Enzyme Conversion Assignment Discussion Paper

Enzyme Conversion Assignment Discussion Paper

CLASS: PSYCHOPHARMACOLOGY Module 1 Assignment Enzyme Conversion After studying Module 1: Lecture Materials & Resources, submit the following: • • Starting with the precursor substance tyrosine, draw three diagrams showing how the various enzymes convert this substance to serotonin, dopamine and norepinephrine. Identify and briefly describe each chemical step required to create each neurotransmitter. Submission Instructions: • • • • Your diagrams must be hand-drawn. Scan your diagrams and submit them as an attachment of an image file or PDF. Follow APA 7th Edition formatting guidelines for graphs and figures (Links to an external site.) Complete and submit the assignment by 11:59 PM ET on Sunday. Late work policies, expectations regarding proper citations, acceptable means of responding to peer feedback, and other expectations are at the discretion of the instructor. Enzyme Conversion Assignment Discussion Paper

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Neurobiology and Pharmacokinetics NUR 520 P SYCHOP HARMACOLOGY Receptor: configured so that precisely shaped molecules fit and cause or prevent a response Ligand: a transmitter substance that fits and evokes a response from a receptor Neurobiological Definitions Synapse: A structure that permits a neuron to pass an electrical or chemical signal to another neuron Neurotransmission: Communication between neurons Neurotransmitters: The electrochemical messengers that send signals to from neuron to neuron. They either excite or stimulate an action in the cells (excitatory) or inhibit or stop an action (inhibitory). BRAIN FUNCTIONS FOREBRAIN MIDBRAIN HINDGRAIN The Forebrain: Functions of the Brain ◦ Controls all the higher mental functions, such as learning, speech, thought, and memory Thalamus: ◦ “Relay station;” transmits nerve impulses throughout brain Hypothalamus: ◦ Regulates bodily drives and body conditions Limbic system: ◦ Involves experiencing and expressing emotions and motivation The Midbrain: Functions of the Brain • Involved in vision and hearing, and along with the hindbrain, controls sleep, alertness, and pain • Manufactures serotonin, norepinephrine, and dopamine The Hindbrain: Enzyme Conversion Assignment Discussion Paper

• Controls motor movements, heart rate, sleep, and respiration • Manufactures norepinephrine and serotonin Pharmacokinetics Absorption: getting the drug into the bloodstream Distribution: getting the drug from the bloodstream to the tissues and organs Metabolism: breaking the drug down into inactive and typically water-soluble form Excretion: getting the drug out of the body Affects 90% of all drugs, 25% of all psychotropic drugs by CYP2D6 Found primarily in the liver. Also in the intestine, lungs, brain, and kidney Definitions ➢Substrate: Enzyme surfaces that receive inducers or inhibitor enzymes ➢Inducers: Increases the drug metabolism=decrease serum drug concentration. Takes several days to weeks to develop. ➢Inhibitors: Decreases the drug metabolism=increases serum drug concentration. Happens almost immediately. CYP-450 System Smoking and CYP 450 Cigarette smoking causes the induction of CYP-450 1A2, which causes more of this enzyme to be synthesized. Maximum enzyme induction occurs with 7 to 12 cigarettes per day for some medications, such as clozapine and olanzapine. Leads to a 40% to 50% reduction in serum level. If a patient smokes half of a pack or more, a higher dose of medication is needed. Same effects occur from secondhand smoke. The CYP1A2 Enzyme ❖Amitriptyline ❖Propranolol ❖Theophylline ❖Olanzapine ❖Naproxen ❖Nortriptyline ❖Acetaminophen ❖Desipramine ❖ Carbamazepine ❖ Cigarette smoking (PAH) ❖ Charbroiled Food ❖ Echinacea ❖Clozapine ❖Fluvoxamine ❖Coumadin ❖Haloperidol ❖ Mirtazapine ❖Imipramine ❖ Phenobarbital ❖ St. John’s Wort ❖ Broccoli ❖ Cabbage ❖ Phenytoin ❖ Insulin ❖ Cauliflower Retrieved from : https://apotential.wordpress.com/ 2011/08/22/how-to-memorize-cyp450/ Normal metabolizers: persons with one or two functioning copies of CYP2D6 or CYP2C19 Metabolism and Genetics Ultra-rapid metabolizers: multiple copies of CYP2D6 or CYPC19. High risk for poor efficacy. About 10% to 29% of people who are of East African or Middle Eastern descent are ultra-rapid metabolizers of CYP2D6 drugs Poor metabolizers: Patients with two inactivated copies of either CYP2D6 or CYPC19. High risk for toxicity. About 5% to 10% Caucasians higher likelihood to have lower CYP2D6 activity, making them poor metabolizers of CYP2D6 drugs Metabolism: Genetic Considerations Some Examples: Cardiovascular effects of propranolol ◦ Asian descent – more sensitive ◦ African descent – less sensitive Caucasians ◦ 5-10 % of Caucasians are poor metabolizers of CYP 2D6 Asian descent ◦ 20% people of Asian descent have educed activity CYP 2C19 ◦ May require lower doses of certain psychotropics Block metabolism: Enzyme Conversion Assignment Discussion Paper

TCAs and drugs for Alzheimer’s disease Block reuptake: SSRI and other antidepressants Block receptors: antagonists Psychotropics, Drugs and Neurotransmitters Stimulate or block auto-receptors Stimulate receptors (agonists) Stimulate receptor affinity (Benzodiazepines) Stimulate release of neurotransmitter (Amphetamines stimulate release of dopamine) High concentration in brain Point-to-point communication Amino Acid Neurotransmitters Consistently excitatory or inhibitory Fast acting, short duration Glutamate Aspartate GABA Glycine Glutamate ➢Principal excitatory NT ➢Biosynthesized as byproduct of cell metabolism ➢Removed by reuptake Major receptor types ◦ NMDA ◦ AMPA ◦ Kainate ➢ At high levels, can have major neurotoxic effects. ➢ Implicated in the brain damage caused by stroke, hypoglycemia, sustained hypoxia or ischemia, and some degenerative diseases such as Huntington’s or Alzheimer’s. Gamma Aminobutyric Acid (GABA) ➢ Principal Inhibitory NT ➢ Biosynthesis: Glu Glutamic Acid Decarboxylase (GAD) and B6 • Agonists Benzodiazepines Barbiturates Ethyl alcohol (EToH) GABA ➢ Found in the brain. ➢ Modulate other neurotransmitter systems rather than to provide a direct stimulus. ➢ Prevents brain from overstimulation ➢ Reduction in GABA results in epilepsy GABAa Binding Sites Benzodiazepine (Agonist) ◦ Probably also site for alcohol Barbiturate (indirect agonist) Steroid (indirect agonist) Picrotoxin (inverse agonist) Kandel, 2013 Biogenic Amines Medium concentration in brain Modulatory functions ◦ Excitatory or inhibitory as a function of receptor Slow acting, long duration Examples: ◦Acetylcholine ◦Epinephrine ◦Norepinephrine ◦Dopamine ◦Serotonin The role of histamine in mental illness is under investigation Enzyme Conversion Assignment Discussion Paper