Drugs Affecting The Autonomic Nervous System

Adrenergic Agents and AdrenergicBlocking Agents

Instructors may choose to insert EIC Image #48: The Sympathetic Nervous System in Relationship to the Entire Nervous System

Adrenergic Agents
Drugs that stimulate the sympathetic nervous system (SNS)

Adrenergic Agents
Also known as adrenergic agonists or sympathomimetics

Adrenergic Agents
Mimic the effects of the SNS neurotransmitters: norepinephrine (NE) and epinephrine (EPI)

Adrenergic Receptors
Located throughout the body Are receptors for the sympathetic neurotransmitters Alpha-adrenergic receptors: respond to NE Beta-adrenergic receptors: respond to EPI

Alpha-Adrenergic Receptors
Divided into alpha1 and alpha2 receptors Differentiated by their location on nerves

Alpha1-Adrenergic Receptors
Located on postsynaptic effector cells (the cell, muscle, or organ that the nerve stimulates)

Alpha2-Adrenergic Receptors
Located on presynaptic nerve terminals (the nerve that stimulates the effector cells) Control the release of neurotransmitters

The predominant alpha-adrenergic agonist responses are:

Vasoconstriction and CNS stimulation

Beta-Adrenergic Receptors
All are located on postsynaptic effector cells
Beta1-adrenergic receptorslocated primarily in the heart Beta2-adrenergic receptorslocated in smooth muscle of the bronchioles, arterioles, and visceral organs

The beta-adrenergic agonist response results in:

Bronchial, GI, and uterine smooth muscle relaxation Glycogenolysis Cardiac stimulation

Dopaminergic Receptors
An additional adrenergic receptor Stimulated by dopamine Causes dilation of the following blood vessels, resulting in INCREASED blood flow
Renal Mesenteric Coronary Cerebral

Adrenergic Receptor Responses to Stimulation

LOCATION
Cardiovascular Blood vessels
Cardiac muscle AV Node

RECEPTOR
alpha1 and beta2 beta1 beta1

RESPONSE
Constriction / dilation Increased contractility Increased heart rate Increased heart rate

SA Node

beta1

Adrenergic Receptor Responses to Stimulation

LOCATION
Gastrointestinal Muscle
Sphincters

RECEPTOR
beta2 alpha1

RESPONSE
Decreased motility Constriction

Adrenergic Receptor Responses to Stimulation

LOCATION
Genitourinary Bladder sphincter Penis Uterus

RECEPTOR
alpha1 alpha1 alpha1 and beta2

RESPONSE
Constriction Ejaculation Contraction/ relaxation

Adrenergic Receptor Responses to Stimulation

LOCATION
Respiratory Bronchial muscles

RECEPTOR
beta2

RESPONSE
Dilation/relaxation

Catecholamines
Substances that can produce a sympathomimetic response

Endogenous:
epinephrine, norepinephrine,dopamine

Synthetic:
isoproterenol, dobutamine, phenylephrine

Adrenergic Agents Mechanism of Action

Direct-acting sympathomimetic:
Binds directly to the receptor and causes a physiologic response

Instructors may choose to insert EIC Image #52:

Direct-Acting Sympathomimetics

Adrenergic Agents Mechanism of Action

Indirect-acting sympathomimetic:
Causes the release of catecholamine from the storage sites (vesicles) in the nerve endings The catecholamine then binds to the receptors and causes a physiologic response

Instructors may choose to insert EIC Image #53: Indirect-Acting Sympathomimetics

Adrenergic Agents Mechanism of Action

Mixed-acting sympathomimetic:
Directly stimulates the receptor by binding to it AND Indirectly stimulates the receptor by causing the release of stored neurotransmitters from the vesicles in the nerve endings

Instructors may choose to insert EIC Image #54: Mixed-Acting Sympathomimetics

Drug Effects of Adrenergic Agents

Stimulation of alpha-adrenergic receptors on smooth muscles results in:
Vasoconstriction of blood vessels Relaxation of GI smooth muscles Contraction of the uterus and bladder Male ejaculation Decreased insulin release Contraction of the ciliary muscles of the eye (dilated pupils)

Drug Effects of Adrenergic Agents

Stimulation of beta2-adrenergic receptors on the airways results in:
Bronchodilation (relaxation of the bronchi) Uterine relaxation Glycogenolysis in the liver

Drug Effects of Adrenergic Agents

Stimulation of beta1-adrenergic receptors on the myocardium, AV node, and SA node results in CARDIAC STIMULATION:
Increased force of contraction (positive inotropic effect) Increased heart rate (positive chronotropic effect) Increased conduction through the AV node (positive dromotropic effect)

Adrenergic Agents: Therapeutic Uses

Anorexiants: adjuncts to diet in the short-term management of obesity
Examples: benzphetamine phentermine dextroamphetamine Dexedrine

Adrenergic Agents: Therapeutic Uses

Bronchodilators: treatment of asthma and bronchitis
Agents that stimulate beta2-adrenergic receptors of bronchial smooth muscles causing relaxation Examples: albuterol ephedrine epinephrine isoetharine isoproterenol levalbuterol metaproterenol salmeterol terbutaline These agents may also affect uterine and vascular smooth muscles.

Adrenergic Agents: Therapeutic Uses

Reduction of intraocular pressure and mydriasis (pupil dilation): treatment of open-angle glaucoma
Examples: epinephrine and dipivefrin

Adrenergic Agents: Therapeutic Uses

Nasal decongestant:
Intranasal (topical) application causes constriction of dilated arterioles and reduction of nasal blood flow, thus decreasing congestion. Examples: epinephrine ephedrine naphazoline phenylephrine tetrahydrozoline

Adrenergic Agents: Therapeutic Uses

Ophthalmic Topical application to the eye surface affects the vasculature of the eye, stimulating alpha receptors on small arterioles, thus relieving conjunctival congestion.
Examples: epinephrine phenylephrine naphazoline tetrahydrozoline

Adrenergic Agents: Therapeutic Uses

Vasoactive sympathomimetics (pressors, inotropes), also called cardioselective sympathomimetics
Used to support the heart during cardiac failure or shock. Examples: dobutamine dopamine ephedrine epinephrine fenoldopam isoproterenol methoxamine norepinephrine phenylephrine

Adrenergic Agents: Side Effects

Alpha-Adrenergic Effects
CNS:

headache, restlessness, excitement, insomnia, euphoria

Cardiovascular:

palpitations (dysrhythmias), tachycardia, vasoconstriction, hypertension

Other:

anorexia, dry mouth, nausea, vomiting, taste changes (rare)

Adrenergic Agents: Side Effects

Beta-Adrenergic Effects
CNS:
mild tremors, headache, nervousness, dizziness

Cardiovascular:
increased heart rate, palpitations (dysrhythmias), fluctuations in BP

Other:
sweating, nausea, vomiting, muscle cramps

Adrenergic Agents: Interactions

Anesthetic agents Tricyclic antidepressants MAOIs

Antihistamines
Thyroid preparations Antihypertensives Will directly antagonize another adrenergic agent, resulting in reduced effects

Adrenergic Agents: Nursing Implications

Assess for allergies and history of hypertension, cardiac dysrhythmias, or other cardiovascular disease. Assess renal, hepatic, and cardiac function before treatment. Perform baseline assessment of vital signs, peripheral pulses, skin color, temperature, and capillary refill. Include postural blood pressure and pulse. Follow administration guidelines carefully.

Adrenergic Agents: Nursing Implications

IV administration:
Check IV site often for infiltration Use clear IV solutions Use an infusion device/IV pump Infuse agent slowly to avoid dangerous cardiovascular effects Monitor cardiac rhythm

Adrenergic Agents: Nursing Implications

With chronic lung disease:
Instruct patients to avoid factors that exacerbate their condition. Encourage fluid intake (up to 3000 mL per day) if permitted. Educate about proper dosing and equipment care.
Salmeterol is indicated for PREVENTION of bronchospasms, not management of acute symptoms.

Adrenergic Agents: Nursing Implications

Overuse of nasal decongestants may cause rebound nasal congestion or ulcerations. Avoid OTC or other medications because of possible interactions. Administering two adrenergic agents together may precipitate severe cardiovascular effects such as tachycardia or hypertension. Inform patients taking inhaled isoproterenol that their sputum or saliva may turn pink.

Adrenergic Agents: Nursing Implications

Monitor for therapeutic effects (cardiovascular uses):
Decreased edema Increased urinary output Return to normal vital signs Improved skin color and temperature Increased LOC

Adrenergic Agents: Nursing Implications

Monitor for therapeutic effects (asthma):
Return to normal respiratory rate Improved breath sounds, fewer rales Increased air exchange Decreased cough Less dyspnea Improved blood gases Increased activity tolerance

Adrenergic-Blocking Agents
Bind to adrenergic receptors, but inhibit or block stimulation of the sympathetic nervous system (SNS)

Adrenergic Blocking Agents

Have the opposite effect of adrenergic agents Also known as
adrenergic antagonists or sympatholytics

Adrenergic Blocking Agents

Sympatholytics inhibitor LYSEsympathetic neurotransmitters (norepinephrine and epinephrine)

Adrenergic Blocking Agents

Classified by the type of adrenergic receptor they block
Alpha1 and alpha2 receptors Beta1 and beta2 receptors

Instructors may choose to insert EIC Image #55:

Alpha-Blocker Mechanisms

Adrenergic-Blocking Agents: Drug Effects and Therapeutic Uses

Ergot Alkaloids (Alpha-Blockers)
Constrict dilated arteries going to the brain (carotid arteries) Used to treat vascular headaches (migraines) Stimulate uterine contractions by inducing vasoconstriction Used to control postpartum bleeding

Adrenergic-Blocking Agents: Drug Effects and Therapeutic Uses

Alpha-Blockers
Cause both arterial and venous dilation, reducing peripheral vascular resistance and BP Used to treat hypertension Effect on receptors on prostate gland and bladder decreased resistance to urinary outflow, thus reducing urinary obstruction and relieving effects of BPH

Adrenergic-Blocking Agents: Drug Effects and Therapeutic Uses

Alpha-Blockers
Phentolamine
Quickly reverses the potent vasoconstrictive effects of extravasated vasopressors such as norepinephrine or epinephrine. Restores blood flow and prevents tissue necrosis.

Adrenergic-Blocking Agents: Side Effects

Alpha Blockers Body System Side/Adverse Effects
Cardiovascular Palpitations, orthostatic hypotension, tachycardia, edema, dysrhythmias, chest pain Dizziness, headache, drowsiness, anxiety, depression, vertigo, weakness, numbness, fatigue

CNS

Adrenergic-Blocking Agents: Side Effects

Alpha Blockers Body System Side/Adverse Effects
Gastrointestinal Nausea, vomiting, diarrhea, constipation, abdominal pain Incontinence, nose bleeding, tinnitus, dry mouth, pharyngitis, rhinitis

Other

Beta Blockers
Block stimulation of beta receptors in the SNS Compete with norepinephrine and epinephrine Selective and nonselective beta blockers

Beta Receptors
Beta1 Receptors
Located primarily on the heart Beta blockers selective for these receptors are called cardioselective beta blockers

Beta Receptors
Beta2 Receptors Located primarily on smooth muscles of bronchioles and blood vessels

Nonspecific Beta Blockers

Beta blockers that block both beta1 and beta2 receptors

Beta Blockers: Mechanism of Action

Cardioselective (Beta1)
Decreases heart rate Prolongs SA node recovery Slows conduction rate through the AV node Decreases myocardial contractility, thus decreasing myocardial oxygen demand

Beta Blockers: Mechanism of Action

Nonspecific (Beta1 and Beta2)
Effects on heart: Bronchioles: Same as cardioselective Constriction, resulting in narrowing of airways and shortness of breath Vasoconstriction

Blood vessels:

Beta Blockers: Therapeutic Uses

Anti-angina: Cardioprotective: Class II antidysrhythmic decreases demand for myocardial oxygen inhibits stimulation by circulating catecholamines

Beta Blockers: Therapeutic Uses

Antihypertensive Treatment of migraine headaches Glaucoma (topical use)

Beta Blockers: Side Effects

Body System
Blood

Side/Adverse Effects
Agranulocytosis, thrombocytopenia

Cardiovascular

AV block, bradycardia, congestive heart failure, peripheral vascular insufficiency Dizziness, mental depression, lethargy, hallucinations

CNS

Adrenergic-Blocking Agents: Side Effects

Beta Blockers Body System
Gastrointestinal

Side/Adverse Effects
Nausea, dry mouth, vomiting, diarrhea, cramps, ischemic colitis Impotence, rash, alopecia, bronchospasms

Other

Adrenergic Blocking Agents: Nursing Implications

Assess for allergies and history of COPD, hypotension, cardiac dysrhythmias, bradycardia, CHF, or other cardiovascular problems
Any preexisting condition that might be exacerbated by the use of these agents might be a CONTRAINDICATION to their use.

Adrenergic Blocking Agents: Nursing Implications

Remember that alpha blockers may precipitate hypotension. Remember that beta blockers may precipitate bradycardia, hypotension, heart block, CHF, and bronchoconstriction.

Adrenergic Blocking Agents: Nursing Implications

Avoid OTC medications because of possible interactions. Possible drug interactions may occur with:
Antacids (aluminum hydroxide type) Antimuscarinics/anticholinergics Diuretics and cardiovascular drugs

Neuromuscular blocking agents

Oral hypoglycemic agents

Adrenergic Blocking Agents: Nursing Implications

Encourage patients to take medications as prescribed. These medications should never be stopped abruptly. Report constipation or the development of any urinary hesitancy or bladder distention.

Adrenergic Blocking Agents: Nursing Implications

Teach patients to change positions slowly to prevent or minimize postural hypotension. Avoid caffeine (excessive irritability). Avoid alcohol ingestion and hazardous activities until blood levels become stable. Patients should notify their physician if palpitations, dyspnea, nausea, or vomiting occur.

Beta Blocking Agents: Nursing Implications

Rebound hypertension or chest pain may occur if this medication is discontinued abruptly. Patients should notify their physician if they become ill and unable to take medication. Inform patients that they may notice a decrease in their tolerance for exercise; dizziness and fainting may occur with increased activity. Notify the physician if these problems occur.

Beta Blocking Agents: Nursing Implications

Patients should report the following to their physician:
Weight gain of more than 2 pounds (1 kg) within a week Edema of the feet or ankles Shortness of breath Excessive fatigue or weakness Syncope or dizziness

Adrenergic Blocking Agents: Nursing Implications

Monitor for side effects, including:
Hypotension Tachycardia (alpha blockers) Bradycardia Heart block CHF
Increased airway resistance

Fatigue Lethargy Depression Insomnia Vivid nightmares

Adrenergic Blocking Agents: Nursing Implications

Monitor for therapeutic effects
Decreased chest pain in patients with angina Return to normal BP and P Other specific effects, depending on the use