACEinhibitor?Ctreated heart failure patients versus those taking AT II blockers. As noted from randomized controlled trials, AT II blockers remain a beneficial class of drugs in the treatment of patients with heart failure despite their lack of effects on bradykinin metabolism. They are still recommended second to ACE inhibitors, however, in patients with heart failure, because evidence from the trials shows similar end points for either treated group, but a trend toward reduced CV end points with ACE-inhibitor therapy.19 This finding suggests additional beneficial action of ACE inhibitors beyond inhibition of AT-II production, and it helps to support the importance of bradykinin in heart failure management.
Case 2 Discussion
The answer to Case Scenario 2 is (c). Answer (a) is not correct because, in actuality, ACE inhibitors are the drugs of choice when treating patients with renal insufficiency due to their renal protective effects. One must check serum creatinine and potassium shortly after ACE initiation (1-2 weeks) to ensure that no significant increases in serum creatinine are noted (a possible indication of renal artery stenosis if the increase is >20%). One also must ensure that the potassium level remains within normal limits; it is particularly important to monitor this level in a patient who already has renal insufficiency.
Answer (b) also is incorrect. Several compelling indications exist for this patient, including systolic heart failure, CAD (evidence from the HOPE [Heart Outcomes Prevention Evaluation] trial) with risk factors, and diabetes mellitus with renal insufficiency. Thiazides may be good add-on agents, but ACE inhibitors and beta-blockers have absolute, compelling indications in this patient. An alternative to thiazide diuretics in this patient is a loop diuretic, which can help with any fluid accumulation that may be occurring.
The correct answer is (c). As discussed above, there is no contraindication to using aspirin and lisinopril together, but the higher dose of aspirin does not appear to be necessary. In addition to filling the lisinopril prescription, pharmacists should be aware of this interaction because of its frequency and the likelihood of a patient hearing about the interaction through non?Chealth care personnel (eg, the lay press). The patient could have a lack of complete education and the potential to stop the medication(s) inappropriately. Counseling the patient to adhere by explaining the potential interaction is appropriate.
Calcium Channel Blockers
Case Scenario 3
DF is a 50-year-old man who had a titration of his amlodipine 2.5 mg qd to 5 mg qd 1 month ago. Since the titration, DF noticed swelling in his ankles. Despite raising his feet and reducing water intake, his feet continued to swell. He therefore stopped taking the amlodipine 1 week ago, and the symptoms subsided. DF has a history of hypertension, for which he also takes hydrochlorothiazide (HCTZ) 25 mg qd. His BP reading from today is 170/82 mm Hg, and 1 month ago it was 160/80. Which of the following options is the most appropriate for DF at this time?
The use of calcium channel blockers is common in the treatment of hypertension. They generally are more expensive than thiazide diuretics and beta-blockers. Patients, however, often require more than 1 or 2 agents to achieve goal BP, and, with their complementary mechanism of action, combination therapy is very effective. In addition, the side-effect profile of this class of drugs is favorable, with flushing and peripheral edema occurring most frequently. Although not all the dihydropyridine calcium channel blockers cause peripheral edema to the same extent, it remains a commonly encountered side effect with this class of drug. Appropriate pharmacologic therapy to reduce the frequency of this side effect would be desirable and could lead to a reduction in compliance issues. Because this side effect can lead to drug-use discontinuation, methods of attenuation of the effect would be desirable.
Dihydropyridine calcium channel blockers have the dose-dependent potential to cause ankle edema through their specific effects on precapillary resistance vessel diameter and capillary hydrostatic pressure. The role of capillary beds in any tissue is to efficiently deliver oxygen and nutrients to active tissues, while carrying away carbon dioxide and metabolic by-products. In order to function properly, capillary vessels must be relatively porous, allowing for the free flow of fluid, small molecules, and electrolytes across vessel walls. The magnitude and direction of fluid movement across capillary membranes is governed by 2 forces: hydrostatic and osmotic pressure. Hydrostatic pressure is a measurement of the force exerted by plasma against the capillary wall and is a direct result of BP. Hydrostatic pressure tends to favor the movement of fluid out of capillaries and into the interstitial space. Osmotic pressure is generated by the net movement of water from an area of low solute concentration to an area of high solute concentration. The high levels of proteins and electrolytes in the plasma tend to favor the movement of water from the interstitial space into the capillary. An imbalance between these 2 forces can cause an abnormal movement of fluid out of the capillary and into the interstitial space, leading to edema. Whereas the exact mechanism causing calcium channel blocker?C induced ankle edema remains unclear, the evidence points to a drug-induced increase in capillary hydrostatic pressure as a causative factor. It has been suggested that selective vasodilation of precapillary resistance vessels by calcium channel blockers may increase blood flow into the capillary bed, subsequently increasing hydrostatic pressure. This increase would force fluid out of the capillaries and into the interstitial space, causing edema (Figure 2).20
Many clinical studies have demonstrated a reduction in dihydropyridine calcium channel blocker?Cinduced ankle edema with ACE-inhibitor use.21-23 The most likely explanation for why ACE inhibitors can reverse this side effect of calcium channel blockers is their ability to dilate postcapillary venous capacitance vessels. Dilation of these vessels would reduce capillary hydrostatic pressure and eliminate fluid exudation from the capillaries into the interstitial space (Figure 2).24 Although diuretics have been used to reduce this type of edema, they tend to be less effective than ACE inhibitors. The causative factor for edema in this case is not renal but vascular in origin. By correcting the plasma input-to-output ratio across a capillary bed, ACE inhibitors are much more effective in reducing ankle edema than diuretics.
Case 3 Discussion
The answer to the question in Case Scenario 3 can be (a), (b), or (d). All of these are options for this patient at this time. Answer (a) simply replaces the cause of the side effect with another agent. In many situations, this prescribing occurs, as no compelling reason may exist to continue the previous therapy (as in this case). Often, however, a compelling reason exists for the patient to use the drug class, or few other choices are available. Answer (b) also is acceptable because the patient received a benefit from amlodipine at 2.5 mg qd and did not develop the dose-dependent side effect of edema at that dose. HCTZ doses above 25 mg qd generally are not much more effective at lowering BP, and hence another agent would be recommended. Answer (d), as discussed above, is acceptable because the ACE inhibitor may balance out the hydrostatic pressure differences. Answer (c) is the only option that would not correct the underlying issue of side-effect development, along with noncompliance. Despite the reduction in fluid volume that can be induced by diuretic therapy, the increased hydrostatic pressure remains in the capillaries.
In this situation, the patient became less compliant with therapy because of the development of a side effect. A pharmacist can improve compliance by educating the patient on what to expect??both positive and negative??from drug therapy. Of course, the pharmacist needs to determine which side effects are important to discuss with the patient at the time of the visit. For example, calcium channel blockers have been implicated in hepatotoxicity, but this side effect is very rare (<1%), occurs generally within 2 to 3 weeks of initiation, is generally asymptomatic, and rarely requires discontinuation of the drug. If it is described to the patient without mentioning the infrequency of the reaction, the patient may think that the risks of therapy are greater than the benefit. The patient described here developed a discomforting side effect, about which he might not have been notified, and he stopped the medication. Patients should be informed of the risks associated with drug therapy, which are more likely to occur, and the potential complications of discontinuing the drug therapy if done without the advice of their health care provider.
Case Scenario 4
KH is a 58-year-old man who had a dose titration of his metoprolol tartrate from 50 mg bid to 100 mg bid 1 month ago. KH was nearly at his BP goal of <140/90 4 weeks ago (BP was 144/86 taken twice, pulse was 68), but today his BP was 170/96 taken twice, with a pulse of 88. He was diagnosed with hypertension 6 months ago and has no other past medical history. KH admits to not having taken his BP medication for the past 2 days. Which of the following mechanisms explains the pharmacologic basis for this drastic BP increase?
Sudden rises in BP place patients at a greater risk of CV complications (often stroke). One of the most likely reasons for sudden increases in blood pressure and hence stroke development is cessation of drug therapy, generally caused by nonadherence. Of the classes of agents used for the treatment of hypertension, beta-blockers have one of the greatest propensities to cause this rebound in blood pressure to pretreatment levels following abrupt discontinuation. The mechanistic reasons for this are herein explained.
Patients who are receiving prolonged beta-blocker therapy for hypertension may experience a withdrawal syndrome, characterized by tachycardia and an increase in BP, if their treatment is discontinued abruptly.25
Tissues that are regulated by the nervous system are comprised of cells that respond to nerve or hormonal agonists via cell-membrane receptors. During situations where there is an abnormal increase or decrease in these signals, an adaptational response can occur. This response is characterized by a change in the density of cell surface receptors. Cells that are overstimulated for a prolonged period of time can respond through the process of receptor downregulation. This process involves the internalization and degradation of cell-membrane receptors, leading ultimately to a decrease in the responsiveness of the tissue to the agonist. Conversely, if a tissue is understimulated for a prolonged period of time, the cells making up that tissue can respond by increasing the production and subsequent density of cellsurface receptors. This process, known as receptor upregulation, can occur during circumstances where there is a neurotransmitter or neurohormone deficiency or when drug antagonists are blocking the cell-membrane receptors. This process ultimately leads to an increase in the tissue sensitivity to these neurotransmitters.
Whereas these adaptive changes can be beneficial under the above-mentioned circumstances, they also can be detrimental, especially if the environmental conditions change. A classic example of this type of situation involves chronic beta-blocker therapy for hypertension and the consequences of abrupt cessation of this therapy (Figure 3). The rate and force by which the heart contracts are regulated in part by beta receptors found on the surface of cardiac cells. These receptors normally are activated by endogenous catecholamines such as epinephrine and norepinephrine. One of the primary ways in which beta-blocker therapy reduces BP is by preventing catecholamine activation of cardiac beta receptor, thereby slowing the heart rate and decreasing the contractile force of cardiac muscle. In response to chronic beta-blocker therapy, there is an upregulation of beta receptors on cardiac tissue.26,27 When a patient is suddenly taken off of a beta-blocker, an abnormally large number of cardiac beta receptors suddenly are available for activation by sympathetic neurotransmitters. This fact causes cardiac tissue to become supersensitive to catecholamine stimulation. This super-sensitivity causes the tachycardia and rebound hypertension that are sometimes seen with the abrupt withdrawal of these agents. This withdrawal syndrome will abate in a short time, as heart cells begin to downregulate and readjust their beta-receptor density to account for the absence of the beta blockade. By slowly tapering patients off of beta-blockers, cardiac tissue is given an adequate amount of time to readjust its beta-receptor population, and the patient will not experience the withdrawal symptoms mentioned above.
With the abrupt discontinuation of beta-blocker therapy, patients place themselves at a high risk for complications of hypertension. This risk is particularly high because of the upregulation of beta receptors that occurs on cardiac tissue as a result of chronic therapy. Following abrupt cessation, the neurotransmitters stimulate an abnormally large number of beta receptors on the heart, causing significant increases in inotropy and chronotropy, resulting in acute BP elevation (referred to as rebound hypertension). Because the body is not used to the elevated BP, the risk of complications rises.
Case 4 Discussion
In Case Scenario 4, the correct answer to the question is (a), as described above. The clinical significance of the pharmacology for this scenario is clear. As with all antihypertensive agents, it is imperative for patients to remain compliant. This is particularly so with beta-blockers for the reasons discussed. Because patients are responsible for compliance, they should be given all the tools needed to succeed in proper adherence. It is important, however, not to "cookie-cutter" patients into the pattern of "what works for one will work for all." It is critical to individualize counseling and assisting of patients in adhering to their regimen, as no one method has proven universally effective.28
It is important to educate the case patient on the use of metoprolol, its side effects, and the reasons to continue therapy. Adverse consequences of discontinuation should be explained, and the patient should be encouraged to talk to his pharmacist or provider if concerns regarding the therapy or continuation arise. This communication is especially important for new-onset hypertensive patients. Even if such matters have been discussed with the patient already, the nature of the disease, complications, and ways to improve BP, including lifestyle modifications, should be discussed. The effect of distributing this information, however, depends on the way the information is given to the patient. The pharmacist should use basic terminology (defining the terminology where appropriate) and show empathy and trust. Without taking these approaches, counseling is less effective (Table 2).2,29
Although each of the pharmacologic examples discussed above may be familiar to the practicing pharmacist, particular gaps of information or incompleteness of the mechanism surrounding the situations can ultimately lead to a reduction in therapeutic achievement. Several methods can be employed by pharmacists to improve their patients' medication use. Improving patient adherence and ensuring proper drug recommendations are important functions of pharmacists. The pharmacist's knowledge alone does not automatically transfer into improved pharmacotherapeutic outcomes. Pharmacists must effectively communicate with other health care providers and patients and show empathy and confidence to achieve therapeutic success.
Particularly in the treatment of chronic diseases such as hypertension, proper drug selection and compliance are essential to ensuring expected outcomes. Pharmacists are in a position to affect either of these states through the interaction they have with their patients and other health care providers. Information that is correct and provided in an appropriate manner can best assist hypertensive patients in achieving their therapeutic goals.
Eric A. Wright, PharmD, BCPS: Assistant Professor, Department of Pharmacy Practice, Wilkes University; Clinical Pharmacy Specialist, Wilkes-Barre VAMC
James M. Culhane, PhD: Associate Professor, Department of Pharmaceutical Sciences, Wilkes University
For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Stahl, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: email@example.com.
(Based on the article starting on page 107.) Choose the 1 most correct answer.
1. Which of the following can contribute to poor hypertension control?
2. When describing a new medication to a patient, one should include information in lay language about the drug's pharmacologic basis for its:
3. Which of the following pharmacologic mechanisms is characteristic of the subacute phase of treatment with thiazide diuretics?
4. AL is a 50-year-old man who is getting the first prescription for his hypertension filled at your pharmacy today. You are aware that the medication reduces BP by first causing a short (1-2 week) natriuresis, then begins to reduce the resistance to blood flow through the blood vessels. Which of the following medication classes does this mechanism you are describing represent?
5. The defining physiologic change during the acute phase of thiazide diuretic treatment is:
6. The defining physiologic change during the subacute phase of thiazide diuretic treatment is:
7. The BP-lowering effects of chronic thiazide diuretic therapy are primarily due to:
8. Bradykinin can stimulate the release of 3 vasodilatory substances from the endothelial layer of blood vessels. The synthesis and release of which one of these is affected by aspirin?
9. Inhibition of ACE by an ACE inhibitor would lead to which of the following physiologic changes?
10. SW is a 65-year-old woman who has a history of heart failure, coronary artery disease status post myocardial infarction 3 years ago, and hypertension. Your prescription profile states that she is taking lisinopril 20 mg qd, metoprolol succinate 50 mg qd, and furosemide 40 mg qd. SW also usually buys a bottle of aspirin with her prescription, but she states that she is not sure that she is comfortable with taking aspirin because she has heard that it interacts with her heart medication. What advice can you give to SW?
11. Dihydropyridine Ca2+ channel blocker?Cinduced ankle edema is due to:
12. ACE inhibitors are thought to relieve dihydropyridine Ca2+ channel blocker?Cinduced ankle edema by:
13. While filling a prescription for nifedipine XL, your questioning of the patient reveals that he has had an increase in swelling in his ankles over the last month since his dosage increase. While discussing the patient's case with his primary care provider, you are asked for a recommendation to help improve his BP and reduce or eliminate the edema. The primary provider also would like to continue the patient on nifedipine. Which of the following would be the most appropriate recommendation?
14. Which of the following should not be discussed with the patient regarding calcium channel blocker therapy?
15. The withdrawal syndrome following the abrupt cessation of a beta-antagonist is characterized by:
16. The ultimate concern with a patient stopping beta-blockers abruptly is:
17. Which of the following is the most likely pharmacologic rationale for slowly tapering a patient off of a beta-antagonist in order to avoid the withdrawal syndrome?
18. Which of the following suggestions would lessen the likelihood of abrupt beta-blocker cessation?
19. All of the following are examples of methods used to improve patient adherence to a hypertensive regimen except:
20. Barriers to the optimal control of BP include all of the following except:
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