Download Adrenergic drugs

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
Normal
SBP
<120
DBP
<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.
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Hypertension and
associated risk
factors
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an
affiliate of Elsevier Inc.
Slid
 Lifestyle
modification
Nutritional therapy
Alcohol consumption
Physical activity
Tobacco avoidance
Stress 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 seconds
Increases Heart Rate - chronotropic
Increased 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 demand
Postural 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
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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

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
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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
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Post-MI
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High cardiovascular risk
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Heart failure
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Diabetes mellitus
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Chronic kidney disease
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Previous stroke
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CNS
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Autonomic Nervous System
◦ Adrenergic Drugs:
 Central & peripheral acting adrenergic neuron blockers
 Central acting a2 receptor blockers
 Peripherally acting a1 receptor blockers
 Peripherally acting b receptor blockers
 Cardioselective beta1 receptor blockers
 Nonselective b1 and b 2 receptor blockers
 Peripherally acting dual a & b receptor blockers
b

Angiotensin-Converting Enzyme Inhibitors (ACE Inhibitors)

Calcium Channel Blockers
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Diuretics
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Vasodilators
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Adrenergic drugs
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Angiotensin converting enzyme (ACE) inhibitors
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Angiotensin II receptor blockers (ARBs)
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Calcium channel blockers (CCBs)
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Diuretics
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Vasodilators
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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
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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
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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
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Adrenergic drugs
 B-Adrenergic Blockers
 Central Acting Adrenergic Antagonists
 Peripheral Acting Adrenergic Antagonists
 A-Adrenergic Blockers
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Angiotensin converting enzyme (ACE) inhibitors
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Angiotensin II receptor blockers (ARBs)
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Calcium channel blockers (CCBs)
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Diuretics
 Thiazide
 Loop
 K+ Sparing
Vasodilators
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Centrally and peripherally acting adrenergic neuron blockers
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Centrally acting a2-receptor agonists
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Peripherally acting a1-receptor blockers
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Peripherally acting b-receptor blockers
(b-blockers)
◦ cardioselective (b1 receptors)
◦ nonselective (both b1 and b2 receptors)
Peripherally acting dual a1- and b-receptor blockers
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Centrally acting a2-receptor agonists
◦
◦
◦
◦
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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)
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Drug of choice for hypertension in pregnancy
Block the a1-adrenergic receptors
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doxazosin (Cardura)
prazosin (Minipress)
terazosin (Hytrin)
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Result: decreased blood pressure
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Reduce BP by reducing heart rate through b1-blockade
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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 a1-adrenergic receptors
◦ Reduction of heart rate (b1-receptor blockade)
◦ Vasodilation (a1-receptor blockade)
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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
Sedation
Drowsiness
Constipation
Other
Headaches
Sleep disturbances:
Nausea
Rash
Cardiac disturbances (palpitations), others
HIGH INCIDENCE OF
ORTHOSTATIC HYPOTENSION
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(ACE inhibitors, or ACEIs)
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Large group of safe and effective drugs
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Often used as first-line drugs for HF & HTN
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May be combined with a thiazide diuretic or
calcium channel blocker
Renin-Angiotensin-Aldosterone System
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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
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Prevent the breakdown of the vasodilating substance, bradykinin
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Result: decreased systemic vascular resistance (afterload),
vasodilation, and therefore decreased blood pressure
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Hypertension

Heart Failure (HF) (either alone or in combination with
diuretics or other drugs)
◦ drug of choice
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To slow progression of left ventricular hypertrophy after
an MI (cardioprotective)
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Renal protective effects in patients with diabetes
◦ drug of choice for DM patients
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captopril (Capoten)
◦ Very short half-life
◦ Prevents - L ventricular dilation & dysfunction (ventricular
remodeling)
enalapril (Vasotec)
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lisinopril (Prinivil and Zestril)
quinapril (Accupril)
◦ Newer drugs, long half-lives, once-a-day dosing
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ramipril (Altace)
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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!
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Allow angiotensin I to be converted to angiotensin II
Block the receptors that receive angiotensin II
Result: Block vasoconstriction and release of aldosterone
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losartan (Cozaar, Hyzaar)
valsartan (Diovan)
◦ Both safe to use during pregnancy
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Indications
◦
◦
◦
◦
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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
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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
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Benzothiazepines
◦ diltiazem (Cardizem)
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Phenylalkamines
◦ verapamil (Calan, Isoptin, Verelan)
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Dihydropyridines
◦ amlodipine (Norvasc), bepridil (Vascor),
nicardipine (Cardene)
◦ nifedipine (Procardia)
◦ nimodipine (Nimotop)
Indications:
Angina
Hypertension
Dysrhythmias
Migraine headaches
Raynaud’s disease
Adverse Effects:
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Cardiovascular:
◦ Hypotension, palpitations, tachycardia
Gastrointestinal
◦ Constipation, nausea
Other
◦ Rash, flushing, peripheral edema, dermatitis
Action:
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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
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May be used in combination with other drugs
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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
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Sodium nitroprusside
◦ Bradycardia, hypotension, possible cyanide toxicity
(rare); solution must be protected from light
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Diazoxide
◦ Dizziness, headache, anxiety, orthostatic hypotension,
dysrhythmias, sodium and water retention, nausea,
vomiting, hyperglycemia in diabetic patients, others
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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
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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
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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
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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

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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.
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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
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Answers
1. N
2. E
3. M
4. J
5. A
6. H
7. I
8. G
9. D
10. B