1. Cardiovascular System
Hypertension
Lilley – Reading & Workbook, Chap 24

2. Antihypertensive Drugs Hypertension
50 million people in US
Major risk factor for –
Cardiovascular Disease
Coronary Artery Disease
Congestive heart failure
Cerebrovascular
Stroke
Renal Failure
Peripheral Vascular Disease/Arterial Disease

3. Antihypertensive Drugs Hypertension
Classification SBP DBP
Normal < <80
Prehypertension
Stage 1 HTN
Stage 1 HTN < <100
The previous labels of “mild,” “moderate,” and “severe” HTN have been dropped

4. Antihypertensive Drugs Hypertension - Definition
BP = Cardiac Output x Systemic vascular resistance
BP = CO x SVR
CO = Amount of blood ejected from left ventricle per minute – measured in L/min
SVR = the force or resistance the left ventricle has to overcome to eject its volume of blood.

5. Antihypertensive Drugs Hypertension Disease Process
Hypertension and associated risk factors
How does cigarette smoking contribute to high blood pressure? (Smoking causes vasoconstriction, which increases the heart’s work.)
What effect does high cholesterol have on blood pressure? (Increased circulation of cholesterol causes plaque formation within the blood vessel walls, resulting in a narrowed lumen, which increases vascular resistance.)
Can stress affect blood pressure? (Stress can increase the pulse rate, which increases the systolic pressure.)
Of the major risk factors identified, which are those that can be controlled with lifestyle modifications?
Identify the types of organ damage that occur with hypertension.
How can the nurse approach education to those patients unwilling to modify lifestyle changes?
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

6. Hypertension Nutrition

7. Primary Hypertension Medical Management
Lifestyle modification
Nutritional therapy
Alcohol consumption
Physical activity
Tobacco avoidance
Stress management
Drug Therapy

8. Hypertension Mechanisms that Regulate BP
Sympathetic Nervous System
Vascular Endothelium
Renal System
Endocrine System

9. Hypertension Mechanisms that Regulate BP
Sympathetic Nervous System (SNS) – norepinephrine released from sympathetic nerve endings - to receptors alpha1, alpha2, beta 1 & beta2
Reacts within seconds
Increases Heart Rate - chronotropic
Increased cardiac contractility - inotropic
Produces widespread vasoconstriction in peripheral arterioles
Promotes release of renin from the kidney

10. Hypertension SNS Receptors Influencing B/P

11. Hypertension Mechanisms that Regulate BP
Sympathetic Nervous System (SNS)–
Sympathetic Vasomotor Center – located in the medulla – interacts with many areas of the brain to maintain BP within normal range under various conditions
Exercise – changes to meet oxygen demand
Postural Changes – peripheral vasoconstriction

12. Hypertension Mechanisms that Regulate BP
Sympathetic Nervous System (SNS) –
Baroreceptors: specialized nerve cells the carotid arteries and the aortic arch
Sensitive to BP changes:
Increased BP: Inhibits SNS – peripheral vessel dilation. Decreased heart rate & decreased contractility of the heart + increased parasympathetic activity (vagus nerve) decreased heart rate
Decreased BP: Activates SNS – peripheral vessel constriction, increased heart rate, and increased contractility of the heart

13. Hypertension Mechanisms that Regulate BP
Vascular Endothelium
Single cell layer that lines the blood vessels
Produce vasoactive substances:
EDRF Endothelium-derive relaxing factor –
Helps maintain low arterial tone at rest
Inhibits growth of the smooth muscle layer
Inhibits platelet aggregation
Vasodilation – prostacyclin
Endothelin (ET) potent vasoconstrictor
Endothelial dysfunction may contribute to atherosclerosis & primary hypertension

14. Hypertension Mechanisms that Regulate BP
Renal System
Controls Na+ excretion & extracellular fluid volume
Renal - Renin-angiotensin-aldosterone
Renin converts angiotensinogen to angiotensin I
Angiotensin-converting enzyme (ACE) converts I into angiotensin II
Immediate: Vasoconstrictor – increased systemic vascular resistance
Prolonged: Stimulates the adrenal cortex to secret Aldosterone – Na+ and Water retention
Renal Medulla - Prostaglandins - vasodilator effect

15. Hypertension Mechanisms that Regulate BP
Endocrine System
Stimulates the SNS with
Epinephrine – increases HR and contractility
Activates B2-adrenergic receptors in peripheral arterioles of skeletal muscle = vasodilation
Activates A1-adrenergic receptors in peripheral arterioles of skin and kidneys = vasoconstiction
Adrenal Cortex – Aldosterone – stimulates kidneys to retain Na+
Increased Na+ stimulates posterior pituitary – ADH – reabsorbs ECF/water

16. Antihypertensive Drugs Compelling Indications to Treat HTN
Post-MI
High cardiovascular risk
Heart failure
Diabetes mellitus
Chronic kidney disease
Previous stroke

17. Antihypertensive Drugs Regulation of Blood Pressure
CNS
Autonomic Nervous System
Adrenergic Drugs:
Central & peripheral acting adrenergic neuron blockers
Central acting a2 receptor blockers
Peripherally acting a1 receptor blockers
Peripherally acting b b receptor blockers
Cardioselective beta1 receptor blockers
Nonselective b1 and b 2 receptor blockers
Peripherally acting dual a & b receptor blockers
Angiotensin-Converting Enzyme Inhibitors (ACE Inhibitors)
Calcium Channel Blockers
Diuretics
Vasodilators

18. Antihypertensive Drugs Regulation of Blood Pressure

19. Antihypertensive Drugs: Categories
Adrenergic drugs
Angiotensin converting enzyme (ACE) inhibitors
Angiotensin II receptor blockers (ARBs)
Calcium channel blockers (CCBs)
Diuretics
Vasodilators

20. Antihypertensive Drugs
High diastolic BP (DBP) is no longer considered to be more dangerous than high systolic BP (SBP)
Studies have shown that elevated SBP is strongly associated with heart failure, stroke, and renal failure
For those older than age 50, SBP is a more important risk factor for
cardiovascular disease (CVD) than DBP
“Prehypertensive” BPs are no longer considered “high normal”
Require lifestyle modifications to prevent CVD
Thiazide-type diuretics-initial drug therapy for HTN
Alone or with other medications

21. Antihypertensive Drugs Cultural Considerations
b-blockers and ACE inhibitors have been found to be more effective in white patients than African-American patients
CCBs and diuretics have been shown to be more effective in African-American patients than in white patients

22. Antihypertensive Drugs Classification of HTN
Hypertension can also be defined by its cause
Unknown cause
Known as essential, idiopathic, or primary hypertension
90% of the cases
Known cause
Secondary hypertension
10% of the cases

23. Antihypertensive Drugs

24. Antihypertensive Drugs
Adrenergic drugs
B-Adrenergic Blockers
Central Acting Adrenergic Antagonists
Peripheral Acting Adrenergic Antagonists
A-Adrenergic Blockers
Angiotensin converting enzyme (ACE) inhibitors
Angiotensin II receptor blockers (ARBs)
Calcium channel blockers (CCBs)
Diuretics
Thiazide
Loop
K+ Sparing
Vasodilators

26. Antihypertensive Drugs Adrenergic Drugs: Five Subcategories
Centrally and peripherally acting adrenergic neuron blockers
Centrally acting a2-receptor agonists
Peripherally acting a1-receptor blockers
Peripherally acting b-receptor blockers (b-blockers)
cardioselective (b1 receptors)
nonselective (both b1 and b2 receptors)
Peripherally acting dual a1- and b-receptor blockers

27. Antihypertensive Drugs Adrenergics - Action-a2-Receptor Agonists
Centrally acting a2-receptor agonists
Stimulate a2-adrenergic receptors in the brain
Sympathetic outflow from the CNS is decreased
Norepinephrine production is decreased
Stimulation of the a2-adrenergic receptors reduces renin activity in the kidneys
Result: decreased blood pressure
clonidine (Catapres)
guanfacine (Tenex)
methyldopa (Aldomet)
Drug of choice for hypertension in pregnancy

28. Antihypertensive Drugs Adrenergic Drugs: Peripheral a1-blockers/antagonists
Block the a1-adrenergic receptors
doxazosin (Cardura)
prazosin (Minipress)
terazosin (Hytrin)
Result: decreased blood pressure

29. Antihypertensive Drugs Adrenergic Drugs: b-blockers
Reduce BP by reducing heart rate through b1-blockade
Cause reduced secretion of renin
Long-term use causes reduced peripheral vascular resistance
metoprolol (Lopressor, Toprol XL) – IV (dysrhythmias) or po
propranolol (Inderal)
atenolol (Tenormin)
Result: decreased blood pressure

30. Adrenergic Drugs: Dual-action a1- and b-receptor blockers
Block the a1-adrenergic receptors
Reduction of heart rate (b1-receptor blockade)
Vasodilation (a1-receptor blockade)
labetalol (Normodyne, Trandate)
carvedilol (Coreg)
Result: decreased blood pressure

31. Antihypertensive Drugs Centrally and Peripherally Acting Neuron Blocker
Reserpine -
The only centrally and peripherally acting neuron blocker still available in the United States, but is rarely used
Seldom used because of frequent adverse effects

32. Antihypertensive Drugs Adrenergic Drugs
Adverse Effects
Most common: Dry mouth Drowsiness
Sedation Constipation
Other Headaches Sleep disturbances: Nausea Rash
Cardiac disturbances (palpitations), others
HIGH INCIDENCE OF
ORTHOSTATIC HYPOTENSION

33. Antihypertensive Drugs Angiotensin Converting Enzyme Inhibitors
(ACE inhibitors, or ACEIs)
Large group of safe and effective drugs
Often used as first-line drugs for HF & HTN
May be combined with a thiazide diuretic or calcium channel blocker

34. Antihypertensive Drugs ACE Inhibitors
Renin-Angiotensin-Aldosterone System
Inhibit angiotensin-converting enzyme, which is responsible for converting angiotensin I (through the action of renin) to angiotensin II
Angiotensin II is a potent vasoconstrictor and causes aldosterone secretion from the adrenals
Aldosterone stimulates water and sodium reabsorption
Result: increased blood volume, increased preload, and increased BP
Prevent the breakdown of the vasodilating substance, bradykinin
Result: decreased systemic vascular resistance (afterload), vasodilation, and therefore decreased blood pressure

35. Antihypertensive Drugs ACE Inhibitors-- Indications
Hypertension
Heart Failure (HF) (either alone or in combination with diuretics or other drugs)
drug of choice
To slow progression of left ventricular hypertrophy after an MI (cardioprotective)
Renal protective effects in patients with diabetes
drug of choice for DM patients

36. Antihypertensive Drugs ACE Inhibitors
captopril (Capoten)
Very short half-life
Prevents - L ventricular dilation & dysfunction (ventricular remodeling)
enalapril (Vasotec)
lisinopril (Prinivil and Zestril)
quinapril (Accupril)
Newer drugs, long half-lives, once-a-day dosing
ramipril (Altace)

37. Antihypertensive Drugs ACE Inhibitors - Considerations
Captopril and lisinopril are NOT prodrugs
Prodrugs are inactive in their administered form and must be metabolized in the liver to an active form in order to be effective
Captopril and lisinopril can be used if a patient has liver dysfunction, unlike other ACE inhibitors that are prodrugs

38. Antihypertensive Drugs ACE Inhibitors -- Adverse Effects
Fatigue Dizziness
Headache Mood changes
Impaired taste Possible hyperkalemia
Dry, nonproductive cough, which reverses when therapy is stopped
Angioedema: rare but potentially fatal
NOTE: first-dose hypotensive effect may occur!

39. Antihypertensive Drugs Angiotensin II Receptor Blockers
Allow angiotensin I to be converted to angiotensin II
Block the receptors that receive angiotensin II
Result: Block vasoconstriction and release of aldosterone
losartan (Cozaar, Hyzaar)
valsartan (Diovan)
Both safe to use during pregnancy

40. Antihypertensive Drugs Angiotensin II Receptor Blockers
Indications
Hypertension
Adjunctive drugs for the treatment of HF
May be used alone or with other drugs such as diuretics
Used primarily in patients who cannot tolerate ACE inhibitors
Adverse Effects
Upper respiratory infections
Headache
May cause occasional dizziness, inability to sleep, diarrhea, dyspnea, heartburn, nasal congestion, back pain, fatigue
Hyperkalemia much less likely to occur

41. Antihypertensive Drugs Calcium Channel Blockers
Action:
Cause smooth muscle relaxation:
blocks the binding of calcium to its receptors, preventing muscle contraction
Inhibit movement of calcium ions across the cell membrane
This causes:
decreased peripheral smooth muscle tone - vasodilation
decreased systemic vascular resistance
Slower rate of myocardial contraction
Result: decreased blood pressure

42. Calcium Channel Blockers Classified by Structure
Benzothiazepines
diltiazem (Cardizem)
Phenylalkamines
verapamil (Calan, Isoptin, Verelan)
Dihydropyridines
amlodipine (Norvasc), bepridil (Vascor), nicardipine (Cardene)
nifedipine (Procardia)
nimodipine (Nimotop)

43. Antihypertensive Drugs Calcium Channel Blockers
Indications:
Angina Hypertension Dysrhythmias
Migraine headaches Raynaud’s disease
Adverse Effects:
Cardiovascular:
Hypotension, palpitations, tachycardia
Gastrointestinal
Constipation, nausea
Other
Rash, flushing, peripheral edema, dermatitis

44. Antihypertensive Drugs Vasodilators
Action:
Directly relax arteriolar and/or venous smooth muscle
Result: decreased systemic vascular response, decreased afterload, and peripheral vasodilation
diazoxide (Hyperstat)
hydralazine HCl (Apresoline)
minoxidil (Loniten)
sodium nitroprusside (Nipride, Nitropress)
Directly dilates arterial and venous smooth muscle

45. Antihypertensive Drugs Vasodilators
Treatment of hypertension
May be used in combination with other drugs
Oral diazoxide may be used as an antihypoglycemic
Sodium nitroprusside & IV diazoxide are reserved for the management of hypertensive emergencies
given intravenously on monitored patients

46. Vasodilators - Adverse Effects
Hydralazine
Dizziness, headache, anxiety, tachycardia, nausea and vomiting, diarrhea, anemia, dyspnea, edema, nasal congestion, others
Sodium nitroprusside
Bradycardia, hypotension, possible cyanide toxicity (rare); solution must be protected from light
Diazoxide
Dizziness, headache, anxiety, orthostatic hypotension, dysrhythmias, sodium and water retention, nausea, vomiting, hyperglycemia in diabetic patients, others

47. Antihypertensive Drugs Nursing Implications
Thorough health history & physical examination
Assess for contraindications to specific antihypertensive drugs
Assess for conditions that require cautious use of these drugs
Administer IV forms with extreme caution and use an IV pump

48. Antihypertensive Drugs Patient Education
Educate patients about the importance of not missing a dose and taking the medications exactly as prescribed
Never double up on doses if a dose is missed
Check with physician for instructions on what to do if a dose is missed
Monitor BP during therapy; instruct patients to keep a journal of regular BP checks
Men taking these drugs may not be aware that impotence is an expected effect. This may influence compliance with drug therapy

49. Antihypertensive Drugs Patient Education
Remind patients that medication is only part of therapy. Encourage patients to watch their diet, stress level, weight, and alcohol intake
Patients should avoid smoking and eating foods high in sodium
Encourage supervised exercise
Instruct patients to change positions slowly to avoid syncope from postural hypotension**
Instruct patients that these drugs should not be stopped abruptly because this may cause a rebound hypertensive crisis, and perhaps lead to stroke
Oral forms should be given with meals so that absorption is more gradual and effective

50. Antihypertensive Drugs Patient Education
Avoid: Hot tubs, showers, or baths; hot weather; prolonged sitting or standing; physical exercise; and alcohol ingestion may aggravate low blood pressure, leading to fainting and injury. Patients should sit or lie down until symptoms subside
Patients should not take any other medications, including OTC drugs, without first getting the approval of their physician
Contact physician:
If patients are experiencing serious adverse effects, or believe that the dose or medication needs to be changed
Unusual shortness of breath; difficulty breathing; swelling of the feet, ankles, face, or around the eyes; weight gain or loss; chest pain; palpitations; or excessive fatigue

51. Antihypertensive Drugs Nursing Implications
Monitor for adverse effects (dizziness, orthostatic hypotension, fatigue) and for toxic effects
Monitor for therapeutic effects
Blood pressure should be maintained <130/90 mm Hg
Patients with hypertension also has DM or renal disease:
the BP goal is <130/80 mm Hg

53. Review
1. Angiotensin-converting enzyme (ACE) inhibitors include drugs such as _______________ and_____________.
2. Diazoxide and sodium nitroprusside are classified as __________________ and result in __________.
3. Prazosin (Minipress) is a(n) ____________________.
4. Propranolol works to decrease blood pressure by ___________________.
5. Nonpharmacologic treatment approaches to hypertension include ________________, ___________________, and _____________.
6. __________ and __________ are the only two ACE inhibitors that are not prodrugs.

54. Review Answers
1. ACE inhibitors include drugs such as captopril (Capoten), benazepril (Lotensin), enalapril (Vasotec), fosinopril (Monopril), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), and trandolapril (Mavik).
2. Diazoxide and sodium nitroprusside are classified as vasodilators and result in peripheral vasodilation, resulting in a reduction in systemic vascular resistance and reduced blood pressure.
3. Prazosin (Minipress) is a peripherally acting alpha1-blocker.
4. Propranolol works to decrease blood pressure by its β-blocking effects. It decreases heart rate and cardiac output, which are the components of blood pressure.
5. Nonpharmacologic treatment approaches to hypertension include weight loss, smoking cessation, sodium restriction, stress reduction, and supervised exercise.
6. Captopril and lisinopril are the only two ACE inhibitors that are not prodrugs.

55. Review: Match each definition with its corresponding term
Review: Match each definition with its corresponding term. Not all terms will be used.
A. prodrug
B. orthostatic hypotension
C. secondary
D. essential
E. cardiac output
F. diazoxide (Hyperstat)
G. losartan (Cozaar)
H. doxazosin (Cardura)
I. captopril (Capoten)
J. angiotensin II–receptor blockers
M. ACE inhibitors
N. α1-blockers
O. Ejection fraction
 1. _____ Drugs that primarily cause arterial and venous dilation through blocking the SNS
2. _____ Blood pressure is determined by the product of _______ and systemic vascular resistance (SVR)
3. _____ Drugs in this class cause a characteristic dry, nonproductive cough
4. _____ These drugs block vasoconstriction and the secretion of aldosterone.
5. _____ A drug that is inactive in its administered form and must be biotransformed in the liver to its active form.
6. _____ An example of a drug in the class mentioned in #1
7. _____ An example of a drug in the class mentioned in #3
8. _____ An example of a drug in the class mentioned in #4
9. _____ An elevated systemic arterial pressure for which no cause can be found
10. _____ A common adverse effect of adrenergic drugs that involves a sudden drop in blood pressure

56. Review - Matching Answers
4. J
5. A
6. H
7. I
8. G
9. D
10. B