Adrenergic Agonists and Antagonists - Unit IV Autonomic Nervous System Drugs - PDF

UNIT IV Autonomic Nervous System Drugs 15 Adrenergic Agonists and Antagonists...

UNIT IV Autonomic Nervous System Drugs 15 Adrenergic Agonists and Antagonists http://evolve.elsevier.com/McCuistion/pharmacology OBJECTIVES Explain major responses to stimulation of adrenergic receptors. Describe nursing interventions, including patient teaching, Differentiate between selective and nonselective adrenergic associated with adrenergic agonists and adrenergic antagonists. agonists. Apply the Clinical Judgment [Nursing Process] for the patient Contrast the uses of alpha and beta antagonists. taking beta-adrenergic antagonists. Compare general side effects of adrenergic agonists and adrenergic Compare the indications of adrenergic agonists and adrenergic antagonists. antagonists. OUTLINE Sympathetic Nervous System, 175 Adrenergic Antagonists (Adrenergic Blockers), 182 Adrenergic Agonists, 175 Alpha-Adrenergic Antagonists, 183 Inactivation of Neurotransmitters, 177 Beta-Adrenergic Antagonists, 183 Classification of Sympathomimetics, 177 Clinical Judgment [Nursing Process]—Adrenergic Neuron Epinephrine, 180 Antagonists, 185 Central-Acting Alpha Agonists, 180 Adrenergic Neuron Antagonists, 186 Clonidine and Methyldopa, 180 Critical Thinking Case Study, 186 Clinical Judgment [Nursing Process]—Adrenergic Agonists, 182 Review Questions, 186 This chapter discusses two groups of drugs that affect the sympathetic ner- the effector organ cells. The efferent pathways in the ANS are divided vous system—adrenergic agonists, or sympathomimetics, and adrener- into two branches: the sympathetic and the parasympathetic nerves. gic antagonists, also called adrenergic blockers or sympatholytics—along Collectively, these two branches are called the sympathetic nervous sys- with their dosages and uses. tem and the parasympathetic nervous system (Fig. 15.1). The central nervous system (CNS) is the body’s primary nervous sys- The sympathetic and parasympathetic nervous systems act on the tem and consists of the brain and spinal cord. The peripheral nervous same organs but produce opposite responses to provide homeostasis system (PNS), located outside the brain and spinal cord, is made up of (balance; Fig. 15.2). Drugs act on the sympathetic and parasympathetic two divisions: the autonomic and the somatic. After interpretation by the nervous systems by either stimulating or depressing responses. CNS, the PNS receives stimuli and initiates responses to these stimuli. The autonomic nervous system (ANS), also called the visceral sys- tem, acts on smooth muscles and glands. Its functions include control SYMPATHETIC NERVOUS SYSTEM and regulation of the heart, respiratory system, gastrointestinal (GI) The sympathetic nervous system is also called the adrenergic system. tract, bladder, eyes, and glands. The ANS is an involuntary nervous Norepinephrine is the neurotransmitter that innervates smooth muscle. system, over which we have little or no control: we breathe, our hearts The adrenergic receptor organ cells are of four types: alpha1, alpha2, beat, and peristalsis continues without our realizing it. However, unlike beta1, and beta2 (Fig. 15.3). Norepinephrine is released from the ter- the ANS, the somatic nervous system is a voluntary system that inner- minal nerve ending and stimulates the cell receptors to produce a vates skeletal muscles, over which there is control. response. The two sets of neurons in the autonomic component of the PNS are the (1) afferent, or sensory, neurons and the (2) efferent, or motor, neurons. The afferent neurons send impulses to the CNS, where they ADRENERGIC AGONISTS are interpreted. The efferent neurons receive the impulses (information) Drugs that stimulate the sympathetic nervous system are called adren- from the brain and transmit these impulses through the spinal cord to ergic agonists, adrenergics, or sympathomimetics because they mimic 175 176 UNIT IV Autonomic Nervous System Drugs CENTRAL NERVOUS SYSTEM PERIPHERAL NERVOUS SYSTEM Brain Spinal cord Autonomic Somatic nervous system nervous system Sympathetic Parasympathetic nervous system nervous system Fig. 15.1 Subdivisions of the peripheral nervous system. BODY TISSUE/ORGAN SYMPATHETIC PARASYMPATHETIC RESPONSE RESPONSE Eye Dilates pupils Constricts pupils Lungs Dilates bronchioles Constricts bronchioles and increases secretions Heart Increases heart rate Decreases heart rate Blood vessels Constricts blood vessels Dilates blood vessels Gastrointestinal Relaxes smooth muscles Increases peristalsis of gastrointestinal tract Bladder Relaxes bladder muscle Constricts bladder Uterus Relaxes uterine muscle Salivary gland Increases salivation Fig. 15.2 Sympathetic and Parasympathetic Effects on Body Tissues. The sympathetic and parasympa- thetic nervous systems have opposite responses on body tissues and organs.  CHAPTER 15 Adrenergic Agonists and Antagonists 177 Adrenergic TABLE 15.1 Effects of Adrenergic Agonists terminal Cell with at Receptors nerve ending receptors Receptor Physiologic Responses Alpha Alpha1 Increases force of heart contraction; vasoconstriction increases NE blood pressure; mydriasis (dilation of pupils) occurs; Beta1 NE secretion in salivary glands decreases; urinary bladder NE relaxation and urinary sphincter contraction increases Beta2 Alpha2 Inhibits release of norepinephrine; dilates blood vessels; produces hypotension; decreases gastrointestinal motility and tone Beta1 Increases heart rate and force of contraction; increases renin secretion, which increases blood pressure Fig. 15.3 Sympathetic transmitters and receptors. NE, norepinephrine. Beta2 Dilates bronchioles; promotes gastrointestinal and uterine relaxation; promotes increase in blood glucose through PATIENT SAFETY glycogenolysis in the liver; increases blood flow in skeletal Intravenous (IV) adrenergic agonists and antagonists are high-alert medica- muscles tions because they can cause significant harm to a patient in the event of a medication error. the transmitter in the neuron, the transmitter may be degraded or reused. The two enzymes that inactivate norepinephrine are mono- the sympathetic neurotransmitters norepinephrine and epinephrine. amine oxidase (MAO), which is inside the neuron, and catechol-O- They act on one or more adrenergic receptor sites located in the effec- methyltransferase (COMT), which is outside the neuron. tor cells of muscles such as the heart, bronchiole walls, GI tract, uri- Drugs can prolong the action of the neurotransmitter (e.g., norepi- nary bladder, and ciliary muscles of the eye. There are many adrenergic nephrine) by either inhibiting reuptake, which prolongs the action of receptors. The four main receptors are alpha1, alpha2, beta1, and beta2, the transmitter, or inhibiting the degradation by enzymatic action. which mediate the major responses described in Table 15.1 and illus- trated in Fig. 15.4. Classification of Sympathomimetics The alpha-adrenergic receptors are located in the blood vessels, The sympathomimetic (adrenergic agonist) drugs that stimulate adren- eyes, bladder, and prostate. When the alpha1 receptors in vascular tis- ergic receptors are classified into three categories according to their sues (vessels) of muscles are stimulated, the arterioles and venules con- effects on organ cells. Categories include (1) direct-acting sympatho- strict; this increases peripheral resistance and blood return to the heart, mimetics, which directly stimulate the adrenergic receptor (e.g., epi- circulation improves, and blood pressure is increased. When too much nephrine or norepinephrine); (2) indirect-acting sympathomimetics, stimulation occurs, blood flow is decreased to the vital organs. which stimulate the release of norepinephrine from the terminal nerve The alpha2 receptors are located in the postganglionic sympathetic endings (e.g., amphetamine); and (3) mixed-acting (both direct- and nerve endings. When stimulated, they inhibit the release of norepi- indirect-acting) sympathomimetics, which stimulate the adrenergic nephrine, which leads to a decrease in vasoconstriction. This results in receptor sites and stimulate the release of norepinephrine from the ter- vasodilation and a decrease in blood pressure. minal nerve endings (e.g., ephedrine (Fig. 15.6). The beta1 receptors are located primarily in the heart but are also Pseudoephedrine is an example of a mixed-acting sympathomi- found in the kidneys. Stimulation of the beta1 receptors increases myo- metic. It acts indirectly by stimulating the release of norepinephrine cardial contractility and heart rate. from the nerve terminals, and it acts directly on the alpha1 and beta1 The beta2 receptors are found mostly in the smooth muscles of the receptors. Pseudoephedrine, like epinephrine, increases heart rate. lung and GI tract, the liver, and the uterine muscle. Stimulation of the It is not as potent a vasoconstrictor as epinephrine, and the risk of beta2 receptor causes (1) relaxation of the smooth muscles of the lungs, hemorrhagic stroke and hypertensive crisis is less. Pseudoephedrine, which results in bronchodilation; (2) a decrease in GI tone and motil- an over-the-counter (OTC) drug but controlled, is helpful to relieve ity; (3) activation of glycogenolysis in the liver and increased blood nasal and sinus congestion without rebound congestion. This drug is glucose; and (4) relaxation of the uterine muscle, which results in a contraindicated in hypertension, closed-angle glaucoma, bronchitis, decrease in uterine contraction (Fig. 15.5; see also Table 15.1). emphysema, and urinary retention, and should be used with caution Other adrenergic receptors are dopaminergic and are located in the in diabetes mellitus. renal, mesenteric, coronary, and cerebral arteries. When these recep- Catecholamines are the chemical structures of a substance, either tors are stimulated, the vessels dilate and blood flow increases. Only endogenous or synthetic, that can produce a sympathomimetic dopamine can activate these receptors. response. Examples of endogenous catecholamines are epinephrine, norepinephrine, and dopamine. The synthetic catecholamines are iso- Inactivation of Neurotransmitters proterenol and dobutamine. Noncatecholamines such as phenyleph- After the neurotransmitter (e.g., norepinephrine) has performed rine, metaproterenol, and albuterol stimulate the adrenergic receptors. its function, the action must be stopped to prevent prolonging the Most noncatecholamines have a longer duration of action than the effect. Transmitters are inactivated by (1) reuptake of the transmitter endogenous or synthetic catecholamines. back into the neuron (nerve cell terminal), (2) enzymatic transfor- Many of the adrenergic agonists stimulate more than one of the mation or degradation, and (3) diffusion away from the receptor. The adrenergic receptor sites. An example is epinephrine, which acts on mechanism of norepinephrine reuptake plays a more important role alpha1-, beta1-, and beta2-adrenergic receptor sites. The responses from in inactivation than does the enzymatic action. After the reuptake of these receptor sites include increase in blood pressure, pupil dilation, 178 UNIT IV Autonomic Nervous System Drugs Alpha1 receptor Alpha2 receptor Blood vessels Eye Bladder Prostate Blood vessels Smooth muscle (gastrointestinal tract) Vasoconstriction Mydriasis Relaxation Contraction Decreased (pupil dilation) blood pressure (reduced Decreased norepinephrine) gastrointestinal tone and Increased motility blood pressure Increased contractibility of the heart Beta1 receptor Beta2 receptor Heart Kidney Smooth muscle Lungs Uterus Liver (gastrointestinal tract) Increased Increased Bronchodilation Relaxation of Activation of heart renin Decreased uterine smooth glycogenolysis contraction secretion gastrointestinal muscle tone and motility Increased Increased Increased blood sugar heart rate angiotensin Increased blood pressure Fig. 15.4 Effects of activation of alpha1, alpha2, beta1, and beta2 receptors. increase in heart rate (tachycardia), and bronchodilation. In anaphy- muscle and bronchodilation to prevent and treat bronchospasm. A lactic shock, epinephrine is useful because it increases blood pressure, patient with asthma may tolerate albuterol better than isoproterenol, heart rate, and airflow through the lungs. Because epinephrine affects which activates beta1 and beta2 receptors, because albuterol’s action is different adrenergic receptors, it is nonselective. Additional side effects more selective; it activates only the beta2 receptors of smooth muscle result when more responses occur than are desired. Pseudoephedrine in the lungs and uterus, and in the vasculature that supplies the skel- is commonly used for illegal production of amphetamine and meth- etal muscles. By using selective sympathomimetics, fewer undesired amphetamine. National regulatory measures control pseudoephedrine adverse effects will occur. However, high dosages of albuterol may drug sales with individual limits of 3.6 g/day and 9 g within 30 days. affect beta1 receptors, causing an increase in heart rate. Identifications are scanned with each purchase. The database is linked Tremors, headache, and nervousness are the most common side nationally and keeps a 2-year tally. Prototype Drug Chart: Epineph- effects of oral or inhalation albuterol. Other side effects include tachy- rine lists the pharmacologic behavior of epinephrine. cardia, palpitations, dizziness, dysrhythmia, nausea, vomiting, and Albuterol sulfate, a beta2-adrenergic agonist, is selective for beta2- urinary retention. Beta antagonists (beta blockers) may inhibit the adrenergic receptors, so the response is relaxation of bronchial smooth action of albuterol.  CHAPTER 15 Adrenergic Agonists and Antagonists 179 Eye (dilate pupil) Lung (dilate bronchioles) Heart SYMPATHETIC (increased heart rate) Blood vessel (constrict) Ganglion Spinal cord Gastrointestinal (relax) Bladder (relax) Uterus (relax) Fig. 15.5 Sympathetic Responses. Stimulation of the sympathetic nervous system or use of sympathomi- metic (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. Direct-acting Indirect-acting Mixed-acting sympathomimetic sympathomimetic sympathomimetic D R D D R D R D E NE E D E NE C N E C NE C NE D E E NE E NE P NE P P NE NE T NE T NE T D O NE O D NE O D R D R R D A B C D = Sympathomimetic drug NE = Norepinephrine Fig. 15.6 (A) Direct-acting sympathomimetics. (B) Indirect-acting sympathomimetics. (C) Mixed-acting sym- pathomimetics. 180 UNIT IV Autonomic Nervous System Drugs PROTOTYPE DRUG CHART Epinephrine Pharmacokinetics. Epinephrine is usually administered intramus- Epinephrine cularly, intravenously, or endotracheally. It is not given orally because it is rapidly metabolized in the GI tract and liver, which results in unsta- Drug Class Dosage ble serum levels. Subcutaneous administration is not recommended as Sympathomimetic: adrenergic Anaphylaxis: absorption is slower and less dependable for anaphylaxis. The half-life agonist A: IM/subcut: 0.3 mg EpiPen auto of epinephrine is less than 5 minutes intravenously (IV), and the per- injector, may repeat in 5–20 min; centage by which the drug is protein bound is unknown. Epinephrine max: 2 doses is metabolized by the liver and is excreted in the urine. IV: 0.1–0.25 mg of 0.1 mg/mL Pharmacodynamics. Epinephrine is frequently used in emergencies solution, may repeat q5–15min to treat anaphylaxis, a life-threatening allergic response. Epinephrine is PRN; may follow with 1–4 mcg/ a potent inotropic (myocardial contraction-strengthening) drug that min infusion increases cardiac output, promotes vasoconstriction and systolic blood pressure elevation, increases heart rate, and produces bronchodilation. Contraindications Drug-Lab-Food Interactions High doses can result in cardiac dysrhythmia, which necessitates Caution: Parkinsonism, closed-angle Drug: Increased effects with TCAs electrocardiogram (ECG) monitoring. Epinephrine can also cause glaucoma, cerebrovascular and MAOIs; methyldopa and beta renal vasoconstriction, thereby decreasing renal perfusion and urinary disease, labor, hypertension, blockers antagonize epinephrine output. cardiac disease, hyperthyroidism, effects; digoxin may cause The onset of action and peak concentration times are rapid. The diabetes mellitus, renal dysrhythmias with epinephrine use of decongestants with epinephrine has an additive effect. When dysfunction, hypovolemia, renal Lab: Increased blood glucose, serum epinephrine is administered with digoxin, cardiac dysrhythmia may disease, breastfeeding, pregnancy lactic acid 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. Pharmacokinetics Pharmacodynamics Absorption: Subcut/IM/IV: Rapidly; Subcut: Onset: 5–10 min Side Effects and Adverse Reactions inactivated in GI tract Peak: 20 min Undesired side effects frequently result when the adrenergic drug dos- Distribution: PB: UK Duration: 1–4 h age is increased or when the drug is nonselective. Side effects com- Metabolism: t½: , Greater than;