Download Antihypertensive Agents: Diuretics

Antihypertensive Agents
Drug Management of
Hypertension
February, 2017
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Hypertension:
Introduction
• Systemic hypertension is a common disorder that, if
not effectively treated, increases the risk of coronary
thrombosis, strokes and renal failure
• Until about 1950, there was no effective treatment,
and the development of antihypertensive drugs has
been a major therapeutic success story.
• Systemic blood pressure is an excellent ‘surrogate
marker’ for increased cardiovascular risk in that there
is good evidence from randomized controlled trials
that common antihypertensive drugs (diuretics, ACEIs,
calcium antagonists)
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Hypertension:
Definition
• High blood pressure i.e. Elevation of
arterial blood pressure above 140/90
mm Hg.
• Can be caused by idiopathic process
or an underlying disease process
• Normal : Systolic < 130 mm Hg
Diastolic < 85 mm Hg
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Classification of Blood Pressure
Category
Normal
Systemic BP
(mm Hg)
<130
Diastolic BP
(mm Hg)
<85
High Normal
130-139
85-89
Stage 1
140-159
90-99
Stage 2
160-179
100-109
Stage 3
180-209
110-119
Stage 4
 210
 120
Hypertension:-
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Classification of Blood
Pressure…
• Primary Hypertension
Also known as essential or idiopathic
hypertension
90% of the cases
• Secondary Hypertension
10% of the cases
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Essential or Idiopathic or
Primary Hypertension


- most (90%) patients with persistent
arterial hypertension
genesis of hypertension unknown
predisposing factors:
-(obesity, stress, salt intake, lack of Mg2+,
K+, Ca2+, ethanol  dose, smoking)
 (positive family history, insulin resistance,
age, sex, defect of local vasomotoric
regulation

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Secondary Hypertension








Cause is known
is secondary to some distinct disease like:
Renal + renovascular disease (artery stenosis)
Hormonal defects (Cushing´s syndrome,
phaeochromocytoma)
Mechanical defect (coarctation of aorta)
Hypertension in pregnancy (eclampsia of
pregnancy),
hypertension (sympathomimetics,
glucocorticoids)
Neurological disease
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Blood Pressure = CO x SVR
• CO = Cardiac output
• SVR = Systemic vascular resistance
Ways of lowering Blood pressure:Reduce cardiac output (ß-blockers, Ca2+
channel blockers)
Reduce plasma volume (Diuretics)
Reduce peripheral vascular resistance (
Vasodilators)
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Treatment Rationale
• Short-term goal of antihypertensive
therapy:
• Reduce blood pressure
• Primary (essential) hypertension
• Secondary hypertension
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Treatment Rationale…
• Long-term goal of antihypertensive
therapy:
• Reduce mortality due to hypertensioninduced disease
•
•
•
•
•
•
Stroke
Congestive heart failure
Coronary artery disease
Nephropathy
Peripheral artery disease
Retinopathy
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Major Risk Factors That Increase
Mortality in Hypertension
•
•
•
•
•
•
Smoking
Dyslipidemias
Diabetes Mellitus
Age >60
Gender: men, postmenopausal women
Family history
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"Individualized Care"
• Risk factors considered
• Monotherapy is instituted
• Non pharmacological therapy tried first
• Considerations for choice of initial
monotherapy:
– Renin status
– Coexisting cardiovascular conditions
– Other conditions
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Treatment Thresholds for Essential Hypertension
Stages
Risk group A
Risk Group B
Risk Group C
(no major risk
factors, no target
organ damage)
One or more major
risk factors
(except diabetes),
no organ damage
Target organ
damage and/or
diabetes
High
Normal
Lifestyle
Modification
Lifestyle
Modification
Lifestyle
Modification and
Drug Therapy
Stage 1
Lifestyle
Modification (up
to 12 months)
Lifestyle
Modification and
Drug Therapy
Lifestyle
Modification and
Drug Therapy
Stages 2,
3 and 4
Lifestyle
Modification and
Drug Therapy
Lifestyle
Modification and
Drug Therapy
Lifestyle
Modification and
Drug Therapy
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Antihypertensive Agents
• Medications used to treat hypertension
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Antihypertensive Agents:
Categories
•
•
•
•
•
•
Adrenergic agents
Angiotensin-converting enzyme inhibitors
Angiotensin II receptor blockers
Calcium channel blockers
Diuretics
Vasodilators
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Antihypertensive Agents:
Categories…
• Adrenergic Agents
– Alpha1adrenoceptor blockers
– Beta–adrenoceptor blockers (cardioselective
and nonselective)
– Centrally acting alpha blockers
– Combined alpha-beta blockers
– Peripheral-acting adrenergic agents
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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
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Antihypertensive Agents:
Adrenergic Agents
Alpha1 Blockers
• doxazosin (Cardura)
• prazosin (Minipress)
• terazosin (Hytrin)
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Antihypertensive Agents:
Mechanism of Action
Adrenergic Agents
Central-Acting Adrenergics
• Stimulate alpha2-adrenergic receptors
• Sympathetic outflow from the CNS is decreased
Result: decreased blood pressure
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Antihypertensive Agents:
Adrenergic Agents
Central-Acting Adrenergics
• clonidine (Catapres)
• methyldopa (Aldomet)
(drug of choice for hypertension in pregnancy)
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Antihypertensive Agents:
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
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Antihypertensive Agents:
Adrenergic Agents
Adrenergic Neuronal Blockers
(peripherally acting)…
• reserpine
• guanadrel (Hylorel)
• guanethidine (Ismelin)
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Antihypertensive Agents:
Adrenergic Agents
Therapeutic Uses
• Alpha1 blockers (peripherally acting)
– Treatment of hypertension
– Relief of symptoms of BPH (benign prostatic
hyperplasia)
– Management of severe CHF (congestive heart
failure) when used with cardiac glycosides and
diuretics
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Antihypertensive Agents:
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
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Antihypertensive Agents:
Adrenergic Agents
Therapeutic Uses…
• Adrenergic neuronal blockers
(peripherally acting)
– Treatment of hypertension, either alone or
with other agents
– Seldom used because of frequent side effects
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Antihypertensive Agents:
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
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Antihypertensive Agents:
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
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Antihypertensive Agents:
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
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Antihypertensive Agents:
Mechanism of Action
ACE Inhibitors…
• Aldosterone stimulates water and sodium
resorption.
• Result: increased blood volume, increased
preload, and increased BP
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Antihypertensive Agents:
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
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Antihypertensive Agents
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
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Antihypertensive Agents:
Therapeutic Uses
ACE Inhibitors…
• Hypertension
• CHF (either alone or in combination with
diuretics or other agents)
• Slows progression of left ventricular hypertrophy
after a MI (Myocardial Infarction)
• Renal protective effects in patients with diabetes
Drugs of choice in hypertensive patients with CHF
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Antihypertensive Agents:
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!!
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Antihypertensive Agents:
Categories
Angiotensin II Receptor Blockers
(A II Blockers or ARBs)
• Newer class
• Well-tolerated
• Do not cause coughing
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Antihypertensive Agents:
Mechanism of Action
Angiotensin II Receptor Blockers…
• Allow angiotensin I to be converted to
angiotensin II, but block the receptors that
receive angiotensin II
• Block vasoconstriction and release of
aldosterone
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Antihypertensive Agents:
Angiotensin II Receptor Blockers:
•
•
•
•
•
•
Losartan (Cozaar)
eposartan (Teveten)
valsartan (Diovan)
irbesartan (Avapro)
candesartan (Atacand)
telmisartan (Micardis)
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Antihypertensive Agents:
Therapeutic Uses
Angiotensin II Receptor Blockers…
• Hypertension
• Adjunctive agents for the treatment of CHF
• May be used alone or with other agents such
as diuretics
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Antihypertensive Agents:
Side Effects
Angiotensin II Receptor Blockers
• Upper respiratory infections
• Headache
• May cause occasional dizziness, inability to
sleep, diarrhea, dyspnea, heartburn, nasal
congestion, back pain, fatigue
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Antihypertensive Agents:
Categories
Calcium Channel Blockers
• Benzothiazepines
• Dihydropyridines
• Phenylalkylamines
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Antihypertensive Agents:
Mechanism of Action
Calcium Channel Blockers…
• 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
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Antihypertensive Agents
Calcium Channel Blockers:• Benzothiazepines:
– diltiazem (Cardizem, Dilacor)
• Phenylalkamines:
– verapamil (Calan, Isoptin)
• Dihydropyridines:
– amlodipine (Norvasc), bepridil (Vascor),
nicardipine (Cardene)
– nifedipine (Procardia), nimodipine (Nimotop)
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Antihypertensive Agents:
Therapeutic Uses
Calcium Channel Blockers
•
•
•
•
Angina
Hypertension
Dysrhythmias
Migraine headaches
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Antihypertensive Agents:
Side Effects
Calcium Channel Blockers…
• Cardiovascular
– hypotension, palpitations, tachycardia
• Gastrointestinal
– constipation, nausea
• Other
– rash, flushing, peripheral edema, dermatitis
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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
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Antihypertensive Agents:
Diuretics…
• Examples of Diuretics used???
• Therapeutic uses???
• Side effects???
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Antihypertensive Agents:
Mechanism of Action
Vasodilators
• Directly relaxes arteriolar smooth muscle
• Result:
decreased systemic vascular
response, decreased afterload, and
PERIPHERAL VASODILATION
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Antihypertensive Agents
Vasodilators….
•
•
•
•
diazoxide (Hyperstat)
hydralazine HCl (Apresoline)
minoxidil (Loniten, Rogaine)
sodium nitroprusside (Nipride, Nitropress)
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Antihypertensive Agents:
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
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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
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Antihypertensive Agents:
Nursing Implications
• Before beginning therapy, obtain a
thorough health history and head-totoe physical examination.
• Assess for contraindications to specific
antihypertensive agents.
• Assess for conditions that require cautious
use of these agents.
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Antihypertensive Agents:
Nursing Implications
• 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.
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Antihypertensive Agents:
Nursing Implications
• Instruct patients that these drugs should not be
stopped abruptly, as this may cause a rebound
hypertensive crisis, and perhaps lead to CVA
(Cerebral Vascular Accident) or Stroke.
• 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.
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Antihypertensive Agents:
Nursing Implications
• 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.
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Antihypertensive Agents:
Nursing Implications
• 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.
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Antihypertensive Agents:
Nursing Implications
• 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.
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Antihypertensive Agents:
Nursing Implications
• 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.
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Antihypertensive Agents:
Nursing Implications
• 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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