Drugs Affecting Blood Pressure

Drugs Affecting
Blood Pressure
Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Blood Pressure Control
• Elements
– Heart Rate
– Stroke Volume
– Peripheral Vascular
Resistance

Blood Pressure Control
• Baroreceptors
• Renin-Angiotensin System

Hypertension
High blood pressure

• Normal: Systolic < 130 mmHg
» Diastolic < 85 mm Hg

Classification of Blood Pressure
Category Systemic BP (mm Hg) Diastolic BP (mm Hg)
Normal <130 <85
High normal 130-139 85-89
Hypertension
Stage 1 140-159 90-99
Stage 2 160-169 100-109
Stage 3 180-209 110-119
Stage 4  210  120

Classification of Blood Pressure
Primary Hypertension
• Specific cause unknown
• 90% of the cases
• Also known as essential or idiopathic hypertension
Secondary Hypertension
• Cause is known (such as eclampsia of pregnancy,
renal artery disease, pheochromocytoma)
• 10% of the cases

Stepped-Care Management of HPN
by JNC 7
Step 1: Lifestyle modification
weight reduction
reduction
moderation of alcohol intake
smoking cessation
physical activity increase

by JNC 7
Step 2 : Inadequate Response
continue lifestyle modification
initial drug selection
1. Diuretic or Beta blocker
2. ACE inhibitor, calcium channel
blocker, ARB

by JNC 7
increase drug dose, or
substitute another drug, or
add a 2nd drug from another class

by JNC 7
add a 2nd or 3rd agent or diuretic if not already
prescribed

Hypotension
• Hypotensive states:
– Heart muscle is damaged

Blood Pressure = CO x SVR
• CO = Cardiac output
• SVR = Systemic vascular resistance

Antihypertensive Agents
• Medications used to treat hypertension

Antihypertensive Agents:
Categories
• Sympathetic Nervous System
Blockers/Adrenergic agents
• Angiotensin-converting enzyme inhibitors
• Angiotensin II receptor blockers
• Calcium channel blockers
• Diuretics
• Vasodilators
Antihypertensive Agents: Categories
• Sympathetic Nervous System Blockers/

Adrenergic agents
– Alpha1 blockers
– Beta blockers (cardioselective and nonselective)
– Centrally acting alpha blockers
– Combined alpha-beta blockers
– Peripheral-acting adrenergic agents

Mechanism of Action
Adrenergic Agents
Alpha1 Blockers (peripherally acting)
• Block the alpha1-adrenergic receptors
• The SNS is not stimulated
Result: DECREASED blood pressure
• Stimulation of alpha1-adrenergic receptors

causes HYPERtension
• Blocking alpha1-adrenergic receptors causes decreased
blood pressure

Adrenergic Agents
Alpha1 Blockers
• doxazosin (Cardura)
• prazosin (Minipress)
• terazosin (Hytrin)

Mechanism of Action
Adrenergic Agents
Central-Acting Adrenergics
• Stimulate alpha2-adrenergic receptors
• Sympathetic outflow from the CNS is decreased
Result: decreased blood pressure

Adrenergic Agents
Central-Acting Adrenergics
• clonidine (Catapres)
• methyldopa (Aldomet)
(drug of choice for hypertension in pregnancy)

Mechanism of Action
Adrenergic Agents
Adrenergic Neuronal Blockers
(peripherally acting)
• Inhibit release of norepinephrine
• Also deplete norepinephrine stores
• SNS (peripheral adrenergic nerves) is not stimulated
Result: decreased blood pressure

Adrenergic Agents
Adrenergic Neuronal Blockers
• reserpine
• guanadrel (Hylorel)
• guanethidine (Ismelin)

Adrenergic Agents
Therapeutic Uses
• Alpha1 blockers (peripherally acting)
– Treatment of hypertension
– Relief of symptoms of BPH
– Management of of severe CHF when used
with cardiac glycosides and diuretics

Adrenergic Agents
Therapeutic Uses
• Central-Acting Adrenergics
– Treatment of hypertension, either alone or
with other agents
– Usually used after other agents have failed
due to side effects
– Also may be used for treatment of severe
dysmenorrhea, menopausal flushing, glaucoma
– Clonidine is useful in the management of
withdrawal symptoms in opioid- or nicotine-
dependent persons
Adrenergic Agents
Therapeutic Uses
• Adrenergic neuronal blockers
– Treatment of hypertension, either alone or with
other agents
– Seldom used because of frequent side effects

Adrenergic Agents
Side Effects
Most common: dry mouth drowsiness
sedation constipation
Other: headaches sleep disturbances
nausea rash
cardiac disturbances (palpitations)
HIGH INCIDENCE OF ORTHOSTATIC HYPOTENSION

Categories
Angiotensin-Converting Enzyme Inhibitors
(ACE Inhibitors)
• Large group of safe and effective drugs
• Often used as first-line agents for CHF
and hypertension
• May be combined with a thiazide diuretic
or calcium channel blocker

Mechanism of Action
ACE Inhibitors
RAAS: Renin Angiotensin-Aldosterone System

• When the enzyme angiotensin I is converted to
angiotensin II, the result is potent vasoconstriction
and stimulation of aldosterone
• Result of vasoconstriction: increased systemic

vascular resistance and increased afterload
• Therefore, increased BP
Mechanism of Action
ACE Inhibitors
• Aldosterone stimulates water and sodium resorption.
• Result: increased blood volume, increased preload,
and increased B

Mechanism of Action
ACE Inhibitors
• ACE Inhibitors block the angiotensin-converting
enzyme, thus preventing the formation of
angiotensin II.
• Also prevent the breakdown of the vasodilating
substance, bradykinin
Result: decreased systemic vascular resistance (afterload),

vasodilation, and therefore, decreased blood pressure

ACE Inhibitors
• captopril (Capoten)
• Short half-life, must be dosed more frequently
than others
• enalapril (Vasotec)
• The only ACE inhibitor available in oral and
parenteral forms
• lisinopril (Prinivil and Zestril) and quinapril (Accupril)
• Newer agents, long half-lives, once-a-day dosing
• Several other agents available
Therapeutic Uses
ACE Inhibitors
• Hypertension
• CHF (either alone or in combination with diuretics
or other agents)
• Slows progression of left ventricular hypertrophy
after an MI
• Renal protective effects in patients with diabetes
Drugs of choice in hypertensive patients with CHF

Side Effects
ACE Inhibitors
• Fatigue Dizziness
• Headache Mood changes
• Impaired taste
Dry, nonproductive cough, reverses when therapy is stopped
NOTE: first-dose hypotensive effect may occur!!

Categories
Angiotensin II Receptor Blockers
(A II Blockers or ARBs)
• Newer class
• Well-tolerated
• Do not cause coughing

Mechanism of Action
• Allow angiotensin I to be converted to angiotensin II,
but block the receptors that receive angiotensin II
• Block vasoconstriction and release of aldosterone


• losartan (Cozaar)
• eposartan (Teveten)
• valsartan (Diovan)
• irbesartan (Avapro)
• candesartan (Atacand)
• telmisartan (Micardis)

Therapeutic Uses
• Hypertension
• Adjunctive agents for the treatment of CHF
• May be used alone or with other agents such
as diuretics

Side Effects
• Upper respiratory infections
• Headache
• May cause occasional dizziness, inability to sleep,
diarrhea, dyspnea, heartburn, nasal congestion,
back pain, fatigue

Categories
Calcium Channel Blockers
• Benzothiazepines
• Dihydropyridines
• Phenylalkylamines

Mechanism of Action
• Cause smooth muscle relaxation by blocking the
binding of calcium to its receptors, preventing
muscle contraction
• This causes decreased peripheral smooth muscle
tone, decreased systemic vascular resistance
• Result: decreased blood pressure


• Benzothiazepines:
– diltiazem (Cardizem, Dilacor)
• Phenylalkamines:
– verapamil (Calan, Isoptin)
• Dihydropyridines:
– amlodipine (Norvasc), bepridil (Vascor),
nicardipine (Cardene)
– nifedipine (Procardia), nimodipine (Nimotop)
Therapeutic Uses
• Angina
• Hypertension
• Dysrhythmias
• Migraine headaches

Side Effects
• Cardiovascular
– hypotension, palpitations, tachycardia
• Gastrointestinal
– constipation, nausea
• Other
– rash, flushing, peripheral edema, dermatitis

Antihypertensive Agents: Diuretics
• Decrease the plasma and extracellular fluid volumes

• Results: decreased preload
decreased cardiac output
decreased total peripheral resistance
• Overall effect: decreased workload of the heart,

and decreased blood pressure

Mechanism of Action
Vasodilators
• Directly relaxes arteriolar smooth muscle
• Result: decreased systemic vascular response,

decreased afterload, and
PERIPHERAL VASODILATION

Vasodilators
• diazoxide (Hyperstat)
• hydralazine HCl (Apresoline)
• minoxidil (Loniten, Rogaine)
• sodium nitroprusside (Nipride, Nitropress)

Therapeutic Uses
Vasodilators
• Treatment of hypertension
• May be used in combination with other agents
• Sodium nitroprusside and diazoxide IV are reserved
for the management of hypertensive emergencies

Antihypertensive Agents: Side
Effects
Vasodilators
• Hydralazine:
– dizziness, headache, anxiety, tachycardia, nausea
and vomiting, diarrhea, anemia,
dyspnea, edema, nasal congestion
• Sodium nitroprusside:
– bradycardia, hypotension, possible
cyanide toxicity

Nursing Implications
• Before beginning therapy, obtain a thorough
health history and head-to-toe physical
examination.
• Assess for contraindications to specific

antihypertensive agents.
• Assess for conditions that require cautious

use of these agents.

• Educate patients about the importance of not
missing a dose and taking the medications exactly
as prescribed.
• Patients should 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.

• Instruct patients that these drugs should not be
stopped abruptly, as this may cause a rebound
hypertensive crisis, and perhaps lead to CVA.
• Oral forms should be given with meals so that

absorption is more gradual and effective.
• Administer IV forms with extreme caution and

use an IV pump.

• Remind patients that medications 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.
• Patients should report 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.

• Men taking these agents may not be aware that
impotence is an expected effect. This may influence
compliance with drug therapy.
• If patients are experiencing serious side effects,

or believe that the dose or medication needs to
be changed, they should contact their physician
immediately.

• 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.

• Monitor for side/adverse effects
(dizziness, orthostatic hypotension, fatigue)
and for toxic effects.
• Monitor for therapeutic effects
• Blood pressure should be maintained at less

than 140/90 mm Hg

Drugs Affecting Blood Pressure

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Drugs Affecting

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

High blood pressure

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Category Systemic BP (mm Hg) Diastolic BP (mm Hg)

Normal <130 <85

High normal 130-139 85-89

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

• Medications used to treat hypertension

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

• Sympathetic Nervous System Blockers/

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Result: DECREASED blood pressure

• Stimulation of alpha1-adrenergic receptors

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Result: decreased blood pressure

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Result: decreased blood pressure

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

HIGH INCIDENCE OF ORTHOSTATIC HYPOTENSION

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

RAAS: Renin Angiotensin-Aldosterone System

• Result of vasoconstriction: increased systemic

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Result: decreased systemic vascular resistance (afterload),

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Dry, nonproductive cough, reverses when therapy is stopped

NOTE: first-dose hypotensive effect may occur!!

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

• Block vasoconstriction and release of aldosterone

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Angiotensin II Receptor Blockers

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Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Calcium Channel Blockers

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

• Decrease the plasma and extracellular fluid volumes

• Overall effect: decreased workload of the heart,