Autonomic Nervous System Drugs

Nursing 220: Pharmacology Module IV: Autonomic Nervous System Drugs Presented by: Ronda M. Overdiek, MSN, CCRN, RNC Overview (Chapters 12-18) • Anatomy/Physiology of Nervous System • Cholinergic Agents – – – – – Muscarinic Agonists Muscarinic Antagonists Cholinesterase Inhibitors Neuromuscular Blocking Agents Ganglionic Blocking Agents • Adrenergic Agonists • Adrenergic Antagonists Chapter #12 Neuropharmacology • Neuropharmacology: Study of drugs that alter processes controlled by the nervous system. • Divided into two categories: – Central nervous system drugs – Peripheral nervous system drugs • Alter: – Axonal Conduction: the process of conducting an action potential down the axon of the neuron – Synaptic Transmission: the process by which information is carried across the gap between the neuron and the postsynaptic cell. ***most alter synaptic transmission.*** • Neuropharmacologic drugs: Impact of a drug on a neuronally regulated process is dependent upon the ability of that drug to directly or indirectly influence receptor activity on the target cells. Chapter #12 Neuropharmacology • Predicting the effects of a PNS drug: 1. The identity of the receptors that the drug acts 2. The normal responses to activation of those receptors 3. Whether the drug increases or decreases receptor activation • Receptor Activation: An effect on receptor function equivalent to that produced by the natural neurotransmitter at a particular synapse. – – Increased receptor activation: drug whose effects mimic the effects of the natural transmitter Decreased receptor activation: drug whose effects were equivalent to reducing the amount of natural transmitter available for receptor binding. Chapter #13: Physiology of PNS Central Nervous System Peripheral Nervous System Brain Spinal Cord Cranial Nerves Structural Components Spinal Nerves Functional Components Somatic Nervous System Autonomic Nervous System Sympathetic Parasympathetic Chapter #13: Physiology of PNS • Autonomic Nervous System Functions: – Regulation of heart – Regulation of secretory glands (salivary, gastric, sweat, bronchial) – Regulation of smooth muscles (muscles of bronchi, blood vessels, urogenital system, GI tract) • Regulatory functions shared between sympathetic & parasympathetic nervous system Chapter #13: Physiology of PNS • Functions of Parasympathetic Nervous System: – – – – – – – – – – – – Slowing of heart rate Increased gastric secretion Emptying of the bladder Emptying of the bowel Focusing of the eye for near vision Constriction of pupil Contraction of bronchial smooth muscle GI tract Bladder Eye Heart Lungs • Drugs affecting parasympathetic nervous system: Chapter #13: Physiology of PNS • Functions of Sympathetic Nervous System: – Regulation of cardiovascular system – Regulation of body temperature – Implementation of ―flight-or-flight‖ reaction • Increased heart rate/blood pressure • Shunting of blood away from the skin and viscera and into the skeletal muscles • Dilation of the bronchi to improve oxygenation • Dilation of the pupils • Mobilization of stored energy, providing glucose for the brain and fatty acids for muscles – Homeostasis is maintained by: • Maintenance of blood flow to the brain, redistribution of blood flow during exercise, compensation for loss of blood by vasoconstriction. Chapter #13: Physiology of PNS Chapter #13: Receptors of PNS • Two basic categories of PNS receptors: – Cholinergic Receptors • Receptors that mediate response to Ach • Receptor subtypes: – NicotinicN, NicotinicM, Muscarinic – Adrenergic Receptors • Receptors that mediate responses to epinephrine (adrenaline) and norepinephrine • Receptor subtypes: – Alpha1, alpha2, beta1, beta2, – Dopamine receptors: do not respond to epi or norepi, but respond to dopamine (neurotransmitter in CNS) Chapter #13: Location of cholinergic/adrenergic receptor subtypes Chapter #13: Physiology of PNS • Functions of Cholinergic Receptors: (Table 13-2; Pg 106). – NicotinicN (Neuronal): • Stimulation of parasympathetic/sympathetic postganglionic nerves and release of epinephrine from the adrenal medulla – NicotinicM: • Cause contraction of skeletal muscle – Muscarinic Receptors: • Causes increased glandular secretions, contraction of smooth muscle in the bronchi, bladder, and GI tract, slowing of heart rate, contraction of sphincter muscle of the iris, contraction of the ciliary muscle of the eye • Drugs affecting muscarinic receptors will cause vasodilation on blood vessels, causing B.P. to fall Chapter #13: Physiology of PNS • Functions of Adrenergic Receptors (Table 13-3 Pg. 107): – Alpha1: • Located in eyes, blood vessels, male sex organs, bladder, prostatic capsule. • Dilation of the pupil, vasoconstriction, ejaculation, contraction of the bladder neck and prostatic capsule – Alpha2: • • • • Located on nerve terminals Regulate transmitter release PNS alpha2 activation has minimal significance CNS alpha2 activation are relevant Chapter #13: Physiology of PNS • Functions of Adrenergic Receptors (Table 13-3 Pg. 107): – Beta1 (located in heart/kidney) • Cardiac: increases heart rate, force of contraction, velocity of impulse conduction through the AV node • Kidney: release of renin>>angiotensin>>vasoconstrictor>>>elevates blood pressure – Beta2: • • • • Lungs: bronchial dilation Uterus: relaxation of uterine smooth muscle Arterioles of heart, lungs, skeletal muscle: vasodilation Liver/skeletal muscle: promotes glycogenolysis (breakdown of glycogen into glucose) • Skeletal muscle: promotes contraction – Dopamine: • PNS: Kidney: dilates renal blood vessels-enhancing renal perfusion • CNS: great therapeutic significance (Parkinson’s; antipsychotic agents) Chapter #13: Receptor Specificity of Adrenergic Neurotransmitters Alpha1 Epinephrine Alpha2 Beta1 Beta2 Dopamine * * * * * * Norepinephrine * Dopamine * * * Cholinergic Drugs • Cholinergic Agents – – – – – Muscarinic Agonists (Bethanechol) Muscarinic Antagonists (Atropine) Cholinesterase Inhibitors (Neostigmine) Neuromuscular Blocking Agents (Tubocurarine) Ganglionic Blocking Agents (Trimethaphan) • Muscarinic receptors: Chapter #14 Muscarinic Agonists and Antagonists – Located on all organs regulated by the parasympathetic nervous system, they are also located on sweat glands. • Causes increased glandular secretions, contraction of smooth muscle in the bronchi, bladder, and GI tract, slowing of heart rate, contraction of sphincter muscle of the iris, contraction of the ciliary muscle of the eye • Drugs affecting muscarinic receptors will cause vasodilation on blood vessels, causing B.P. to fall • Muscarinic Agonists: – Cause muscarinic receptor activation • Muscarinic Antagonists: – Cause muscarinic receptor blockade • Muscarinic Agonists: Chapter #14 Muscarinic Agonists and Antagonists – Resemble those responses produced by stimulation of parasympathetic nerves: called parasympathomimetic agents. – Prototype: Bethanechol • Binds to muscarinic receptors causing activation – Pharmacologic Effects: • Heart: bradycardia • Exocrine glands: increase sweating, salivation, bronchial secretions, secretion of gastric acid • Smooth muscles of lung, GI tract, bladder: promote contraction resulting in bronchoconstriction, increased tone and motility of the GI smooth muscle, contraction of the detrusor muscle of the bladder • Eye: miosis (pupillary constriction), contraction of ciliary muscle (focuses eye for near vision) • Bethanechol: – Uses: Chapter #14 Muscarinic Agonists and Antagonists • Urinary retention: relieves urinary retention by activating muscarinic receptors of the urinary tract--relaxes the urinary sphincters and increases voiding pressure. – Adverse Effects: • Hypotension, bradycardia, excessive salivation, increased secretion of gastric acid, abdominal cramps, diarrhea, exacerbation of asthma (bronchoconstriction). • Muscarinic Antagonists: Chapter #14 Muscarinic Agonists and Antagonists – Competitively block the actions of acetylcholine at muscarinic receptors. – Known as: parasympatholytic drugs, anticholinergic drugs – Prototype: Atropine • Competitive blockade at muscarinic receptors (prevents receptor activation by acetylcholine) • Atropine: Chapter #14 Muscarinic Agonists and Antagonists – Heart: increases heart rate – Exocrine glands: decreases secretion from salivary glands, bronchial glands, sweat glands, and acidsecreting cells of the stomach – Smooth muscle: relaxation of bronchi, decreased tone of the urinary bladder, decreased tone/motility of GI tract – Eye: mydriasis (dilation of the pupil), focuses lens for far vision (relaxing the ciliary muscle) • Effects of atropine on muscarinic receptors are dose dependent (Table 14-1 page 116) • Atropine: – Uses: • • • • • Chapter #14 Muscarinic Agonists and Antagonists Preanesthetic medication: limit secretions, offset bradycardia Eye: mydriasis/paralysis of eye-assist during surgery Bradycardia: speed up heart rate Reduce frequency of bowel movements and abdominal cramping Muscarinic Agonist poisoning: blocks overdose at receptor site – Adverse Effects: • Dry mouth, blurred vision, photophobia, urinary retention, constipation, tachycardia, thickening/drying of bronchial secretions (watch in asthma patients) Chapter #15: Cholinesterase Inhibitors • Life Cycle of Acetylcholine: – Synthesized from choline and acetylcoenzyme A. – Stored in vesicles, released in response to action potential >>binds to receptor (nicotinicN, nicotinicM, muscarinic). – Dissociates from receptor, Ach is destroyed by acetylcholinesterase (enzyme present on postjunctional cell)>>degrades it into acetate and choline – Acetylcholinesterase is also known as cholinesterase Chapter #15: Cholinesterase Inhibitors • Cholinesterase Inhibitors: – Prevent the degradation of acetylcholine by cholinesterase. – By preventing inactivation of acetylcholine, these drugs enhance the actions of Ach released from cholinergic neurons. – Alternative name: anticholinesterase agents – Two basic categories: • Reversible inhibitors • Irreversible inhibitors Chapter #15: Cholinesterase Inhibitors • Reversible Cholinesterase Inhibitors: – Prototype: Neostigmine – Indicated for: Myasthenia Gravis • Chronic autoimmune disease that effects the neuromuscular junction. • Characterized by: – Muscle weakness and fatigability • Pathophysiology: – Defect in nerve impulse transmission at the neuromuscular junction. – Postsynaptic acetylcholine receptors on the muscle’s cell’s plasma membrane are no longer recognized as ―self‖ and elicit the generation of autoantibodies. Chapter #15: Cholinesterase Inhibitors • Myasthenia Gravis: – Clinical Manifestations: • Weakness, fatigue, muscles of facial expression, mastication, swallowing, and speech are impaired. Pt’s at risk for aspiration/respiratory infections. Eventually, require ventilatory support. – Treatment: • Drugs (steroids, immunosuppressants), supportive measures (respiratory needs). Chapter #15: Cholinesterase Inhibitors • Neostigmine: – Prevents inactivation of Ach, intensifying transmission oat virtually all junctions where Ach is the transmitter. – Produce: • Skeletal muscle stimulation, increased glandular secretions, increased tone and motility of GI smooth muscle. – Adverse Effects: • Toxic doses can produce paralysis of respiratory muscles—too high of accumulation can produce depolarizing neuromuscular blockade. • Treatment is atropine Chapter #15: Cholinesterase Inhibitors • Irreversible Cholinesterase Inhibitors: – Highly toxic: insecticides – Highly lipid soluble: absorb rapidly through all routes of administration – Response to irreversible inhibitors last a long time, whereas response to reversible inhibitors are short lived – Symptoms of toxicity: • Excessive muscarinic stimulation and depolarizing neuromuscular blockade (profuse secretions from salivary and bronchial glands, involuntary urination and defecation, laryngospasm, and bronchoconstriction, paralysis, convulsions, death. • Treatment: atropine, mechanical ventilation, diazepam. Drug called Pralidoxime. • Assessment: Chapter #15: Cholinesterase Inhibitors Using the Nursing Process… • Determine extent of neuromuscular dysfunction by assessing muscle strength, fatigue, ability to swallow – Why is patient receiving this drug? – Myasthenia Gravis: – Assess own knowledge of drug • Diagnosis: – Specific to patient • Planning: – Specific to patient and nursing diagnosis identified • Chapter #15: Cholinesterase Inhibitors Using the Nursing Process… Implementation: – Administration (seven rights) • Assess patient’s ability to swallow • Evaluation: – Evaluate therapeutic effects: • Monitor and record times of drug administration, times at which fatigue occurs, state of muscle strength including ability to swallow, signs of excessive muscarinic stimulation. Dose is increased or decreased based on these observations. • Inform patients about signs of excessive muscarinic stimulation: profuse salivation, increased tone and motility of the gut, urinary urgency, sweating, miosis, bronchoconstriction, bradycardia. • Cholinergic Crisis: results from cholinesterase inhibitor overdose. Symptoms include paralysis and signs of excessive muscarinic stimulation. • Neuromuscular and Ganglionic Blocking Agents block nicotinic cholinergic receptors. • Neuromuscular Blocking agents: – Block NictonicM receptors Chapter #16: Neuromuscular Blocking Agents and Ganglionic Blocking Agents • Ganglionic Blocking agents: – Block NictonicN receptors • Chapter #16: Neuromuscular Blocking Agents and GanglionicAgents: Blocking Agents Neuromuscular Blocking – Prevent ACh from activating nicotinicM receptors on skeletal muscles, causing muscle relaxation. – NicotinicM: • Cause contraction of skeletal muscle – Uses: • Muscle relaxation during surgery – Does NOT enter CNS—therefore anesthesia required to produce unconsciousness • • • • Facilitation of mechanical ventilation Adjunct to electroconvulsive therapy Endotracheal intubation Diagnosis of Myasthenia Gravis (small amount that would normally not affect normal person will have affect on MG patient)—if diagnosis is made, reversal is given (neostigmine-cholinesterase inhibitor) will have increase in ACh at the NMJ which will reverse neuromuscular blocking agent. • Neuromuscular Blocking Agents Chapter #16: Neuromuscular Blocking Agents and Ganglionic Blocking Agents – Prototype: Tubocurarine – Action: Competes with Ach for binding to nicotinicM receptors on the motor end plate. Muscle relaxation persists as long as the amount of Tubocurarine at the NMJ is sufficient to prevent receptor occupation by Ach. – Adverse Effects: respiratory arrest, hypotension, bradycardia, dysrhythmias, cardiac arrest. Hyperkalemia can reduce paralysis, hypokalemia can enhance paralysis. Monitor electrolyte levels! • Neuromuscular Blocking Agents: Chapter #16: Neuromuscular Blocking Agents and Ganglionic Blocking Agents – Long-Acting: (Duration: 60-120 minutes) • Tubocurarine, Doxacurium, Metocurine – Intermediate Acting: (20-45 minutes) • Pancuronium, Rocuronium, Vecuronium – Short Acting: (10-15 minutes) • Mivacurium – Ultrashort Acting: (4-6 minutes) • Succinylcholine • Ganglionic Blocking Agents: Chapter #16: Neuromuscular Blocking Agents and Ganglionic Blocking Agents – Used to lower blood pressure • Controlled hypotension in surgery (reduce blood loss) • Hypertensive Crisis – Prototype: (Trimethaphan) – Interrupts impulse transmission through ganglia of the autonomic nervous system – Blocks transmission to all ganglia in sympathetic and parasympathetic nervous system – Blocks transmission by competing with Ach for binding to nicotinicN receptors. – Causes vasodilation and release of histamine, dropping blood pressure Question #1 After a neuromuscular blocking agent is used, the nurse monitors the patient for: A. Diarrhea and constipation B. Gastrointestinal upset C. Hypertension D. Respiratory depression Question #2 The hypotension and bronchospasm often seen with the administration of ganglionic blocking agents are associated with the release of: A. B. C. D. Epinephrine Histamine Norepinephrine Acetylcholine Chapter #17: Adrenergic Agonists • Adrenergic Agonists: – Produce effects by activating adrenergic receptors – Also called sympathomimetics • Sympathetic nervous system acts through same receptors, responses to adrenergic agonists and stimulation by sympathetic nervous system is similar. Chapter #17: Adrenergic Agonists • Adrenergic Receptor Activation occurs in four ways: – Direct receptor binding: • Bind to adrenergic receptors and mimic the actions of natural transmitters (epi, NE, dopamine) – Promotion of NE release: • Act on terminals of sympathetic nerves to cause NE release – Inhibition of NE Reuptake: • Reuptake of NE into terminals of sympathetic nerves is the major mechanism by which adrenergic transmission is terminated. If NE uptake is blocked, NE accumulates in the synaptic gap and increase receptor activation. – Inhibition of NE Inactivation: • NE in the terminals can be inactivated by MAO (monoamine oxidase). Drugs that inhibit MAO can increase the amount of NE available for release, enhancing receptor activation. Chapter #17: Adrenergic Agonists • Understanding Adrenergic Agonists: 1. The identity of the receptors at which the drug acts 2. The effects produced by activating those receptors Receptors include: Alpha1, alpha2, beta1, beta2, dopamine. Chapter #17: Adrenergic Agonists • Activation of Alpha1 Adrenergic Receptors: – Drugs: epinephrine, norepinephrine, phenylephrine, ephedrine, dopamine. – Responses: • Vasoconstriction (blood vessels of the skin, viscera, mucous membranes) • Mydriasis (dilation of pupil) – Uses: • • • • • Hemostasis (arrest of bleeding) (topical epinephrine) Nasal Decongestion: vasoconstriction (Phenylephrine/ephedrine) Adjunct to local Anesthesia: delay anesthetic absorption Elevation of blood pressure Mydriasis – Adverse Effects: • Hypertension • Necrosis (IV infusion of drug-vasoconstriction) • Bradycardia (reflex slowing of heart) Chapter #17: Adrenergic Agonists • Activation of Alpha2 Adrenergic receptors: – Drugs: Epinephrine, NE, ephedrine – Peripheral Nervous System: • Little or no clinical significance – Central Nervous System: • Great clinical significance Chapter #17: Adrenergic Agonists • Activation of Beta1 Adrenergic receptors: – Activated by: Epinephrine, NE, isoproterenol, dopamine, dobutamine, ephedrine – Beta1 (located in heart/kidney) • Cardiac: increases heart rate, force of contraction, velocity of impulse conduction through the AV node • Kidney: release of renin>>angiotensin>>vasoconstrictor>>>elevates blood pressure Chapter #17: Adrenergic Agonists • Uses: – Cardiac arrest: initiate contraction in a heart that has stopped beating (epinephrine) – Heart failure: insufficient cardiac output. Activation of beta1 receptors has a positive inotropic effect (increases force of contraction), drugs that activate these receptors can improve cardiac performance. – Shock: Characterized by profound hypotension and reduced tissue perfusion. Increase heart rate/force of contraction beta1 stimulants can increase cardiac output and improve tissue perfusion. – AV Heart block: Impulse conduction from atria to ventricles is impeded or blocked. Activation of beta1 receptors can enhance impulse conduction through the AV node. • Adverse Effects: – Altered heart rate or rhythm and angina. Chapter #17: Adrenergic Agonists • Activation of Beta2 Adrenergic Receptors: – Drugs: • Epinephrine, isoproteronol, terbutaline – Beta2: • • • • • Lungs: bronchial dilation Uterus: relaxation of uterine smooth muscle Arterioles of heart, lungs, skeletal muscle: vasodilation Liver/skeletal muscle: promotes glycogenolysis (breakdown of glycogen into glucose) Skeletal muscle: promotes contraction Lungs: asthma for bronchodilation Uterus: delay of preterm labor Hyperglycemia, tremor – Therapeutic applications limited to lungs/uterus. • • – Adverse Effects: • Chapter #17: Adrenergic Agonists • Activation of Dopamine receptors: – Dilation of the vasculature of the kidneys – Drug: Dopamine • Drugs that are Adrenergic Agonists: – Epinephrine, NE, Isoproterenol, Dopamine, Dobutamine, Phenylephrine, Terbutaline, Ephedrine. Chapter #17: Adrenergic Agonists • Epinephrine: – Receptor specificity: alpha1, alpha2, beta1, beta2 – Uses: • Alpha1: Vasoconstriction, delay absorption of local anesthetics, control superficial bleeding, reduce nasal congestion, elevate blood pressure, produce mydriasis. • Alpha2: PNS is limited • Beta1: overcome AV block, restore cardiac function in patients undergoing cardiac arrest. • Beta2: promotes bronchodilation in patients w/asthma • Combination of alpha/beta: treatment of choice for anaphylactic shock – Elevate blood pressure, vasoconstriction-suppress glottal edema, counteracts bronchocnstriction Chapter #17: Adrenergic Agonists • Epinephrine: – Adverse Effects: • Hypertensive crisis (cerebral hemorrhage), dysrhythmias, angina, necrosis following extravasation, hyperglycemia. – Watch for different concentrations when administering (route dependent): • 1:100 to 1:100,000 concentrations Chapter #17: Adrenergic Agonists • Isoproterenol: – Receptor specificity: beta1 and beta2 – Uses: • Cardiovascular: overcome AV block, restart the heart following cardiac arrest, increase cardiac output during shock • Asthma and bronchospasm: bronchodilation – Adverse Effects: • Dysrhythmias and angina Chapter #17: Adrenergic Agonists • Dopamine: – Receptor specificity: dopamine, beta1, (high doses alpha1) • Dose dependent: Low therapeutic doses, acts on dopamine receptors only. Moderate doses acts on beta1, and highest doses alpha1. • Shock: increase cardiac output improving tissue perfusion • Heart failure: increase myocardial contractility, increasing cardiac output • Acute renal failure: increase renal blood flow and urine output – Adverse Effects: tachycardia, dysrhythmias, angina Chapter #18: Adrenergic Antagonists • Adrenergic Antagonists: – Cause direct blockage of adrenergic receptors – Divided into two groups: • Alpha-Adrenergic blocking agents • Beta-Adrenergic blocking agents