DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Table 27–5
Classification of Antihypertensive Drugs by Their Primary Site or Mechanism of Action
Diuretics (Chapter 25)
1. Thiazides and related agents (hydrochlorothiazide, chlorthalidone, chlorothiazide, indapamide, methylclothiazide,
metolazone)
2. Loop diuretics (furosemide, bumetanide, torsemide, ethacrynic acid)
3. K + -sparing diuretics (amiloride, triamterene, spironolactone)
Sympatholytic drugs (Chapter 12)
1. β receptor antagonists (metoprolol, atenolol, betaxolol, bisoprolol, carteolol, esmolol, nadolol, nebivolol, penbutolol,
pindolol, propranolol, timolol)
2. α receptor antagonists (prazosin, terazosin, doxazosin, phenoxybenzamine, phentolamine)
3. Mixed α-β receptor antagonists (labetalol, carvedilol)
4. Centrally acting adrenergic agents (methyldopa, clonidine, guanabenz, guanfacine)
5. Adrenergic neuron blocking agents (guanadrel, reserpine)
Ca 2+ channel blockers (verapamil, diltiazem, nisoldipine, felodipine, nicardipine, isradipine, amlodipine, clevidipine,
nifedipine a )
Angiotensin-converting enzyme inhibitors (Chapter 26; captopril, enalapril, lisinopril, quinapril, ramipril, benazepril,
fosinopril, moexipril, perindopril, trandolapril)
AngII receptor antagonists (Chapter 26; losartan, candesartan, irbesartan, valsartan, telmisartan, eprosartan, olmesartan)
Direct Renin Inhibitor (Chapter 26; aliskiren)
Vasodilators
1. Arterial (hydralazine, minoxidil, diazoxide, fenoldopam)
2. Arterial and venous (nitroprusside)
a
Extended-release nifedipine is approved for hypertension.
be classified according to their sites or mechanisms of
action (Table 27–5).
The hemodynamic consequences of long-term
treatment with antihypertensive agents (Table 27–6)
provide a rationale for potential complementary effects
of concurrent therapy with two or more drugs. The
simultaneous use of drugs with similar mechanisms of
action and hemodynamic effects often produces little
additional benefit. However, concurrent use of drugs
from different classes is a strategy for achieving effective
control of blood pressure while minimizing doserelated
adverse effects.
It generally is not possible to predict the responses of individuals
with hypertension to any specific drug. For example, for some
antihypertensive drugs, on average about two-thirds of patients will
have a meaningful clinical response, whereas about one-third of
patients will not respond to the same drug. Racial origin and age
may have modest influence on the likelihood of a favorable response
to a particular class of drugs. There is considerable interest in identifying
genetic variation to improve selection of antihypertensive
drugs in individual patients. Polymorphisms in a number of genes
involved in the metabolism of antihypertensive drugs have been
identified, for example in the CYP family (phase I metabolism) and
in phase II metabolism, such as catechol-O-methyltransferase (see
Chapters 6 and 7). While these polymorphisms change the pharmacokinetics
of specific drugs, it is not clear that there will be substantial
differences in efficacy given the dose range available clinically
for these drugs. Consequently, identification of polymorphisms that
influence pharmacodynamic responses to antihypertensive drugs are
of considerable interest. Polymorphisms influencing the actions of a
number of classes of antihypertensive drugs, including ACE
inhibitors and diuretics, have been identified; so far, individual genes
have not been found to have a major impact on pharmacodynamic
responses. Genome-wide scanning may lead to identification of
novel genes that are more clinically significant. Likewise, treatment
may benefit from an increased understanding of the molecular and
genetic bases of hypertension (Charchar et al., 2008; Shih and
O’Connor, 2008).
DIURETICS
An early strategy for the management of hypertension
was to alter Na + balance by restriction of salt in the diet.
Pharmacological alteration of Na + balance became
practical with the development of the orally active thiazide
diuretics (see Chapter 25). These and related
diuretic agents have antihypertensive effects when used