Nervous System PDF

Chapter 12 Basic Principles of Neuropharmacology Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved.  Basic Principles of Neuropharmacology  Neuropharmacology is the study of drugs that alter processes controlled by the nerv...

Chapter 12 Basic Principles of Neuropharmacology Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved.  Basic Principles of Neuropharmacology  Neuropharmacology is the study of drugs that alter processes controlled by the nervous system  These drugs:  Produce effects equivalent to those produced by excitation or suppression of neuronal activity  are used to treat conditions that range from depression to epilepsy to hypertension to asthma  Neuropharmacologic agents can be divided into two broad categories:  Peripheral nervous system drugs  Central nervous system drugs Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 2  Basic Principles of Neuropharmacology  Neuropharmacologic drugs can modify many diverse processes:  Skeletal muscle contraction  Cardiac output  Vascular tone  Respiration  Gastrointestinal function  Uterine motility  Glandular secretion  Ideation, mood, and perception of pain Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 3  Basic Principles of Neuropharmacology  How neurons regulate physiologic processes  Basic mechanisms by which neuropharmacologic agents act:  Sites of action: Axons vs. synapses  Steps in synaptic transmission  Effects of drugs on the steps of synaptic transmission Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 4 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 5  Basic Mechanisms of Neuropharmacologic Agents  Sites of action: Axons vs. synapses  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  Receptors THE IMPACT OF A DRUG ON A NEURONALLY REGULATED PROCESS IS DEPENDENT ON THE ABILITY OF THAT DRUG TO DIRECTLY OR INDIRECTLY INFLUENCE RECEPTOR ACTIVITY ON TARGET CELLS Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 6 How Neurons Regulate Physiologic Processes in Two Basic Steps  Axonal conduction  Action potential down the axon  Synaptic transmission  Information carried across the neuron gap and the postsynaptic cell  Postsynaptic cell Another neuron, muscle cell, or cell within a secretory gland Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 7 Basic Mechanisms: Steps in Synaptic Transmission 1. Transmitte r synthesis 5. Terminatio 2. n of Transmitte transmissi r storage on Steps in synaptic transmissio n: 4. 3. Receptor Transmitte binding r release Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 8  Basic Mechanisms of Neuropharmacologic Agents  Effects of drugs on the steps of synaptic transmission  Transmitter synthesis  Increase transmitter synthesis  Decrease transmitter synthesis  Cause synthesis of transmitter molecules  Transmitter storage  Cause receptor activation to decrease  Transmitter release  Promote or inhibit release Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 9  Basic Mechanisms of Neuropharmacologic Agents  Effects of drugs on the steps of synaptic transmission (con’t)  Receptor binding  Cause activation  Block activation  Enhance activation  Termination of transmission  Block transmitter reuptake  Inhibit transmitter degradation Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 10  Multiple Receptor Types and Selectivity of Drug Action  Selectivity  Most desirable quality a drug can have  Able to alter a disease process while leaving other physiologic processes largely unaffected  Drugs that alter axonal conduction are not very selective  Drugs that alter synaptic transmission are highly selective Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 11  Basic Principles of Neuropharmacology  An approach to learning about peripheral nervous system drugs:  Knowing the type (or types) of receptor(s) through which the drug acts (i.e. alpha1, alpha2, beta1, beta2)  Knowing the normal responses to the activation of those receptors (agonist vs. antagonist)  Knowing whether the drug in question increases or decreases receptor activation Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 12  Question 1 A patient receives a medication that results in the activation of the acetylcholine receptors of the heart. The nurse should assess the patient for which intended effect? A. Decreased heart rate B. Dysrhythmia suppression C. Increased heart rate D. Improved contractility Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 13  Question 2 The nurse teaches a student nurse about the action of an antagonist medication. The nurse determines that the teaching is successful if the student makes which statement? A. “Antagonists enhance the effects of natural transmitters.” B. “Antagonists bind directly to nervous system receptors.” C. “Antagonist medications prevent receptor activation.” D. “Drugs that activate receptors are called antagonists.” Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 14  Chapter 13 Physiology of the Peripheral Nervous System Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Divisions of the Nervous System  Central nervous system  Brain and spinal cord  Peripheral nervous system  Somatic motor system controls voluntary movements of muscles  Autonomic nervous system (ANS) regulates involuntary processes Parasympathetic (PNS) Sympathetic (SNS) Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 16  Overview of Autonomic Nervous System Functions  Three principal functions  Regulate the heart  Regulate the secretory glands (salivary, gastric, sweat, and bronchial)  Regulate the smooth muscles (bronchi, blood vessels, urogenital system, and gastrointestinal tract) Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 17 Parasympathetic Nervous System (PNS)  Seven regulatory functions  Slowing the heart rate  Increasing the gastric secretions  Emptying the bladder  Emptying the bowel  Focusing the eye for near vision  Constricting the pupil  Contracting the bronchial smooth muscle Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 18 Parasympathetic Nervous System (PNS)  Parasympathetic nervous system drugs are used primarily for their effects on:  GI tract  Bladder  Eye  Heart  Lung Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 19  Sympathetic Nervous System Functions (SNS)  Three main functions 1. Regulation of the cardiovascular system Maintaining blood flow to the brain Redistributing blood Compensating for the loss of blood 2. Regulation of the body temperature Regulates blood flow to the skin Promotes the secretion of sweat Induces piloerection (erection of hair) Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 20  Sympathetic Nervous System Functions (SNS)  Three main functions (con’t) 3. Implementation of the “fight-or-flight” reaction Increasing heart rate and blood pressure Shunting blood away from the skin and viscera Dilating the bronchi Dilating the pupils Mobilizing stored energy Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 21  Sympathetic Nervous System (SNS)  Drugs that affect the SNS are used primarily for their effects on:  Heart  Blood vessels  Lungs Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 22  Patterns of Innervation and Control  In many organs that receive innervation from both the sympathetic and parasympathetic nerves; the sympathetic nerves opposes that of the parasympathetic nerves  i.e. Heart-sympathetic nerves increase heart rate whereas parasympathetic nerves slow the heart rate. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 23  Sympathomimetic Drugs  Produce physiological effects characteristic of the sympathetic nervous system by promoting the stimulation of sympathetic nerves  Primarily used for effects on the following areas:  Heart and blood vessels Hypertension, heart failure, and angina pectoris  Lungs Primarily asthma Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 24  Neurotransmitters of the Peripheral Nervous System Employed at most Acetylcholine junctions of the peripheral nervous system Norepinephrin Released by most e postganglionic neurons Released by the adrenal Epinephrine medulla Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 25  Receptors of the Peripheral Nervous System Cholinergic Adrenergic receptors receptors Mediated by Mediated by acetylcholine epinephrine and Two norepinephrin basic e categori es of receptor s Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 26  Receptors of the Peripheral Nervous System Subtypes of cholinergic and adrenergic receptors Subtypes of cholinergic receptors NicotinicN NicotinicM Muscarinic Subtypes of adrenergic receptors Alpha1 Alpha2 Beta1 Beta2 Dopamine Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 27 Classification of Cholinergic and Adrenergic Receptors Cholinergi Mediated by c acetylcholine Receptors Mediated by Adrenergi epinephrine c and norepinephri Receptors ne Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 28  Functions of Cholinergic Receptor Subtypes (Table 13-2, pg 110)  Functions of cholinergic receptor subtypes:  Activation of nicotinicN (neuronal) receptors  Activation of nicotinicM (muscle) receptors  Activation of muscarinic receptors Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 29  Functions of Adrenergic Receptor Subtypes (Alpha1 and Alpha2) (Table 13-3, pg 111)  Alpha1 receptor locations  Eye  Arterioles  Veins  Bladder  Effects of receptor activation  Eye: contraction  Arterioles: constriction  Veins: constriction  Bladder: contraction  Alpha2 receptor locations  Presynaptic nerve terminals  Effects of receptor activation Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 30   Functions of Adrenergic Receptor Subtypes (Beta1)  Beta1 receptor locations  Heart  Kidney  Effects of receptor activation  Heart: increased rate, increased force of contraction, increased velocity of conduction in atrioventricular (AV) node  Kidney: release of renin Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 31  Functions of Adrenergic Receptor Subtypes (Beta2 and Dopamine)  Beta2 receptor locations  Bronchi  Uterus  Arterioles (heart, lung, skeletal muscle)  Liver  Skeletal muscle  Effects of receptor activation  Bronchi: dilation  Uterus: relaxation  Arterioles: dilation  Liver: glycogenolysis  Skeletal muscle: enhanced contraction  Dopamine  Dilates renal blood vessels Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 32  Receptor Specificity of the Adrenergic Neurotransmitters  Epinephrine can activate all alpha and beta receptors but not dopamine receptors  Norepinephrine can activate alpha1, alpha2, and beta receptors but not beta2 or dopamine receptors  Dopamine can activate alpha1, beta1, and dopamine receptors Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 33  Question 1 The nurse administers a medication to a patient that stimulates the function of the parasympathetic nervous system. The nurse should assess the patient for which intended effect? A. Reduced esophageal motility B. Improved bladder emptying C. Dilation of the pupils D. Decreased gastric secretions Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 34  Question 2 The nurse administers a medication to a patient that stimulates the sympathetic nervous system. The nurse should assess the patient for which intended effect? A. Increased heart rate B. Blood pressure reduction C. Bronchial constriction D. Decreased blood glucose level Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 35  Chapter 14 Muscarinic Agonists and Antagonists Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved.  Cholinergic Drugs  Agents that influence the activity of cholinergic receptors  Most mimic or block the actions of acetylcholine  Cholinesterase inhibitors  influence cholinergic receptors indirectly by preventing the breakdown of acetylcholine Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 37  Acetylcholine  Excitatory neurotransmitter  Parts in the body that use or are affected by acetylcholine are referred to as cholinergic  It is the chemical that motor neurons of the nervous system release in order to activate muscles  This property means that drugs that affect cholinergic systems can have very dangerous effects ranging from paralysis to convulsions Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 38 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 39  Tips for Understanding the Cholinergic Drugs  Know the receptors that the drug affects  Know the normal responses to the activation of those receptors  Know whether the drug in question increases or decreases receptor activation Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 40  Cholinergic Drugs and Muscarinic Receptors (Table 13-2, pg 110)  Muscarinic receptor locations  Sweat glands  Blood vessels  All organs regulated by the parasympathetic nervous system (GI tract, bladder, eye, heart, lung)  Effects of receptor activation  Eye: pupillary constriction and ciliary contraction  Heart: decreased heart rate (bradycardia)  Lung: constriction of bronchi, promotion of secretions  Sweat glands: Increased gland secretion  Bladder: Smooth muscle contraction  GI tract: salivation, increased gastric secretion, increased motility  Blood vessels: relaxation, vasodilation, and hypotension Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 41  Muscarinic Agonists  Bind to muscarinic receptors and cause receptor activation  Reponses to these agents are similar to those produced by stimulation of the parasympathetic nervous system, thus aka: paraympathomimetic agents  Muscarinic agonist (Bethanechol)  Uses: urinary retention, GERD, postoperative abdominal distention  Adverse effects: Cardiovascular system: Hypotension Gastrointestinal system: Increased tone and motility Exacerbation of asthma Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 42  Muscarinic Agonists  Toxicology of muscarinic agonists  Source: Ingestion of certain mushrooms, direct-acting muscarinic agonists, and cholinesterase inhibitors  Symptoms: Profuse salivation, lacrimation (tearing), visual disturbances, bronchospasm, diarrhea, bradycardia, and hypotension with possible cardiovascular collapse  Treatment: Atropine and supportive therapy Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 43  Muscarinic Antagonists  Block the actions of acetylcholine at muscarinic receptors  Because the majority of muscarinic receptors are located on structure innervated by parasympathetic nerves these agents aka parasympatholytic, antimuscarinic drugs, muscarinic blockers and anticholinergic drugs  Muscarinic antagonist  i.e. Atropine Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 44  Muscarinic Antagonists (Anticholinergic Drugs)  Atropine  Best-known muscarinic antagonist  Mechanism of action: Muscarinic receptor blockade (produces effects through competative blockade at muscarinic receptors) Responses result from preventing receptor activation  Therapeutic uses (action) Preanesthetic medication Disorders of the eye (by dilating the pupil) Bradycardia (by increasing heart rate) Intestinal hypertonicity and hypermotility (by decreasing GI tone and motility) Asthma (by relaxes bronchi) Biliary colic Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 45  Muscarinic Antagonists (Anticholinergic Drugs)  Atropine  Pharmacologic effects (receptor blockade) Heart: Increases heart rate Exocrine glands: Decreases secretions Smooth muscle: Relaxes the bronchi, decreases the tone of the urinary bladder detrusor, and decreases the tone and motility of the gastrointestinal tract Eyes: Mydriasis and cycloplegia Central nervous system: Mild excitation to hallucinations and delirium Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 46  Muscarinic Antagonists (Anticholinergic Drugs)  Atropine (Cont.)  Adverse effects Xerostomia (dry mouth) Blurred vision and photophobia Elevation of intraocular pressure Urinary retention Constipation Anhidrosis Tachycardia Asthma Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 47  Other Muscarinic Antagonists Scopolamine  Anticholinergic drug with actions much like those of atropine  Therapeutic doses of atropine produce mild central nervous system excitation; therapeutic doses of scopolamine produce sedation  Scopolamine suppresses emesis and motion sickness, whereas atropine does not  Principal uses for scopolamine: Motion sickness, production of cycloplegia and mydriasis for ophthalmic procedures, and production of preanesthetic sedation and obstetric amnesia Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 48  Other Muscarinic Antagonists Ipratropium bromide  Anticholinergic drug  Used to treat asthma, chronic obstructive pulmonary disease (COPD), and rhinitis caused by allergies or the common cold  Inhalation or nasal spray routes: Not associated with typical antimuscarinic side effects (dry mouth, blurred vision, urinary hesitancy, constipation) Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 49 Toxicology of Muscarinic Agonists  Source of muscarinic poisoning  Direct-acting muscarinic agonists  Cholinesterase inhibitors  Symptoms  Result from the excessive activation of muscarinic receptors  Treatment  Muscarinic blocking agent, such as atropine Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 50 Toxicology of Muscarinic Antagonists  Symptoms  Dry mouth  Blurred vision  Photophobia  Hyperthermia  Central nervous system effects  Hot, dry, and flushed skin Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 51  Chapter 15 Cholinesterase Inhibitors and Their Use in Myasthenia Gravis Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved.  Cholinesterase Inhibitors  Drugs that prevent the breakdown of acetylcholine by acetylcholinesterase, aka anticholinesterase agents  Two basic categories  Reversible-produce effects of moderate duration  Irreversible-produce long lasting effects Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 53 “Reversible” Cholinesterase Inhibitors Neostigmine [Prostigmin]  Management of myasthenia gravis  Mechanism of action  Pharmacologic effects By decreasing the breakdown of ACh, neostigmine and the other cholinesterase inhibitors make more ACh available; this can intensify transmission at virtually all junctions where ACh is the transmitter Therapeutic administration: Muscarinic receptors  Muscarinic responses Identical to muscarinic agonist response Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 54  Neostigmine [Prostigmin]  Muscarinic response  Identical to those of the direct-acting muscarinic agonists  Prevents breakdown of Ach  Cholinesterase inhibitors can cause bradycardia, bronchial constriction, urinary urgency, increased glandular secretions, increased tone and motility of gastrointestinal smooth muscle, miosis, and focusing of the lens for near vision Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 55  “Irreversible” Cholinesterase Inhibitors  Same action as reversible cholinesterase inhibitors  Are longer acting  Used primarily in the treatment of glaucoma  Highly toxic  Primarily used as insecticides  Produced in WWII as nerve gas (chemical warfare) Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 56  “Irreversible” Cholinesterase Inhibitors(Organophosphate)  Produces a state of cholinergic crisis- overstimulation of muscarinic receptors  Caution with agricultural workers (ingestion or absorption)  Toxicology  Sources of poisoning  Symptoms Cholinergic crisis  Treatment Mechanical ventilation Pralidoxime Diazepam  Pralidoxime Specific antidote to poisoning Effectiveness affected by early administration Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 57  Myasthenia Gravis  Pathophysiology  Neuromuscular disorder characterized by fluctuating muscle weakness and predisposition to rapid fatigue  Common symptoms Drooping eyelids (Ptosis), difficulty swallowing (dysphagia), and weakness of skeletal muscles  Autoimmune process in which antibodies attack nicotinicM receptors on skeletal muscle Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 58  Myasthenia Gravis  Treatment with cholinesterase inhibitors  Beneficial effects Increased muscle strength  Side effects Excessive muscarinic response  Dosage adjustment Start small and adjust to patient response May need to modify dosage in anticipation of exertion Signs of undermedication  Ptosis and difficulty swallowing Signs of overmedication  Excessive salivation and other muscarinic responses Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 59  Myasthenia Gravis  Myasthenic crisis and cholinergic crisis  Cholinergic crisis Characterized by extreme muscle weakness or frank paralysis and signs of excessive muscarinic stimulation Treatment with respiratory support and atropine  Myasthenic crisis Inadequate medication Extreme muscle weakness Caused by insufficient ACh at the neuromuscular junction Left untreated, myasthenic crisis can result in death as a result of paralysis of the muscles of respiration-thus requires respiratory support A cholinesterase inhibitor (such as neostigmine) is Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 60 used to relieve the crisis  Question 1 The nurse cares for a patient with myasthenia gravis. Before administering pyridostigmine [Mestinon], it is most important for the nurse to take which action? A. Assess the patient’s ability to swallow a sip of water. B. Cleanse the patient’s skin before applying the transdermal patch. C. Ask whether the patient has an allergy to aspirin. D. Give the patient food or milk to prevent stomach upset. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 61  Chapter 17 Adrenergic Agonists Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved.  Adrenergic Agonists  Produce their effects by activating adrenergic receptors  Since the sympathetic nervous system (SNS) acts through these same receptors, responses to adrenergic agonists and responses to the SNS are very similar; aka Sympathomimetic  Adrenergic receptors are: Alpha1, Alpha2, Beta1, Beta2, and Dopamine  Broad spectrum of applications  Congestive heart failure Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 63   Mechanisms of Adrenergic Receptor Activation  Direct receptor binding- produce effects by binding to adrenergic receptors and mimicking the actions of natural transmitters  Promotion of norepinephrine (NE) release- thereby activating adrenergic receptors  Inhibition of NE reuptake- thereby activating adrenergic receptors  Inhibition of NE inactivation- thereby activating adrenergic receptors Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 64  Overview of the Adrenergic Agonists Cannot be used orally Catecholamin Brief duration of action es Cannot cross the blood-brain barrier (polar molecules) Can be given orally Metabolized slowly; longer Noncatecholami half-life nes More able to cross the blood- brain barrier Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 65  Therapeutic Applications of Adrenergic Receptor Activation  Therapeutic applications of alpha1 activation  Hemostasis Arrests bleeding via vasoconstriction  Nasal decongestion Mucosal vasoconstriction  Adjunct to local anesthesia Delays absorption of local anesthetic  Elevation of blood pressure Vasoconstriction  Mydriasis Dilation of the radial muscle of the iris Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 66  Adverse Effects of Adrenergic Receptor Activation  Vasoconstriction  Hypertension  Necrosis: Alpha1-blocking agent  Bradycardia Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 67 Therapeutic Applications and Adverse Effects of Adrenergic Receptor Activation  Drugs capable of activating alpha1 receptors  Epinephrine  Norepinephrine  Phenylephrine  Dopamine Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 68  Therapeutic Applications of Adrenergic Receptor Activation  Clinical consequences of alpha2 activation  Reduction of sympathetic outflow to the heart and the blood vessels  Relief of severe pain Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 69  Therapeutic Applications of Adrenergic Receptor Activation  Clinical consequences of beta1 activation  All of the clinically relevant responses to activation of beta1 receptors result from activating beta1 receptors in the heart  Activation of renal beta1 receptors is not associated with either beneficial or adverse effects  Beta1 receptors can be activated by epinephrine, NE, isoproterenol, dopamine, dobutamine, and ephedrine Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 70  Therapeutic Applications of Adrenergic Receptor Activation  Therapeutic application of beta1 activation  Shock  Profound hypotension and greatly reduced tissue perfusion  Primary goal of treatment is to maintain blood flow to vital organs  Beta1 stimulation increases heart rate and force of contraction  Increases cardiac output  Improves tissue perfusion Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 71  Therapeutic Applications of Adrenergic Receptor Activation  Therapeutic application of beta1 activation  Heart failure Activation of beta1 receptors in the heart has a positive inotropic effect (i.e., increases the force of contraction) Drugs that activate these receptors can improve cardiac performance Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 72  Therapeutic Applications of Adrenergic Receptor Activation  Therapeutic application of beta1 activation  ​Cardiac arrest Activation of cardiac beta1 receptors can initiate contraction in a heart that has stopped beating Drugs are not the preferred treatment Initial management focuses on cardiopulmonary resuscitation, external pacing, or defibrillation as well as the identification and treatment of the underlying cause  EpinephrineAtrioventricular (AV) heart block Activation of cardiac beta1 receptors can enhance impulse conduction through the AV node Beta1 stimulants can help overcome AV block 73 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Therapeutic Applications and Adverse Effects of Adrenergic Receptor Activation  Adverse effects of beta1 activation  Dysrhythmias  Angina pectoris: Because beta1 agonists increase cardiac oxygen demand by increasing the heart rate and the force of contraction, patients with compromised coronary circulation are at risk of an anginal attack Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 74  Clinical Consequences of Beta2 Activation  Applications of beta2 activation are limited to the following:  Lungs  Uterus  Beta2 activating drugs  Epinephrine  Isoproterenol  Albuterol Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 75  Therapeutic Application of Beta2 Activation  Asthma  Activate beta2 receptors in the lung to promote bronchodilation  Help relieve or prevent asthma attacks  Selective for beta2 receptors (such as albuterol)  Less selective agents (such as isoproterenol)  Delay of preterm labor  Activation of beta2 receptors in the uterus  Relaxes uterine smooth muscle  Used to delay preterm labor Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 76  Adverse Effects of Beta2 Activation  Hyperglycemia  Activation of beta2 receptors in the liver and the skeletal muscles  Breakdown of glycogen into glucose  Beta2 agonists cause hyperglycemia only in patients with diabetes  In patients with normal pancreatic function, insulin release will maintain blood glucose at an appropriate level  Tremor  Tremor is the most common side effect of beta2 agonists  Tremor generally fades over time and can be minimized by initiating therapy at low doses Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 77  Clinical Consequences of Dopamine Receptor Activation  Used to treat shock: Dilation of the renal blood vessels reduces the risk of renal failure  Dopamine dilates the renal vasculature  Enhances cardiac performance by activating beta1 receptors in the heart Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 78  Multiple Receptor Activation: Treatment of Anaphylactic Shock  Pathophysiology of anaphylaxis  Severe allergic response  Hypotension, bronchoconstriction, and edema of the glottis  Treatment  Epinephrine: Treatment of choice for anaphylactic shock It activates all 4 adrenergic receptors and produces broad spectrum sympathomimetic effects Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 79  Chapter 18 Adrenergic Antagonists Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved.  Adrenergic Antagonists  Cause direct blockade of adrenergic receptors  Two major groups:  Alpha-adrenergic blocking agents  Beta-adrenergic blocking agents Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 81  Therapeutic Applications of Alpha-adrenergic Blockade  Essential hypertension  Lower blood pressure by causing vasodilation by blocking alpha1 receptors on arterioles and veins  In response to venous dilation: Return of blood to the heart decreases Cardiac output decreases Arterial pressure is reduced  Benign prostatic hyperplasia (BPH)  Symptoms: Dysuria, increased frequency of daytime urination, nocturia, urinary hesitancy, urinary urgency, a sensation of incomplete voiding, and a reduction in the size and force of the urinary stream  Alpha1 receptors: Reduce the contraction of smooth muscle in the prostatic capsule and the bladder neck (trigone and sphincter) 82 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved.  Therapeutic Applications of Alpha Blockade  Pheochromocytoma  Catecholamine-secreting tumor, usually in the adrenal medulla  Principal cause of hypertension is usually activation of alpha1 receptors, but beta1 receptors can also contribute  Treatment: Best option is surgery Inoperable tumor: Alpha antagonists suppress 1 hypertension  Raynaud’s disease  Peripheral vascular disorder  Vasospasms in the toes and fingers  Suppress symptoms by preventing alpha-mediated vasoconstriction, thus promoting vasodilation Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 83  Adverse Effects of Alpha1 Blockade  Detrimental effects result from the blockade of alpha1 receptors  Effects from alpha receptors are minor 2  Orthostatic hypotension  Blockade of alpha receptors on veins  Reduced muscle tone in the venous wall  Upon standing, blood pools in the veins  Return of blood to the heart is reduced  Cardiac output decreased: Blood pressure drops Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 84  Adverse Effects of Alpha1 Blockade  Reflex tachycardia  Reflex to increase heart rate via the autonomic nervous system (ANS)  Nasal congestion  Dilates the blood vessels of the nasal mucosa  Inhibition of ejaculation  Alpha1 activation required for ejaculation  Impotence is reversible; resolves when drug is discontinued  Sodium retention and increased blood volume  Reduced blood pressure promotes renal retention of sodium and water  Usually combined with diuretic when used for hypertension Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 85  Adverse Effects of Alpha2 Blockade  Most significant adverse effect associated with alpha2 blockade: Potentiation of reflex tachycardia Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 86  Beta-Adrenergic Antagonists  The major consequence of blocking these receptors are:  Reduced heart rate  Reduced force of contraction  Reduced velocity of impulse conduction through the AV node  Because of these effects, beta blockers are useful in a variety of cardiovascular disorders Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 87  Beta-Adrenergic Antagonists  Nonselective  Blocks beta1 and beta2 receptors  i.e. Propranolol (Inderal)  Cardioselective  Blocks beta1 receptors  i.e. Metoprolol (Lopressor) Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 88  Beta-Adrenergic Antagonists  Therapeutic applications of beta blockade  Angina pectoris  Hypertension  Heart failure  Cardiac dysrhythmias  Myocardial infarction (MI)  Hyperthyroidism  Migraine  Glaucoma Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 89  Beta-Adrenergic Antagonists  Adverse effects of beta blockade  Bradycardia  Reduced cardiac output  Heart failure  AV heart block  Bronchoconstriction  Hypoglycemia Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 90  Chapter 20 Introduction to Central Nervous System Pharmacology Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved.  Central Nervous System (CNS) Drugs  Agents that act on the brain and spinal cord  More than a dozen neurotransmitters of the CNS (i.e dopamine, norepinephrine, serotonin)  Medical uses  Relief of pain  Suppression of seizures  Production of anesthesia  Treatment of psychiatric disorders  Nonmedical uses  Stimulant, depressant, euphoriant, and other “mind-altering” abilities Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 92  Adaptation of the CNS to Prolonged Drug Exposure  Different effects possible when drug is taken chronically vs. the initial use of the drug  Increased therapeutic effects  Certain drugs used in psychiatry (such as antipsychotics or antidepressants) must be taken for several weeks before full therapeutic effects develop  Beneficial responses may be delayed because they result from adaptive changes and not from the direct effects of drugs on synaptic function  Full therapeutic effects are not seen until the CNS has had time to modify itself in response to prolonged drug exposure Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 93  Adaptation of the CNS to Prolonged Drug Exposure  Decreased side effects: When CNS drugs are taken chronically, the intensity of the side effects may decrease, but the therapeutic effects remain undiminished  Example:  Morphine is taken to control pain  Nausea is a common side effect early on  Treatment continues, nausea diminishes, and analgesic effects persist Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 94  Adaptation of the CNS to Prolonged Drug Exposure  Tolerance  Decreased response occurring during the course of prolonged drug use  Physical dependence  State in which abrupt discontinuation of drug use will precipitate a withdrawal syndrome Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 95  Question 1 The nurse receives a phone call from a patient who has been taking a CNS drug (morphine) for 3 days for pain control. The patient tells the nurse that the medication causes nausea. Which response by the nurse is best? A. “Nausea is not a common side effect of this drug.” B. “You should stop taking the medication immediately.” C. “The nausea will most likely decrease over time.” D. “Try taking the medication on an empty stomach.” Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 96  Question 2 A patient has been taking a medication for 2 months. Which statement, if made by the patient, would indicate to the nurse that drug tolerance is occurring? A. “The medication seems to be working better than it did at first.” B. “I feel really sick if I do not take the medication every day.” C. “The side effects are not bothering me anymore.” D. “The medication does not seem to be working as well.” Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 97  Chapter 24 Drugs for Epilepsy Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved.  Definition of Epilepsy  Group of disorders characterized by excessive excitability of neurons in the central nervous system  Can produce a variety of symptoms that range from brief periods of unconsciousness to violent convulsions  May also cause problems with learning, memory, and mood Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 99  Types of Seizures  Partial (focal) seizures  Simple partial- convulsions in a single limb or muscle group, consciousness not impaired  Complex partial- manifest as attack of confused or bizarre behaviour, consciousness is impaired Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 100  Types of Seizures  Generalized seizures  Tonic-clonic (grand mal)- period of muscle rigidity (tonic) and synchronous muscle jerks (clonic), impaired consciousness and CNS depression  Absence (petit mal)- children and teens, loss of consciousness for a brief time (10-30 sec) mild, symmetric motor activity (eye blinking)  Atonic- sudden loss of muscle tone, ‘head drop’, ‘drop attack’  Myoclonic- sudden, rapid muscle contractions, may involve one limb (focal) or entire body (massive)  Status epilepticus- persists for more than 30 min, can be 101 life threatening Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved.  Antiepileptic Drugs  Effects  Suppress discharge of neurons within a seizure focus  Suppress propagation of seizure activity from the focus to other areas of the brain  Mechanisms of action  Suppression of sodium influx  Suppression of calcium influx  Antagonism of glutamate  Potentiation of gamma-aminobutyric acid (GABA)-inhibitory neurotransmitter that is widely distributed in the brain Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 102  Epilepsy-Therapeutic Considerations  Treatment goal  Diagnosis  Drug selection  Plasma drug levels  Adherence  Withdrawal  Seizure logs Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 103  Classification of Antiepileptic Drugs  Two major categories  Traditional AEDs Phenytoin, fosphenytoin, carbamazepine, valproic acid, ethosuximate, phenobarbital, and primidone  Newer AEDs: Total of 14 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 104  Phenytoin [Dilantin]  Partial and tonic-clonic seizures  Mechanism of action: Selective inhibition of sodium channels  Varied oral absorption  Half-life: 8 to 60 hours  Therapeutic levels: 10 to 20 mcg/mL  Therapeutic uses:  Epilepsy  Cardiac dysrhythmias Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 105  Phenytoin [Dilantin]  Adverse effects  Nystagmus-continuous back and forth movement of eyes  Sedation  Ataxia-gait  Diplopia-double vision  Cognitive impairment  Gingival hyperplasia  Skin rash  Effects in pregnancy  Cardiovascular effects Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 106  Phenytoin [Dilantin]  Drug interactions  Decreases the effects of oral contraceptives, warfarin, and glucocorticoids  Increases levels of diazepam, isoniazid, cimetidine, alcohol, and valproic acid  Dosing: Highly individualized  Administration: With food Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 107  Carbamazepine [Tegretol]  Uses  Epilepsy  Bipolar disorder  Trigeminal and glossopharyngeal neuralgias  Mechanism of action  Suppresses high-frequency neuronal discharge in and around seizure foci Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 108  Carbamazepine [Tegretol]  Adverse effects  Neurologic effects: Nystagmus and ataxia  Hematologic effects: Leukopenia, anemia, and thrombocytopenia  Birth defects  Dermatologic effects: Rash and photosensitivity reactions Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 109  Carbamazepine [Tegretol]  Drug-drug and drug-food interactions  Hepatic drug-metabolizing enzymes  Warfarin  Oral contraceptives  Phenytoin  Phenobarbital  Grapefruit juice Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 110  Valproic Acid [Depakene, Depakote, Depacon]  Mechanism of action  Suppresses high-frequency neuronal firing through the blockade of sodium channels  Suppresses calcium influx through T-type calcium channels  May augment the inhibitory influence of GABA Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 111  Valproic Acid [Depakene, Depakote, Depacon]  Therapeutic uses  Seizure disorders  Bipolar disorder  Migraine  Adverse effects  Gastrointestinal effects  Hepatotoxicity: Liver failure  Pancreatitis  Teratogenic effects  Hyperammonemia Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 112  Phenobarbital  Actions  Reduces seizures without causing sedation  Anticonvulsant barbiturate  Potentiates the effects of GABA  Uses  Epilepsy (partial and generalized tonic- clonic seizures)  Sedation  Induction of sleep Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 113  Phenobarbital  Adverse effects  Neuropsychologic effects  Dependency  Exacerbation of intermittent porphyria  Rickets and osteomalacia  Nystagmus  Ataxia Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 114  Phenobarbital  Drug interactions  Oral contraceptives  Warfarin  Central nervous system depressants  Valproic acid  Drug withdrawal Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 115  Chapter 28 Opioid Analgesics, Opioid Antagonists, and Nonopioid Centrally Acting Analgesics Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved.  Analgesics and Opioids  Analgesics are drugs that relieve pain without causing the loss of consciousness  Opioids  a general term defined as any drug, natural or synthetic that has actions similar to morphine  Opiate  a term that applies only to compounds present in opium Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 117  Opioid Receptors  Three main classes of opioid receptors  Mu receptors: Analgesia, respiratory depression, euphoria, sedation, and physical dependence  Kappa receptors: Analgesia and sedation; kappa activation may underlie psychotomimetic effects seen with certain opioids  Delta receptors Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 118 Opioid Agonists and Antagonists  Agonists  Morphine  Fentanyl  Codeine  Oxycodone  Hydrocodone  Antagoinist  Naloxone [Narcan] Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 119  Morphine  Therapeutic use: Relief of pain  Relieves pain without affecting other senses (for example, sight, touch, smell, and hearing)  No loss of consciousness  Relieve pain by mimicking the actions of endogenous opioid peptides, primarily at mu receptors Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 120  Morphine  Adverse effects  Respiratory depression  Constipation  Urinary retention  Orthostatic hypotension  Emesis  Miosis  Cough suppression  Biliary colic  Tolerance and physical dependence  Sedation Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 121  Morphine  Tolerance and physical dependence  Tolerance Increased doses needed to obtain the same response Develops with analgesia, euphoria, sedation, and respiratory depression Cross-tolerance to other opioid agonists Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 122  Morphine  Tolerance and physical dependence  Physical dependence Abstinence syndrome with abrupt discontinuation About 10 hours after last dose, the initial reaction occurs and includes yawning, rhinorrhea, and sweating Progresses to violent sneezing, weakness, nausea, vomiting, diarrhea, abdominal cramps, bone and muscle pain, muscle spasms, and kicking movements Lasts 7 to 10 days if untreated Withdrawal is unpleasant but not lethal, as it may be with CNS depressants Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 123  Morphine  Drug interactions  CNS depressants  Anticholinergic drugs  Hypotensive drugs  Monoamine oxidase inhibitors  Agonist-antagonist opioids  Opioid antagonists  Other interactions Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 124  Morphine  Toxicity  Clinical manifestations Classic triad  Coma  Respiratory depression  Pinpoint pupils  Treatment Ventilatory support Antagonist: Naloxone [Narcan]  General guidelines Monitor vital signs before giving Give on a fixed schedule Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 125  Clinical Use of Opioids  Pain assessment  Essential component of management  Based on patient’s description  Evaluate: Pain location, characteristics, and duration Things that improve or worsen pain Status before taking drug and 1 hour after Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 126  Clinical Use of Opioids  Physical dependence  State in which an abstinence syndrome will occur if the dependence-producing drug is abruptly withdrawn; it is NOT equated with addiction  Abuse  Drug use that is inconsistent with medical or social norms  Addiction  Behavior pattern characterized by continued use of a psychoactive substance despite physical, psychologic, or social harm Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 127  Chapter 34 Sedative-Hypnotic Drugs Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved.  Sedative-Hypnotic Drugs  Drugs that depress central nervous system (CNS) function  Primarily used to treat:  anxiety (antianxiety agents or anxiolytics)  Insomnia (hypnotic-drugs to promote sleep)  Distinction between antianxiety effects and hypnotic effects is often a matter of dosage  Sedative hypnotics relieve anxiety in low doses  Sedative hypnotics induce sleep in higher doses Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 129  Sedative-Hypnotic Drugs  Benzodiazepines  Potentiate the actions of GABA-enhance the actions of GABA)  Highly lipid soluble so they cross placental and blood brain barriers  Varied half-life among agents  Barbiturates  CNS depressants  Not as safe as benzodiazepines Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 130  Benzodiazepines and Benzodiazepine Receptor Agonists  Drugs of choice to treat insomnia and anxiety  Used to induce general anesthesia  Used to manage seizure disorders, muscle spasms, panic disorder, and withdrawal from alcohol  Most familiar member: Diazepam [Valium]  Most prescribed: Lorazepam and alprazolam  Safer than general CNS depressants  Lower potential for abuse  Produce less tolerance and physical dependence Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 131   Benzodiazepines  Adverse effects  CNS depression  Anterograde amnesia- impaired recall of events that take place after dosing  Sleep driving  Paradoxical effects  Respiratory depression- when administered IV, not orally  Abuse  Use in pregnancy and lactation Highly lipid soluble Cross the placental barrier Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 132  Benzodiazepines  Drug interactions  CNS depressants  Tolerance and physical dependence  Tolerance With prolonged use, tolerance develops to some effects but not others  Physical dependence Can cause physical dependence, but the incidence of substantial dependence is low Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 133  Benzodiazepines  Acute toxicity  Oral overdose: Drowsiness, lethargy, and confusion  Intravenous toxicity: Life-threatening reactions, profound hypotension, respiratory arrest, and cardiac arrest  General treatment measures Oral: Gastric lavage, activated charcoal, saline cathartic, and dialysis Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 134  Barbiturates  Cause tolerance and dependence  High abuse potential  Multiple drug interactions  Powerful respiratory depressants that can be fatal with overdose  Barbiturates are used much less than they were in the past because they have been replaced by newer and safer drugs, primarily the benzodiazepines Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 135  Barbiturates  Three classifications  Ultrashort-acting (thiopental)  Short- to intermediate-acting (secobarbital)  Long-acting (phenobarbital)  Mechanism of action  Binds to the GABA receptor–chloride channel complex Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 136  Barbiturates  Pharmacologic effects  CNS depression  Cardiovascular effects  Induction of hepatic drug-metabolizing enzymes  Tolerance and physical dependence  Tolerance Develops to many—but not all—of the CNS effects Very little tolerance develops to respiratory depression  Physical dependence Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 137  Barbiturates  Pharmacokinetics  Lipid solubility has a significant impact  Rapid onset and brief duration  Therapeutic uses  Seizure disorders  Induction of anesthesia  Insomnia  Other uses Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 138  Barbiturates  Drug interactions  CNS depressants  Interactions that result from the induction of drug-metabolizing enzymes  Chloral hydrate  Meprobamate Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 139  Barbiturates  Adverse effects  Respiratory depression  Suicide  Abuse Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 140  Barbiturates  Acute toxicity  Symptoms Respiratory depression Coma Pinpoint pupils  Treatment Removal of barbiturate from the body: Activated charcoal Maintenance of an adequate oxygen supply to the brain Maintain body heat Support blood pressure No specific antidote Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 141  Management of Insomnia  Sleep physiology  Sleep phases-REM and NREM  Causes of insomnia  pain, psychiatric disorders, situational insomnia  Treatment  Hypnotic drugs  Nondrug therapy-sleep fitness Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 142  Sleep Physiology  Sleep phases  Rapid-eye-movement (REM) sleep  Non–rapid-eye-movement (NREM) sleep Stages I and II: Relatively light sleep Stages III and IV: Deep sleep Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 143  Chapter 35 Management of Anxiety Disorders Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved.  Anxiety  An uncomfortable state with psychologic and physical components  Characterized by fear, apprehension, dread, and uneasiness  Among the most common psychiatric illnesses Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 145  Types of Anxiety Disorders  Generalized anxiety disorder  Panic disorder  Obsessive-compulsive disorder (OCD)  Social anxiety disorder (social phobia)  Post-traumatic stress disorder (PTSD) Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 146  Classes of Drugs Used for Anxiety Disorders  Benzodiazepines  Selective serotonin reuptake inhibitors (SSRI’s)-now used for many anxiety disorders Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. 147