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 Answer Central nervous system (CNS) 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

Communication by Neurotransmitters Neurotransmitters are released from one axon and received by another neuron’s dendrites.

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

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

Types of Receptors Alpha Beta-1 Beta-2 Vasoconstriction, raise BP 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 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 receptors—located primarily in the heart Beta2-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 LOCATION RECEPTOR RESPONSE Cardiovascular Blood vessels alpha1 and beta2 Constriction / dilation Cardiac muscle beta1 Increased contractility AV Node beta1 Increased heart rate SA Node beta1 Increased heart rate

Adrenergic Receptor Responses to Stimulation LOCATION RECEPTOR RESPONSE Gastrointestinal Muscle beta2 Decreased motility Sphincters alpha1 Constriction

Adrenergic Receptor Responses to Stimulation LOCATION RECEPTOR RESPONSE Genitourinary Bladder alpha1 Constriction sphincter Penis alpha1 Ejaculation Uterus alpha1 and beta2 Contraction/ relaxation

Adrenergic Receptor Responses to Stimulation LOCATION RECEPTOR RESPONSE Respiratory Bronchial beta2 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 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 naphazoline phenylephrine 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 inhibit—or LYSE—sympathetic neurotransmitters (norepinephrine and epinephrine)

Adrenergic Blocking Agents Classified by the type of adrenergic receptor they block Alpha1 and alpha2 receptors Beta1 and beta2 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 System Side/Adverse Effects Cardiovascular Palpitations, orthostatic hypotension, tachycardia, edema, dysrhythmias, chest pain CNS Dizziness, headache, drowsiness, anxiety, depression, vertigo, weakness, numbness, fatigue

Adrenergic-Blocking Agents: Side Effects Alpha Blockers Body System Side/Adverse Effects Gastrointestinal Nausea, vomiting, diarrhea, constipation, abdominal pain Other Incontinence, 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 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

Salbutamol (ventolin) selective b2-adrenomimetic of direct action Administration inhalations during attacks of bronchial asthma and bronchial spasms of other etiology, передчасних child delivery, бурхливій child delivery

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: 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 System Side/Adverse Effects Blood Agranulocytosis, thrombocytopenia Cardiovascular AV block, bradycardia, congestive heart failure, peripheral vascular insufficiency CNS Dizziness, mental depression, lethargy, hallucinations

Adrenergic-Blocking Agents: Side Effects Beta Blockers Body System Side/Adverse Effects Gastrointestinal Nausea, dry mouth, vomiting, diarrhea, cramps, ischemic colitis Other Impotence, rash, alopecia, bronchospasms

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 Fatigue Tachycardia (alpha blockers) Lethargy Bradycardia Depression Heart block Insomnia CHF Vivid nightmares Increased airway resistance

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

б) adrenomimetics of indirect action or sympathomimetics а) adrenomimetics of direct action б) adrenomimetics of indirect action or sympathomimetics Adrenoblockers or adrenolytics Sympatholytics

І. Adrenomimetics - і -adrenomimetics (adrenalin hydrochloride, noradrenalin hydrotartrate) 2. dopamine-, -, -adrenomimetics (dopamine) 3. -adrenomimetics (mesatone, naftizin, galazoline) 4. -adrenomimetics (isadrine, salbutamol, phenoterol, terbutalin, dobutamine) ІІ. Sympathomimetics (ephedrine hydrochloride) ІІІ. Adrenoblockers 1. -adrenoblockers (phentolamine, tropaphen, prasosine, pyroxan) 2. -adrenoblockers (anaprilin, athenolol, talinolol, acebutolol) 3. - і -adrenoblockers (labetalol) ІІІ. Sympatholytics (reserpine, octadine)

Adrenomimetcs

adrenaline hydrochloride Administration Adrenalin (epinephrine) is a hormone of medullar layer of adrenal glands which is used in a form of a remedy adrenaline hydrochloride It is an adrenomimetic which stimulates 1,- 2- and 1,- 2-adrenoreceptors Administration sudden stoppage of heart, for example, during surgical narcosis electric trauma shock and collapse conditions bronchial spasm hypoglycemic coma treatment of open-angle glaucoma

Noradrenalin hydrotartrate (norepinephrine) Is an adrenomimetic of direct action which stimulates 1-, 2- and 1-adrenal receptors Administration in cases of acute decreasing of blood pressure - shock and collapse conditions, surgeries, traumas The drug is absolutely contraindicated for subcutaneous and intramuscular introductions

Dopamine shock and collapse Drug of choice for treatment of of different etiology, including cardiogenic and hemorrhagic

Mesaton (phenilefrin) Is a synthetic a1-adrenomimetic drug of direct action Administration acute hypotensive conditions, prophylaxis of decreasing of blood pressure in case of infectious diseases, poisonings, decreasing of blood pressure during narcosis with fluorothan and cyclopropan nose drops in case of rhinits

Naphtisin Xylometazolin are a2-adrenomimetics of direct action Usage for rhinitis in a form of nose drops – 1-2 drops 2-3 times a day It is not recommended to use the drug in case of chronic cold

Isadrin (isoprenalin, novodrin, euspiran) – is a synthetic catecholamine, which is a strong stimulant of b1- і b2-adrenal receptors Administration bradycardia, atrio-ventricular blockade bronchial spasm complex therapy of some kinds of shock (if the patient doesn’t have hypovolemia) Side effects nausea, hands tremor, dryness in mouth, in patients with ischemic heart disease – attack of stenocardia, heavy cardiac tachyarrhythmias, even fibrillation of ventricles

Salbutamol (ventolin) selective b2-adrenomimetic of direct action Administration inhalations during attacks of bronchial asthma and bronchial spasms of other etiology, передчасних child delivery, бурхливій child delivery

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

Dobutamin Administration Is a synthetic 1-adrenomimetic Cardiotonic effects of dobutamin is 5 times stronger than action of dopamine Administration some forms of acute and chronic cardiac insufficiency intravenous dropping infusion with the speed of 2,5-10 mcg / (kg.min)

Sympathomimetics

Ephedrine hydrochloride (Ephedrini hydrochloridum) It is an alkaloid of plants of Ephedra family, which has indirect a-, b-adrenomimetic (sympathomimetic) action Administration collapse conditions, for prophylaxis of decreasing of blood pressure before spinal anesthesia, infectious diseases treatment of rhinitis (2 %, 3 % solution to drop into nose). prophylaxis and elimination of bronchial spasm (inhalations 0,5 %-1 % solutions of drug) SIDE EFFECTS неспокій, excitement, tremor, inconsiderable euphoria, insomnia, seizures drug addiction tachyphylaxy

Adrenoblockers

Alfa-adrenoblockers

Phentolamine, tropaphen are synthetic a1, 2-аdrenoblockers administration diagnostics and symptomatic treatment of feochromocytoma disturbances of peripheral blood circulation in case of endarteritis, Reino’s disease, trophic ulcers, decubitus complex treatment of hypertensive crises, acute cardiac insufficiency complex therapy of hypovolemic and cardiogenic shock

Selective a1- adrenoblocker Prasosin Selective a1- adrenoblocker Administration treatment of essential hypertension stabile cardiac insufficiency Side effects “phenomenon of first dose”: sudden decreasing of blood pressure and even development of orthostatic collapse after first administrations of the drug Prophylaxis: administration of half-dose before sleep

Beta-adrenoblockers

Anaprilin Administration essential hypertension Is a selective b1- і b2-adrenoblocker Administration ischemic heart disease essential hypertension cardiac tachyarrhythmias acute myocardium infarction

Talinolol or cordanum Administration is a cardioselective b-adrenoblocker Administration disorders of cardiac rhythm (extrasystolies, paroxysmal tachycardia, fibrillation and scintillation of atria) stenocardia arterial hypetension .

Atenolol (tenormin) essential hypertension cardiac arrhythmias cardioselelctive -adrenoblocker of long action Indications for administration ischemic heart disease essential hypertension cardiac arrhythmias acute myocardium infarction

1-adrenoblocker with internal sympathomimetic activity Acebutolol (sectral) 1-adrenoblocker with internal sympathomimetic activity Indications disorders of cardiac rhythm (tachyarrhythmias) hypertension ischemic heart disease

Labetolol Contraindications -, -adrenoblocker. The drug blocks 1, 2, 1 and 2-adrenoreceptors Administration treatment of patients with essential hypertension hypertensive crisis Contraindications Atrio-ventricular blockade, cardiac insufficiency

Sympatholytics

Reserpin Administration Side effects manifestations of parkinsonism is a sum of раувольфії (plant) alkaloids. Maximal hypotensive action develops after 5-7 days of regular administration of the drug. After the treatment coarse effect can still stay for two weeks. Administration treatment of different forms of essential hypertension (combined drugs trirezid, cristepin, adelfan, brinerdin) Side effects manifestations of parkinsonism в’ялість, somnolence, depression, bradycardia increasing of motor and secretory activity of gastro-intestinal tract, acute attacks of ulcer disease, diarrhea swelling of nose mucous membrane with complication of nose breathing

Octadin Is a sympatholytic with strong hypotensive effect. During administration of the drug decreasing of blood pressure develops gradually, after 2-3 days. After quitting of drug administration the effect still stays for 2 weeks. Administration heavy forms of arterial hypertension Side effects general weakness, nausea, vomiting, swelling of nose mucous membrane, diarrhea, storing of liquid in the organism, orthostatic collapse.

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