Thinking Outside the Box: Prescribing by Synthesis & Integration

Transcription

1 Thinking Outside the Box: Prescribing by Synthesis & Integration Barbara J. Limandri, DNSc, APRN, BC Linfield College School of Nursing Portland DBT Program AGENDA Neuroanatomy and neurophysiology review Pharmacokinetics (Cytochrome P-450) Pharmacodynamics (Drug response) Integrating & synthesis: brain, drugs, prescribing Case studies Barbara J. Limandri, DNSc, APRN, BC 1

2 RELATIONSHIP OF NEUROPATHOLOGY, DIAGNOSIS AND PHARMACOLOGY Modern genetics in many ways has freed clinicians from the tyranny of nosology in order to focus on symptoms. (Stahl, 2008) NEURO GEOGRAPHY Barbara J. Limandri, DNSc, APRN, BC 2

3 THE EXECUTIVE BRAIN Frontal and prefrontal cortex Dorsolateral prefrontal cortex (DLPFC) Orbital frontal cortex (OFC) Anterior cingulate cortex (ACC) THE EMOTIONAL BRAIN Limbic system Hypothalamus Pituitary Amygdala Hippocampus Related structures Basal ganglia (nuclei) Ventral tegmental area Barbara J. Limandri, DNSc, APRN, BC 3

4 HIGHWAY IN BETWEEN Corticortical circuits Cortico-striatal-thalamic-cortical circuits Neurotransmitter circuits Dopamine Serotonin Norepinephrine GABA Acetylcholine DOPAMINE Barbara J. Limandri, DNSc, APRN, BC 4

5 DOPAMINE RECEPTOR SUBTYPES SEROTONIN Barbara J. Limandri, DNSc, APRN, BC 5

6 SEROTONIN RECEPTOR SUBTYPES NOREPINEPHRINE Barbara J. Limandri, DNSc, APRN, BC 6

7 GABA ACETYLCHOLINE Barbara J. Limandri, DNSc, APRN, BC 7

8 RELATIONSHIP OF NEUROPATHOLOGY AND PHARMACOLOGY PHARMACOKINETICS What the body does to the drug Transforms the product to be used by the body Metabolism Phase I Hydroxylation (Cyp 450) Phase II Conjugation Barbara J. Limandri, DNSc, APRN, BC 8

9 CYP 450 SUPERFAMILIES CYP 1 A2 CYP 2 B6 C2 C9 C19 D6 E CYP 3 A4, 5, 7 CYTOCHROME P-450 SYSTEM Superfamily of enzymes produced by genes CYP 1 family A subtype 2 gene product Genetic polymorphism (not all livers are the same) Poor metabolizers (PM) Extensive metabolizers (EM) AmpliChip CYP450 Test for genotype Barbara J. Limandri, DNSc, APRN, BC 9

10 Factors Affecting Human CYP450 Factor Nutrition Smoking Alcohol Drugs Somatic* Genetic polymorphism Enzymes Affected 1A2, 2E1, 3A3 1A2 2E1 1A2, 2C, 2D6, 3A3 1A2, 2E1, 3A3 2C9, 2C19, 2D6, 2E1 *E.g. liver size, intestinal metabolism Source: Goshman, Fish, Roller (1999) EFFECTS OF CYP-450 Substrates-what it acts on Induction-what it makes it do or converts into Inhibition-what it slows down or prevents Barbara J. Limandri, DNSc, APRN, BC 10

11 DRUG GROUPS Serotonin Reuptake Inhibitors Serotonin Antagonist and Reuptake Inhibitors Serotonin and Norepinephrine Reuptake Inhibitors Norepinephrine Reuptake Inhibitors DRUG GROUPS CON T GABA-ergics Dopamine Antagonists Serotonin Dopamine Antagonists Serotonin agonists Beta blockers Barbara J. Limandri, DNSc, APRN, BC 11

12 Serotonin Reuptake Inhibitors Serotonin Agonist Reuptake Inhibitor Barbara J. Limandri, DNSc, APRN, BC 12

13 Serotonin & Norepinephrine Reuptake Inhibitor Norepinephrine Reuptake Inhibitor Barbara J. Limandri, DNSc, APRN, BC 13

14 GABA-ergics Dopamine Antagonist Barbara J. Limandri, DNSc, APRN, BC 14

15 Serotonin-Dopamine Antagonist Depressed Brain Barbara J. Limandri, DNSc, APRN, BC 15

16 Depression Algorithm Dysregulated Mood Algorithm Barbara J. Limandri, DNSc, APRN, BC 16

17 Anxious Brain Traumagenic Brain Barbara J. Limandri, DNSc, APRN, BC 17

18 CASE STUDY Persistent worry, ruminating about bad things Impulsive, sometimes aggressively so Poor appetite, difficulty with onset of sleep, no energy No motivation, no joy Difficulty concentrating, poor judgment, suicidal thinking APPLICATION OF THEORY Thyroid panel is normal Also has hypertension and takes losartan Smokes 1 ½ packs of cigarettes a day Has tried all the SRIs and they don t work Barbara J. Limandri, DNSc, APRN, BC 18

19 APPLICATION OF THEORY What medication? What side effects? What drug-drug interactions? What client education? What else? ADDITIONAL CASE STUDIES Barbara J. Limandri, DNSc, APRN, BC 19

20 RESOURCES Cytochrome P 450 Drug Interaction Table: Brain explorer: Videos =related related GABA s affect at the synaptic cleft Resources Con t Goodman, M & New, A (2000). Impulsive aggression in borderline personality disorder. Psychiatry Reports, 2, Norman, T.R. (2006). Prospects for the treatment of depression. Australian and New Zealand Journal of Psychiatry, 40: Pestka, E.L,; Hale, AM; Johnson, B.L.; Lee, J.L.; Poppe, K.A. (2007). Cytochrome p450 testing for better psychiatric care. Journal of Psychosocial Nursing, 45, Barbara J. Limandri, DNSc, APRN, BC 20