Shiken

Chapter 18: Adrenergic Drugs
Key Points
Anatomy, Physiology, and Pathophysiology Overview
 The body’s nervous system is divided into two major branches: the central nervous
system (CNS) and the peripheral nervous system.
 The central nervous system contains the brain and the spinal cord.
 The peripheral nervous system is subdivided into somatic and autonomic nervous
systems, and the autonomic nervous system is further subdivided into the
parasympathetic (cholinergic) and the sympathetic (adrenergic) nervous systems.
 Adrenergic compounds include several exogenous (synthetic) and endogenous
(produced in the body naturally) substances. They have a wide variety of therapeutic
uses depending on their site of action and their effect on different types of adrenergic
receptors.
 Catecholamines are substances that produce a sympathomimetic response (stimulate
the SNS). The naturally occurring or endogenous catecholamines include epinephrine,
norepinephrine, and dopamine. An example of an exogenous catecholamine is
dobutamine.
 There are receptor sites for the catecholamines norepinephrine and epinephrine
throughout the body referred to as adrenergic receptors. At these receptors, adrenergic
drugs bind and produce effects.
 The beta-adrenergic receptors are all located on postsynaptic effector cells. The beta1-
adrenergic receptors are primarily located in the heart, whereas the beta2-adrenergic
receptors are located in the smooth muscle fibers of the bronchioles, arterioles, and
visceral organs.
 Another type of adrenergic receptor is the dopaminergic receptor. When stimulated by
dopamine (only), these receptors cause the vessels of the renal, mesenteric, coronary,
and cerebral arteries to dilate, which increases blood flow to these tissues.
Pharmacology Overview
Adrenergic Drugs
 Adrenergics are drugs with effects that are similar to or mimic the effects of the SNS
neurotransmitters norepinephrine, epinephrine, and dopamine.
 They are either endogenous substances such as epinephrine, norepinephrine, and
dopamine, or synthetic substances such as dobutamine and phenylephrine. The three
endogenous catecholamines are also available in synthetic drug form.
 Non-catecholamine adrenergic drugs, such as phenylephrine, metaproterenol, and
albuterol, are structurally dissimilar to the endogenous catecholamines and have a
longer duration of action than either the endogenous or synthetic catecholamines.
 Epinephrine is available in two strengths for IV use, and was historically labeled as a
ratio, which led to many medication errors. It is available as 1 : 1000 (1 mg/mL) and also
as 1 : 10,000 (0.1 mg/mL). The FDA required the removal of ratio expressions of strength
Key Points
from the labeling of single-entry injectable drug products and replacement with the
amount per unit of volume, related to errors that occurred.
Mechanism of Action and Drug Effects
 A direct-acting sympathomimetic, such as epinephrine, binds directly to the receptor and
causes a physiologic response.
 An indirect-acting sympathomimetic causes the release of the catecholamine from the
storage sites (vesicles) in the nerve endings; it then binds to the receptors and causes a
physiologic response.
 Adrenergic agents can also be classified as either selective or nonselective in their
actions, meaning they affect only one receptor subtype.
 Although adrenergics work primarily at postganglionic receptors peripherally, they may
also work more centrally in the nervous system at the preganglionic sympathetic nerve
trunks.
 When beta1-adrenergic receptors, located on the myocardium and in the conduction
system of the heart, are stimulated by an adrenergic drug, three things result:
1. An increase in the force of contraction (positive inotropic effect)
2. An increase in heart rate (positive chronotropic effect) and
3. An increase in the conduction of cardiac electrical nerve impulses through the
atrioventricular node (positive dromotropic effect)
 In addition, stimulation of beta1 receptors in the kidney causes an increase in renin
secretion.
 Activation of beta2-adrenergic receptors produces relaxation of the bronchi
(bronchodilation) and uterus and also causes increased glycogenolysis (glucose release)
from the liver.
 Epinephrine is available in two strengths for IV use and was historically labeled as a
ratio, which led to many medication errors. Starting in May 2016, epinephrine injections
are labeled like all other injectable drugs in a mg/ml concentration, as 1 mg/mL or 0.1
mg/mL.
Indications
 Adrenergics, or sympathomimetics, are used in the treatment of a wide variety of
illnesses and conditions.
 Bronchodilators are drugs that have an affinity for the adrenergic receptors in the
respiratory system, preferentially stimulating the beta2-adrenergic receptors and
causing bronchodilation.
 The intranasal application of certain adrenergics can cause the constriction of dilated
arterioles and a reduction in nasal blood flow, which thus decreases congestion.
 Some adrenergics, called ophthalmics, are applied to the surface of the eye. They work
in much the same way as nasal decongestants except that they affect the vasculature of
the eye.
 Adrenergics can also be used to reduce intraocular pressure, which makes them useful
in the treatment of open-angle glaucoma. They can also dilate the pupils (mydriasis),
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Key Points
which makes them useful for diagnostic eye examinations. They produce these effects
by stimulating alpha- or beta2-adrenergic receptors, or both.
 Adrenergic agents are also used to support the cardiovascular system during cardiac
failure or shock and are referred to as vasoactive sympathomimetics, vasoconstrictive
drugs (known as vasopressive drugs, pressor drugs, or pressors), inotropes, or
cardioselective sympathomimetics.
 Adrenergics that have primarily cardioselective effects are referred to as vasoactive
adrenergics and are used to support a failing heart or treat shock or orthostatic
hypotension.
 The beta3 agonist, mirabegron (Myrbetriq), relaxes the detrusor muscle during the
storage phase of the bladder fill cycle which leads to an increase in bladder storage
capacity. This new mechanism of action is an improvement over other drugs for
overactive bladder.
 Mirabegron should not be used with silodosin, thioridazine, and certain
chemotherapeutic agents. It can increase the effects of desipramine, digoxin,
aripiprazole, colchicine, and others. It may decrease the effects of metoprolol,
tamoxifen, tramadol, and codeine.
 In 2014, a new oral drug called droxidopa (Northera) was approved for the treatment of
neurogenic orthostatic hypotension. Droxidopa is converted to norepinephrine in the
body. The most common adverse events are headache, dizziness, nausea, hypertension,
and fatigue.
Adverse Effects
 Unwanted CNS effects of the alpha-adrenergic drugs include headache, restlessness,
excitement, insomnia, and euphoria. Possible cardiovascular adverse effects of the
alpha-adrenergic drugs include chest pain, vasoconstriction, hypertension, tachycardia,
and palpitations or dysrhythmias. Effects on other body systems include anorexia (loss
of appetite), dry mouth, nausea, vomiting, and, rarely, taste changes.
 The beta-adrenergic drugs can adversely stimulate the CNS, causing mild tremors,
headache, nervousness, and dizziness, or the cardiovascular system, including increased
heart rate (positive chronotropy), palpitations (dysrhythmias), and fluctuations in blood
pressure.
 The toxic effects of adrenergic drugs are an extension of their common adverse effects,
such as seizures from excessive CNS stimulation, hypotension or hypertension,
dysrhythmias, palpitations, nervousness, dizziness, fatigue, malaise, insomnia,
headache, tremor, dry mouth, and nausea.
 The two most life-threatening effects involve the CNS and cardiovascular system.
Interactions
 Numerous drug interactions can occur and although many of the interactions result only
in a diminished effect because of direct antagonism at and competition for receptor
sites, some reactions can be life threatening.
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Key Points
Nursing Process
 Use of adrenergic agonists requires careful patient assessment and monitoring to
maximize therapeutic effects and minimize possible adverse effects.
 Focus assessment on a comprehensive health history with past and present medical
history, and obtain a past/present medication history. Also include specific system-
based questions and identify cautions, contraindications, and drug interactions.
 Perform a thorough head-to-toe physical assessment and thoroughly assess baseline
vital signs, including breath sounds, heart sounds, peripheral pulses, skin color, and
capillary refill.
 There are several nursing interventions that may maximize the therapeutic effects of
adrenergic drugs and minimize their adverse effects, such as checking package inserts
for the types and amounts of dilutional solutions to use with parenteral dosage forms.
 When these drugs are given via an inhaler or nebulizer, provide the patient with
complete, thorough, and age-appropriate instructions about correct use, storage, and
care of equipment.
 Patients with chronic lung disease who are receiving adrenergic drugs need to avoid
anything that may exacerbate their respiratory condition (e.g., food or other allergens,
cigarette smoking).
 If the patient has a chronic respiratory disease, such as emphysema or chronic asthma
or bronchitis, it is important for the patient to avoid contact with individuals who may
have infections to help minimize situations that would exacerbate the original problem.
Respiratory irritants must be avoided.
 With nasal preparations, rebound nasal congestion or ulcerations of the nasal mucosa
may occur if drugs are overused; therefore, educate patients to use these products only
as directed.
 Midodrine use requires careful blood pressure monitoring, so patient education about
supine blood pressure measurement and journaling of measured blood pressure values
is very important to the effective use of the drug.
 Myrbetriq, a newer drug for overactive bladder, is associated with dizziness and so
encourage the patient to avoid hazardous activities if this occurs. As with any patient
with overactive bladder, avoid liquids before bedtime.
 Inhaled forms of beta2 agonists are used for their bronchodilating action and must be
taken only as prescribed, with caution to avoid any overuse of the drug. Overdosage of
these drugs may lead to severe cardiovascular, CNS, and cerebrovascular adverse effects
and stimulation.
 Monitor for therapeutic effects of the adrenergic drugs. To evaluate for the occurrence
of adverse effects with adrenergic drugs, monitor for stimulation of the systems that are
affected, such as the cardiac system and the CNS.
18-4 create mnemonics for everything above