Page 204 - Basic _ Clinical Pharmacology ( PDFDrive )

190 SECTION III Cardiovascular-Renal Drugs

Hypertension & Polypharmacy). Thiazide diuretics, ACE inhibi- blood pressure telemonitoring with pharmacist case management,
tors, angiotensin receptor blockers, and calcium channel blockers which has been shown to improve blood pressure control.
have all been shown to reduce complications of hypertension In addition to noncompliance with medication, causes of fail-
and may be used for initial drug therapy. There has been con- ure to respond to drug therapy include excessive sodium intake
cern that diuretics, by adversely affecting the serum lipid profile and inadequate diuretic therapy with excessive blood volume,
or impairing glucose tolerance, may add to the risk of coronary and drugs such as tricyclic antidepressants, nonsteroidal anti-
disease, thereby offsetting the benefit of blood pressure reduc- inflammatory drugs, over-the-counter sympathomimetics, abuse
tion. However, a large clinical trial comparing different classes of stimulants (amphetamine or cocaine), or excessive doses of
of antihypertensive mediations for initial therapy found that caffeine and oral contraceptives that can interfere with actions of
chlorthalidone (a thiazide diuretic) was as effective as other agents some antihypertensive drugs or directly raise blood pressure.
in reducing coronary heart disease death and nonfatal myocardial
infarction, and was superior to amlodipine in preventing heart MANAGEMENT OF HYPERTENSIVE
failure and superior to lisinopril in preventing stroke. Beta block- EMERGENCIES
ers are less effective in reducing cardiovascular events and are cur-
rently not recommended as first-line treatment for uncomplicated Despite the large number of patients with chronic hypertension,
hypertension. hypertensive emergencies are relatively rare. Marked or sudden
The presence of concomitant disease should influence selection elevation of blood pressure may be a serious threat to life, how-
of antihypertensive drugs because two diseases may benefit from a ever, and prompt control of blood pressure is indicated. Most
single drug. For example, drugs that inhibit the renin-angiotensin frequently, hypertensive emergencies occur in patients whose
system are particularly useful in patients with diabetes or evi- hypertension is severe and poorly controlled and in those who
dence of chronic kidney disease with proteinuria. Beta blockers suddenly discontinue antihypertensive medications.
or calcium channel blockers are useful in patients who also have
angina; diuretics, ACE inhibitors, angiotensin receptor blockers, Clinical Presentation & Pathophysiology
β blockers, or hydralazine combined with nitrates in patients who
also have heart failure; and α blockers in men who have benign Hypertensive emergencies include hypertension associated with
1
prostatic hyperplasia. Race may also affect drug selection: African vascular damage (termed malignant hypertension) and hyperten-
Americans respond better on average to diuretics and calcium sion associated with hemodynamic complications such as heart
channel blockers than to β blockers and ACE inhibitors. Chinese failure, stroke, or dissecting aortic aneurysm. The underlying
patients are more sensitive to the effects of β blockers and may pathologic process in malignant hypertension is a progressive
require lower doses. arteriopathy with inflammation and necrosis of arterioles. Vascular
If a single drug does not adequately control blood pressure, lesions occur in the kidney, which releases renin, which in turn
drugs with different sites of action can be combined to effectively stimulates production of angiotensin and aldosterone, which
lower blood pressure while minimizing toxicity (“stepped care”). If further increase blood pressure.
three drugs are required, combining a diuretic, an ACE inhibitor Hypertensive encephalopathy is a classic feature of malignant
or angiotensin receptor blocker, and a calcium channel blocker is hypertension. Its clinical presentation consists of severe headache,
often effective. If a fourth drug is needed, a sympathoplegic agent mental confusion, and apprehension. Blurred vision, nausea and
such as a β blocker or clonidine should be considered. In the vomiting, and focal neurologic deficits are common. If untreated,
USA, fixed-dose drug combinations containing a β blocker, plus the syndrome may progress over a period of 12–48 hours to
an ACE inhibitor or angiotensin receptor blocker, plus a thiazide; convulsions, stupor, coma, and even death.
and a calcium channel blocker plus an ACE inhibitor are available.
Fixed-dose combinations have the drawback of not allowing for Treatment of Hypertensive Emergencies
titration of individual drug doses but have the advantage of allow- The general management of hypertensive emergencies requires
ing fewer pills to be taken, potentially enhancing compliance. monitoring the patient in an intensive care unit with continuous
Assessment of blood pressure during office visits should recording of arterial blood pressure. Fluid intake and output must
include measurement of recumbent, sitting, and standing pres- be monitored carefully and body weight measured daily as an
sures. An attempt should be made to normalize blood pressure indicator of total body fluid volume during the course of therapy.
in the posture or activity level that is customary for the patient. Parenteral antihypertensive medications are used to lower
Although there is still some debate about how much blood blood pressure rapidly (within a few hours); as soon as reasonable
pressure should be lowered, the recent Systolic Blood Pressure blood pressure control is achieved, oral antihypertensive therapy
Intervention Trial (SPRINT) and several meta-analyses suggest a should be substituted because this allows smoother long-term
target systolic blood pressure of 120 mm Hg for patients at high management of hypertension. The goal of treatment in the first
cardiovascular risk. Systolic hypertension (> 150 mm Hg in the few hours or days is not complete normalization of blood pressure
presence of normal diastolic blood pressure) is a strong cardiovas- because chronic hypertension is associated with autoregula-
cular risk factor in people older than 60 years of age and should tory changes in cerebral blood flow. Thus, rapid normaliza-
be treated. Recent advances in outpatient treatment include home tion of blood pressure may lead to cerebral hypoperfusion