Adrenergics & Cholinergics - Students PDF

Adrenergics & Cholinergics Ann M. Bowling, PhD, APRN, CPNP-PC, CNE, CHSE Copyright © 2022, Else Autonom ic Nervous System  Class Activity Diagram and Pneumonic What Drugs Do I Need to Know?  Drug Classes ◦ Indications (Drug Effects) ◦ Mec...

Adrenergics & Cholinergics Ann M. Bowling, PhD, APRN, CPNP-PC, CNE, CHSE Copyright © 2022, Else Autonom ic Nervous System  Class Activity Diagram and Pneumonic What Drugs Do I Need to Know?  Drug Classes ◦ Indications (Drug Effects) ◦ Mechanism of Action ◦ Adverse Effects (Side Effects) ◦ Contraindications/Drug Interactions  Drugs ◦ Own Slide (after the drug class information). ◦ Bold and Underlined (usually on slide with drug class information). Adrenergic Drugs Chapter 18 Adrenergic Receptors  Located throughout the body  Are receptors for the sympathetic neurotransmitters – Catecholamines (norepinephrine (NE), epinephrine (Epi), and dopamine) ◦ Alpha-adrenergic receptors ◦ Beta-adrenergic receptors ◦ Dopaminergic receptors: respond only to dopamine  Adrenergic Drugs: Drugs that Stimulate the sympathetic nervous system (SNS) ◦ Also known as sympathomimetics or adrenergic agonists. Alpha-Adrenergic Receptors  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  Main Responses to Stimulation: ◦ Vasoconstriction ◦ Central nervous system (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  Responses: ◦ Bronchial, gastrointestinal (GI), and uterine smooth muscle relaxation ◦ Glycogenolysis ◦ Cardiac stimulation Dopaminergic Receptors  An additional adrenergic receptor  Stimulated by dopamine (catecholamine)  Causes vasodilation – increasing blood flow ◦ Renal ◦ Mesenteric ◦ Coronary ◦ Cerebral Adrenergi c Receptors and Where they Are. Table 18.1 – Page 291 Fight Or Fligh t Catecholamines  Substances that can produce a sympathomimetic response (SNS neurotransmitters (catecholamines)  Endogenous ◦ Epinephrine, norepinephrine, dopamine  Synthetic ◦ Dobutamine ◦ Phenylephrine  Mechanism of Action: Direct-acting, indirect acting, or by a combination of the two (mixed-acting) Mechanism of Action: Direct acting sympathomimetic  Binds directly to the receptor and causes physiologic responses Copyright © 2022, Elsevier Inc. All rights reserved. Mechanism of Action: Indirect- acting sympathomimetic  Causes release of catecholamine from storage sites (vesicles) in nerve endings ◦ Catecholamine then binds to receptors and causes a physiologic response Copyright © 2022, Elsevier Inc. All rights reserved. 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 vesicles in the nerve endings Copyright © 2022, Elsevier Inc. All rights reserved. Indications – Adrenergic Drugs  Respiratory Indications: Treatment of asthma and COPD (chronic obstructive pulmonary disease) ◦ Bronchodilators: drugs that stimulate beta2-adrenergic receptors of bronchial smooth muscles, causing relaxation, resulting in bronchodilation ◦ Examples: Epinephrine and Drugs ending in “ol” (albuterol and salmeterol)  Nasal Decongestant: ◦ Intranasal (topical) application – constriction of dilated arterioles and reduction of nasal blood flow – thus decreasing congestion. ◦ Alpha1-adrenergic receptors ◦ Examples: phenylephrine Indications – Adrenergic Drugs – Cont.  Ophthalmic Indications ◦ Temporary relief of conjunctival congestion (eyes)  Alpha-adrenergic receptors  Examples: epinephrine and phenylephrine ◦ Reduction of intraocular pressure and dilation of pupils: treatment of open-angle glaucoma  Alpha-adrenergic receptors  Examples: epinephrine ◦ DILATE Pupils  Overactive Bladder Indications ◦ Beta3 Agonist – Mirabegron (Myrbetriq) ◦ Relaxes detrusor muscle, ultimately increasing bladder storage capacity  Cardiovascular Indications: Cardiac failure or shock. ◦ Variety of effects on various alpha- and beta-adrenergic receptors. ◦ Effect is related to the specific dose of the drug. Drug Effects – Alpha- Adrenergic  Stimulation of alpha-adrenergic receptors on smooth muscles results in ◦ Vasoconstriction of blood vessels ◦ Relaxation of GI smooth muscles (decreased motility) ◦ Constriction of bladder sphincter ◦ Contraction of uterus ◦ Male ejaculation ◦ DILATE Pupils - Contraction of pupillary muscles of the eye. Alpha-Adrenergic Adverse Effects  CNS ◦ Headache, restlessness, excitement, insomnia, euphoria  Cardiovascular ◦ Palpitations (dysrhythmias), tachycardia, vasoconstriction, hypertension  Other ◦ Loss of appetite, dry mouth, nausea, vomiting, taste changes (rare) Drug Effects - Beta1- Adrenergic  Stimulation of beta1-adrenergic receptors on the myocardium, atrioventricular (AV) node, and sinoatrial (SA) node results in cardiac stimulation ◦ Increased force of contraction (positive inotropic effect) ◦ Increased heart rate (positive chronotropic effect) ◦ Increased conduction through AV node (positive dromotropic effect) Drug Effects – Beta2- Adrenergic  Stimulation of beta2-adrenergic receptors on the airways results in ◦ Bronchodilation (relaxation of the bronchi)  Other effects of beta2-adrenergic stimulation ◦ Uterine relaxation ◦ Glycogenolysis in the liver ◦ Increased renin secretion in the kidneys ◦ Relaxation of GI smooth muscles (decreased motility) Beta-Adrenergic Adverse Effects  CNS ◦ Mild tremors, headache, nervousness, dizziness  Cardiovascular ◦ Increased heart rate, palpitations (dysrhythmias), fluctuations in blood pressure  Other ◦ Sweating, nausea, vomiting, muscle cramp Vasoactive Adrenergics (Pressors, Inotropes  Also called cardioselective sympathomimetics  Used to support the heart during cardiac failure or shock; various alpha and beta receptors affected  Examples ◦ Dobutamine, dopamine, epinephrine, phenylephrine, and norepinephrine. Dobutamine  Beta1-selective vasoactive adrenergic drug  Structurally similar to the naturally occurring catecholamine dopamine  Stimulates beta1 receptors on heart muscle (myocardium) ◦ Increases cardiac output by increasing contractility (positive inotropy)  Which increases the stroke volume, especially in patients with heart failure.  Intravenous drug; given by continuous infusion Dopamine  Naturally occurring catecholamine neurotransmitter  Potent dopaminergic as well as beta1- and alpha1- adrenergic receptor activity  Low dosages – Dilate blood vessels in the brain, heart, kidneys, and mesentery (dopaminergic receptor activity). ◦ Increases blood flow  Higher infusion rates: improve cardiac contractility and output (beta1-adrenergic receptor activity).  Highest doses: vasoconstriction (alpha1- adrenergic receptor activity). Epinephrine (Adrenalin)  Endogenous vasoactive catecholamine  Acts directly on both the alpha- and beta- adrenergic receptors of tissues innervated by the SNS  Prototypical nonselective adrenergic agonist  Administered in emergency situations  One of the primary vasoactive drugs used in many advanced cardiac life support protocols Norepinephrine (Levophed)  Stimulates alpha-adrenergic receptors  Causes vasoconstriction  Direct-stimulating beta-adrenergic effects on the heart (beta1-adrenergic receptors) ◦ No stimulation to beta2-adrenergic receptors of the lung  Treatment of hypotension and shock  Administered by continuous IV infusion Phenylephrine (Neo- Synephrine)  Works almost exclusively on the alpha- adrenergic receptors  Used primarily for short-term treatment to raise blood pressure in patients in shock  Control of supraventricular tachycardia  Vasoconstriction in regional anesthesia  Discussed in Future Lectures ◦ Topical ophthalmic drug ◦ Nasal decongestant Interactions  Anesthetic drugs  Tricyclic antidepressants  MAOIs (Monoamine Oxidase Inhibitors) ◦ Treats depression and nervous system disorders.  Antihistamines  Thyroid preparations  Adrenergic antagonists ◦ Will directly antagonize each other, resulting in reduced effects ◦ Includes some antihypertensives Assessment & Patient Education  Assess for allergies, asthma, and history of hypertension, cardiac dysrhythmias, and other cardiovascular disease.  Assess renal, hepatic, and cardiac function before treatment.  Overuse of nasal decongestants may cause rebound nasal congestion or ulcerations.  Avoid over-the-counter and other medications because of possible interactions.  Note: Administering two adrenergic drugs together may precipitate severe cardiovascular effects such as tachycardia or hypertension Monitoring Therapeutic Effects   Decreased edema Return to normal  Increased urinary respiratory rate  output Improved breath sounds, fewer crackles  Return to normal vital  Increased air signs exchange   Improved skin color Decreased cough  and temperature Less dyspnea   Increased LOC Improved blood gases  Increased activity tolerance Cardiovascular Uses Respiratory Diseases Adrenergic-Blocking Drugs Chapter 19 Adrenergic Blockers – End in “amine” or “osin”  Bind to adrenergic receptors but inhibit or block stimulation of the sympathetic nervous system (SNS)  Have the opposite effect of adrenergic drugs  Inhibit—or lyse—sympathetic stimulation  Also known as: ◦ Adrenergic antagonists ◦ Sympatholytics ◦ Alpha blockers, beta blockers, or alpha-beta blockers  Classified by the type of adrenergic receptor they block ◦ Alpha1 and alpha2 receptors ◦ Beta1 and beta2 receptors Alpha-adrenergic competitive Mechanisms for alpha-adrenergic andcompetitive noncompetitive blockade and noncompetitive blockade by alpha blocker drugs Copyright © 2022, Elsevier Inc. All rights reserved. Drug Effects and Indications: Alpha Blockers  Dilation of blood vessels (arterial and venous) ◦ Treats Hypertension  Reduces peripheral vascular resistance and blood pressure (BP)  Relaxes smooth muscles ◦ PREVENTS stimulation of alpha1 receptors – prevents muscle contraction. ◦ Treat benign prostatic hyperplasia (BPH) (decreases resistance to urinary outflow).  Help to inhibit response to adrenergic stimulation (norepinephrine) through noncompetitive blockage. ◦ Pheochromocytoma (tumor on adrenal gland) – Prevents hypertension. ◦ Raynaud’s disease, acrocyanosis, and frostbite – Increased endogenous alpha-adrenergic agonists activity (catecholamines) which cause vasoconstriction.  Vasoconstriction will make these disease states worse. Alpha Blockers: Adverse Effects  Primary adverse effect – Hypotension (prevent vasoconstriction & promote vasodilation). ◦ Educate patients on risk for orthostatic hypotension  Cardiovascular: Palpitations, orthostatic hypotension, tachycardia, edema, chest pain  CNS: Dizziness, headache, anxiety, depression, weakness, numbness, fatigue  Gastrointestinal: Nausea, vomiting, diarrhea, constipation, abdominal pain  Other: Incontinence, dry mouth, pharyngitis Question #1 When administering an alpha blocker for the first time, it is most important for the nurse to assess the patient for the development of what adverse effect? A. Renal failure. B. Hypotension. C. Blood dyscrasia. D. Dysrhythmias. Copyright © 2022, Elsevier Inc. All rights reserved. Phentolamine (Regitine)  Alpha blocker - Reduces peripheral vascular resistance ◦ Used to treat hypertension. ◦ Helpful in establishing a diagnosis of pheochromocytoma ◦ Additional Use: Treatment of extravasation of vasoconstricting drugs such as norepinephrine, epinephrine, and dopamine  Contraindicated in known hypersensitivity, myocardial infarction (MI), and coronary artery disease. Tamsulosin (Flomax)  Uses: BPH and Kidney stones. ◦ Relax smooth muscle.  Contraindications: known drug allergy and concurrent use of erectile dysfunction drugs such as sildenafil.  Adverse effects: headache, abnormal ejaculation, rhinitis, and others Beta Blockers – End in “lol”  Block stimulation of beta receptors in the SNS  Compete with norepinephrine and epinephrine  Can be selective or nonselective ◦ Cardioselective beta blockers – Block only Beta1 ◦ Nonselective beta blockers - Block both Beta1 and Beta2  Beta2 receptors located primarily in smooth muscles of bronchioles and blood vessels. ◦ Blocks Beta2 receptors resulting in smooth muscle contraction and narrowing of the airways. Indications  Angina ◦ Decreases demand for myocardial oxygen  Cardioprotective ◦ Inhibits stimulation of the heart from circulating catecholamines  Beta blocker is given following a Myocardial Infarction (MI)  Dysrhythmias  Antihypertensive  Migraine headache ◦ Lipophilicity allows entry into CNS  Heart failure  Glaucoma (topical use) Mechanism of Action  Cardioselective beta blockers (beta1) ◦ Reduce SNS stimulation of the heart ◦ Decrease heart rate ◦ Prolong sinoatrial (SA) node recovery ◦ Slow conduction rate through the AV node ◦ Decrease myocardial contractility, thus reducing myocardial oxygen demand Atenolol (Tenormin)  Cardioselective beta blocker  Uses: ◦ Commonly used to prevent future heart attacks in patients who have had one. ◦ Hypertension and angina ◦ Management of thyrotoxicosis to help block the symptoms of excessive thyroid activity  Atenolol is available for oral use Metoprolol (Lopressor)  Most commonly used beta1 blocker - Cardioselective  Uses: Cardioprotective, hypertension, angina, and dysrhythmias.  Oral and injectable  Monitoring required when giving IV  Two oral forms ◦ Metoprolol succinate: extended release, usually ordered once daily ◦ Metoprolol tartrate: immediate release, usually ordered twice daily Mechanism of Action (Cont.)  Nonselective beta blockers (beta1 and beta2) ◦ Cause same effects on heart as cardioselective beta blockers ◦ Constrict bronchioles, resulting in narrowing of airways and shortness of breath ◦ Produce vasoconstriction of blood vessels Propranolol (Inderal)  Prototypical nonselective beta1 and beta2- blocking drug  Uses: HTN, Angina, Anxiety (Physical symptoms). ◦ Tachydysrhythmias ◦ Subaortic stenosis ◦ Migraine headaches ◦ Essential tremor  Oral and injectable form Carvedilol (Coreg)  Nonselective beta blocker, an alpha1-blocker, a calcium channel blocker, and possibly an antioxidant  Uses: heart failure, hypertension, and angina ◦ Slows progression of heart failure and to decrease the frequency of hospitalization in patients with mild to moderate (class II or III) heart failure  Most commonly added to digoxin, furosemide, and angiotensin-converting enzyme inhibitors (ACE inhibitors) when used to treat heart failure Question #2 A 58-year-old patient is recovering in the intensive care unit after a myocardial infarction (MI). A beta blocker metoprolol (Lopressor) has been ordered for this patient. What is the purpose of this drug? A. Dilate the coronary arteries. B. Inhibit stimulation of the myocardium by circulating catecholamines. C. Provide a positive inotropic effect. D. Maintain the patient’s BP. Copyright © 2022, Elsevier Inc. All rights reserved. Beta Blockers – Drug Interactions  Avoid over-the-counter medications because of possible interactions.  Possible drug interactions may occur with ◦ Antacids (aluminum hydroxide type) ◦ Antimuscarinics or anticholinergics ◦ Diuretics and cardiovascular drugs ◦ Neuromuscular blocking drugs ◦ Oral hypoglycemic drugs Adverse Effects: Beta Blockers  Blood: Agranulocytosis, thrombocytopenia  Cardiovascular: AV block, bradycardia, heart failure  CNS: Dizziness, depression, unusual dreams, drowsiness  Gastrointestinal: Nausea, vomiting, constipation diarrhea  Other: Impotence, alopecia, wheezing, bronchospasm, dry mouth  Nonselective beta blockers may interfere with normal responses to hypoglycemia (tremor, tachycardia, nervousness). ◦ May mask signs and symptoms of hypoglycemia ◦ Use with caution in patients with diabetes mellitus Question #3 The nurse knows that the adverse effects of a nonselective beta blocker are likely to be the most immediately life threatening in which patient? A. Patient with type I diabetes B. Patient with asthma C. Patient with gastroesophageal reflux disease D. Patient with hypertension Copyright © 2022, Elsevier Inc. All rights reserved. Adrenergic – Blocking Drugs – Nursing Implications  Assess for allergies and history of COPD, hypotension, cardiac dysrhythmias, bradycardia, heart failure, and other cardiovascular problems. ◦ Any preexisting condition that might be exacerbated by the use of these drugs might be a contraindication to their use.  May cause hypotension, bradycardia, heart block, heart failure, and bronchoconstriction. Adrenergic-Blocking Drugs – Patient Education  Never stop medication abruptly.  Report constipation or development of urinary hesitancy or bladder distention.  Change position slowly to minimize postural hypotension.  Avoid caffeine (excessive irritability).  Avoid alcohol ingestion and hazardous activities until blood levels become stable.  Notify healthcare provider if palpitations, dyspnea, nausea, or vomiting occurs.  Goals ◦ No adverse effects. ◦ Therapeutic effects  Decreased chest pain in patients with angina  Return to normal BP and heart rate  Other specific effects, depending on the use Question #4 A patient with type 2 diabetes is taking a beta blocker as part of treatment for hypertension. Which complication is most likely to develop? A. Hypertension B. Hyperkalemia C. Hypoglycemia D. Angina Copyright © 2022, Elsevier Inc. All rights reserved. Assessing for Adverse Effects - Edema  Inform patients to report the following to their physicians ◦ Weight gain of more than 2 lb. in 1 day or 5 lb. in 1 week ◦ Edema of the feet or ankles ◦ Shortness of breath ◦ Excessive fatigue or weakness ◦ Syncope or dizziness  Alpha or Beta Blocker ◦ Assess apical pulse for one full minute and supine and standing blood pressure  If apical pulse less than 60 or systolic blood pressure less than 100 – Notify physician. Cholinergic Drugs Chapter 20 Cholinergic Drugs  Drugs that stimulate the parasympathetic nervous system (PSNS) ◦ The PSNS is the opposing system to the sympathetic nervous system (SNS).  Also known as cholinergic agonists or parasympathomimetics  Mimic effects of the PSNS neurotransmitter acetylcholine (ACh) Copyright © 2022, Elsevier Inc. All rights reserved.  Rest and Digest Cholinergic Drugs: Mechanism of Action  Mimic the effects of acetylcholine  Direct-acting cholinergic agonists ◦ Bind to cholinergic receptors, activating them  Indirect-acting cholinergic agonists ◦ Inhibit the enzyme acetylcholinesterase, which breaks down acetylcholine (ACh).  Results in more ACh available at the receptors ◦ Also known as cholinesterase inhibitors Indirect Acting (Cholinesterase Inhibitors)  Reversible ◦ Bind to cholinesterase for a short period of time  Irreversible ◦ Bind to cholinesterase for a long period of time and form a permanent bond.  The body must make new cholinesterase to break these bonds. Cholinergic Receptors  Muscarinic receptors ◦ Located postsynaptically in the effector organs of the PSNS  Smooth muscle  Cardiac muscle  Glands ◦ Named muscarinic because they can be stimulated by the substance, muscarine (alkaloid)  Nicotinic receptors ◦ Located in the ganglia of both the PSNS and SNS ◦ Named nicotinic because also stimulated by nicotine - undesirable Cholinergic Drug Effects  Effects seen when PSNS is stimulated  The PSNS is the “rest and digest” system ◦ Sympathetic nervous system: “flight or fight”  Stimulate intestine and bladder ◦ Increased gastric secretions ◦ Increased gastrointestinal motility ◦ Increased urinary frequency  Stimulate pupils ◦ CONSTRICT pupils ◦ Reduced intraocular pressure  Increased salivation and sweating  Cardiovascular effects ◦ Decreased heart rate ◦ Vasodilation  Respiratory effects ◦ Bronchial constriction, narrowed airways Cholinergic Drug Effects (Cont.)  At recommended doses, cholinergics primarily affect muscarinic receptors.  At high doses, cholinergics stimulate nicotinic receptors – NOT desired  Desired effects are from muscarinic receptor stimulation.  Many undesirable effects – Stimulation of nicotinic receptors. Question #5 You are assessing a patient who has been taking a cholinergic drug for 3 days. The patient has flushed skin and orthostatic blood pressure changes and is complaining of abdominal cramps and nausea. You recognize that the patient is most likely experiencing A. early signs of a cholinergic crisis. B. late signs of a cholinergic crisis. C. an allergic reaction to the drug. D. expected adverse effects. Copyright © 2022, Elsevier Inc. All rights reserved. Indications – Cholinergic Drugs  Indications - Direct-acting drugs ◦ Reduce intraocular pressure ◦ Increased gastrointestinal and bladder tone and motility. Also relaxes bladder sphincter. ◦ Treats excessive dry mouth ◦ Neuromuscular blocker (general anesthesia)  Indications – Indirect-acting drugs ◦ Increases Ach (Acetylcholine) – stimulates cells. ◦ Skeletal muscle contractions ◦ Diagnosis and treatment of myasthenia gravis ◦ Reverses neuromuscular blocking drugs ◦ Used to reverse anticholinergic poisoning (antidote)  Indications – Indirect-acting anticholinesterase drugs ◦ Treatment of mild to moderate Alzheimer’s disease – increase concentrations of acetylcholine in the brain by inhibiting cholinesterase.  donepezil (Aricept) Contraindications – Cholinergic Drugs  Known drug allergy  GI or genitourinary (GU) tract obstruction  Bradycardia  Defects in cardiac impulse conduction  Hyperthyroidism  Epilepsy  Hypotension  Chronic obstructive pulmonary disease  Parkinson’s disease Adverse Effects – Cholinergic Drugs  Due to Overstimulation of the PSNS  Cardiovascular ◦ Bradycardia, hypotension, syncope, conduction abnormalities (AV block and cardiac arrest)  Central nervous system ◦ Headache, dizziness, convulsions, ataxia  Gastrointestinal ◦ Abdominal cramps, increased secretions, nausea, vomiting  Respiratory ◦ Increased bronchial secretions, bronchospasms  Other ◦ Lacrimation, sweating, salivation, constricted pupil (miosis) Cholinergic Crisis - Toxicity  Circulatory collapse, hypotension, bloody diarrhea, shock, and cardiac arrest.  SLUDGE, which stands for salivation, lacrimation, urinary incontinence, diarrhea, GI cramps, and emesis  Early signs ◦ Abdominal cramps, salivation, flushing of the skin, nausea, and vomiting, transient syncope, transient complete heart block, dyspnea, and orthostatic hypotension  Treatment in early phase: Atropine (cholinergic antagonist)  Treatment of severe cardiovascular reactions or bronchoconstriction: epinephrine – adrenergic agonist Interactions – Cholinergic Drugs  Anticholinergics, antihistamines, sympathomimetics ◦ Antagonize cholinergic drugs, resulting in decreased responses  Other cholinergic drugs ◦ Additive effects Bethanechol (Urecholine)  Direct-acting cholinergic agonist ◦ Oral dose or subcutaneous injection  Uses: Urinary retention – neurogenic bladder or postoperatively or postpartum (nonobstructive). ◦ Increases tone and motility of bladder and gastrointestinal (GI) tract ◦ Relaxes sphincters in bladder and GI tract, allowing them to empty  Contraindications: known drug allergy, hyperthyroidism, peptic ulcer, active bronchial asthma, cardiac disease or coronary artery disease, epilepsy, and parkinsonism  Adverse effects: syncope, hypotension with reflex tachycardia, headache, seizure, GI upset, and asthma attacks  Interactions: acetylcholinesterase inhibitors (i.e., indirect-acting cholinergics) Donepezil (Aricept)  Cholinesterase inhibitor – Inhibits acetylcholinesterase resulting in an increase in Ach.  Treats mild to moderate Alzheimer’s disease  Adverse effects: GI upset (including ulcer risk caused by increased gastric secretions), drowsiness, dizziness, insomnia, and muscle cramps. ◦ Cardiovascular system effects: May include bradycardia, syncope, hypotension with reflex tachycardia, or hypertension.  Interacting drugs: anticholinergics (counteract donepezil effects) and nonsteroidal anti- inflammatory drugs (NSAIDs) Indirect-Acting Cholinergic Drugs  Increases ACh by inhibiting acetylcholinesterase  Pyridostigmine (Mestinon): Treats Myasthenia Gravis – Relieve the symptoms.  Neostigmine, Pyridostigmine, and Physostigmine ◦ Reverse the effects of nondepolarizing neuromuscular blocking drugs ◦ Treating severe overdose of tricyclic antidepressants ◦ Antidote for toxic exposure to nondrug anticholinergic agents (chemical warfare). memantine (Namenda)  Not a cholinergic drug  Treatment of Alzheimer’s disease  Classified as an n-methyl-D-asparate (NMDA) receptor antagonist ◦ Inhibits activity of NMDA receptors in the central nervous system.  Improved quality of life (may be a temporary effect). Herbal Products: Gingko  Common uses ◦ Prevent memory loss ◦ Peripheral arterial occlusive disease ◦ Vertigo ◦ Tinnitus  May cause GI upset, headache, bleeding, allergic skin reaction  Potential interactions ◦ Aspirin ◦ NSAIDs ◦ Anticoagulants - Warfarin ◦ Anticonvulsants Question #6 A 60-year-old woman asks you about taking ginkgo to help with her memory. The patient has a history of arthritis, type 2 diabetes, thyroid disease, and hypertension. She is currently taking NSAIDs for arthritis, oral antidiabetic medications, thyroid replacement hormone, and a beta blocker for blood pressure. What potential adverse effect from the gingko would be of most concern for this patient? A. Stomach upset B. Diarrhea C. Bleeding D. Drowsiness Copyright © 2022, Elsevier Inc. All rights reserved. Patient Education – Cholinergic Drugs  Myasthenia Gravis: Take medication 30 minutes before eating to help improve chewing and swallowing.  Alzheimer’s Disease: Be honest with caregivers and patients that the drugs are for management of symptoms (not a cure). ◦ Therapeutic effects of anti-Alzheimer’s drugs may not occur for up to 6 weeks. Question #7 A patient with Alzheimer’s disease accidentally took 2 weeks’ worth of a cholinergic medication. He is brought to the emergency department, is going into shock, and experiencing severe hypotension and vomiting. The nurse will expect which initial treatment? A. Administration of physostigmine B. Administration of atropine C. Administration of epinephrine D. Cardiovascular support with dopamine Copyright © 2022, Elsevier Inc. All rights reserved. Monitor for Therapeutic Effects – Cholinergic Drugs  Myasthenia Gravis: Alleviated signs and symptoms.  Postoperative patients with decreased GI peristalsis: ◦ Increased bowel sounds ◦ Passage of flatus ◦ Occurrence of bowel movements  Urinary Retention: Urination should occur within 60 minutes of bethanechol administration  Alzheimer’s Disease: ◦ Improvement in symptoms ◦ Improvement in mood and decrease in confusion Cholinergic-Blocking Drugs Chapter 21 Cholinergic-Blocking Drugs  Drugs that block or inhibit the actions of acetylcholine (ACh) in the parasympathetic nervous system (PSNS)  Also known as anticholinergics, parasympatholytics, and antimuscarinic drugs  Mechanism of Action: Compete with ACh for binding at muscarinic receptors in the PSNS ◦ As a result, ACh is unable to bind to the receptor site and cause a cholinergic effect.  Site of action of cholinergic blockers in the parasympathetic nervous system. ACh, Acetylcholine Copyright © 2022, Elsevier Inc. All rights reserved. Cholinergic-Blocking Drugs  atropine  dicyclomine (Bentyl)  glycopyrrolate (Robinul)  oxybutynin (Ditropan)  scopolamine (Transderm-Scōp)  tolterodine (Detrol)  Note: Each drug has a different use, so endings are not similar for these drugs. Drug Effects – Cholinergic- Blocking Drugs  Cardiovascular - Affects the heart’s conduction system ◦ Small doses: Decrease heart rate ◦ Large doses: Blocks inhibitory vagal effects on sinoatrial (SA) and atrioventricular node (AV) pacemaker cells  Results in increased heart rate  Central nervous system (CNS) ◦ Small doses: decrease muscle rigidity and tremors (Parkinson’s Disease – will discuss more later).  Also Drug-induced extrapyramidal reactions (tremors) – associated with antipsychotic drugs). ◦ Large doses: drowsiness, disorientation, hallucinations  Eye ◦ Dilated pupils (mydriasis) ◦ Decreased accommodation caused by paralysis of ciliary muscles (cycloplegia)  Glandular ◦ Decreased bronchial secretions, salivation, sweating Question #8 Which finding would you anticipate observing (assessing) in a patient with an atropine overdose? A. Moist skin B. Miosis C. Bradycardia D. Altered mental status Copyright © 2022, Elsevier Inc. All rights reserved. Drug Effects – Cholinergic- Blocking Drugs (Cont.)  Gastrointestinal (GI) – Irritable bowel disease and GI hypersecretory states ◦ Relax smooth muscle tone of GI tract ◦ Decrease intestinal and gastric secretions ◦ Decrease motility and peristalsis  Genitourinary (GU) – Reflux neurogenic bladder and incontinence. ◦ Relaxed detrusor muscle ◦ Increased constriction of internal sphincter  May result in: urinary retention  Respiratory: Blocks cholinergic stimulation of the PSNS allows unopposed action of the SNS. – Asthma and COPD. ◦ Results  Decreased bronchial secretions (nose, mouth, pharynx, and bronchi)  Relaxed smooth muscles in the bronchi and bronchioles  Decreased airway resistance  Bronchodilation Question #9 Glycopyrrolate (Robinul) and an opioid are administered to a patient before surgery in the preoperative area. What is the intended effect of the glycopyrrolate? A. Potentiate the action of the opioid. B. Assist the patient in retaining urine during surgery. C. Control secretions during surgery. D. Prevent nausea. Copyright © 2022, Elsevier Inc. All rights reserved. Contraindications – Cholinergic- Blocking Drugs  Known drug allergy  Angle-closure glaucoma  Acute asthma or other respiratory distress  Myasthenia gravis  Acute cardiovascular instability  GI or GU tract obstruction (e.g., benign prostatic hyperplasia [BPH]) Adverse Effects – Cholinergic- Blocking Drugs  Cardiovascular – Increased heart rate, dysrhythmias  CNS – CNS excitation, restlessness, irritability, disorientation, hallucinations, delirium  Eye – Dilated pupils (causing blurred vision), increase intraocular pressure  GI – Decreased salivation, decreased gastric secretions, decreased motility (constipation)  GU – Urinary retention  Glandular – Decreased sweating  Respiratory – Decreased bronchial secretions Question #10 Before administering tolterodine (Detrol), it is most important to assess the patient for a history of which condition? A. Angle-closure glaucoma B. Cataracts C. Hypothyroidism D. Hyponatremia Copyright © 2022, Elsevier Inc. All rights reserved. Toxicity – Managing Overdose  Symptomatic and supportive therapy  Continuous electrocardiographic monitoring  Activated charcoal  Treatment of shock – Fluid resuscitation Interactions – Cholinergic- Blocking Drugs  Amantadine, antihistamines, phenothiazines, tricyclic antidepressants, digoxin  When given with other cholinergic blocking drugs, cause additive cholinergic effects, resulting in increased effects atropine  Naturally occurring antimuscarinic (belladonna alkaloids)  Uses: bradycardia and ventricular asystole ◦ Causes increased heart rate  Other Uses: antidote for anticholinesterase inhibitor toxicity or poisoning and preoperatively (Reduces salivation and GI secretions)  Contraindications: angle-closure glaucoma, advanced hepatic and renal dysfunction, hiatal hernia associated with reflux esophagitis, intestinal atony, obstructive GI or GU conditions, and severe ulcerative colitis dicyclomine (Bentyl)  Synthetic antispasmodic cholinergic blocker  Uses: functional disturbances of GI motility such as irritable bowel syndrome.  Contraindications: known hypersensitivity to anticholinergics, angle-closure glaucoma, GI tract obstruction, myasthenia gravis, paralytic ileus, GI atony, and toxic megacolon glycopyrrolate (Robinul)  Synthetic antimuscarinic drug  Blocks receptor sites in the autonomic nervous system that control the production of secretions  Use: preoperatively – Decreases saliva and excess respiratory and GI secretions.  Contraindications: hypersensitivity, angle- closure glaucoma, myasthenia gravis, GI or GU tract obstruction, tachycardia, myocardial ischemia, hepatic disease, ulcerative colitis, and toxic megacolon oxybutynin (Ditropan)  Synthetic antimuscarinic drug  Uses: Overactive bladder and antispasmodic effect for neurogenic bladders (associated with spinal cord injury and spina bifida).  Contraindications: drug allergy, urinary or gastric retention, and uncontrolled closed-angle glaucoma scopolamine  Naturally occurring cholinergic blocker ◦ Principal belladonna alkaloids  Uses: Prevention of motion sickness and prevent postoperative, postanesthesia nausea and vomiting  Contraindications: angle-closure glaucoma, advanced hepatic and renal dysfunction, hiatal hernia associated with reflux esophagitis, intestinal atony, obstructive GI or GU conditions, and severe ulcerative colitis  Adverse effects: drowsiness, dry mouth, and blurred vision  Using scopolamine with CNS depressants or alcohol may increase sedation.  Application: Patch behind the ear - Changed every 3 days. tolterodine (Detrol)  Muscarinic receptor blocker  Uses: urinary frequency, urgency, and urge incontinence caused by bladder overactivity (detrusor muscle)  Note: Newer drugs – Have less incidence of dry mouth due to affecting the bladder only ◦ No affect on the salivary glands. mirabegron (Myrbetriq)  Used to treat overactive bladder  Beta3 agonist; represents a new class of therapy for this condition ◦ Adrenergic Drug  Stimulates the Beta Receptors (urothelium and detrusor muscle) ◦ Relaxes the Detrusor muscles during storage phase, increasing the bladder capacity.  Does not have same side effects as other drugs to treat overactive bladder ◦ Since Adrenergic drug instead of a muscarinic blocker. Patient Education  Assess for allergies, presence of BPH, urinary retention, glaucoma, tachycardia, myocardial infarction, heart failure, hiatal hernia, and GI or GU obstruction.  Sensitivity to light – Wear dark glasses or sunglasses.  Administering ophthalmic solutions: Apply pressure to the inner canthus to prevent systemic absorption.  Check with physician before taking any other medication, including over-the-counter medications.  Emphasize the importance of adequate fluid and salt intake Monitor for Therapeutic Effects – Cholinergic-Blocking Drugs  Parkinson’s disease: Fewer tremors and decreased salivation and drooling  Urologic problems: Improved urinary patterns, less hypermotility, increased time between voiding  AND Adverse Effects: Urinary hesitancy or retention, constipation, tachycardia, palpitations, tremors, confusion, sedation, hallucinations, and decreased sweating (leading to hot, dry skin). Questions