2. Hypertension
Hypertension is blood pressure elevated enough to perfuse tissues and organs
Primary (or essential) hypertension, in which no specific cause can be
identified, constitutes 90% of all cases of systemic hypertension. Th e average
age of onset is about 35 years.
Secondary hypertension, resulting from an identifiable cause, such as renal
disease or adrenal hyperfunction,
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4. Blood pressure = (stroke volume X heart rate) X total peripheral vascular
resistance (TPR)
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5. Predisposing factors
a. Family history of essential hypertension, stroke, and premature cardiac
disease.
b. Patient history of intermittent elevations in blood pressure.
c. Racial predisposition. Hypertension is more common among African Americans
than
Whites.
d. Obesity. Weight reduction has been shown to reduce blood pressure in a large
proportion of
hypertensive patients who are 10% above ideal body weight.
e. Smoking, resulting in vasoconstriction and activation of the sympathetic
nervous system, is a
major risk factor for cardiovascular disease.
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6. Predisposing factors
f. Stress
g. High dietary intake of saturated fats or sodium
h. Sedentary lifestyle
i. Diabetes mellitus
j. Hyperlipidemia
k. Major risk factors according to the JNC-7 include smoking, diabetes mellitus, age ( 55 for
men; 65 for women), family history of cardiovascular disease, and dyslipidemia.
l. Target-organ damage/clinical cardiovascular disease according to the JNC-7 includes heart
disease (e.g., left ventricular hypertrophy, angina, prior MI, heart failure), stroke or transient
ischemic attacks, nephropathy, peripheral artery disease, and retinopathy.
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7. Treatment
Candidates for treatment
(1) All patients with a diastolic pressure of 90 mm Hg, a systolic pressure of 140 mm Hg,or a combination
of both should receive antihypertensive drug therapy.
(2) For those patients with a diastolic pressure of 80 to 89 mm Hg or a systolic pressure of 120 to 139 mm
Hg (prehypertension), no drug treatment is indicated unless the patient has a compelling indication.
However, lifestyle modifications, such as weight reduction, dietary sodium reduction, increased physical
activity, and moderation of alcohol consumption, should be initiated.
For patients with hypertension who have diabetes or renal disease, the blood pressure goal recommended
by the JNC-7 is 130/80 mm Hg.
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8. Pharmacological treatment
most hypertensive patients will require two or more antihypertensive drugs.
Thiazide diuretics should be considered initial agents for treatment unless
there are compelling indications for other medications.
Agents such as ACE inhibitors, angiotensin-receptor blockers, -blockers, and
calcium channel blockers have all been recommended for patients who
cannot receive a thiazide diuretic or in combination with a thiazide diuretic
for adequate control of blood pressure. This may include the use of ACE
inhibitors in hypertensive patients having systolic dysfunction after a MI, a
diabetic nephropathy patient who might benefit from an ACE inhibitor in
combination with a diuretic, or a patient with HF.
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9. Diuretics: Thiazide diuretic
Antihypertensive effects are produced by directly dilating the arterioles and
reducing the total fluid volume.
Thiazide diuretics increase the following:
(a) Urinary excretion of sodium and water by inhibiting sodium and chloride
reabsorption in the distal convoluted (renal) tubules
(b) Urinary excretion of potassium and, to a lesser extent, bicarbonate
(c) The effectiveness of other antihypertensive agents by preventing re
expansion of extracellular and plasma volumes
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10. Diuretics: Thiazide diuretic
NSAIDs, interact to diminish the antihypertensive effects of the thiazide diuretics.
Precautions and monitoring effects
(a) Potassium ion (K) depletion may require supplementation, increased dietary
intake,or the use of a potassium-sparing diuretic, such as spironolactone
(b) Uric acid retention may occur; this is potentially significant in patients who are
predisposed to gout and related disorders.
(c) Blood glucose levels may increase, which may be significant in patients with
diabetes.
(d) Calcium levels may increase because of the potential for retaining calcium
ions.
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11. Diuretics: Loop diuretics
These agents are indicated when patients are unable to tolerate thiazides,
experience a loss of thiazide effectiveness, or have impaired renal function
(clearance <30 mL/min).
act primarily in the ascending loop of Henle; hence, they are called “loop”
diuretics. By acting within the loop of Henle, they decrease sodium
reabsorption.Their action is more intense but of shorter duration (1 to 4 hrs)
than that of the thiazides
As with the thiazides, the antihypertensive effect of loop diuretics may be
diminished by NSAIDs.
must be monitored closely for signs of hypovolemia
Transient deafness has been reported. If the patient is taking a potentially
ototoxic drug (e.g., an aminoglycoside antibiotic), another class of diuretic
(e.g., a thiazide diuretic) should be substituted
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12. Diuretics: Potassium-sparing diuretics
They are indicated for patients in whom potassium loss is significant and
supplementation is not feasible. These agents are often used in combination
with a thiazide diuretic because they potentiate the effects of the thiazide
while minimizing potassium loss.
Spironolactone is particularly useful in patients with hyperaldosteronism,as it
has direct antagonistic effects on aldosterone (aldosterone-receptor blocker).
Less potent than the thiazides and loop diuretics.
promote potassium retention.
Coadministration with ACE inhibitors or potassium supplements significantly
increases the risk of hyperkalemia
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13. Diuretics: Potassium-sparing diuretics
should be avoided in patients with acute renal failure and used with caution
in patients with impaired renal function (monitor serum creatinine) because
they can retain potassium.
Triamterene should not be used in patients with a history of kidneystones or
hepatic disease
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14. Beta Blocker
a) Relative cardioselective activity. blockers have a greater tendency to
occupy the 1-receptor in the heart, rather than the 2-receptors in the lungs.
(b) Intrinsic sympathomimetic activity. These agents have the ability to
release catecholamines and to maintain a satisfactory heart rate. Intrinsic
sympathomimetic activity may also prevent bronchoconstriction and other
direct -blocking actions
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15. Beta Blocker
Propranolol was the first -adrenergic blocking agent shown to block both 1-
and 2-receptors. The usual daily dose range is 40 to 160 mg. It is available
both as a rapid-acting product and a long-acting product (Inderal-LA®)
Metoprolol (Lopressor®) show relative cardioselective blocking activity, with
relatively less blockade of the beta2-receptors in the lung when compared to
propranolol. The usual daily dose is 50 to 100 mg. A sustained- release form
of the drug is now available, as the succinate salt (Toprol XL®), which
requires less frequent dosing (daily vs. once or twice daily for immediate-
release metoprolol).
Atenolol (Tenormin®) was the first -adrenergic blocking agent to combine
oncedaily dosing (nadolol) with relative cardioselective blocking activity
(metoprolol).The usual daily dose is 25 to 100 mg.
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16. Beta Blocker
Bisoprolol (Zebeta®) is a -adrenergic blocking agent that is cardioselective
and has no intrinsic sympathomimetic activity. It allows for once-daily dosing,
and the usual daily dose is 2.5 to 10 mg
Carvedilol (Coreg®) is a -adrenergic blocking agent that has -blocking
properties as well as -blocking properties, with a resultant vasodilation. Th e
drug is administered twice daily with a starting dose of 6.25 mg titrated at 7-
to 14-day intervals to a dose of 25 mg twice daily. Usual daily doses are 12.5
to 50 mg daily.
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19. Peripheral alpha1-adrenergic blockers
prazosin (Minipress®), terazosin (Hytrin®),and doxazosin (Cardura®)
Used for hypertensive patients who have not responded to initial antihypertensive
therapy
The alpha1-blockers (indirect vasodilators) block the peripheral postsynaptic
alpha1-adrenergic receptor, causing vasodilation of both arteries and veins. Also,
the incidence of reflex tachycardia is lower with these agents than with the
vasodilator hydralazine
First-dose phenomenon. A syncopal episode may occur within 30 to 90 mins of
the first dose; similarly associated are postural hypotension, nausea, dizziness,
headache,palpitations, and sweating. To minimize these eff ects, the first dose
should be limited to a small dose (1 mg) and administered just before bedtime
Additional adverse effects include diarrhea, weight gain, peripheral edema, dry
mouth, urinary urgency, constipation, and priapism.
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20. Centrally active alpha-agonists
Methyldopa, Clonidine
act primarily within the CNS on 2-receptors to decrease sympathetic outflow
to the cardiovascular system
Methyldopa decreases total peripheral resistance through the aforementioned
mechanism while having little effect on cardiac output or heart rate (except
in older patients).
Common untoward effects include orthostatic hypotension, fl uid
accumulation (in the absence of a diuretic), and rebound hypertension on
abrupt withdrawal. Sedation is a common finding upon initiating therapy and
when increasing doses; however, the sedative effect usually decreases with
continued therapy.
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21. Centrally active alpha-agonists
Clonidine
Clonidine is effective in patients with renal impairment, although they may
require a reduced dose or a longer dosing interval.
Clonidine stimulates 2-receptors centrally, decreasing vasomotor tone and
heart rate.
Intravenous administration causes an initial paradoxical increase in pressure
(diastolic and systolic) that is followed by a prolonged drop. As with
methyldopa, abrupt withdrawal can cause rebound hypertension
Clonidine has a tendency to cause or worsen depression, and it heightens the
depressant effects of alcohol and other sedating substances
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