Hypertension

Lilley – Reading & Workbook, Chap 24

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

Classification SBP DBP Normal <120 <80

Prehypertension 120-129 80-89

Stage 1 HTN 140-159 90-99

Stage 1 HTN <160 <100

The previous labels of “mild,” “moderate,” and “severe” HTN have been dropped

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.

Slide 5Mosby items and derived items © 2007, 2004 by Mosby, Inc., an

affiliate of Elsevier Inc.

Hypertension and associated risk factors

Lifestyle modification

Nutritional therapyAlcohol consumptionPhysical activityTobacco avoidanceStress management

Drug Therapy

Sympathetic Nervous System

Vascular Endothelium

Renal System

Endocrine System

Sympathetic Nervous System (SNS) – norepinephrine released from sympathetic nerve endings - to receptors alpha1, alpha2, beta 1 & beta2

Reacts within secondsIncreases Heart Rate - chronotropicIncreased cardiac contractility - inotropic

Produces widespread vasoconstriction in peripheral arterioles

Promotes release of renin from the kidney

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 demandPostural Changes – peripheral vasoconstriction

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

Vascular Endothelium

Single cell layer that lines the blood vesselsProduce 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 – prostacyclinEndothelin (ET) potent vasoconstrictor

Endothelial dysfunction may contribute to atherosclerosis & primary hypertension

Renal System Controls Na+ excretion & extracellular fluid

volumeRenal - Renin-angiotensin-aldosterone

Renin converts angiotensinogen to angiotensin IAngiotensin-converting enzyme (ACE) converts I

into angiotensin II Immediate: Vasoconstrictor – increased

systemic vascular resistanceProlonged: Stimulates the adrenal cortex

to secret Aldosterone – Na+ and Water retention

Renal Medulla - Prostaglandins - vasodilator effect

Endocrine System Stimulates the SNS with

Epinephrine – increases HR and contractilityActivates B2-adrenergic receptors in peripheral

arterioles of skeletal muscle = vasodilation Activates A1-adrenergic receptors in peripheral

arterioles of skin and kidneys = vasoconstictionAdrenal Cortex – Aldosterone – stimulates kidneys

to retain Na+Increased Na+ stimulates posterior pituitary –

ADH – reabsorbs ECF/water

Post-MI

High cardiovascular risk

Heart failure

Diabetes mellitus

Chronic kidney disease

Previous stroke

CNS

Autonomic Nervous System

◦ Adrenergic Drugs: Central & peripheral acting adrenergic neuron blockers Central acting 2 receptor blockers

Peripherally acting 1 receptor blockers Peripherally acting receptor blockers

Cardioselective beta1 receptor blockers Nonselective 1 and 2 receptor blockers

Peripherally acting dual & receptor blockers

Angiotensin-Converting Enzyme Inhibitors (ACE Inhibitors)

Calcium Channel Blockers

Diuretics

Vasodilators

Adrenergic drugs

Angiotensin converting enzyme (ACE) inhibitors

Angiotensin II receptor blockers (ARBs)

Calcium channel blockers (CCBs)

Diuretics

Vasodilators

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

-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

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

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

Centrally and peripherally acting adrenergic neuron blockers

Centrally acting 2-receptor agonists

Peripherally acting 1-receptor blockers

Peripherally acting -receptor blockers (-blockers)◦ cardioselective (1 receptors)

◦ nonselective (both 1 and 2 receptors)

Peripherally acting dual 1- and -receptor blockers

Centrally acting 2-receptor agonists ◦ Stimulate 2-adrenergic receptors in the brain◦ Sympathetic outflow from the CNS is decreased◦ Norepinephrine production is decreased◦ Stimulation of the 2-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

Block the 1-adrenergic receptors

doxazosin (Cardura) prazosin (Minipress) terazosin (Hytrin)

Result: decreased blood pressure

Reduce BP by reducing heart rate through 1-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

Block the 1-adrenergic receptors

◦ Reduction of heart rate (1-receptor blockade)

◦ Vasodilation (1-receptor blockade)

labetalol (Normodyne, Trandate) carvedilol (Coreg)

Result: decreased blood pressure

◦ 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

Adverse Effects

Most common:Dry mouth DrowsinessSedation Constipation

Other Headaches Sleep disturbances:Nausea Rash

Cardiac disturbances (palpitations), others

HIGH INCIDENCE OF ORTHOSTATIC HYPOTENSION

(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

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

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

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)

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

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!

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

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

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

Benzothiazepines◦ diltiazem (Cardizem)

Phenylalkamines◦ verapamil (Calan, Isoptin, Verelan)

Dihydropyridines◦ amlodipine (Norvasc), bepridil (Vascor),

nicardipine (Cardene)◦ nifedipine (Procardia)◦ nimodipine (Nimotop)

Indications:Angina Hypertension DysrhythmiasMigraine headaches Raynaud’s disease

Adverse Effects: Cardiovascular:

◦ Hypotension, palpitations, tachycardia Gastrointestinal

◦ Constipation, nausea Other

◦ Rash, flushing, peripheral edema, dermatitis

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

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

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

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

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

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

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

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

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.

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.  

  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

Answers 1. N 2. E 3. M 4. J 5. A 6. H 7. I 8. G 9. D 10. B