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Psychiatric Nursing: Biological Basis for Understanding Psychotropic Drugs NUR 145 Sandy Mishkin, RN, BC, MSN, MEd © 2008 The Nervous System The Central Nervous System (CNS) Brain Spinal Cord The Peripheral Nervous System (PNS) Sensory nerves Motor nerves Physiological Organization of the Nervous System Somatic Nervous System Sensory nerves: React to the external environment Motor nerves: Regulate skeletal muscle Autonomic Nervous System Regulates the internal environment Two subsystems: Sympathetic Parasympathetic Autonomic Nervous System Sympathetic System Prepares the body for stressful situations Parasympathetic System Regulates the internal environment during rest Function of the Brain Brain as coordinator and director of the body’s reaction to the internal and external environments Goal: Maintain homeostasis in order to preserve life The Brain’s Response to the External World Peripheral nerves relay sensory information to the brain Dysfunction leads to hallucinations and illusions of schizophrenia Brain controls skeletal muscle Dysfunction of movement can result from the psychiatric illness itself or the medications used to treat it. Respiratory rate Speech The Brain’s Response to the Internal World The autonomic nervous system & stress Sympathetic division The hormonal system & stress Activates arterioles to increase BP Parasympathetic division Activates the GI tract and causes hypermotility and diarrhea Hypothalamus releases corticotropin- releasing hormone (CRH) that causes the pituitary to release corticotropin which results in the release of cortisol by the adrenal glands All three hormones overactive during states of anxiety and depression. Areas of Brain Dysregulation Common In Psychiatric Disorders Sex drive Appetite Circadian rhythm Alertness Focus/concentration Cognition Speech Reality testing Memory Learning Social skills Cellular Composition of the Brain Neurons (nerve cells of the brain) Three functions: 1) respond to stimuli, 2) conduct electrical impulses, 3) release neurotransmitters Conduction of electrical impulse Inward flow of sodium ions (positive charge from outside to inside membrane) and outward flow of potassium ions ( positive charge from inside to outside membrane) Activity of Neurons Electrical impulse causes release of neurotransmitter from presynaptic neuron. Neurotransmitter travels across synapse to postsynaptic neuron. Neurotransmitter attaches to postsynaptic receptors. Postsynaptic neuron either initiates or inhibits electrical impulse. Fate of Neurotransmitters Some are destroyed : For example, acetylcholine destroyed by the enzyme acetylcholinesterase Some are reabsorbed by the presynaptic neuron (reuptake): They are either reused or destroyed. Monoamine oxidase (MAO) breaks down monoamine transmitters (norepinephrine, dopamine, serotonin) Other Chemicals Influencing Brain Function Steroid hormones Estrogen, testosterone, and cortisol exert short-term and long-term influence on neurons Cortisol and prednisone can cause psychosis. Organization of the Nervous System Brainstem Cerebellum Cerebrum Brainstem Regulation of internal organs and vital functions, processing of sensory input Hypothalamus Reticular Activating System (RAS) Basic drives Link between thought and emotion and internal organs Regulation of sleep-wake cycle Conscious mental activity Mesolimbic and mesocortical pathways Linked to limbic system (emotional and psychological status) Cerebellum Skeletal muscle coordination Maintenance of equilibrium Cerebrum Cerebral cortex (outer layer) Basal ganglia Conscious sensation Initiation of movement Touch, sound, vision Language Movement Amygdala and hippocampus Emotions, learning, memory, basic drives Disturbances of Mental Function Genetics, the environment (including psychosocial stress), and physical disease all can increase the probability of psychiatric disorders. Specific neurotransmitters also are associated with mental dysfunction. Reduced norepinephrine & serotonin: depression Increased dopamine: thought disorders, psychosis Reduced response to γ-aminobutyric acid (GABA): anxiety Overview of Psychotropic Medications First-generation antipsychotics Second-generation/atypical antipsychotics Mood stabilizers Antianxiety (Anxiolytic) drugs Herbal formulations First-Generation Antipsychotics Antagonists of dopamine (D2) receptors Reduce positive symptoms of schizophrenia: hallucinations, delusions, & disorganized thinking Can cause extrapyramidal side effects (EPS) Increase prolactin Block D2 receptors in basal ganglia Parkinsonism, akinesia, akathisia, dyskinesia, tardive dyskinesia Amenorrhea, galactorrhea, gynecomastia Can cause Neuroleptic Malignant Syndrome (NMS) First-Generation Antipsychotics Block muscarinic receptors (reducing effect of acetylcholine) Block receptors for norepinephrine (reducing smooth muscle contraction) Anticholinergic effects: Confusion, blurred vision, dry mouth, tachycardia, constipation, urinary hesitancy/retention Orthostatic hypotension, prevent ejaculation Block receptors for histamine Sedation, weight gain Second-Generation/Atypical Antipsychotics Less blocking of D2 receptors basal ganglia Less risk of EPS Less risk of NMS Reduce negative as well as positive symptoms of schizophrenia May also improve cognition in schizophrenia Preferential blocking of dopamine receptors in limbic system Block 5-HT2 receptors for serotonin May explain reduction in negative symptoms Second-Generation/Atypical Antipsychotics Clozapine (Clozaril) Risperidone (Risperdal/Risperdal Consta) Agranulocytosis Regular WBC count Increased risk CVA in elderly Quetiapine (Seroquel) Olanzapine (Zyprexa) Ziprasidone (Geodon) Aripiprazole (Abilify) Partial dopamine agonist Very long-acting Paliperidone (Invega) Active metabolite of risperidone Mood Stabilizers Lithium Positively charged ion May stabilize electrical activity in brain First-line treatment for bipolar disorder Numerous side effects Low therapeutic index 0.6-1.2 mEq Regular blood levels Antiepileptics Carbamazepine (Tegretol) Baseline lab Regular blood levels Divalproex/Valproic Acid (Depakote/Depakene) Baseline lab Regular blood levels First-line treatment for bipolar disorder Mood Stabilizers Deficiency of norepinephrine &/or serotonin in limbic system major cause of depression Tricyclic antidepressants (TCAs) Mostly increase NE Anticholinergic effects Antihistaminic effects Sedation, drowsiness, weight gain Selective Serotonin Reuptake Inhibitors (SSRIs) Less anticholinergic and antihistaminic effects Excess serotonin can cause Serotonin Syndrome Current drugs of choice for depression Mood Stabilizers Monoamine Oxidase Inhibitors (MAOIs) Interfere with the breakdown of monoamine neurotransmitters (norepinephrine, epinephrine, dopamine, serotonin) Can interfere with breakdown of tyramine, a monoamine in GI tract Can cause hypertensive crisis Avoid foods with tyramine (aged cheese, pickled or smoked fish, wine) Mood Stabilizers Atypical antidepressants Venlafaxine (Effexor) Desvenlafaxine (Pristiq) Duloxetine (Cymbalta) Buproprion (Wellbutrin) Mirtazapine (Remeron) Trazodone (Desyrel) Used only for hypnotic effect Antianxiety Drugs Enhance effect of GABA to reduce anxiety Benzodiazepines Diazepam (Valium) Clonazepam (Klonopin) Alprazolam (Xanax) Can cause respiratory depression when combined with other CNS depressants Tolerance and addiction Avoid in the elderly Buspirone Buspar No CNS depression Less risk of tolerance or addiction Psychotropic Medication For Various Disorders Antidepressants for various anxiety disorders and eating disorders Second-generation antipsychotics for depression and bipolar disorder Psychostimulant drugs for ADHD Nonstimulant drug: atomoxetine HCL (Strattera) Anticholinesterase drugs for AD (DAT) Donepezil (Aricept), rivastigmine (Exelon), and galantamine (Reminyl) N-methyl-D-aspartate (NMDA) receptor antagonist: memantine (Namenda, Ebixa) Herbal Formulations for Psychiatric Disorders Not FDA-regulated Effectiveness? Adverse effects? Long-term effects? St. John’s Wort: Serotonin Syndrome when taken with other drugs that increase serotonin References Varcarolis, E., Carson, V., & Shoemaker, N. (2006). Foundations of psychiatric mental health nursing: A clinical approach (5th ed.). St. Louis: Saunders.