Adrenergic Agonists and Antagonists

Here we shall discuss two groups of drugs that affect the sympathetic nervous
system—adrenergic agonists, or sympathomimetics, and adrenergic
antagonists, also called adrenergic blockers or sympatholytics—along with their
dosages and uses.

Adrenergic Agonists
Drugs that stimulate the sympathetic nervous system are called adrenergic
agonists, adrenergics, or sympathomimetics because they mimic the sympathetic
neurotransmitters norepinephrine and epinephrine. They act on one or
more adrenergic receptor sites located in the effector cells of muscles such as the
heart, bronchiole walls, gastrointestinal (GI) tract, urinary bladder, and ciliary
muscles of the eye. There are many adrenergic receptors. The four main receptors
are alpha1, alpha2, beta1, and beta2, which mediate the major responses described
in Table 15.1 and illustrated in Fig. 15.1.
The alpha-adrenergic receptors are located in the blood vessels, eyes, bladder, and
prostate. When the alpha1 receptors in vascular tissues (vessels) of muscles are
stimulated, the arterioles and venules constrict; this increases peripheral resistance
and blood return to the heart, circulation improves, and blood pressure is increased.
When too much stimulation occurs, blood flow is decreased to the vital organs.
The alpha2 receptors are located in the postganglionic sympathetic nerve endings.
When stimulated, they inhibit the release of norepinephrine, which leads to a
decrease in vasoconstriction. This results in vasodilation and a decrease in blood
pressure.
TABLE 15.1
Effects of Adrenergic Agonists at Receptors
Recepto
Physiologic Responses
r
Increases force of heart contraction; vasoconstriction increases blood
pressure; mydriasis (dilation of pupils) occurs; secretion in salivary
Alpha1
glands decreases; urinary bladder relaxation and urinary sphincter
contraction increases
Inhibits release of norepinephrine; dilates blood vessels; produces
Alpha2
hypotension; decreases gastrointestinal motility and tone
Increases heart rate and force of contraction; increases renin secretion,
Beta1
which increases blood pressure
Beta2 Dilates bronchioles; promotes gastrointestinal and uterine relaxation;
promotes increase in blood glucose through glycogenolysis in the liver;
Recepto
Physiologic Responses
r
increases blood flow in skeletal muscles
The beta1 receptors are located primarily in the heart but are also found in the
kidney. Stimulation of the beta 1 receptors increases myocardial contractility and
heart rate.
The beta2 receptors are found mostly in the smooth muscles of the lung and GI
tract, the liver, and the uterine muscle. Stimulation of the beta 2 receptor causes (1)
relaxation of the smooth muscles of the lungs, which results in bronchodilation; (2)
a decrease in GI tone and motility; (3) activation of glycogenolysis in the liver and
increased blood glucose; and (4) relaxation of the uterine muscle, which results in
a decrease in uterine contraction (Fig. 15.2; see also Table 15.1).
Other adrenergic receptors are dopaminergic and are located in the renal,
mesenteric, coronary, and cerebral arteries. When these receptors are stimulated,
the vessels dilate and blood flow increases. Only dopamine can activate these
receptors.
FIG. 15.1 Effects of activation of alpha1, alpha2, beta1, and beta2 receptors.
FIG. 15.2 Sympathetic responses. Stimulation of the sympathetic nervous system
or use of sympathomimetic (adrenergic agonist) drugs can cause the pupils and
bronchioles to dilate; heart rate to increase; blood vessels to constrict; and muscles
of the gastrointestinal tract, bladder, and uterus to relax, thereby decreasing
contractions.
Inactivation of Neurotransmitters
After the neurotransmitter (e.g., norepinephrine) has performed its function, the
action must be stopped to prevent prolonging the effect. Transmitters are
inactivated by (1) reuptake of the transmitter back into the neuron (nerve cell
terminal), (2) enzymatic transformation or degradation, and (3) diffusion away
from the receptor. The mechanism of norepinephrine reuptake plays a more
important role in inactivation than does the enzymatic action. Following the
reuptake of the transmitter in the neuron, the transmitter may be degraded or
reused. The two enzymes that inactivate norepinephrine are monoamine oxidase
(MAO), which is inside the neuron, and catechol-O-methyltransferase (COMT),
which is outside the neuron.
Drugs can prolong the action of the neurotransmitter (e.g., norepinephrine) by
either inhibiting reuptake, which prolongs the action of the transmitter, or
inhibiting the degradation by enzymatic action.
Classification of Sympathomimetics
The sympathomimetic (adrenergic agonist) drugs that stimulate adrenergic
receptors are classified into three categories according to their effects on organ
cells. Categories include (1) direct-acting sympathomimetics, which directly
stimulate the adrenergic receptor (e.g., epinephrine or norepinephrine); (2)
indirect-acting sympathomimetics, which stimulate the release of norepinephrine
from the terminal nerve endings (e.g., amphetamine); and (3) mixed-acting (both
direct- and indirect-acting) sympathomimetics, which stimulate the adrenergic
receptor sites and stimulate the release of norepinephrine from the terminal nerve
endings (e.g., ephedrine, Fig. 15.3).
Pseudoephedrine is an example of a mixed-acting sympathomimetic: It acts
indirectly by stimulating the release of norepinephrine from the nerve terminals,
and it acts directly on the alpha 1 and beta1 receptors. Pseudoephedrine, like
epinephrine, increases heart rate. It is not as potent a vasoconstrictor as
epinephrine, and the risk of hemorrhagic stroke and hypertensive crisis is less.
Pseudoephedrine is helpful to relieve nasal and sinus congestion without rebound
congestion.
Catecholamines are the chemical structures of a substance, either endogenous or
synthetic, that can produce a sympathomimetic response. Examples of endogenous
catecholamines are epinephrine, norepinephrine, and dopamine. The synthetic
catecholamines are isoproterenol and dobutamine. Noncatecholamines such as
phenylephrine, metaproterenol, and albuterol stimulate the adrenergic receptors.
Most noncatecholamines have a longer duration of action than the endogenous or
synthetic catecholamines.
FIG. 15.3 A, Direct-acting sympathomimetics. B, Indirect-acting
sympathomimetics. C, Mixed-acting sympathomimetics.
Many of the adrenergic agonists stimulate more than one of the adrenergic receptor
sites. An example is epinephrine, which acts on alpha 1-, beta1-, and beta2-
adrenergic receptor sites. The responses from these receptor sites include increase
in blood pressure, pupil dilation, increase in heart rate (tachycardia), and
bronchodilation. In anaphylactic shock, epinephrine is useful because it increases
blood pressure, heart rate, and airflow through the lungs. Because epinephrine
affects different adrenergic receptors, it is nonselective. Additional side effects
result when more responses occur than are desired. Pseudoephedrine is commonly
used for illegal production of amphetamine and methamphetamine. National
regulatory measures control pseudoephedrine drug sales with individual limits of
3.6 g/day and 9 g within 30 days. Identifications are scanned with each purchase.
The database is linked nationally and keeps a 2-year tally. Prototype Drug Chart
15.1 lists the pharmacologic behavior of epinephrine.
Epinephrine
Pharmacokinetics
Epinephrine can be administered subcutaneously, intravascularly (vastus lateralis),
intravenously, topically, by inhalation, or via intracardiac administration. It is not
given orally because it is rapidly metabolized in the GI tract and liver, which
results in unstable serum levels. The half-life of epinephrine and the percentage by
which the drug is protein bound are unknown. Epinephrine is metabolized by the
liver and is excreted in the urine.
Pharmacodynamics
Epinephrine is frequently used in emergencies to treat anaphylaxis, a life-
threatening allergic response. Epinephrine is a potent inotropic (myocardial
contraction–strengthening) drug that increases cardiac output, promotes
vasoconstriction and systolic blood pressure elevation, increases heart rate, and
produces bronchodilation. High doses can result in cardiac dysrhythmia, which
necessitates electrocardiogram (ECG) monitoring. Epinephrine can also cause
renal vasoconstriction, thereby decreasing renal perfusion and urinary output.
The onset of action and peak concentration times are rapid. The use of
decongestants with epinephrine has an additive effect. When epinephrine is
administered with digoxin, cardiac dysrhythmia may occur. Beta blockers can
antagonize the action of epinephrine. Tricyclic antidepressants (TCAs) and
monoamine oxidase inhibitors (MAOIs) allow epinephrine’s effects to be
intensified and prolonged.

PROTOTYPE DRUG CHART 15.1 Epinephrine

<, Less than; A, adult; CNS, central nervous
system; GI, gastrointestinal; h, hours; IM, intramuscular; IV, intravenous; MAOI,
monoamine oxidase inhibitor; max, maximum; min, minute; PB, protein
binding; PRN, as needed; q5min, every 5 minutes; subcut, subcutaneous; t½, half-
life; TCA, tricyclic antidepressant; UK, unknown.
∗ Pregnancy categories have been revised.
See www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/
Labeling/ucm093307.htm for more information.
Side Effects and Adverse Reactions
Undesired side effects frequently result when the adrenergic drug dosage is
increased or when the drug is nonselective. Side effects commonly associated with
adrenergic agonists include hypertension, tachycardia, palpitations, restlessness,
tremors, dysrhythmia, dizziness, urinary retention, nausea, vomiting, dyspnea, and
pulmonary edema.
Names of adrenergic drugs, the receptors they activate, dosage information, and
common uses are listed in Table 15.2. Epinephrine is also discussed in Chapter
55 as one of the drugs used during emergencies.
Albuterol
Albuterol sulfate, a beta2-adrenergic agonist, is selective for beta2-adrenergic
receptors, so the response is relaxation of bronchial smooth muscle and
bronchodilation. A patient with asthma may tolerate albuterol better than
isoproterenol, which activates beta1 and beta2 receptors, because albuterol’s action
is more selective; it activates only the beta 2 receptors of smooth muscle in the
lungs and uterus and in the vasculature that supplies the skeletal muscles. By using
selective sympathomimetics, fewer undesired adverse effects will occur. However,
high dosages of albuterol may affect beta1 receptors, causing an increase in heart
rate. Prototype Drug Chart 15.2 lists the drug data related to albuterol.
Pharmacokinetics
Albuterol sulfate is well absorbed from the GI tract and is extensively metabolized
by the liver. The half-life of albuterol via oral inhalation is 2.7 to 6 hours.
Pharmacodynamics
The primary use of albuterol is to prevent and treat bronchospasm. With inhalation,
the onset of action of albuterol is 5 to 15 minutes by inhalation, and the duration of
action is 2 to 6 hours.
Side Effects and Adverse Reactions
Tremors, restlessness, and nervousness are the most common side effects of oral or
inhalation albuterol. If albuterol is taken with an MAOI, a hypertensive crisis can
result. Other side effects include tachycardia, palpitations, dizziness, dysrhythmia,
nausea, vomiting, and urinary retention. Beta antagonists (beta blockers) may
inhibit the action of albuterol. Albuterol and the beta 2 drugs are also discussed
in Chapters 36 and 39, respectively.

Nursing Process: Patient-Centered Collaborative Care

Adrenergic Agonists
Assessment
• Record baseline vital signs for future comparisons.
• Assess the patient’s drug history.
• Determine patient’s health history. Most adrenergic agonists are contraindicated
if the patient has a cardiac dysrhythmia, narrow-angle glaucoma, or cardiogenic
shock.
• Determine baseline glucose level.
Nursing Diagnoses
• Sleep Pattern, Disturbed related to the adverse drug effect of insomnia
• Knowledge, Deficient related to drug administration
Planning
• Patient’s vital signs will be within acceptable ranges.
• Patient will experience therapeutic effects by improved blood pressure, breathing
pattern, and cardiac output.
Nursing Interventions
• Administer IV epinephrine 1 mg (10 mL of a 1:10,000 concentration per
American Heart Association [AHA] guidelines) for cardiac resuscitation; may
repeat every 3 to 5 minutes. Follow each dose with a 20-mL saline flush to ensure
proper delivery. Normally, epinephrine is administered 1 mg IV over 1 minute or
more.
• Monitor IV site frequently when administering norepinephrine bitartrate or
dopamine because extravasation of these drugs causes tissue damage and necrosis
within 12 hours. These drugs should be diluted sufficiently in IV fluids.
• Administer antidote, phentolamine mesylate, 5 to 10 mg, diluted in 10 to 15 mL
of normal saline infiltrated into the area for IV extravasation of norepinephrine and
dopamine.
• Record patient’s vital signs. Report signs of increasing blood pressure and
increasing heart rate. If the patient receives an alpha-adrenergic agonist
intravenously for shock, check the blood pressure every 3 to 5 minutes or as
indicated to avoid severe hypertension.
• Monitor ECG for dysrhythmia when adrenergic agonists are given intravenously.
• Report side effects of adrenergic drugs such as tachycardia, palpitations, tremors,
dizziness, and increased blood pressure.
• Check patient’s urinary output and assess for bladder distension. Urinary
retention can result from a high drug dose or continuous use of adrenergic agonists.
• Offer food to the patient when giving adrenergic agonists to avoid nausea and
vomiting.