Page 203 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 11 Antihypertensive Agents 189

Captopril, particularly when given in high doses to patients with Once the presence of hypertension is established, the question
renal insufficiency, may cause neutropenia or proteinuria. Minor of whether to treat and which drugs to use must be considered.
toxic effects seen more typically include altered sense of taste, The level of blood pressure, the age of the patient, the severity of
allergic skin rashes, and drug fever, which may occur in up to 10% organ damage (if any) due to high blood pressure, and the pres-
of patients. ence of cardiovascular risk factors all must be considered. Assess-
Important drug interactions include those with potassium ment of renal function and the presence of proteinuria are useful
supplements or potassium-sparing diuretics, which can result in in antihypertensive drug selection. Treatment thresholds and goals
hyperkalemia. Nonsteroidal anti-inflammatory drugs may impair are described in Table 11–1. At this stage, the patient must be
the hypotensive effects of ACE inhibitors by blocking bradykinin- educated about the nature of hypertension and the importance
mediated vasodilation, which is at least in part prostaglandin of treatment so that he or she can make an informed decision
mediated. regarding therapy.
Once the decision is made to treat, a therapeutic regimen must
be developed. Selection of drugs is dictated by the level of blood
ANGIOTENSIN RECEPTOR-BLOCKING pressure, the presence and severity of end-organ damage, and the
AGENTS presence of other diseases. Severe high blood pressure with life-
threatening complications requires more rapid treatment with
Losartan and valsartan were the first marketed blockers of the more efficacious drugs. Most patients with essential hypertension,
angiotensin II type 1 (AT ) receptor. Azilsartan, candesartan, however, have had elevated blood pressure for months or years,
1
eprosartan, irbesartan, olmesartan, and telmisartan are also and therapy is best initiated in a gradual fashion.
available. They have no effect on bradykinin metabolism and are Education about the natural history of hypertension and the
therefore more selective blockers of angiotensin effects than ACE importance of treatment adherence as well as potential adverse
inhibitors. They also have the potential for more complete inhibi- effects of drugs is essential. Obesity should be treated and drugs
tion of angiotensin action compared with ACE inhibitors because that increase blood pressure (sympathomimetic decongestants,
there are enzymes other than ACE that are capable of generating nonsteroidal anti-inflammatory drugs, oral contraceptives, and
angiotensin II. Angiotensin receptor blockers provide benefits some herbal medications) should be eliminated if possible. Follow-
similar to those of ACE inhibitors in patients with heart failure up visits should be frequent enough to convince the patient that
and chronic kidney disease. Losartan’s pharmacokinetic parameters the physician thinks the illness is serious. With each follow-up
are listed in Table 11–2. The adverse effects are similar to those visit, the importance of treatment should be reinforced and ques-
described for ACE inhibitors, including the hazard of use during tions concerning dosing or side effects of medication encouraged.
pregnancy. Cough and angioedema can occur but are uncom- Other factors that may improve compliance are simplifying dosing
mon. Angiotensin receptor-blocking drugs are most commonly regimens and having the patient monitor blood pressure at home.
used in patients who have had adverse reactions to ACE inhibi-
tors. Combinations of ACE inhibitors and angiotensin receptor
blockers or aliskiren, which had once been considered useful for OUTPATIENT THERAPY OF
more complete inhibition of the renin-angiotensin system, are not HYPERTENSION
recommended due to toxicity demonstrated in recent clinical trials.
The initial step in treating hypertension may be nonpharmaco-
logic. Sodium restriction may be effective treatment for some
CLINICAL PHARMACOLOGY OF patients with mild hypertension. The average American diet con-
ANTIHYPERTENSIVE AGENTS tains about 200 mEq of sodium per day. A reasonable dietary goal
in treating hypertension is 70–100 mEq of sodium per day, which
Hypertension presents a unique problem in therapeutics. It is usu- can be achieved by not salting food during or after cooking and by
ally a lifelong disease that causes few symptoms until the advanced avoiding processed foods that contain large amounts of sodium.
stage. For effective treatment, medicines that may be expensive Eating a diet rich in fruits, vegetables, and low-fat dairy products
and sometimes produce adverse effects must be consumed daily. with a reduced content of saturated and total fat, and moderation
Thus, the physician must establish with certainty that hypertension of alcohol intake (no more than two drinks per day) also lower
is persistent and requires treatment and must exclude secondary blood pressure.
causes of hypertension that might be treated by definitive surgical Weight reduction even without sodium restriction has been
procedures. Persistence of hypertension, particularly in persons shown to normalize blood pressure in up to 75% of overweight
with mild elevation of blood pressure, should be established by patients with mild to moderate hypertension. Regular exercise has
finding an elevated blood pressure on at least three different office been shown in some but not all studies to lower blood pressure in
visits. Ambulatory blood pressure monitoring may be the best pre- hypertensive patients.
dictor of risk and therefore of need for therapy in mild hyperten- For pharmacologic management of mild hypertension, blood
sion, and is recommended for initial evaluation of all patients in pressure can be normalized in many patients with a single drug.
the guidelines of some countries. Isolated systolic hypertension and Most patients with moderate to severe hypertension require
hypertension in the elderly also benefit from therapy. two or more antihypertensive medications (see Box: Resistant