662
P A R T 8
Drugs acting on the cardiovascular system
• When the heart muscle is damaged and unable to
pump effectively.
• With severe blood loss, when volume drops
dramatically.
• When there is extreme stress and the body’s levels of
noradrenaline are depleted, leaving the body unable to
respond to stimuli to raise blood pressure.
■■
The cardiovascular system depends on pressure
changes to circulate blood to the tissues and back to
the heart.
■■
Heart rate, stroke volume and peripheral vascular
resistance are factors that determine blood pressure.
■■
Constriction and relaxation of the arterioles result in
peripheral resistance.
■■
The baroreceptors stimulate the medulla, which
stimulates the sympathetic nervous system to
constrict the blood vessels and increase fluid retention
if pressure is low in the aorta and the carotid arteries.
If pressure is too high, vasodilation and loss of fluid
result.
■■
A decrease in blood flow to the kidneys triggers the
renin–angiotensin–aldosterone system, by which the
blood vessels constrict and water is retained. This
activity increases blood pressure and restores blood
flow to the kidney.
■■
Hypertension is a sustained state of higher-than-
normal blood pressure that can lead to blood vessel
damage, atherosclerosis and damage to small vessels
in end organs.
■■
The cause of essential hypertension is unknown;
treatment varies among individuals.
ANTIHYPERTENSIVE AGENTS
Because an underlying cause of hypertension is usually
unknown, altering the body’s regulatory mechanisms
is the best treatment currently available. Drugs used to
treat hypertension work to alter the normal reflexes that
control blood pressure. See Figure 43.3 for a review of
the sites of action of drugs used to treat hypertension.
Treatment for essential hypertension does not cure the
disease but is aimed at maintaining the blood pressure
within normal limits to prevent the damage that hyper-
tension can cause. Not all people respond in the same
way to antihypertensive drugs because different factors
may contribute to each person’s hypertension. Individu-
als may have complicating conditions, such as diabetes
or acute myocardial infarction (AMI), that make it
unwise to use certain drugs.
Several different types of drugs that affect differ-
ent areas of blood pressure control may need to be used
in combination to maintain a person’s blood pressure
KEY POINTS
within normal limits. Trials of drugs and combina-
tions of drugs are often needed to develop an individual
regimen that is effective without producing adverse
effects that are unacceptable to the person (Box 43.2).
Research is ongoing into the treatment of more specific
hypertensions (e.g. pulmonary hypertension). The devel-
opment of drugs that target specific blood vessel sites
and chemicals could lead to a new approach to the treat-
ment of essential hypertension (Box 43.3).
Antihypertensive agents include angiotensin-
converting enzyme inhibitors, angiotensin II–receptor
blockers, calcium channel blockers, vasodilators and
other antihypertensive agents, including diuretic agents,
ganglionic receptors, renin inhibitors and sympathetic
nervous system drugs. See Table 43.2 for a complete list
of antihypertensive agents. See Box 43.4 for use of these
agents across the lifespan.
Treating hypertension
The importance of treating hypertension has been
proven in numerous research studies. If hypertension is
controlled, the person’s risk of cardiovascular death and
disease is reduced. The risk of developing cardiovascular
complications is directly related to the person’s degree
of hypertension (see Table 43.1). Lowering the degree of
hypertension lowers the risk.
Hypertensive treatment is further complicated by the
presence of other chronic conditions. The Heart Foun-
dation has published an algorithm for the treatment of
hypertension to help prescribers select an antihyper-
tensive agent in the light of complicating conditions
(Figure 43.4). A person’s response to a given antihyper-
tensive agent is very individual, so the drug of choice
for one person may have little to no effect on another
person.
A
ngiotensin
-
converting
-
enzyme
inhibitors
The
angiotensin-converting-enzyme (ACE) inhibi-
tors
include the following agents: captopril (
Capoten
,
Zedace
, others), enalapril (
Acetec
,
Amprace
,
Renitec
,
others), fosinopril (
Monace
,
Monopril
), lisinopril
(
Fibsol
,
Prinivil
,
Zestril
, others), perindopril (
Coversyl
,
Indopril, Perindo
), quinapril (
Accupril
,
Acquin, Qpril
),
ramipril (
Prilace
,
Ramace
) and trandolapril (
Dolapril,
Gopten
).
Therapeutic actions and indications
ACE inhibitors act in the lungs to prevent ACE from
converting angiotensin I to angiotensin II, a powerful
vasoconstrictor and stimulator of aldosterone release
(see Figure 43.3). This action leads to a decrease in blood
pressure and in aldosterone secretion, with a resultant
slight increase in serum potassium and a loss of serum
sodium and fluid.
