Anti hypertensives agents

Antihypertensive Agents

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

Hypertension

High blood pressure
• Normal: Systolic < 130 mm
Hg 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

Blood Pressure = CO x SVR

• CO = Cardiac output
• SVR = Systemic vascular resistance


Instructors may want to insert
EIC Image #69:

Blood Pressure: Normal Regulation



• Medications used to treat hypertension


Antihypertensive Agents: Categories

• Adrenergic agents
• Angiotensin-converting enzyme inhibitors
• Angiotensin II receptor blockers
• Calcium channel blockers
• Diuretics
• Vasodilators


Antihypertensive Agents: Categories

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


Antihypertensive 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


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