HYPERTENSION Julie A. Johnson, Pharm.D.

, BCPS, FCCP, FAHA HTN Prevalence: Its on the rise Hypertension is usually one of the earliest forms of the cardiovascular diseases, and is the 1st cardiovascular disease a patient acquires. Guidelines used: The 7th Report of the Joint National Committee on the Detection, Evaluation and Treatment of High Blood Pressure (JNC 7). Expected update (JNC 8) November 2011. Approximately 75 million Americans have HTN It is the most common medical condition among adults It is the most common reason why patients take chronic medications There are an additional 70 million patients with prehypertension Over half of the population are either hypertensive or prehypertensive 1 billion worldwide 1 in 3 of adults has HTN From 1990 2000 US population within this decade increased 13%, but Hypertension increased 30%. The rate of hypertension is exceeding our population growth. Increase is attributed largely to 2 factors: 1. Aging population 2. Obesity epidemic (more importantly) Differences in prevalence among ethnic groups Caucasians: 28.1% African Americans: 41.4% (Highest rate of HTN) Mexican-Americans: 30% Asian-Americans and Pacific Islanders: 26% American Indians: 32% Prevalence increases with age Ages 20 to 34 the rate of hypertension is relatively low (<10%) with a much higher rate in men than women at this age group With the increase of each decade of life the prevalence of hypertension also increases Approximately 10% increase per year after the 20 to 34 year mark Approximately 70% of individuals over the age of 70 have hypertension resulting in a very common disease with aging Up to age 55, prevalence is greater among men than women, after which the reverse is true. in life be Reasons being that men who have HTN earlier gin to die, AND women at the age of ~55 begin to experience menopause Among those 60 or older with HTN 60% of Caucasians 71% of African Americans 61% of Hispanic Americans

Trends in awareness of hypertension Are patients aware that they have high blood pressure, are they treated for their high blood pressure, and is their blood pressure under control? This is data over several decades. In the mid-70s the awareness rate of hypertension was only around 50%. This caused the federal government to become very aggressive in promoting a public awareness campaign to increase public knowledge about the risk of hypertension and its detection. Home blood pressure monitors did not exist in the mid-70s. In the most recent surveys hypertension awareness has increased to 78% with still leaves over 20% of patients who are unaware of their HTN. There has been dramatic improvements in the number of patients being treated for hypertension over the past few decades. From the mid-70s to the next decade and a half the number of patients treated for hypertension nearly doubled, and has now leveled off at around 70%. We now have a high percent of patients that are aware of their hypertension and are treated Control is defined as blood pressure < 140/90. The rate of control in the mid-70s was terrible at only 10%. This percentage has continued to rise, BUT now still < 50% of patients who have high blood pressure have their condition under control Statistics point out that a large number of patients who are unaware they have hypertension have been seen by their physician the previous year thus the major problem is lack of healthcare providers taking action in recognizing and addressing hypertension.

Pharmacists can make a difference in HTN! Prevention Obesity is major preventable cause of HTN educate your patients about lifestyle modifications and risks of obesity! Identification gap 22% of patients dont know they are hypertensive. Pharmacist can encourage patients to check their blood pressure. Ask patients about their blood pressure and if YOU can check for BP control Treatment gap 10% who know they have HTN are not treated - May be due to patients not experiencing symptoms with HTN, but later experiencing side effects from the treatment of HTN and deciding not to take their medications - Patients take medication for their HTN and find that it does not lower their blood pressure and therefore become noncompliant - Not being educated on the long-term risk of elevated blood pressure, and physicians are not sensitive enough to patients having side effects from there medications which could affect their adherence. In this situation we might need to look at an alternative Treatment intensity gap (therapeutic inertia) 47.5% have BP controlled - Only 68% of those being treated are controlled - Only 13% of office visits w/high BP result in a regimen change

Etiology of HTN Primary (essential) HTN In 90-95% of the cases, the cause of hypertension is unknown Secondary HTN In 5-10% there is an identifiable cause of the hypertension. In many cases, correction of the primary abnormality will correct the blood pressure. The most common causes of the secondary hypertension are related to renal disease (constituting about 4% of all patients with hypertension). Note drugs that cause HTN. Majority of secondary HTN - renal which includes - Renovascular disease - Chronic kidney disease Drug induced Other uncommon causes - Coarctation of the aorta, Primary Aldosteronism, Cushings syndrome or chronic steroid therapy, Pheochromocytoma, Sleep apnea, Thyroid or parathyroid disease Drug Induced HTN NSAIDS and COX-2 inhibitors lead to sodium and water retention which results in HTN Oral contraceptives have consistently shown to elevate blood pressure Adrenocorticoids also leads to sodium and water retention Sympathomimetics (e.g. decongestants, anorectics, cocaine, amphetamine) E.g. Pseudoephedrine should be avoided in patients with HTN Erythropoetin Cyclosporine/tacrolimus cause very predictable elevations of BP Licorice (included in chewing tobacco) Certain OTC herbal products (e.g. ephedra, Ma Huang, bitter orange) Proposed Pathophysiologic Mechanisms Of Primary (Essential) Hypertension

Cardiac output x Peripheral resistance = blood pressure Elevation in blood pressure occurs by increasing either of the 2 variables (cardiac output / peripheral resistance) Cardiac output is determined by preload and contractility

Excess sodium intake (salt sensitive hypertension) leads to an increase in fluid volume (preload) which results in increased blood pressure. Salt sensitive HTN is one phenotype of HTN Genetic alterations may cause patients to hold on to sodium more avidly than others Stress causes Sympathetic nervous system [norepinephrine beta-1 selective ( contractility) and alpha-1( vasoconstriction) receptor agonist] and increases Renin which activates the renin angiotensin aldosterone system (RAS) and results in angiotensin-2 which is one of the most potent vasoconstrictors in the body. The renin angiotensin system ALSO releases norepinephrine Angiotensin-2 results in vasoconstriction of the arterial wall, but also causes structural hypertrophy in the arterial vessels. This causes a stiffening of the arterial wall which results in higher pressure that the heart must pump against leading to an increase in BP. Cell membrane calcium alterations leads to vasoconstriction due to the increases of intracellular calcium. This may also lead to structural hypertrophy Obesity clearly causes a hyper-insulinemia which contributes to a structural hypertrophy. There may also be some stimulation of the RAS and sympathetic nervous system. Were to the major antihypertensive drug classes work in this scheme

Beta blockers work primarily by blocking beta-1 adrenergic receptor which reduces contractility and HR seen with sympathetic activation. Beta blockers also decrease the release of renin Thiazide diuretics work by affecting sodium renal retention, BUT long-term use of thiazide diuretics affect the cell membrane in the arterial vasculature, and not in the kidney. How do we know this? Loop diuretics are much more potent at affecting sodium retention in the kidney, but are less effective antihypertensives than thiazide diuretics. Loop diuretics are believed NOT to have the cell membrane affect. Thiazide diuretics cause diuresis early in therapy, but the volume returns to baseline over several weeks so the long-term lowering of blood pressure by thiazide diuretics is believed to be caused by this cell membrane mechanism ACEIs / ARBs are mediated on the renin-angiotensin side of the equation by either inhibiting the formation of angiotensin-2 (ACEI) or blocking angiotensin-2 and the receptor level. Secondarily they decrease the release of norepinephrine and have affects of lowering the sympathetic nervous system activation Calcium channel blockers (CCBs) work at the cell membrane level of lowering blood pressure From this it should be apparent that many of the drugs pointed to the same mechanism causing the hypertension.

VERY important concept to LEARN! Studies have generally shown a significant correlation between response to: ACEI/ARB and -blockers CCB and Thiazide diuretics Good combinations would include CCB + ACEI or Thiazide diuretic + ACEI This means that those who are responsive e.g. to ACEI/ARB are likely to also be responsive to -blocker and those responsive to Thiazide diuretics are also likely to be responsive to CCB. Inefficacy shares similar correlations. Thus, if a patient fails to achieve a good response to e.g. ACEI, it would be most logical to next try a diuretic or CCB, rather than a -blocker.

Definition and classification of HTN by JNC 7 Categorizing patients based on the higher level whether systolic or diastolic (e.g. 126/94 = stage 1 hypertension). This is based off the diastolic of 94 mmHg. Another example patient with BP of 166/96 = stage 2 hypertension Category Optimal Prehypertension Hypertension Stage 1 Stage 2 140 - 159 160 90 - 99 100 < 120 120 - 139 Systolic (mmHg) < 80 80 - 89 Diastolic (mmHg)

Documented on at least 2 occasions, and least 3 days apart Recommendations for pressure follow-up The recommendation to recheck BP in 1-2 years will probably be changed **Patient should be started on lifestyle modifications

Target Organ Damage/Clinical Cardiovascular Disease These are the 5 organs (heart, peripheral vasculature, kidney, brain, eyes) that can be damaged by high blood pressure. A person is considered to have target organ damage IF those occurrences in the right hand side of this chart have occurred. Cardiac Cerebrovascular Peripheral vascular Renal Retinopathy Left ventricular hypertrophy, angina, prior myocardial infarction, prior coronary revascularization, heart failure Transient ischemic attacks (TIA) or stroke Absence of 1 or more major pulses in the extremities, with or without intermittent claudication, aneurysm. Serum creatinine > 1.5 mg/dl (130 mol/L); proteinuria (1+ or greater); microalbuminuria Hemorrhages or exudates, with or without papilledema

Goals of Therapy Reduce / prevent target organ damage (and associated morbidity and mortality) associated with HBP. This is the primary goal of reducing high blood pressure BP reduction (to < 140/90 or 130/80 in some) is surrogate marker for achieving our primary goal Minimize / control other risk factors Minimize risks / adverse effects of drug therapy this would increase adherence Target blood pressures Uncomplicated HTN: < 140/90 mmHg Diabetes: < 130/80 mmHg this could change with newer guidelines (JNC8) Renal disease: < 130/80 mmHg Notes about BP targets in others For the purposes of this course we will focus only on JNC7 BP targets, which means < 140/90 mmHg except for those with diabetes and renal disease. Recent data have suggested there may be minimal benefits associated with the lower BP targets so these may change with the new JNC8 guidelines. As a health professional you will need to be aware as these recommendations change. For this course we will use the current JNC7. Diabetic patients may be at higher risk with lower blood pressure Benefits of antihypertensives may extend beyond their BP lowering effects, most evident to date w/ACEIs and ARBs Management of HTN

Lifestyle Modifications Sodium restriction Weight reduction (if overweight) Increased physical activity Smoking cessation May not necessarily lower blood pressure but is another risk factor on top of hypertension if continued DASH diet Good data on this diet lowering the pressure similar to monotherapy with a single drug. This is a diet high in fruits and vegetables, low-fat dairy products and low in saturated fats Lifestyle modifications to manage hypertension

Weight reduction maintain normal weight (BMI = 18.5-24.9) 5 to 20mmHg reduction / 10 kg weight loss Adopting DASH diet consume a rich diet in fruits, vegetables, and low-fat dairy products with a reduced content of saturated and total fat 8 to 14 mmHg reduction Dietary sodium restriction reduced dietary sodium intake to no more than 100 mEq/L (2.4 g sodium or 6 g sodium chloride) 2 to 8 mmHg reduction Physical activity engage in regular aerobic exercise such as brisk walking (at least 30 min/ day, most days of the week) 4 to 9 mmHg reduction Moderation of alcohol consumption limit consumption to no more than 2 drinks per day [1 ounce ethanol (e.g. 24 oz beer, 10 oz wine, or 3 oz 80 proof whiskey)] in most men and no more than 1 drink per day in women and lighter weight persons 2 to 4 mmHg reduction

Drug therapy of HTN First line drugs Thiazide diuretics Based on JNC7 guidelines are recommended as preferred initial therapy for all patients with uncomplicated hypertension. This recommendation is controversial to many. There are clear racial differences in response to thiazide diuretics. There are also concerns about adverse metabolic effects and increasing the risk of newly onset diabetes Beta-blockers The role as first-line therapy has recently become controversial. European guidelines have recently removed beta blockers from first-line therapy for uncomplicated HTN. For now JNC7 guidelines still recommend as first-line therapy, BUT this could changed in the JNC8 guidelines. 2 European trials LIFE and ASCOT showed atenolol inferior to comparator drug, BUT this may be due to the half-life of a atenolol not warranting once daily dosing. Metoprolol has now overtaken atenolol as the most commonly used beta blocker in the United States ACE inhibitors Newer to the first-line therapy group, but some data suggest the benefits may extend beyond their blood pressure lowering effects Calcium channel blockers These include both the dihydropyridine and the non-dihydropyridine classes Angiotensin II receptor blockers Smaller number of clinical trials, but still substantial evidence for their benefit as first-line therapy Other drug therapy of HTN Second line Drugs Alpha1-blockers (prazosin, doxazosin, etc.) Have in past been considered appropriate first line therapy but no longer due to poor results with doxazosin in ALLHAT trial, and lack of any clinical trial evidence that they improve outcomes. Aldosterone receptor antagonists Spironolactone and eplerenone. Spironolactone is rarely used as antihypertensive; eplerenone has favorable BP effects as add-on therapy in blacks requiring multi-drug therapy for BP control. Centrally acting agents e.g. clonidine, methyldopa, reserpine. Clonidine most commonly used; as a group are rarely used because of frequency of side effects Direct vasodilators Minoxidil and hydralazine. Rarely used because of side effects; most often used by hypertension specialists on refractory hypertension Renin inhibitors Aliskerin. Similar actions to other drugs affecting RAS system. Approved as first line therapy (but not first line in guidelines yet may be included as first-line therapy in JNC8). Typical use will be in combination, usually with a thiazide or CCB.

Interpatient variability in response to antihypertensive drugs Only 50% of patients will respond well to any single antihypertensive drug This chart is from the VA Cooperative study of antihypertensive drugs This chart shows the percentage of patients that achieved controlled blood pressure Selecting a drug randomly gives about a 1 in 2 chance of achieving control blood pressure Benefits of treatment of HTN Coronary heart disease (ischemic) CHD 15% Stroke 30-40% CHF approximately 50% Renal failure approximately 50% Cardiovascular mortality approximately 15% Total mortality approximately 10% Considerations in Drug Therapy Selection Concomitant diseases Compelling indications - Angina has a compelling indication for beta blockers, and non-dihydropyridine CCBs Concomitant drug benefit - Treating 2 diseases with a single drug Adverse effects of drug on concomitant disease or its therapy - Beta blockers worsen asthma Patient demographics Age, race, and gender Avoidance of adverse effects Treatment costs including lab test, and supplement therapies such as potassium Initial Dosing and Titration Lowest dosage used initially, and titrate up Remember to counsel patients that initial doses does not always control BP adequately If necessary, dosage increases made after several weeks of therapy Dose titrations every 1 to 2 weeks are reasonable Reduce BP slowly, and question patients on adverse effects especially during early therapy Use drugs with once or twice daily dosing. (AVOID tid dosing) If response to treatment is inadequate after 1-3 months assess possible explanations for lack of response to therapy. Reasons for poor response Non-adherence to therapy Drug-related causes Treatment cost Inadequate dose Inadequate patient education on the disease Inappropriate drug state and the risk of HTN Inappropriate drug combinations Adverse effects Effects of other drugs such as NSAIDs Inconvenient dosing

The Pharmacist: Improving BP control and therapy adherence The most effective therapy prescribed by the careful clinician will control HTN only if patients are motivated and adherent. Knowledge is power for patients. Educate patients on disease and risk factors of HTN Once daily dosing has greatest affect adherence Home monitoring of BP also has important positive affect on adherence Ask about BP and encourage patient to see physician when BP not controlled

Special populations, compelling indications, concomitant diseases

African Americans HTN is more common, more severe, and has earlier onset with the African-American patient Onset of action is approximately 10 years earlier More likely to have low plasma renin activity (PRA) and to have salt-sensitive HTN Diuretics - ideal first therapy ACE inhibitors, ARBs and beta-blockers are less effective as monotherapy, BUT in combination with a diuretic, ACEIs and -blockers are equally efficacious in blacks and whites. Calcium channel blockers also seemed to be very effective Eplerenone has shown very good efficacy in black hypertensives. Represents good potential add-on therapy unlikely to have a role as first line therapy. Many African-Americans will require multiple drugs to control HTN, and are most likely to have resistant hypertension which mean blood pressure is not controlled on 3 or more hypertensive medications Caucasians More likely to have high renin, high cardiac output HTN Less likely to have salt-sensitive HTN Beta-blockers, ACE inhibitors or ARBs are good initial therapy. Thiazide diuretics and calcium channel blockers tend to be less effective Although, all first line drugs work reasonably well

Data from a study done at the University of Florida Average response to atenolol monotherapy AA had almost no blood pressure lowering effect Whites had a significant response to monotherapy with atenolol (~10mmHg ) Monotherapy with HCTZ was very significant in AA. Whites had lesser response When HCTZ was added to atenolol monotherapy blacks had a synergistic effect (~12mmHg ). Whites showed a less effect. When atenolol was used as an add-on drug to HCTZ the effect in blacks was significantly decreased. When HCTZ was given 1st there was significant more blood pressure lowering in both blacks and whites The study tended to show that HCTZ may be priming the patients RAS system The combination of the 2 drugs eliminated the racial differences

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Elderly Isolated systolic HTN elevated systolic pressure with a normal diastolic pressure. For many years this was not treated. It was only recognized recently as being a high risk of morbidity and mortality from CHD, stroke and CVD. ISH is due to the stiffening of the vascular wall with aging Treatment benefits in elderly are now well documented Diuretics preferred initial therapy in the elderly The difference spoken of between blacks and whites tend to be in ages < 60 years of age Hypertension in the elderly tend to be more about vascular stiffness in which both calcium channel blockers (specifically diltiazem) and diuretics are very effective at treating Orthostatic hypotension AVOID drugs that cause orthostatic hypotension (alpha1-blockers, labetalol, carvedilol and many older drugs) should be avoided or used cautiously as elderly are more sensitive to the effects and have diminished baroreceptor response. Additionally, the consequences of a fall from hypotension are more likely to be serious in the elderly than in younger patients. Women Pregnancy Chronic hypertension HTN that existed before pregnancy OR diagnosed before the 20th week of gestation Preeclampsia hypertension that occurs after 20 weeks of gestation and goes away after pregnancy The risk of hypertension is substantial for both the mother and baby. This HTN must be treated during pregnancy. Treatment includes magnesium (seizure prevention), labetalol and hydralazine ARBs and ACEIs contraindicated in pregnancy due fetal malformations Package insert says after first trimester Recent data suggest problems also with 1st trimester exposure Many obstetricians are comfortable with using methyldopa, labetalol, hydralazine, CCBs to manage chronic hypertension throughout pregnancy Diuretics should NOT be used because of concern over amniotic fluid volume Oral contraceptives are drugs that elevate blood pressure and consideration needs to be given to women who are hypertensive or pre-hypertensive Estrogen replacement therapy tends to have less effect than contraceptives, but consideration should be given to risk versus benefit of ERT in hypertensive women due to the cardiovascular nature Men Benign prostatic hypertrophy Addition of an alpha 1-blocker for additional BP control in men with HTN and BPH seems reasonable, but should generally not be used as primary monotherapy.

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Case presentations
African American female, overweight, recently diagnosed HTN KR is a 36 year old BF who is 52 and 182 lbs. She has been recently diagnosed with hypertension, with average blood pressure over 3 visits of 146/96. She has no other significant medical history. Her family history is significant for hypertension in both parents and two siblings and her father had CABG at age 51. Which of the following is most appropriate for management of KRs hypertension? a. Initiate lifestyle modifications + start HTCZ - Reduce her caloric intake and increase exercise - Reduce salt intake African American female are more salt sensitive - Educate and implement the DASH diet b. Initiate lifestyle modifications for up to 6 months - NO, patients with documented hypertension are not treated with lifestyle modifications only c. Initiate lifestyle modifications + start amlodipine - JNC7 guidelines recommend HTCZ as preferred first-line therapy in African-Americans d. Initiate lifestyle modifications + start metoprolol - Tends to be less effective with African-Americans as monotherapy White male, recently diagnosed HTN, non-responder to HCTZ, runner PL is a 46 year old white male who was recently diagnosed with HTN; average blood pressure now is 138/98. He has been treated for 3 months with HCTZ 25 mg qd, with minimal BP response. He has no significant past medical history and no significant family or social history. Relevant information is that PL is a runner, averaging 20 miles/week. Which of the following would you recommend for PL? a. Change HCTZ to chlorthalidone - NO, 2 drugs of the same drug class b. D/c HCTZ and start metoprolol - This would be moving to a drug with a different pathophysiologic mechanism - NO, this would decrease his exercise tolerance by decreasing his heart rate c. Increase HCTZ to 50 mg qd - NO, maximal blood pressure lowering dose is 25 mg HCTZ daily - Increasing to 50 mg would probably only increase side effects (hypokalemia) d. D/c HCTZ and start amlodipine - A non-responder to HCTZ would also make him a non-responder to a CCB e. D/c HCTZ and start ramipril Elderly, white male FC is a 72 year old white male whose blood pressure is 152/82. Which of the following is most appropriate? a. Institute lifestyle modifications - Always institute lifestyle modifications + drug therapy b. Start HCTZ - Thiazide diuretics are highly effective in the elderly - Studies show good reductions in adverse cardiac outcomes c. Start doxazosin - Not a first-line drug - Alpha blocking effects would caused orthostatic hypotension d. Start labetalol 12

- Has alpha blocking activity along with beta blocking effects - Need to avoid in elderly because of orthostatic hypotension e. No treatment is warranted - Patient has stage 1 hypertension (SBP 152mmHg) and needs treatment Elderly, white male, stage 2 hypertension FC is a 72 year old white male whose blood pressure is 166/92. His PMH is otherwise nonsignificant. Which of the following is most appropriate? Guidelines in this patient calls for a 2 drug therapy. a. Start HCTZ b. Start HCTZ + amlodipine - This is NOT a good combination because they have the same pathophysiology c. Start HCTZ + carvedilol - Carvedilol is nonselective with alpha blocking effects - The alpha blocking effects leads to orthostatic hypotension d. Start chlorthalidone + atenolol - Atenolol is beta-1 selective agent Young white female, planning to become pregnant GG is a 38 year old white female with a 4 year history of hypertension. She has been well controlled on lisinopril 20 mg qd. She is planning to become pregnant. Which of the following would be the most appropriate management of GG? a. Continue current therapy during her pregnancy - NO, ACEI are contraindicated in pregnancy especially after the 1st trimester b. Discontinue lisinopril and start metoprolol - Beta blockers are not a concern in pregnancy - Also works with the same pathophysiology as lisinopril, AND she was controlled with lisinopril c. Discontinue lisinopril and allow GG to be hypertensive during her pregnancy as the risks of HTN are over a lifetime, and 9 months of uncontrolled HTN will not pose any important risks to GG - NO, elevated blood pressure will present substantial risk to both mother and child d. Discontinue lisinopril and start HCTZ - Thiazide diuretic works at a different pathophysiology and she might not respond - There are theoretical concerns with thiazide diuretics that they would have an effect on the amniotic fluid volume. They tend to be avoided during pregnancy Black male, with benign prostatic hyperplasia HJ is a 58 year old black male with hypertension, currently treated with HCTZ 25 mg qd. His blood pressure has decreased on this medication, but diastolic blood pressure remains consistently >95 mm Hg. HJs medical history is nonsignificant, except that he complains of urinary frequency, especially at nighttime, and hesitation and dribbling during urination. Which of the following would be the most appropriate addition to HJs current antihypertensive regimen? a. Tamsulosin - NO, this drug is more selective, and has less effect blood pressure b. Terazosin - Provides additional therapy needed to control patients blood pressure - Has both blood pressure lowering properties AND effective for BPH symptoms c. Felodipine - Calcium channel blocker + thiazide diuretic is not a combination to consider d. Benazepril - ACEI + thiazide diuretic is a great combination, but does not address the BPH symptoms 13

Treatment of patients with hypertension and concomitant diseases

1. 2. Principles driving treatment of patients with CO-existent CV disease If possible, treat HTN and CO-existent CV disease with the same drug to reduce polypharmacy Insure that antihypertensive therapy is not adversely affecting the concomitant CV disease Elderly, black male, with concomitant angina pectoris BL is a 64 year old black male with a 25 year history of HTN. He has now been referred to cardiology clinic for evaluation of chest pain with exertion. Findings on exercise treadmill test are consistent with ischemic heart disease and a diagnosis of angina pectoris. BLs current medications are HCTZ 25 mg qd and quinapril 20 mg qd. This regimen provides good blood pressure control. Which of the following would you recommend for management of BL? a. Add ISDN 40 mg at 7a.m. and 3 p.m. to current regimen - ISDN are not first-line treatment for angina, and does not have chronic BP lowering properties b. Add metoprolol 50 mg bid - Possible, but do we need 3 antihypertensive medications for this patient c. Substitute metoprolol 50 mg bid for quinapril - Possible, but ACEI have good data showing prevention of MI d. Substitute diltiazem SR 180 mg qd for HCTZ - If we elect to swap out drugs we need to stay within the same pathophysiology - This would be a good choice, because of the same pathophysiology and treatment is with only 2 drugs

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White male, post MI RT is a 56 year old white male who was admitted to the CCU two days ago, and was diagnosed with an anterior STEMI. On hospital day two, he had an episode of SOB, with bilateral rales on auscultation, which responded well to IV furosemide. RT has had HTN for the past 9 years, treated with diltiazem SR 180 mg qd. Which of the following is the most appropriate antihypertensive regimen for RT? a. Continue diltiazem - There is NO role for diltiazem in a post MI patient b. Discontinue diltiazem, start pindolol - Beta blockers that are indicated in post MI patients, but must have NO intrinsic sympathomimetic activity (ISA). This would exclude pindolol c. Discontinue diltiazem, start metoprolol - Guidelines call for an ACEI when evidence of heart failure d. Discontinue diltiazem, start metoprolol and enalapril - Guideline post MI therapy includes a beta blocker and an ACEI - Hopefully, this will also control his blood pressure e. Discontinue diltiazem, start amlodipine and lisinopril - Amlodipine has no role in a post-MI patient and this regimen lacks a beta blocker White female, concomitant heart failure HH is a 72 year old white female who presents to clinic with symptoms of SOB, fatigue, and dyspnea on exertion DOE. On PE she has a 2+ pedal edema, +HJR and +JVD. Her EF is 28% by echo. She has longstanding HTN which has only been recently treated with amlodipine 10 mg qd. Which of the following is the most appropriate pharmacotherapy regimen for HH? a. Add HCTZ 25 mg qd - Not potent enough of a diuretic for this patients fluid overload - This regimen is missing many of the heart failure drugs b. Discontinue amlodipine; add furosemide - Regimen does not include beta blocker or ACEI which are needed for HF c. Discontinue amlodipine; add furosemide and enalapril - Regimen does not include beta blocker d. Discontinue amlodipine; add furosemide, enalapril and carvedilol (titrated slowly) - Again, amlodipine has no role in the treatment of patients with heart failure - Best choice, because it adds the therapies needed in heart failure - Do no harm in adding drugs that could worsen heart failure (e.g. CCB have native inotropic effects)

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Hispanic male, with concomitant atrial fibrillation and HTN DS is a 67 year old Hispanic male with longstanding hypertension, currently controlled with nifedipine and HCTZ. He now presents with atrial fibrillation, which based on his history of present illness has probably been present for at least 3-4 weeks. DSs ventricular response rate is 160 bpm and he is going to be anticoagulated then undergo cardioversion in about 4 weeks. Currently, the therapeutic goal is to control DSs rapid ventricular rate. Which of the following would you recommend? a. Add digoxin to current regimen - Digoxin has NO antihypertensive effects b. Substitute diltiazem for nifedipine - Here we can control the ventricular rate AND blood pressure with a single drug - Diltiazem would slow conduction through the AV node - Nifedipine does not slow conduction through the AV node, and diltiazem would offer the same blood pressure control as nifedipine c. Add atenolol to current regimen - Possible, but this would by using 2 drugs when 2 drugs may not be needed d. Substitute metoprolol for nifedipine - NO, because we would not have confidence in a patient who responded to nifedipine would respond to metoprolol because of the difference in pathophysiology Elderly white female, bradycardia, heart block, or sick sinus syndrome PJ is an 81 year old white female who is brought to the ER by ambulance for a syncopal episode. Paramedics noted a heart rate of 35 bpm and she was admitted to the CCU. PMH significant for HTN treated with HCTZ. After placement of a temporary pacemaker, it is noted that the patients HTN is poorly controlled. Which of the following would be the most appropriate? a. Doxazosin - NO, could cause orthostatic hypotension, and not a drug of 1st choice b. Atenolol - NO, this drug would slow SA node firing and is contraindicated c. Diltiazem - NO, this drug would slow SA node firing and is contraindicated d. Lisinopril - Good choice, good combination with HCTZ, and no detrimental effects on heart rate e. Verapamil - NO, this drug would slow SA node firing and is contraindicated

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Black female with dyslipidemia CV is a 47 year old black female with a recent diagnosis of HTN. A recent lipid profile also revealed the following: total cholesterol - 250 mg/dl; LDL-C-166 mg/dl; HDL-C-62 mg/dl; TG -115 mg/dl. CV has no other significant PMH. Which of the following antihypertensives would you choose for initial therapy for CV? a. Diltiazem - CCB are neutral in effects on lipid profile - More effective as monotherapy in the African-American population b. HCTZ - NO, adverse effects on lipid profile c. Metoprolol - NO, beta blockers can increase triglycerides and lower HDL d. Lisinopril - Not as effective in African-American females as monotherapy Black female, dyslipidemia, and post MI FG is a 56 year old black female with an STEMI 6 weeks ago. She had an inferior MI and has not had any medical problems since her discharge from the hospital for the STEMI. She presents to clinic for a post MI checkup. This a.m. she had a fasting lipid profile run, which is as follows: 250mg/dl; LDL-C=166 mg/dl; HDL-C 62 mg/dl; TG-115 mg/dl. She has a 10 year history of HTN which is now being treated, but inadequately controlled with metoprolol 100 mg bid. Before her MI, her BP had been well controlled with diltiazem. Which of the following would you recommend for management of FGs HTN? a. D/c metoprolol; start diltiazem - NO, beta blockers are first-line therapy in post MI patients b. Add diltiazem - NO, there is no role for CCB in the post MI patient - Never use a non-dihydropyridine CCB and beta blocker together c. Add enalapril - Best choice, beta blockers and ACEI are first-line therapy for post MI d. Add HCTZ - Might lower blood pressure, but no benefits post MI and could adversely affect lipid profile e. D/c metoprolol; start acebutolol and fosinopril - NO, acebutolol has ISA and has no benefits related to post MI therapy - We will not discontinue metoprolol because of the benefits in a post MI patient outweighs the risk of dyslipidemia

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White male with PVD BL is a 59 year old white male with significant peripheral vascular disease and intermittent claudication. Which of the following would be most appropriate antihypertensive therapy for a patient such as BL? a. HCTZ - Thiazide diuretics offer no potential risk or benefits b. Nifedipine - A potent arterial peripheral vasodilator which might help the symptoms of PVD c. Atenolol - Theoretical recommendations are to avoid beta blockers in patients with PVD especially nonselective beta blockers where you have beta-2 blockade d. Ramipril (1st choice) - Arterial vasodilation effect may be beneficial in a patient with PVD - Additionally, we know that ACEI tend to be very beneficial CV protective effects

Treatment of HTN w/coexistent non-CV diseases

1. 2. Try to insure that antihypertensive does not negatively impact other disease If specific antihypertensive beneficial in disease, use it first SD is a 58 year old black male with chronic renal insufficiency (estimated CrCl=30 ml/min) and a 25 year history of HTN. Describe the pros and cons of use of each of the following antihypertensive agents in SD. a. HCTZ - Lose efficacy with decreasing renal function b. Furosemide - Maybe an effective diuretic but have little effect on blood pressure c. HCTZ/triamterene combo - Worst choice then HCTZ alone, because as renal function declines so also does the ability to excrete potassium d. Captopril (ACEI/ARB) - If not titrated appropriately ACEI can cause worsening of renal function, BUT there is an abundance of evidence showing that ACEI slow the progression of renal disease. e. Metoprolol - Not considered drug of 1st choice, and not as effective as ACEI in real failure KL is a 54 year old MAM with Type-2 DM and HTN. Which of the following is the most appropriate antihypertensive for KL? a. Atenolol Beta blockers impaired glucose control, mask symptoms of hypoglycemia, and slow recovery from a hypoglycemic episode b. Diltiazem has no beneficial or detrimental effects in patients with diabetes c. Doxazosin has no beneficial or detrimental effects in patients with diabetes d. Quinapril (ACEI/ARB) ACEIs slow the progression of diabetic nephropathy. May need to add a CCB to get patient controlled at < 130/80 e. HCTZ impair glucose tolerance, and has adverse effects on lipid profile White female with metabolic syndrome JL is a 48 yo white female, who was recently diagnosed with HTN and her average BP is 148/102 mmHg. Her lipid profile is significant for Tg = 212 mg/dl and a waist circumference of 41 inches. Which of the following would be the most appropriate initial pharmacotherapy for her HTN? a. Diltiazem - Patient has stage 2 hypertension and needs combination therapy 18

b. Chlorthalidone + metoprolol - Diuretic + beta blocker would not be a good choice c. HCTZ + lisinopril - Not a good choice because of the HCTZ d. Amlodipine + irbesartan - Best choice because amlodipine is neutral for diabetic risk, and ARBs are potentially protective in diabetes risk the same way ACEI are e. Atenolol + amlodipine - Atenolol provide some risk of newly onset diabetes patients PM is a 41 year old white female with a history of asthma for which she takes chronic inhaled corticosteroids and prn inhaled beta-agonists. She was recently diagnosed with HTN. Which of the following would be the most appropriate initial therapy for the treatment of her HTN? There are not any antihypertensive medications that are beneficial for asthma Avoid beta blockers in patients with asthma a. Atenolol - Beta blockers can worsen asthma, because patients rely on beta-2 stimulation for bronchodilation b. Diltiazem - Not as effective in Caucasians as monotherapy c. HCTZ - Not as effective in Caucasians as monotherapy d. Enalapril - There is a cough associated with ACEIs, and a cough can increase asthma exacerbation e. Irbesartan - Best choice for this patient

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