Module 4 Section 1 (Hypertension)

Question 1

What is hypertension?

Answer 1

Hypertension, or chronically high blood pressure (BP), is the most prevalent cardiovascular disease in North America, occurring in approximately 30% of the adult population. It is estimated that by age 80, 60% to 80% of men and women will have hypertension.

Question 2

Consistently elevated blood pressure damages blood vessels in 3 important organs - the kidneys, heart, and brain How does it do that?

Answer 2

Kidneys: damage to the blood vessels that supply the kidneys can lead to an increased likelihood of kidney failure.

Heart: damage to the blood vessels that supply the heart can lead to heart failure, angina, or stroke.

Brain: damage to the blood vessels that supply the brain may lead to dementia.

Question 3

How is HTN controlled?

Answer 3

Hypertension is controlled through the use of antihypertensive drugs.

The different classes of antihypertensive drugs have diverse mechanisms of action, however, they all have one goal: to decrease blood pressure.

Control of blood pressure by use of antihypertensive drugs has been shown to reduce damage to blood vessels, and thus, reduce mortality and hospitalization rates for vascular disease.

Question 4

What is blood pressure (BP)?

Answer 4

Blood pressure is defined as the force the circulating blood exerts on the arterial walls, and it must be kept within relatively narrow limits.

The body has several mechanisms to achieve control of blood pressure. In some individuals, however, the pressure in blood vessels rises above normal, resulting in hypertension.

Question 5

What is normal BP?

Answer 5

The definition of normal blood pressure depends on age, and the normal value increases with age; in a young adult the normal blood pressure value is 120/80.

• The top figure (120) is the pressure in millimetres of mercury during systole (i.e. when the heart is contracting)
• The lower figure (80) is the pressure in millimetres of mercury during diastole (i.e. between contractions of the heart).

Question 6

What is arterial BP?

Answer 6

Arterial blood pressure is the product of the amount of blood pumped by the heart (i.e. cardiac output, or CO) and the resistance in the peripheral arterioles (peripheral vascular resistance, or PVR).

Question 7

What is cardiac output?

Answer 7

It’s the volume of blood that is pumped by each ventricle per unit time. This value is the same for both the left and right side of the heart.

Question 8

What is heart rate?

Answer 8

The number of heartbeats per unit time. Normal resting heart rate for adults is between 60-100 beats per minute.

Question 9

What is stroke volume?

Answer 9

The amount of blood pumped from a ventricle per unit time. At rest, stroke volume is approximately 70 mL/beat for an adult.

Question 10

Cardiac output is a function of the heart rate and stroke volume of the heart (amount of blood pumped per unit time). What is the formula associated with this?

Answer 10

CO = HR x SV

Question 11

How is arterial blood pressure measured?

Answer 11

Blood pressure (BP) = Cardiac output (CO) x Total peripheral resistance (TPR)

Thus, if the amount of blood pumped per unit time increases, then blood pressure will increase. Likewise, if the resistance of the peripheral arterioles increases, then blood pressure will also increase.

Question 12

What are the 4 factors that influence/regulate BP?

Answer 12

1) Arteriole resistance
- Depends on the degree of constriction/dilation of arterioles
- This is dependent on the activity of the SNS (activation of alpha receptors in the arterioles)
- Activation of SNS = release of NE which binds to the alpha receptors and causes constriction of arterioles -> increased BP
- Decreasing SNS = decrease amount of constriction of arterioles -> decreasing BP

2) Capacitance venules
- Dilation of the venules = less blood returning to the heart, decreasing CO and hence, BP

3) Heart
- The SNS controls HR (activation of B-1 receptors)
- An increase in SNS activity = increase in HR and BP, vice versa

4) Blood volume
- Mainly controlled by the kidneys
- Increasing volume in blood vessels = increase BP, vice versa
- Kidney also controls BP through the renin angiotensin system

Question 13

True or false: hypertension leads to an increase in vascular disease, heart attack, stroke, and renal disease

Answer 13

True

Question 14

When is someone diagnosed with hypertension?

Answer 14

An individual is generally diagnosed with hypertension when their blood pressure is chronically elevated above 140/90 mmHg. However, the diagnosis of hypertension is influenced by age and co-existing disease.

Question 15

What are the usual BP threshold values for initiation of pharmacological treatment?

Answer 15

Diabetes

• SBP = 130
• DBP = 80

High risk (TOD or CV risk factors)

• SBP = 140
• DBP = 90

Low risk (no TOD or CV risk factors)

• SBP = 160
• DBP = 100

Very elderly

• SBP = 160
• DBP = N/A

Question 16

What are the 2 types of HTN?

Answer 16

Primary (essential hypertension): this is the most common type of hypertension, with approximately 90% of hypertensive patients falling into this category. It has no identifiable cause.

Secondary hypertension: this is hypertension caused by an underlying disease, such asrenal disorders (e.g. renal artery stenosis, which is the narrowing of the arteries of the kidney) or endocrine disorders (e.g. pheochromocytoma, which is a tumour in the adrenal medulla, causing increased release of epinephrine and norepinephrine).

Question 17

How can hypertension be controlled?

Answer 17

Behavioural changes (not everyone wants, or is abe to)

• reduced weight
• regular exercise
• low salt diet
• reduced alcohol consumption
• stop smoking
• stress management

Question 18

What are the 4 categories of drugs used in the treatment of hypertension?

Answer 18

1) Drugs that alter sodium and water balance
2) Drugs that decrease sympathetic nervous system activity
3) Vasodilators (i.e. calcium channel blockers)
4) Drugs modifying the renin-angiotensin system

Question 19

How do drugs that alter sodium and water balance work?

Answer 19

Drugs in this category affect the fluid volume of the blood by influencing sodium and water retention in the kidney.

Question 20

Discuss the functional anatomy of the kidney.

Answer 20

Nephron:

• Each kidney is made up of about a million nephrons, which are the basic functional units of the kidney that filter the blood.
• Each nephron consists of a renal corpuscle, and a renal tubule.

Renal corpuscle:

• The renal corpuscle performs the first step in the production of urine by filtering the blood.
• The renal corpuscle is made up of the glomerulus and the Bowman’s capsule.

Glomerulus:
- It’s a cluster of capillaries

Bowman’s capsule:

• It surrounds the glomerulus and collects the fluid from the blood.
• The fluid in the Bowman’s capsule then travels into therenal tubule, where useful materials and some water are reabsorbed back into the blood, while the waste products are left behind in the filtrate.

Renal tubule:
- The renal tubule itself is divided into three sections: the proximal tubule (where 65% of reabsorption takes place), the loop of Henle (where about 25% of reabsorption takes place), and the distal tubule (where about 7% of reabsorption takes place).

Collecting ducts:
The collecting duct contributes about 3% of reabsorption, and is the last stage of urine production.
- From the collecting duct, the urine travels into the ureter which transfers the urine into the bladder.

Question 21

What are diuretics and how do they work?

Answer 21

Drugs commonly used to alter the sodium/water balance in the body are diuretics.

Diuretics function to increase urine volume, thereby decreasing blood volume, and are key drugs in the therapy of hypertension.

They are efficacious when used alone, and enhance the efficacy of most other antihypertensives when given concurrently.

Question 22

True or false: diuretics are efficacious when used alone, and enhance the efficacy of most other antihypertensives when given concurrently.

Answer 22

In recent years, it has been found that smaller doses of diuretics than those used previously are effective and result in a corresponding decrease in the incidence of adverse effects.

Question 23

What else are diuretics used for?

Answer 23

They reduce the incidence of stroke and other problems associated with the cardiovascular system.

Diuretics are also effective in the treatment of other conditions, such as edema and heart failure.

Question 24

What are the major classes of diuretics?

Answer 24

• Loop diuretics
• Thiazide diuretics
• Potassium sparing diuretics

Question 25

How do loop diuretics work? What is the clinical use? What are the adverse effects?

Answer 25

Loop diuretics act within the thick ascending limb of the loop of Henle, where approximately 25% of sodium reabsorption takes place.
- They function to decrease the reabsorption of NaCl, and hence the water stays in the urine rather than be reabsorbed into the blood.

Clinical Use:
- Loop diuretics are the most effective diuretic agents currently available, partly because of the large reabsorptive capacity of the thick ascending loop of Henle.

Adverse Effects:
- In rare cases, ototoxicity can occur (hearing loss) with the use of loop diuretics, however, this is usually reversible.

Question 26

How do thiazide diuretics work? What is the clinical use? What are the adverse effects?

Answer 26

Thiazide diuretics act on the distal convoluted tubule, where about 7% of sodium reabsorption occurs.
- They function to decrease NaCl reabsorption in the distal convoluted tubule, thereby increasing the volume of water in the urine.

Clinical Use:
- An advantage of the thiazide diuretics is that they provide gentle diuresis (since a small percentage of reabsorption occurs at the distal convoluted tubule), and as such are safe to use in the elderly.

Adverse Effects:

• Hypokalemia (common)
• Hyperglycemia
• Hyperlipidemia

Question 27

How do potassium sparing diuretics work?

Answer 27

Potassium sparing diuretics act in areas of the kidney where sodium is exchanged with potassium. They function by increasing the excretion of sodium and water and decreasing the excretion of potassium.

This is opposite to many of the other diuretics, including thiazides, which increase the excretion of sodium and potassium.

Question 28

What are the 2 groups of potassium sparing diuretics?

Answer 28

Aldosterone antagonists: Aldosterone is a steroid hormone that is activated by the renin-angiotensin system and causes increased reabsorption of sodium and water, thereby increasing blood pressure.

• The aldosterone antagonists competitively block aldosterone at receptor sites in the distal convoluted tubule and collecting ducts, leading to increased sodium and water excretion.
• Potential adverse effects include hyperkalemia, and androgen or estrogen-like effects.

Sodium channel blockers: these drugs cause a decrease in sodium reabsorption, increasing the volume of water in the urine. Sodium channel blockers are considered weak diuretics.

Question 29

Using the information provided, select which diuretic would be the most applicable to prescribe to the patient.

Patient information:

• Age: 83
• Gender: Male
• Condition: Hypertension
• Urine Profile: All values are within the normal range

Answer options:

a) Loop Diuretic
b) Aldosterone Antagonist
c) Thiazide Diuretic
d) Sodium channel block

Answer 29

c) Thiazide Diuretic

Prescribing a Thiazide diuretic to this patient would be an effective treatment plan for the patient’s hypertension. Given the unremarkable urine profile, potassium-sparing diuretics such as aldosterone antagonists or sodium channel blockers are not indicated. Also, given the age of the patient, a thiazide diuretic would provide gentle diuresis, making this a good choice for first-line therapy.

Question 30

What drugs are used to decrease the SNS activity?

Answer 30

Three different classes of drugs can be used to decrease the activity of the sympathetic nervous system: β1 blockers, Alpha blockers, and Centrally-acting drugs.

Question 31

How do β1 blockers work? What is the clinical use? What are the adverse effects?

Answer 31

β1 blockers, such as metoprolol, decrease the activity of the sympathetic nervous system by producing a selective blockade of β1-adrenergic receptors in the heart and other organs.
- The major portion of the antihypertensive action of β1 receptor blockade is through reduction of cardiac output.

Clinical Use:

• These drugs are widely used, as clinical trials show a reduction in stroke and other serious cardiovascular problems with β1 blockers.
• However, β1 blockers are less effective than diuretics in the elderly and in African Americans.

Adverse Effects:

• Depending on the degree of selectivity for β1 receptors, a potential adverse effect of beta blockers is blockade of β2 receptors in the bronchi, causing bronchospasm.
• Therefore, β1 selective blockers should be used with caution, or alternative therapies should be considered, in individuals with asthma and other obstructive lung diseases.

Question 32

How do alpha blockers work? What is the clinical use? What are the adverse effects?

Answer 32

Alpha blockers, such as prazosin, bind to and block alpha receptors in the peripheral arterioles and capacitance vessels.
- This action reduces the vasoconstriction produced by the sympathetic neurotransmitter, norepinephrine, and leads to a decrease in peripheral resistance.

Clinical Use:
- Adverse effects have limited the clinical use of alpha blockers.

Adverse Effects:
- Headache, orthostatic hypotension, dizziness, loss of consciousness due to a dramatic drop in blood pressure.

Question 33

How do centrally-acting drugs work? What is the clinical use? What are the adverse effects?

Answer 33

Centrally-acting drugs, such as clonidine, act on the central nervous system. Clonidine, acting in the brainstem, decreases sympathetic nervous system outflow to blood vessels, and as a result, there is reduced resistance of blood vessels leading to decreased blood pressure.

Clinical Use: 
- Adverse effects have limited the use of this class of drugs as well.

Adverse Effects:
- Adverse effects are similar to those of alpha blockers, including headache, orthostatic hypotension, dizziness.

Question 34

What are vasodilators and how do they work?

Answer 34

Vasodilators are a group of drugs that function to widen, or dilate, the blood vessels.

Calcium channel blockers are a specific type of vasodilators that decrease the amount of extracellular calcium reaching sites inside cells of vascular smooth muscle.

• Increased calcium concentrations are required for muscle contraction, therefore the vascular smooth muscle will be in the relaxed state and the vessel dilated, reducing blood pressure.
• Arterioles are more sensitive than veins to calcium channel blockers.

Question 35

Discuss vascular smooth muscle contraction.

Answer 35

1) In the relaxed state, the concentration of calcium inside the vascular smooth muscle cell is several orders of magnitude lower than the concentration of calcium outside the vascular smooth muscle cell.
2) Calcium enters the vascular smooth muscle cell through a voltage-dependent or receptor-operated channel. When calcium enters the cell through the channel, the concentration of calcium rises from 10-7 M to 10-6 M in the fluids (cytoplasm) within the cell.
3) The calcium then binds to calmodulin to form a calcium-calmodulin complex.
4) The calcium-calmodulin complex activates the enzyme myosin kinase.
5) This in turn phosphorylates a light chain of myosin, which permits myosin to interact with actin, and causes contraction and constriction of arterioles.

Question 36

What is the renin-angiotensin system (RAS)?

Answer 36

The renin-angiotensin system (RAS) is a hormone system that regulates blood pressure and fluid balance within the body.

Question 37

What is renin? What does it do?

Answer 37

Renin is an enzyme released into the blood from the kidney. Renin converts angiotensinogen to angiotensin I.

Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II, which has two effects:

1) Vasoconstriction of the renal blood vessels
2) Aldosterone secretion from the adrenal cortex, which increases sodium and water retention by the kidney.

Both of these effects lead to an increase in blood pressure.

Question 38

How do drugs that modify the renin-angiotensin system work?

Answer 38

Because the RAS plays a role in regulating blood pressure within the body, it is an excellent target for antihypertensive therapy.

Question 39

What are the 2 main classes of drugs that can modify the RAS to reduce blood pressure?

Answer 39

• ACE Inhibitors

- Angiotensin Receptor Blocking Drugs (ARBs)

Question 40

How do angiotensin converting enzyme (ACE) inhibitors work? What is the clinical use? What are the adverse effects? What are some examples?

Answer 40

ACE inhibitors act on the renin-angiotensin-aldosterone system to inhibit the conversion of angiotensin I to the potent hypertensive agent angiotensin II.

• As a result, there is less angiotensin II overall, and therefore less constriction of the blood vessels.
• Angiotensin II-mediated release of aldosterone from the adrenal glands is also inhibited.

Examples:
- Benazepril is a common ACE inhibitor used primarily in the treatment of hypertension, congestive heart failure, and heart attacks, and in the prevention of renal and retinal complications of diabetes.

Clinical Use:

• One of the advantages of this group of antihypertensive agents is that they do not cause sexual dysfunction, a problem seen with other antihypertensives.
• They can be used in patients who have asthma.
• ACE inhibitors do not cause alterations in carbohydrate metabolism, or plasma concentration of lipoproteins, and can therefore be used in diabetic patients.
• Some preliminary evidence suggests that ACE inhibitors will reduce the incidence of heart disease in patients with high blood pressure more effectively than other blood pressure lowering drugs.

Adverse effects:

• 5 to 20% of patients develop a bothersome dry cough. Research suggests that this cough is the result of enzyme suppression (specifically a kinase), which causes a build up of substances in the lung.
• ACE inhibitors can cause fetal injury and death when used in the second and third trimesters of pregnancy, and should therefore not be used during pregnancy.
• Elderly African Americans are more resistant to the blood pressure lowering effects of ACE inhibitors, however, it is not known why this occurs.

Question 41

What are angiotensin receptor blocking drugs (ARBs)? How do they work?

Answer 41

This class of drugs block the receptor for angiotensin II (angiotensin II receptor type 1, or AT1), thus preventing the vasoconstrictive effect of angiotensin II.

These drugs may be more effective than the ACE inhibitors, as angiotensin II can be generated by enzymes other than angiotensin converting enzyme. They also produce less cough than the ACE inhibitors.

Question 42

How does one choose an antihypertensive drug?

Answer 42

The goal in choosing an antihypertensive drug is to use the most effective drug with the least adverse effects. Generally, this is a patient to patient decision.

The use of a single antihypertensive drug to control hypertension is generally preferred, as monotherapy is cheaper and compliance is higher.
- However, if the hypertension is only partially controlled with monotherapy, combination therapy may be needed.

Thiazide diuretics, beta blockers, ACE inhibitors or ARBs, and calcium channel blockers are the most commonly prescribed antihypertensive agents.

Alpha-blockers and centrally acting agents are only used if blood pressure is still uncontrolled after trying all of the other classes of antihypertensive agents.

Question 43

Which antihypertensive drug(s) would most likely be the first line treatment for an elderly patient with high blood pressure and early signs of heart failure?

a) Diuretics
b) Vasodilators
c) ACE Inhibitors
d) Angiotensin receptor blockers (ARB)

Answer 43

a) Diuretics

Diuretics are efficacious for treating hypertension and have been shown to be effective in treating other conditions related to the cardiovascular system, such as stroke and heart failure.

Question 44

Which antihypertensive drug(s) would most likely be the first-line treatment for a patient with diabetes mellitus?

a) Diuretics
b) Vasodilators
c) ACE Inhibitors
d) Angiotensin receptor blockers (ARB)

Answer 44

c) ACE Inhibitors
d) Angiotensin receptor blockers (ARB)

These drugs do not alter carbohydrate metabolism or plasma lipoprotein concentration and are therefore safe for individuals with diabetes mellitus.

Question 45

Which antihypertensive drug(s) may be contraindicated in a patient with asthma?

a) Beta-blockers
b) Vasodilators
c) ACE Inhibitors
d) Angiotensin receptor blockers (ARB)

Answer 45

a) Beta-blockers

Beta blockers may cause bronchospasm and in general should be avoided in patients with asthma.

Question 46

Which antihypertensive drug(s) would be contraindicated in a pregnant patient?

a) Beta-blockers
b) Vasodilators
c) ACE Inhibitors
d) Angiotensin receptor blockers (ARB)

Answer 46

c) ACE Inhibitors

ACE inhibitors have been shown to cause fetal injury and death, and should be avoided during pregnancy.

Question 47

A 40-year old man comes to the clinic to get a refill on his asthma medication. The nurse measures his blood pressure and notes that it is high (150/100). Later, the physician also measures his blood pressure and agrees that it is high, and also notes that the patient is about 20 kg overweight. If you were the physician, what would you advise the patient? Secondly, if you were to choose an antihypertensive agent to begin pharmacotherapy, which agent(s) would you potentially avoid?

Answer 47

First, you would need to explain to the patient the potential health consequences of sustained high blood pressure, and why it is important to control blood pressure.

You would then discuss lifestyle changes to decrease his blood pressure, such as eating habits, exercise routines, and stress management.

Finally, you would explain that while lifestyle changes are the most effective means of decreasing blood pressure, sometimes pharmacotherapy is also required.

Since the patient has asthma, you would probably not want to choose a beta blocker because of their potential to constrict the bronchioles.

Also, since the patient is 20 kgoverweight, there is an increased risk that the patient may develop diabetes mellitus. Therefore, an ACE inhibitor or ARB may be a good first choice.

Question 48

Why is the compliance with therapy for HTN so low?

Answer 48

Since antihypertensive drugs do not cure high blood pressure, the drugs may have to be taken indefinitely. This can pose some problems, as many individuals find it difficult to comply with therapy, since therapy often includes diet, salt restriction, exercise, and treatment with one or more drugs.

If an individual does not have a drug payment plan, the cost of drugsmay serve as a deterrent to compliance.

The adverse effects of one or a combination of drugs may also deter an individual from compliance.

Question 49

How can compliance be increased?

Answer 49

Individuals were taught how to measure and record their own blood pressure, as well as record their pill-taking. When an individual would note their blood pressure rising after failure to take their pills, they would take their pills in the appropriate manner.

Question 50

Which one of the following statements regarding blood pressure is correct?

a) Hypertension is a condition in which the pressure of the blood in the arteries is lower than normal
b) The definition of normal blood pressure depends on the age of the individual, with the normal value decreasing with age
c) For a young adult, normal blood pressure is about 120/80; the higher figure is the systolic and the lower figure the diastolic blood pressure (in millimetres of mercury)
d) The diastolic pressure is the pressure in the arteries when the heart is contracting and forcing blood into the arteries.

Answer 50

c) For a young adult, normal blood pressure is about 120/80; the higher figure is the systolic and the lower figure the diastolic blood pressure (in millimetres of mercury)

Question 51

Which one of the following statements regarding antihypertensive therapies is correct?

a) Thiazide diuretics decrease the volume of fluid in blood vessels by enhancing sodium and water excretion in the distal convoluted tubule.
b) Clonidine inhibits sympathetic nervous system activity by depleting noradrenaline stores at nerve endings.
c) ACE inhibitors decrease the reabsorption of sodium bicarbonate from the collecting duct of the nephron.
d) Calcium channel blockers act by blocking beta-adrenergic receptors in the brainstem

Answer 51

a) Thiazide diuretics decrease the volume of fluid in blood vessels by enhancing sodium and water excretion in the distal convoluted tubule.