10/27/09! Psychopharmacology 101 for the LADC! Disclosures! Lecture outline! Structural divisions of the nervous system!

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1 Disclosures! Psychopharmacology 101 for the LADC! David A. Frenz, M.D.! Mental Health & Addiction Services! St. Josephʼs Hospital! I am employed by the HealthEast Care System! I do not have any financial relationships with the pharmaceutical or medical device industries! I do not intend to discuss investigational drugs or the off label use of medications! Lecture outline! General structure of the nervous system! Neurons! Action potentials, synapses and neurotransmission! Putting it all together with some examples! Structural divisions of the nervous system! Central nervous system! Brain! Spinal cord! Peripheral nervous system! Everything else! 1!

2 Functional divisions of the nervous system! Somatic voluntary! Sensory! Motor! Autonomic involuntary! Sensory! Motor! Rizzo D. Fundamentals of anatomy & physiology, 2d ed. Thomson Delmar Learning, 2006.! University of Minnesota full-text electronic resource.! Autonomic nervous system! Sympathetic fight or flight! Parasympathetic rest and digest! Scott A, Fong E. Body structures & functions, 11th ed. Delmar Cengage Learning, 2009.! University of Minnesota full-text electronic resource.! Autonomic nervous system! Key concept! Organ! Sympathetic! Parasympathetic! Eyes (pupils)! Dilate! Constrict! Salivary glands! More saliva! More saliva! Heart! Increased rate! Decreased rate! GI tract! Decreased activity! Increased activity! Bladder! Fill! Empty! Penis! Erection! Ejaculation! Skin! Sweating, goosebumps! Many unintended ( side ) effects of psychotropic medications occur in the autonomic nervous system! 2!

3 Autonomic nervous system! Organ! Sympathetic! Parasympathetic! Eyes (pupils)! Dilate! Constrict! Salivary glands! More saliva! More saliva! Heart! Increased rate! Decreased rate! GI tract! Decreased activity! Increased activity! Bladder! Fill! Empty! Penis! Erection! Ejaculation! Skin! Sweating, goosebumps! Neurons! Neuron! The nervous system is composed of various specialized cells! Neurons process and transmit information by electrochemical signaling! Scott A, Fong E. Body structures & functions, 11th ed. Delmar Cengage Learning, 2009.! University of Minnesota full-text electronic resource.! 3!

4 Neuron! Cell body! Axon! Axon terminals! Action potentials! Are electrochemical impulses (waves) that transmit information within neurons! Cause neurotransmitter release into the synapse! Action potential! Synapse! Signal! Synapses are specialized junctions were neurons communicate with each other and other tissues (e.g., muscles, glands)! Each neuron has up to 15,000 synapses! Each cubic millimeter of cerebral cortex contains about 1 billion synapses! There are roughly trillion synapses in the brain! 4!

5 Synapse! Neurotransmitters! Are chemicals that transmit information from neurons to others cells! Other neurons! Muscles, glands! Are stored in vesicles in the presynaptic neuron! Are released into the synapse by action potentials! Act upon the postsynaptic tissue! Scott A, Fong E. Body structures & functions, 11th ed. Delmar Cengage Learning, 2009.! University of Minnesota full-text electronic resource.! Receptors! Receptor-ligand! Are molecules to which ligands bind! Ligands include! Neurotransmitters! Hormones! Medications and substances that are abused! Poisons and toxins! Receptor-ligand relationships are very specific lock and key! 5!

6 Neurotransmission! Action potential! Neurotransmitter released into the synapse! Wikimedia! Neurotransmitters! Neurotransmission excitation! Can be excitatory or inhibitory! Excitatory neurotransmitters! Make postsynaptic action potentials more likely! Inhibitory neurotransmitters! Make postsynaptic action potentials less likely! Action potential! Action potential! Excitatory neurotransmitter released into the synapse! Muscle,! gland, et cetera! Neurotransmission inhibition! Key concept! Action potential! Psychotropic medications and substances that are abused exert their effects both intended and unintended by affecting neurotransmission at the synaptic level! Inhibitory neurotransmitter released into the synapse! Muscle,! gland, et cetera! 6!

7 Putting it all together! Example Major Depressive Episode! Symptoms brain regions neuronal circuits neurotransmitters medications! Example Major Depressive Episode! 7!

8 Monoamine hypothesis! Major depressive disorder is felt to be due to a relative deficit of serotonin, norepinephrine and dopamine! 8!

9 Stahl SM. J Clin Psychiatry 2007;58:520.! 9!

10 Treatment for depression! Involves medications that increase serotonin, norepinephrine and/or dopamine! Selective serotonin reuptake inhibitors! Generic name! Citalopram! Escitalopram! Fluoxetine! Fluvoxamine! Paroxetine! Sertraline! Trade name! Celexa! Lexapro! Prozac! Luvox! Paxil! Zoloft! Nat Rev Drug Discov 2005;4:764.! 10!

11 Dual reuptake inhibitors! Generic name! Desvenlafaxine! Duloxetine! Milnacipran*! Sibutramine*! Venlafaxine! Trade name! Pristiq! Cymbalta! Savella! Meridia! Effexor! * FDA approved but not as an antidepressant.! Atypical antidepressants! Generic name! Atomoxetine*! Bupropion! Mirtazapine! Nefazodone! Trazodone! Trade name! Strattera! Wellbutrin! Remeron! Serzone! Desyrel! * FDA approved but not as an antidepressant.! 11!

12 Putting it all together! Symptoms brain regions neuronal circuits neurotransmitters medications! Drugtext Internet Library! Example Addiction! Example Addiction! A disorder of reward characterized by continuing compulsive substance use despite harm! Dopamine hypothesis! Dopamine is one the principal neurotransmitters involved in the neurobiology of addiction! 12!

13 Reward circuitry! Other neurotransmitters! Dopamine! Serotonin! Gamma-aminobutyric acid (GABA)! Neuropeptide Y! Dynorphin! Corticotropin-releasing factor (CRF)! Norepinephrine! Glutamate! Pharmacol Ther 2005;108:18.! Annu Rev Psychol 2008;59:29.! Treatment for addiction! FDA approved medications! Involves medications that reduce reward and/or cravings! Medications support but do not replace standard psychosocial interventions! Medication assisted treatment! Generic name! Trade name! Approved uses! Acamprosate! Campral! Alcohol! Naltrexone! ReVia, Vivitrol! Alcohol, opioid! Buprenorphine! Suboxone! Opioid! Methadone! Dolophine! Opioid! Bupropion! Zyban! Nicotine! Nicotine! Nicorette and others! Nicotine! Varenicline! Chantix! Nicotine! 13!

14 Acamprosate (Campral)! Glutamate and GABA! Alcohol alters the balance between glutamate and gamma-aminobutyric acid (GABA)! Acamprosateʼs exact mechanism of action is somewhat uncertain but likely affects the glutamate system and possibly GABA! Acamprosate is felt to reduce cravings for alcohol, especially in early recovery! Addresses negative cravings! Pharmacol Ther 2005;108:18.! Naltrexone (ReVia, Vivitrol)! Alcohol and exogenous opioids increase the activity of the reward pathways! Naltrexone blocks the effects of alcohol and exogenous opioids! Addresses positive cravings! Naltrexone! Pharmacol Ther 2005;108:18.! 14!

15 Buprenorphine (Suboxone) and methadone! Buprenorphine (Suboxone) and methadone! Exogenous opioids increase the activity of the reward pathways! Buprenorphine and methadone also activate the reward pathways, thereby decreasing drug-seeking behavior! Address negative cravings! Buprenorphine and methadone also block the effects of other opioids! Address positive cravings! Pharmacol Ther 2005;108:18.! Varenicline (Chantix) and nicotine! Nicotine increases the activity of the reward pathways! Varenicline and nicotine also activate the reward pathways, thereby decreasing drug-seeking behavior! Address negative cravings! Varenicline also blocks the effects of nicotine! Addresses positive cravings! Varenicline (Chantix) and nicotine! Pharmacol Ther 2005;108:18.! 15!

16 Bupropion (Zyban)! Nicotine increases the activity of the reward pathways! Bupropion indirectly activates the reward pathway, thereby decreasing drug-seeking behavior! Reducing negative cravings! Bupropion (Zyban)! Pharmacol Ther 2005;108:18.! Contact information! David A. Frenz, M.D.! Mental Health & Addiction Services! HealthEast St. Josephʼs Hospital! 45 West 10th Street! St. Paul, MN 55102! (department)! (voice mail)! 16!

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