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We would like to congratulate the following Owen pharmacy technicians who recently became nationally certified:

*To obtain an application for the Pharmacy Technician Certification Exam, please contact the Pharmacy Technician Certification Board (PTCB) at (202) 429-7576, or visit their website at www.ptcb.org.

Since the PTCB began administering the national exam in 1995, over 86,400 pharmacy technicians have become certified through the examination and the transfer process. Congratulations to the CPhT's on this accomplishment!

• Pharmacy Technician Certification Review and Practice Exam Published by ASHP

New Drug & Therapy Highlight

http://www.docguide.com/news/content.nsf/NewsPrint/FDA6D2F36E99648085256A230046CC75

http://www.docguide.com/news/content.nsf/NewsPrint/80A162472686B83B85256A2400543EFD

TrizivirÒ (Lamivudine, Zidovudine, and Abacavir) – Glaxo Wellcome received FDA approval on Nov. 15, 2000 for its newest product TrizivirÒ . It is the first antiretroviral agent to combine three drugs (Lamivudine, Zidovudine, and Abacavir) into a single tablet. Because antiretroviral regimen involves as many as 20 capsules/tablets per day and many food/water restrictions, the introduction of TrizivirÒ offers two benefits – dose simplification and no food or water restrictions. It may be taken once in the morning and once in the evening without food or water. Abacavir may cause life-threatening hypersensitivity and is an agent in TrizivirÒ ; therefore, patients with previous hypersensitivity to abacavir should not be given Trizivir. It also should not be given to patients who weigh less than 40 kilograms (88 lbs) or have renal impairment. Source:

www.docguide.com/news/content.nsf/NewsPrint/A4E6E702BB6CEBD28525699800594CE4

http://www.docguide.com/news/content.nsf/NewsPrint/8A29F0E5EDE56B3185256990005E954F

http://www.docguide.com/news/content.nsf/NewsPrint/512A3CF6514AB95D85256A2A0057752D

http://www.docguide.com/news/content.nsf/NewsPrint/4FDC466EEC7103C285256A310045D366

http://www.pharmacyweek.com/features/article.asp?session_ID=CRFFDPRQ&article_id=144

ypertension, or high blood pressure, is associated with several complications, including increased atherosclerosis and coronary artery disease (clogged arteries), left ventricular hypertrophy (increased muscle of the left ventricle of the heart), stroke (hemorrhage or clogged arteries in the brain), and kidney function problems. In fact, hypertension is the most important risk factor for stroke. High blood pressure usually presents itself without any symptoms until complications develop.¹ Because of the lack of symptoms, hypertension is considered a ‘silent killer’. Around 50 million adults in the US are hypertensive and many of them do not know that they have high blood pressure. In 1996, the direct and indirect costs of treating complications of hypertension in the US was more than $259 billion.²

Many physicians in the 1940s and 1950s did not believe that increased blood pressure increased the risk of cardiovascular disease. Some physicians at that time even believed that an elevated blood pressure was needed to provide an adequate amount of blood to vital organs in elderly people. Treatment of hypertension was simple and usually consisted of strict low-sodium diets, mutilative surgeries, and several medications with toxic effects that prevented their use. Studies in the 1960s showed that lowering blood pressure prevented strokes and cases of heart failure. In the 1960s to 1980s, "data from several large clinical trials confirmed that even slight elevations of pressure above an arbitrary limit of 140/90 mm Hg increased cardiovascular risk, and that lowering pressures from these levels would decrease complications." ³

High blood pressure can be divided into primary (or essential) and secondary hypertension. Around 90% of patients with high blood pressure have primary hypertension. Primary hypertension is of unknown origin and is thought to have a hereditary component. Genetically predisposed individuals are more likely to have their blood pressure affected by environmental factors like dietary sodium, obesity, and stress. Secondary hypertension is caused by other disease states or factors, such as kidney disease, hyperthyroidism, excessive alcohol use, oral contraceptives, and corticosteroids.¹ The classification of blood pressure values for adults (18 years and older) taken from the sixth report of the Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI) are listed in Table 1. This classification system is currently used to help diagnose hypertension and guide treatment to reduce the risk of cardiovascular disease and resulting morbidity and mortality.

The classification of blood pressure in Table 1 is for individuals who are not taking antihypertensive medications and have no acute illness. Also, this classification is based on the average of two or more blood pressure measurements taken at two or more physician visits.²

Risk factors such as target organ damage, smoking, dyslipidemia, and diabetes need to be evaluated together with the level of blood pressure in order to determine a hypertensive patient’s overall risk for cardiovascular disease. These risk factors are listed in Table 2.

Primary hypertension does not have a cure, but can be treated by both non-drug and drug measures to delay complications.

Numerous lifestyle modifications are recommended for lowering blood pressure, as well as for preventing hypertension and reducing other cardiovascular risk factors. Compared to drug treatment, lifestyle modifications contribute very little cost and minimal risk to the patient. In many patients with Stage 1 hypertension, these modifications are enough to bring their blood pressures within normal range. Also, by decreasing blood pressure, lifestyle changes can reduce the dosage and number of antihypertensive medications used to treat a patient. Table 3 lists recommended lifestyle modifications to prevent and treat hypertension.^1,2,4

For Stage 1 hypertensive (140-159 mm Hg) patients with no other risk factors for cardiovascular disease, lifestyle modification should be tried for 6 months before considering drug therapy.^2,3

A large proportion of patients with high blood pressure are obese. Obesity, especially upper body or abdominal obesity (android or apple-shaped body-type), predisposes people to dyslipidemia, hypertension and diabetes. Maintaining normal weight or, if obese, losing weight is the most effective way to prevent the development of hypertension or to lower blood pressure in hypertensive individuals. Weight-loss may be enough to reduce the blood pressure of patients with Stage 1 hypertension to normotensive levels (< 140/90 mm Hg). Physicians can help their patients lose weight by prescribing diet and exercise regimens.^2,3,4

Regular aerobic exercise for 30-45 minutes, 3 to 4 times a week has been shown to reduce the risk of cardiovascular disease. Examples of aerobic exercise include walking and swimming. Exercise reduces weight by burning calories. Exercise may also lower blood pressure by increasing hormones that relax (dilate) blood vessels.^2,3,4

Excessive alcohol consumption is a risk factor for hypertension, resistance to antihypertensive therapy, and stroke.² Studies have shown that an alcohol intake of more than 2 ounces of ethanol (equivalent to 10 ounces of wine and 24 ounces of beer) may increase blood pressure.³

Many Americans eat more salt than they should. The average amount of table salt ingested by an American is 10 grams per day. Scientific studies have found sodium intake (in the form of table salt) to be directly linked to blood pressure. By avoiding added salt to foods and foods made high in salt, individuals can reduce their sodium intake and blood pressure (see Table 4). Reducing salt intake to 6 grams per day (equal to 2.4 grams of sodium per day) may decrease and even normalize blood pressure levels.^2,3,4

Decreasing sodium intake effects blood pressure differently in various individuals. Black, obese, and elderly patients are the most sensitive to a reduction in dietary sodium.^2,3

Studies have shown that a high dietary potassium intake may protect against hypertension, help control hypertension, and prevent strokes. Not eating enough potassium may increase blood pressure. For example, in areas like the rural South where individuals may eat low amounts of potassium and high amounts of sodium, there is a high incidence of hypertension and stroke. It is recommended that people eat a diet high in fruits and vegetables in order to get an adequate potassium intake. Some foods high in potassium are listed in Table 5.^2,3

The use of tobacco is a major risk factor for cardiovascular disease because nicotine raises blood pressure. Smoking cessation is one of the most important lifestyle changes for the prevention of cardiovascular and non-cardiovascular diseases in hypertensive patients. All hypertensive smokers should be counseled on smoking cessation.^2,3

Limited benefit has been found in using stress management techniques such as biofeedback and relaxation therapies (yoga, meditation) in the treatment of hypertension.

The pharmacological treatment of hypertension needs to be as simple as possible and have a low incidence of side effects. Patient compliance with antihypertensive drug therapy is increased with once daily dosing and lack of side effects. Since hypertension is a ‘silent killer’ it is very important to choose a drug regimen that minimizes side effects in order to improve compliance. It is best to start with one drug at a time, in the smallest doses possible, and gradually reduce blood pressure.^2,3

The benefit of drug treatment is highest in high-risk individuals, like the elderly, patients with very elevated blood pressures, and those patients with additional risk factors. In these patients, JNC-VI recommends more immediate drug therapy.²

The JNC-VI’s drugs of choice in treating hypertensive patients with no other risk factors are diuretics or beta-blockers because these medications have been associated with a reduction in morbidity and mortality of patients with hypertension.² JNC-VI also designated special situations for the use of the following antihypertensive medications: ACE inhibitors, angiotensin II receptor blockers, calcium-channel blockers, alpha₁-blockers, central alpha agonists, and direct vasodilators.³

Diuretics, one of the first-line agents used to treat hypertension, can be used alone or in combination with other blood pressure medications. There are several classes of diuretics: thiazide diuretics, loop diuretics, potassium-sparing diuretics, and carbonic anhydrase inhibitors. From these classes, the long-acting thiazide diuretics are the most effective in treating hypertension due to their mild and prolonged diuresis. In the US, the most frequently used thiazide diuretics are (by generic name) hydrochlorothiazide, chlorthalidone, metolazone and indapamide.^1,3

The loop diuretics like furosemide and torsemide are the preferred agents to treat hypertensive patients with chronic renal failure. The potassium-sparing diuretics do not produce much diuresis on their own, but are used in combination with other diuretics to prevent potassium excretion and resulting hypokalemia. This class includes spironolactone, triamterene, and amiloride.^1,3

Diuretics decrease blood pressure by decreasing plasma volume and thereby causing a decrease in cardiac output (amount of blood the heart pumps out). This is accomplished by preventing the reabsorption of sodium from the kidneys, leading to an increase in sodium and water loss from the body. ^1,3

Sexual dysfunction, which occurs in about 5-10% of patients, is the most bothersome side effect from diuretics. Hypokalemia (low serum potassium) is another important side effect from the thiazide and loop diuretics. They may also cause increased uric acid levels (leading to gout), calcium levels, and blood glucose levels.^1,3

Beta-blockers are the second agent of choice in treating hypertension. These agents block beta-receptors on the heart, causing a decrease in heart rate, cardiac output, and the heart’s oxygen demand.^1,3

Because beta-blockers also attach to beta-receptors in other organs besides the heart, they produce unwanted effects such as airway contraction and prevention of insulin secretion. These agents should be used with caution or not at all in asthmatics and diabetics.^1,3

In the US, there are many types of beta-blockers available. Some available agents by generic name are atenolol, metoprolol, and propranolol.

Beta-blockers are well tolerated. The most common side-effects are slow heart rate or bradycardia, fatigue, and sleep disturbances.¹

"Angiotensin-converting enzyme (ACE) inhibitors are among the most effective vasodilating antihypertensive drugs."³ JNC-VI suggests ACE inhibitors as first-line therapy in special patient populations. ACE inhibitors are the medication of choice in hypertensive patients with diabetes because they protect against kidney disease in these patients. ACE inhibitors reduce blood pressure by preventing the formation of the substance angiotensin II, which is a potent vasoconstrictor (constricts blood vessels).^1,2,3

Some of the available ACE inhibitors in the US are lisinopril, enalapril, captopril, ramipril and fosinopril. Dosage and frequency of administration varies among available agents.

One of the major advantages of ACE inhibitors is their low incidence of side effects. Cough is the most common side effect. ACE inhibitors may also increase potassium levels in the blood.

The angiotensin II receptor blockers (ARBs) are relatively new agents available for the treatment of blood pressure. Some studies have shown that these medications are as effective in lowering blood pressure as the ACE inhibitors, when used as monotherapy. ARBs reduce blood pressure by binding to and blocking the angiotensin II receptor.^1,3

ARBs that have been approved by the Food and Drug Administration (FDA) include losartan (Cozaar), valsartan (Diovan), irbesartan (Avapro), candesartan (Atacand), and eprosartan (Teveten).^1,3

ARBs are well tolerated with few side effects. Some side effects include headache and dizziness. The prescribing information for ARBs does not list "dry cough" as a side effect but postmarketing reports of cough have been reported.^1,3

The calcium-channel blockers are another class of agents used to treat high blood pressure. This class of antihypertensives is recommended in hypertensive patients with angina pectoris or Raynaud’s disease. They lower blood pressure by preventing the entry of calcium into the smooth muscle cells of blood vessels, causing dilation of the blood vessels. Some of these agents also prevent the entry of calcium into the heart muscle, preventing heart contraction.^1,3

The calcium-channel blockers approved for the treatment of hypertension include diltiazem, verapamil, nifedipine, amlodipine, felodipine, nicardipine, and isradipine. Diltiazem and verapamil affect both blood pressure and contraction of the heart.¹

Calcium-channel blockers have more adverse effects than the other antihypertensive agents mentioned so far. Side effects include dizziness, flushing, headaches, edema, constipation, and congestive heart failure.¹

Alpha₁-blockers are not used as often or alone in the treatment of hypertension. These agents work by blocking alpha₁ receptors found on veins and arterioles, preventing blood vessel constriction and the resulting increase in blood pressure. The most commonly used agents in the US include prazosin, terazosin, and doxazosin.¹

There is a "first-dose phenomenon" with the alpha₁ blockers; syncope or orthostatic hypotension (rapid decrease in blood pressure upon rising). To avoid possible dizziness or fainting, alpha₁ blockers are initiated at night. that way the blood pressure drops when the patient is sleeping. Alpha₁ blockers also cause impotence which is a reason for non-compliance in men.

Central alpha agonists act in the central nervous system on alpha₂ receptors to decrease sympathetic activity, leading to a reduction in blood pressure and heart rate. These agents are neither used frequently nor for a prolonged period of time. They include clonidine, methyldopa, guanabenz, and guanfacine. Central alpha agonists have multiple adverse effects, including dry mouth, drowsiness, fluid retention, and depression.¹

Alpha agonists must be gradually tapered down. A sudden cessation of an alpha agonist will lead to rebound hypertension which can lead to a hypertensive emergency.

The last class of antihypertensives used in the treatment of hypertension are the direct vasodilators. These agents have been available for many years and are used as a last resort in the treatment of high blood pressure. This class of antihypertensives includes hydralazine and minoxidil.³

Direct vasodilators dilate arterioles by relaxing smooth muscle, causing a decrease in blood pressure. The body senses a decrease in blood pressure and increases heart rate and sympathetic activity, which then leads to fluid retention. Because of these effects direct vasodilators are only used temporarily to reduce blood pressure. Direct vasodilators have numerous side effects that limit their usefulness as single agents in the treatment of high blood pressure:

• Tachycardia
• Fluid retention
• Flushing
• Headaches
• In the case of minoxidil, excessive hair growth on the face, arms, back, and chest ³

Because of these side effects, hydralazine and minoxidil are usually given with a beta-blocker and/or a diuretic.³

Hypertension, the ‘silent killer’, is a major risk factor for cardiovascular disease. This condition presents itself with no symptoms, and then leads to numerous complications. The public needs to be educated on the risk factors for hypertension and cardiovascular disease, as well as lifestyle changes that can minimize the risks. Adequate exercise and a healthy diet needs to be emphasized by health-care professionals. If high blood pressure is diagnosed early, the complications can be delayed with proper treatment using the available antihypertensive medications.

1. Arterial Hypertension, In: The Merck Manual. 17^th ed. Beers MH and Berkow R eds. New Jersey: Merck Research Laboratories; 1999: 1629-1648.
2. The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure and the National High Blood Pressure Education Program Coordinating Committee. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Archives of Internal Medicine. 1997; 157: 2413-2446.
3. Moser M. Clinical Management of Hypertension. 3^rd ed. Caddo, OK: Professional Communications Inc.; 1998. Accessed 2001 Apr 02. Available from http://cardiology.medscape.com/PCI/hypertension/public/hypertension-about.html.; internet.
4. Chalmers J et al. WHO-ISH Hypertension Guidelines Committtee. 1999 World Health Organization-International Society of Hypertension Guidelines for the Management of Hypertension. http://www.who.int/ncd/cvd/ht_guide.html. (accessed 2001 Apr 02).

After reading this article, the reader should be able to:

1. Define hypertension and its classifications.
2. Name the risk factors for cardiovascular disease.
3. Describe the non-drug treatments for hypertension.
4. Name the drug classes used in the treatment of hypertension.
5. Explain how the drug treatments for hypertension work.
6. Name the side effects of the major drug classes used in the treatment of hypertension.

1. Hypertension is the most important risk factor for stroke.

1. True
2. False

1. High blood pressure can be divided into

1. Major and Minor
2. Stages 1,2,and 3
3. Primary and Secondary
4. B and C only
5. All the above

1. Essential hypertension is defined as being of

1. Unknown origin
2. Known origin
3. Completely caused by genetics
4. Completely caused by environmental factors

1. Secondary hypertension can be caused by

1. Kidney disease
2. Hypothyroidism
3. Heart Disease
4. A and B only
5. All the above

1. JNC-VI optimal blood pressure is

1. <120 and >90
2. <120 and <80
3. <130 and <90
4. <130 and <80

2. JNC-VI classifies Stage 1 systolic hypertension as

1. 130-139
2. 140-159
3. 160-179
4. > 180

1. JNC-VI classifies Stage 2 diastolic hypertension as

1. 85-89
2. 90-99
3. 100-109
4. > 110

1. The risk factors for cardiovascular disease include

1. Smoking
2. Stroke
3. Being male
4. > 60 years old
5. All of the above

1. Compared to drug treatment, lifestyle modifications contribute high cost and low risk to the patient.

1. True
2. False

1. In most patients with Stage 1 hypertension, lifestyle modification is

1. Not enough to lower blood pressure
2. Enough to lower blood pressure to normal range, but always started with drug therapy
3. Never considered
4. The first treatment of choice

1. What type of obesity predisposes people to hypertension?

1. Pear-shaped
2. Apple-shaped
3. Both
4. None

1. Reducing sodium intake to 2.4 grams per day may decrease and even normalize blood pressure levels.

1. True
2. False

1. A diet high in potassium may

1. Cause high blood pressure
2. Control hypertension
3. Reduce sodium
4. Cause strokes

1. Foods high in potassium include

1. Bananas
2. Milk
3. Sunflower seeds
4. A and C
5. All of the above

1. Reducing stress is one of the most important ways to treat hypertension.

1. True
2. False

1. Patient compliance with antihypertensive drug therapy is

1. Increased with more drugs
2. Decreased with side effects
3. Increased with a simple drug regimen
4. A and B
5. B and C

1. Based on JNC-VI, the treatment of choice for treating hypertensive patients with no other cardiovascular risk factors is

1. Diuretics and calcium-channel blockers
2. ACE Inhibitors
3. Diuretics
4. Diuretics or Beta-blockers

2. The classes of diuretics include

1. Thiamide diuretics
2. Loop diuretics
3. Sodium-sparing diuretics
4. Carbonic hydrase inducers

1. Hydrochlorothiazide has a prolonged diuresis.

1. True
2. False

1. Which of the following are loop diuretics?

1. Furosemide
2. Hydrochlorothiazide
3. Amiloride
4. Metolazone

1. Side-effects of diuretics include

1. Hypokalemia
2. Hyperuricemia
3. Hypercalcemia
4. All of the above

1. Which of the following is FALSE regarding beta-blockers?

1. They are considered second-line agents in the treatment of hypertension
2. They can cause airway constriction
3. They increase heart rate and decrease cardiac output
4. They can cause hyperglycemia

1. ACE inhibitors

1. Cause vasoconstriction
2. Are considered first-line therapy in hypertensive diabetics
3. Protect against liver disease
4. Prevent the formation of angiotensin-III

1. Which of the following agents is an ACE inhibitor?

1. Terazosin
2. Amlodipine
3. Lisinopril
4. Verapamil

1. Angiotensin II receptor blockers are

1. Not well tolerated
2. As effective as ACE inhibitors
3. Prevent formation of angiotensin II
4. All the above

1. Calcium-channel blockers work by

1. Inhibiting calcium absorption
2. Inhibiting sodium and water reabsorption
3. Work in the central nervous system
4. Dilating blood vessels

1. Which of the following calcium-channel blockers affects heart contraction?

1. Nifedipine
2. Diltiazem
3. Felodipine
4. Amlodipine

1. Which of the following agents can cause severe syncope, especially upon administration of the first dose?

1. Clonidine
2. Doxazosin
3. Hydralazine
4. Amlodipine

1. Which of the following agents can cause rebound hypertension upon abrupt cessation of therapy?

1. Clonidine
2. Doxazosin
3. Hydralazine
4. Amlodipine

1. Direct vasodilators

1. Cause immediate decrease in blood pressure due to arteriolar vasodilation.
2. Can cause tachycardia and therefore should not be used as monotherapy.
3. Are used on a temporary basis only.
4. All the above