Adrenergic agemts

Learning Objectives Understand the central and peripheral nervous systems, their functions, and their relationship to drugs. Become aware of the role of neurotransmitters. Learn how adrenergic drugs affect body systems and where they work in the body.

Learning Objectives Define the action of neuromuscular blocking agents in reducing muscle activity. Distinguish between narcotic and nonnarcotic analgesia. Become familiar with the various types of agents for migraine headaches.

Divisions of the Nervous System Central Nervous System – Brain – Spinal cord Peripheral Nervous System – Nerves – Sense organs

Divisions of the Nervous System Central Nervous System Peripheral Nervous System

Divisions of the Nervous System Central Nervous System Peripheral Nervous System – Somatic Nervous System – Autonomic Nervous System

Divisions of the Nervous System Central Nervous System Peripheral Nervous System – Somatic Nervous System Voluntary action: skeletal muscle contraction and movement – Autonomic Nervous System Involuntary activities: respiration, circulation, digestion, sweating

Autonomic Nervous System

Review The nervous system has two components. What are they?

Review The nervous system has two components. What are they? Answer – Central nervous system (CNS) – Peripheral nervous system (PNS)

Major Neurotransmitters Acetylcholine GABA Dopamine Epinephrine Serotonin

Major Neurotransmitters Acetylcholine (ACh) – Smooth muscle, cardiac muscle, and exocrine glands – Anticholinergics block ACh receptors GABA Dopamine Epinephrine Serotonin

Major Neurotransmitters Acetylcholine GABA (gamma-aminobutyric acid) Regulates message delivery system of the brain Dopamine Epinephrine Serotonin

Major Neurotransmitters Acetylcholine GABA Dopamine Acts on the CNS and kidneys Epinephrine Serotonin

Major Neurotransmitters Acetylcholine GABA Dopamine Epinephrine – Acts on cardiac and bronchodilator receptors – Known as Adrenaline Serotonin

Major Neurotransmitters Acetylcholine GABA Dopamine Epinephrine Serotonin – Acts on smooth muscle and gastric mucosa (causes vasoconstriction) – Emotional responses: depression, anxiety

Discussion What are three important types of receptors in the study of drugs?

Discussion What are three important types of adrenergic receptors in the study of drugs? Answer – Alpha – Beta-1 – Beta-2

Types of Receptors Alpha Vasoconstriction, raise BP Beta-1 Heart stimulation Beta-2 Vasodilation and bronchodilation

Drugs Affecting The Autonomic Nervous System Adrenergic Agents and Adrenergic-Blocking Agents

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 alpha 2 receptors Differentiated by their location on nerves

Alpha 1 -Adrenergic Receptors Located on postsynaptic effector cells (the cell, muscle, or organ that the nerve stimulates)

Alpha 2 -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 Beta 1 -adrenergic receptors—located primarily in the heart Beta 2 -adrenergic receptors—located 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 LOCATIONRECEPTORRESPONSE Cardiovascular Blood vesselsalpha 1 and beta 2 Constriction / dilation Cardiac musclebeta 1 Increased contractility AV Nodebeta 1 Increased heart rate SA Nodebeta 1 Increased heart rate

Adrenergic Receptor Responses to Stimulation LOCATIONRECEPTORRESPONSE Gastrointestinal Musclebeta 2 Decreased motility Sphinctersalpha 1 Constriction

Adrenergic Receptor Responses to Stimulation LOCATIONRECEPTORRESPONSE Genitourinary Bladderalpha 1 Constriction sphincter Penisalpha 1 Ejaculation Uterusalpha 1 and beta 2 Contraction/ relaxation

Adrenergic Receptor Responses to Stimulation LOCATIONRECEPTORRESPONSE Respiratory Bronchialbeta 2 Dilation/relaxation muscles

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

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

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

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 beta 2 -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 beta 2 -adrenergic receptors of bronchial smooth muscles causing relaxation Examples: albuterolephedrineepinephrine isoetharine isoproterenollevalbuterol metaproterenolsalmeterolterbutaline 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: epinephrineephedrinenaphazoline 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:epinephrinenaphazoline phenylephrinetetrahydrozoline

Adrenergic Agents: Therapeutic Uses Vasoactive sympathomimetics (pressors, inotropes), also called cardioselective sympathomimetics Used to support the heart during cardiac failure or shock. Examples: dobutaminedopamineephedrine epinephrinefenoldopamisoproterenol methoxaminenorepinephrine 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 inhibit—or LYSE—sympathetic neurotransmitters (norepinephrine and epinephrine)

Adrenergic Blocking Agents Classified by the type of adrenergic receptor they block Alpha 1 and alpha 2 receptors Beta 1 and beta 2 receptors

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 SystemSide/Adverse Effects CardiovascularPalpitations, orthostatic hypotension, tachycardia, edema, dysrhythmias, chest pain CNSDizziness, headache, drowsiness, anxiety, depression, vertigo, weakness, numbness, fatigue

Adrenergic-Blocking Agents: Side Effects Alpha Blockers Body SystemSide/Adverse Effects GastrointestinalNausea, vomiting, diarrhea, constipation, abdominal pain OtherIncontinence, nose bleeding, tinnitus, dry mouth, pharyngitis, rhinitis

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

Beta Receptors Beta 1 Receptors Located primarily on the heart Beta blockers selective for these receptors are called cardioselective beta blockers

Beta Receptors Beta 2 Receptors Located primarily on smooth muscles of bronchioles and blood vessels

Nonspecific Beta Blockers Beta blockers that block both beta 1 and beta 2 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 (Beta 1 and Beta 2 ) Effects on heart:Same as cardioselective Bronchioles:Constriction, resulting in narrowing of airways and shortness of breath Blood vessels:Vasoconstriction

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

Terbutalin (brikanil) and phenoterol (berotek, partusisten) are stimulants of mostly  2 -adrenal receptors. They posses broncholytic and tokolytic activity

Beta Blockers: Therapeutic Uses Antihypertensive Treatment of migraine headaches Glaucoma (topical use)

Beta Blockers: Side Effects Body SystemSide/Adverse Effects BloodAgranulocytosis, thrombocytopenia CardiovascularAV block, bradycardia, congestive heart failure, peripheral vascular insufficiency CNSDizziness, mental depression, lethargy, hallucinations

Adrenergic-Blocking Agents: Side Effects Beta Blockers Body SystemSide/Adverse Effects GastrointestinalNausea, dry mouth, vomiting, diarrhea, cramps, ischemic colitis OtherImpotence, rash, alopecia, bronchospasms