Barbara J. Limandri, DNSc, APRN, BC 1
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1 Barbara J. Limandri, DNSc, APRN, BC Linfield College Portland Dialectical Behavior Therapy Program At the conclusion of this workshop, the participant can: 1. Associate key regions of the brain with psychiatric symptomatology. 2. Relate the putative neurotransmitter/receptor mechanisms of common drugs used in mental health care. 3. Relate psychiatric symptoms with neurophysiologic mechanism of actions associated with common psychotropic medications. 4. Propose prescribing practice in selected case studies. Barbara J. Limandri, DNSc, APRN, BC 1
2 Mini lecture on neurophysiology Application in small group discussion Report of small group discussion Mini lecture on psychopharmacology Application in small group discussion Report of small group discussion Case presentations and large group response Barbara J. Limandri, DNSc, APRN, BC 2
3 Prefrontal (PFC) Orbital Frontal (OFC) Medial Frontal (MFC) Dorsolateral Prefrontal (DLPFC) Planning complex cognitive behavior, expression of personality Social behavior and adjustment, mood control, drive and responsibility Facial recognition of emotion, especially social reward (e.g., smile) Working memory, task performance, self-efficacy and self-control, conflict induced behavior adjustment Barbara J. Limandri, DNSc, APRN, BC 3
4 Anterior cingulate Focus attention on emotion of significant events. Perseverative concern about mistakes. Monitoring the Sympathetic ANS Emotional response to pain Dorsal cingulate Self-judgments & reward based decision making Cognitive & reward based decision making Information processing, demands & subjective experience of effort Barbara J. Limandri, DNSc, APRN, BC 4
5 Sensory gating Selective attention Visual spatial tracking Relay for perception, especially pain Motor control & execution in OCD Barbara J. Limandri, DNSc, APRN, BC 5
6 Motivation, reward, feeding, impulsivity, goal directed behavior, pleasure Decreased activity in effort demanding & discounting response Activated in aversive conditioning Barbara J. Limandri, DNSc, APRN, BC 6
7 Amygdala Conscious mood control Fear conditioning Emotional memory Regulation and modulation of attention, perception & explicit memory Hippocampus Converts short term to long term memories Formation of new memories Autobiographical episodic memory, encodes memory Acts in collaboration with other structures, esp entorhinal cortex Barbara J. Limandri, DNSc, APRN, BC 7
8 Globus pallidus Putamen Caudate Regulates voluntary movement at the subconscious level Coordinates automatic behavior Something s not right here. Defensive motoric responses Striatum = Putamen + Caudate Barbara J. Limandri, DNSc, APRN, BC 8
9 Coordination of movement Maintenance of movement Regulation of muscle tone Barbara J. Limandri, DNSc, APRN, BC 9
10 Synaptic transmission Neurons Receptors Transmitters Neural firing Action potential Barbara J. Limandri, DNSc, APRN, BC 10
11 Electrical and chemical signaling between neurons One way of classifying neurons is by the chemical used for neurotransmission, e.g., dopaminergic Electricity as a series of ion movement across the cell membrane to change the charge of the membrane com/matthews/c hannel.html Barbara J. Limandri, DNSc, APRN, BC 11
12 Acetylcholine Dopamine GABA (inhibitory NT) Glutamate (excitatory NT) Norepinephrine Serotonin Barbara J. Limandri, DNSc, APRN, BC 12
13 Neurotransmitter Neuroreceptor Subtypes Acetylcholine Muscarinic (M 1&3,M 2 & 4,M 5 Nicotinic (many subtypes) Dopamine D 1&5, D 2, D 3, D 4 GABA GABA A & GABA B Glutamate AMPA, Glu 1-4, NMDA 1, 2 A-D Norepinephrine α 1A-D, α 2 A-C β 1-3 Serotonin 5HT 1A-F, 5HT 2A-C, 5HT 3, 5HT 4,6,7, 5HT 5 Client presentation: Anna O Identify behaviors and associated ated brain areas involved Identify target symptoms for pharmacological treatment Neurotransmitter involvement Neural pathways involved Barbara J. Limandri, DNSc, APRN, BC 13
14 Drugs are chemicals that act on the neurophysiology of the brain Neither the brain nor the drugs know or care about the DSM Therefore, classifying drugs by an antidiagnosis, makes little sense Therefore, I will be naming the drugs by their pharmacodynamics Monamine Oxidase Inhibitors (MAOIs) Multi Receptor Action (aka TCAs) Serotonin Reuptake Inhibitors (SRIs) Serotonin Antagonist & Reuptake Inhibitor (SARI) Barbara J. Limandri, DNSc, APRN, BC 14
15 Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) Norepinephrine mediated Specific Serotonin Antagonist (NaSSA) Norepinephrine Reuptake Inhibitor (NRIs) Dopamine Norepinephrine Reuptake Inhibitor Alpha and Beta Norepinephrine Blockers Barbara J. Limandri, DNSc, APRN, BC 15
16 Citalopram (Celexa) & Escitalopram (Lexapro) Fluoxetine (Prozac) Fluvoxamine (Luvox) Paroxetine (Paxil) Sertraline (Zoloft) Duloxetine (Cymbalta) Milnaciprin (Savella) Venlafaxine (Effexor) & Desvenlafaxine (Pristiq) Barbara J. Limandri, DNSc, APRN, BC 16
17 Trazodone (Desyrel) Nefazodone (Serzone) Vilazodone (Vilbryd) Mirtazapine Unique action of blocking NE α2 at the somatodendritic end of serotonin neuron (autoreceptors) thereby increasing amount of serotonin available at the axonal end Blocks 5HT2A, 5HT2C and 5HT3 Blocks Histamine 1 Barbara J. Limandri, DNSc, APRN, BC 17
18 Armodafinil (Nuvigil) Bupropion (Budeprion, Wellbutrin) Dextroamphetamine (Adderall, Dexadrine) Methylphenidate (Ritalin, Concerta, Metadate, Focalin) Modafinil (Provigil) Nomifensine (Merital) Norepinephrine Reuptake Inhibitor: Atomoxetine (Strattera) Barbara J. Limandri, DNSc, APRN, BC 18
19 Selective alpha-1 blocker: Prazosin (Minipress) Selective alpha-2 blocker: Clonidine (Catapres) & Guanfacine (Tenex) Non selective beta blockers: Propranolol (Inderal), labetolol (Trandate) Selective beta-1 blocker: atenolol (Tenormin), metoprolol (Lopressor) Improved mood Improved anxiety Improved concentration Improved cognition Reduced neuropathic pain Improved motivation Barbara J. Limandri, DNSc, APRN, BC 19
20 Dopamine Antagonist (aka first generation) Serotonin Dopamine Antagonist (aka second generation antipsychotics) What makes an antipsychotic atypical? Rapid dissociation of D2 antagonism Antagonism of 5HT 2A Partial agonism of D2 Partial agonism of 5HT 1a Pathway DA Output Effect Mesolimbic High Positive sx Mesocortical to Low DLPFC Mesocortical to Low VMPFC Nigrostriatal Normal Tuberoinfundibular Normal Cognitive & negative sx Affective and negative sx Barbara J. Limandri, DNSc, APRN, BC 20
21 Aripiprazole pp (Abilify) Amisulpride? (not available in US) Bifeprunox (in phase III testing) SDA + SPA Clozapine (Clozaril) Iloperidone (Fanapt) Quetiapine (Seroquel) Risperidone (Risperdal) & Palperidone (Invega) Ziprazidone (Geodon) SDA + DPA + SPA Aripiprazole (Abilify) Asenapine (Saphris) Lurasidone (Latuda) DPA + SPA Bifeprunox Barbara J. Limandri, DNSc, APRN, BC 21
22 Decrease anxiety, esp ruminative type Decrease positive symptoms Decrease ritualistic behaviors Improved reasoning, therefore reduced impulsivity Improved deliberative behavior GABA neurotransmitter affects regulation of nerve transmission (hyper repolarization) Principle inhibitory neurotransmitter in brain Synthesized from glutamate GABA receptor subtypes GABA-A & C are ligand gated GABA-B are G protein-linked receptors Barbara J. Limandri, DNSc, APRN, BC 22
23 Barbara J. Limandri, DNSc, APRN, BC 23
24 α1 Cortical areas & thalamus, olfactory bulb, neocortex, hippocampus, cerebellum α2, 3, 5 Limbic system, central nucleus of amygdala, reticular activating system β4 Most brain areas δ Cerebellum & Thalamus Alcohol, Benzodiazepines, Barbiturates GABA analogues Pregabalin (Lyrica) Gabapentin (Neurontin) Topiramate (Topamax) Reuptake inhibitor: Tiagabine (Gabitril) Transaminase inhibitor: Valproate (Depakote) Barbara J. Limandri, DNSc, APRN, BC 24
25 Manage seizures Decreases anxiety & arousal Reduces impulsivity Reduced agitation Mood stabilization No effect on memory or cognition Major mediator of excitatory signaling Regulates neural development Determines cellular survival, differentiation, and elimination Receptor subtypes NMDA AMPA/kainate Metabotropic (mglur) Barbara J. Limandri, DNSc, APRN, BC 25
26 Glutamate blockers Lamotrigine (Lamictal) Topiramate (Topamax) Acamprosate (Campral)* NMDA antagonist: Memantine (Namenda) *Also activates GABA-A Barbara J. Limandri, DNSc, APRN, BC 26
27 Management of learning and memory Cognitive enhancer Improved negative & cognitive symptoms of schizophrenia Mood stabilization and improvement of depressive symptoms Neurotransmitter found in the peripheral and central nervous system Excitatory in the Autonomic Nervous System Inhibitory in the Central Nervous System Two receptor types Nicotinic (ligand gated) Muscarinic (G-protein-coupled) p Barbara J. Limandri, DNSc, APRN, BC 27
28 Barbara J. Limandri, DNSc, APRN, BC 28
29 Pons to thalamus cortex Medulla oblongata to cortex Septohippocampal Neuromodulator for synaptic plasticity Reinforcing reward, satiation, and aversion Sustaining attention Memory retention Induction of REM sleep Barbara J. Limandri, DNSc, APRN, BC 29
30 Cholinesterase inhibitors Donepezil (Aricept) Galantamine (Reminyl) Rivastigmine (Exelon) Tacrine (Cognex) Nicotinic receptor Partial agonist Varenicline (Chantix) Antagonist Bupropion (Wellbutrin/Zyban) Anticholinergics Amantadine (Symmatrel) Benztropine (Cogentin) Biperiden (Akineton) Trihexyphenidyl (Artane) Barbara J. Limandri, DNSc, APRN, BC 30
31 Case study of Anna O Clinical discussion Janicak, P.G.; Davis, J.M.; Preskorn, S.H. (2006). Principles and Practice of Psychopharmacology, 4 th ed. Philadelphia: Lippincott Williams & Wilkins. Lichtblau, L. (2011). Psychopharmacology Demystified. Clifton Park, NY: Cengage. Sadock B.J.; Sadock,V.A.; Ruiz P. (2009). Kaplan and Saddock s Synopsis of Psychiatry, 10 th ed. Philadelphia: Lippincott Williams & Wilkins. Stahl, S.M. (2008). Stahl s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications, 3 rd ed. NY: Cambridge Press. Barbara J. Limandri, DNSc, APRN, BC 31
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