Chapter 2: Neurobiologic Theories and Psychopharmacology Central Nervous System Brain (see Figs. 2.1 and 2.2) o Cerebrum o Cerebellum o Brain stem o Limbic system Nerves that control voluntary acts (neurotransmitters) Copyright © 2020 Wolters Kluwer • All Rights Reserved Cerebrum Two hemispheres Four lobes: o Frontal lobe (thought, body movement, memories, emotions, moral behavior) o Parietal lobe (taste, touch, spatial orientation) o Temporal lobe (smell, hearing, memory, emotional expression) o Occipital lobe (language, visual interpretation such as depth perception) Copyright © 2020 Wolters Kluwer • All Rights Reserved Cerebellum Below cerebrum Center for coordination of movements and postural adjustments Reception, integration of information from all body areas to coordinate movement and posture Copyright © 2020 Wolters Kluwer • All Rights Reserved Brain Stem Midbrain: reticular activating system (motor activity, sleep, consciousness, awareness) and extrapyramidal system Pons: primary motor pathway Medulla oblongata: vital centers for cardiac, respiratory function Nuclei for cranial nerves III through XII Locus coeruleus: norepinephrine-producing neurons (stress, anxiety, impulsive behavior) Copyright © 2020 Wolters Kluwer • All Rights Reserved Limbic System Above brain stem o Thalamus (activity, sensation, emotion) o Hypothalamus (temperature regulation, appetite control, endocrine function, sexual drive, impulsive behavior) o Hippocampus and amygdala (emotional arousal, memory) Copyright © 2020 Wolters Kluwer • All Rights Reserved Neurotransmitters #1 Chemical substances to facilitate neurotransmission (see Fig. 2.3) Important in right proportions to relay messages; studies showing differences in brains of people with some mental disorders (see Fig. 2.4) Play role in psychiatric illness and psychotropic medications, including their actions and side effects Copyright © 2020 Wolters Kluwer • All Rights Reserved 1. Neurotransmitters #2 Excitatory or inhibitory (see Table 2.1) o Excitatory Dopamine: complex movements, motivation, cognition, regulation of emotional response Norepinephrine: attention, learning, memory, sleep, wakefulness, mood regulation Epinephrine: fight-or-flight response Glutamate: neurotoxic effects at high levels Copyright © 2020 Wolters Kluwer • All Rights Reserved 2. Neurotransmitters #3 Excitatory or inhibitory (see Table 2.1) (cont.) o Inhibitory Serotonin: food intake, sleep, wakefulness, temperature regulation, pain control, sexual behaviors, regulation of emotions GABA: major inhibitory neurotransmitter; modulation of other neurotransmitters o Excitatory or inhibitory Acetylcholine: sleep-and-wakefulness cycle; signals muscles to become alert Histamine: neuromodulator Copyright © 2020 Wolters Kluwer • All Rights Reserved 1. Question #1 Is the following statement true or false? The cerebellum consists of four lobes. Copyright © 2020 Wolters Kluwer • All Rights Reserved 1. Answer to Question #1 False Rationale: The cerebrum consists of four lobes. The cerebellum is located below the cerebrum. Copyright © 2020 Wolters Kluwer • All Rights Reserved Brain Imaging Techniques Computed tomography (CT) Magnetic resonance imaging (MRI) Positron emission tomography (PET) Single-photon emission computed tomography (SPECT) Limitations o Use of radioactive substances; expense of equipment; client’s inability to tolerate technique o Changes in disorders nondetectable with current techniques Copyright © 2020 Wolters Kluwer • All Rights Reserved Neurobiologic Causes Genetics and heredity: play role but not solely genetic o Twin, adoption, and family studies are used. Psychoimmunology: compromised immune system possibly contributing, especially in genetically at-risk populations Infections: theories include viruses that alter human genes, viruses during fetal development Copyright © 2020 Wolters Kluwer • All Rights Reserved Nurse’s Role in Research and Education Ensure all clients and families are well informed Help distinguish between facts and hypotheses Explain if or how new research may affect client’s treatment or prognosis Provide information and answer questions Copyright © 2020 Wolters Kluwer • All Rights Reserved 2. Question #2 Is the following statement true or false? Single-photon emission computed tomography (SPECT) is considered the best type of brain imaging technique to diagnose disease. Copyright © 2020 Wolters Kluwer • All Rights Reserved 2. Answer to Question #2 False Rationale: Single-photon emission computed tomography (SPECT) is not considered the best type of brain imaging used to diagnose disease. In fact, many of the changes in the brain are not currently detectable with any of the current techniques. Copyright © 2020 Wolters Kluwer • All Rights Reserved Psychopharmacology #1 Psychotropic drugs Efficacy (maximal therapeutic effect) Potency (amount of drug needed for maximum effect) Half-life Role of the FDA Copyright © 2020 Wolters Kluwer • All Rights Reserved Psychopharmacology #2 Off-label use (drug may be effective for treating a disease different from one involved in original testing) Black box warning (serious or life-threatening side effects) Copyright © 2020 Wolters Kluwer • All Rights Reserved Principles of Psychopharmacology Effect on target symptoms Adequate dosage for sufficient time Lowest effective dose Lower doses for older adults Tapering rather than abrupt cessation to avoid rebound, recurrence of symptoms, or withdrawal Follow-up care Simple regimen to increase compliance Copyright © 2020 Wolters Kluwer • All Rights Reserved Antipsychotic Drugs #1 Antipsychotic drugs (see Table 2.3) o Conventional or first generation (e.g., chlorpromazine, fluphenazine, thioridazine, haloperidol, loxapine) o Atypical or second generation (e.g., clozapine, risperidone, olanzapine) o Third generation (dopamine system stabilizers; e.g., aripiprazole) Copyright © 2020 Wolters Kluwer • All Rights Reserved Antipsychotic Drugs #2 Use: treat symptoms of psychosis Mechanism of action: block dopamine receptors Copyright © 2020 Wolters Kluwer • All Rights Reserved Antipsychotics: Side Effects #1 Extrapyramidal symptoms (EPSs): o Acute dystonia Torticollis, opisthotonus, oculogyric crisis Treatment: anticholinergic drugs or diphenhydramine (see Table 2.4) o Pseudoparkinsonism (stooped posture, masklike facies, shuffling gait) o Akathisia (restlessness, anxiety, agitation) Copyright © 2020 Wolters Kluwer • All Rights Reserved 1. Antipsychotics: Side Effects #2 Neuroleptic malignant syndrome (NMS) Tardive dyskinesia (permanent involuntary movements) Anticholinergic side effects (e.g., dry mouth, constipation, urinary hesitancy or retention) Copyright © 2020 Wolters Kluwer • All Rights Reserved 2. Antipsychotics: Side Effects #3 Other side effects: o Increased prolactin levels o Weight gain (most likely with second-generation agents, except ziprasidone) o Metabolic syndrome o Cardiovascular adverse effects o Lengthening of QT interval (thioridazine, droperidol, mesoridazine) o Agranulocytosis (clozapine) Copyright © 2020 Wolters Kluwer • All Rights Reserved Antipsychotics: Client Teaching Adherence to regimen Management of side effects o Thirst/dry mouth (sugar-free candy, liquids) o Constipation (dietary fiber, exercise) o Sleepiness/drowsiness (safety measures) Actions for missed dose (dose if within 4 hours of usual time) Copyright © 2020 Wolters Kluwer • All Rights Reserved 3. Question #3 Which of the following drugs would be classified as a conventional antipsychotic? A. Clozapine B. Risperidone C. Fluphenazine D. Aripiprazole Copyright © 2020 Wolters Kluwer • All Rights Reserved 3. Answer to Question #3 C. Fluphenazine Rationale: Fluphenazine is classified as a conventional antipsychotic. o Clozapine and risperidone are considered secondgeneration antipsychotics. Aripiprazole is considered a third-generation antipsychotic. Copyright © 2020 Wolters Kluwer • All Rights Reserved Antidepressants #1 Use: major depressive illness, anxiety disorders, depressed phase of bipolar disorder, psychotic depression Copyright © 2020 Wolters Kluwer • All Rights Reserved 1. Antidepressants #2 Four groups (see Table 2.5): o Selective serotonin reuptake inhibitors (SSRIs) o Cyclic compounds o Other antidepressants o Monoamine oxidase inhibitors Copyright © 2020 Wolters Kluwer • All Rights Reserved 2. Antidepressants #3 Precise mechanism is not known. Major interaction is with monoamine neurotransmitter systems, especially norepinephrine and serotonin. Copyright © 2020 Wolters Kluwer • All Rights Reserved Antidepressants: Side Effects #1 SSRIs o Anxiety, agitation, akathisia, nausea, insomnia, sexual dysfunction o Weight gain Cyclic antidepressants o Anticholinergic effects o Orthostatic hypotension, sedation, weight gain, tachycardia o Sexual dysfunction Copyright © 2020 Wolters Kluwer • All Rights Reserved 1. Antidepressants: Side Effects #2 MAOIs o Daytime sedation, insomnia, weight gain, dry mouth, orthostatic hypotension, sexual dysfunction o Hypertensive crisis (with foods containing tyramine) Other antidepressants o Sedation, headaches (nefazodone, trazodone) o Loss of appetite, nausea, agitation, insomnia (bupropion, venlafaxine) o Priapism (trazodone) Copyright © 2020 Wolters Kluwer • All Rights Reserved Antidepressants: Drug Interactions Serotonin syndrome o MAOI + SSRI o Agitation, sweating, fever, tachycardia, hypotension, rigidity, hyperreflexia o Coma, death (extreme reactions) Copyright © 2020 Wolters Kluwer • All Rights Reserved Antidepressants: Client Teaching Time of dosage o SSRI first thing in morning o Cyclic compounds at night Actions for missed dose o SSRI up to 8 hours after missed dose o Cyclic within 3 hours of missed dose or omit the day’s dose Safety measures Dietary restrictions with MAOIs (see Box 2.1) Copyright © 2020 Wolters Kluwer • All Rights Reserved Mood-Stabilizing Drugs #1 Lithium, some anticonvulsants (carbamazepine, valproic acid; gabapentin, topiramate, oxcarbazepine, and lamotrigine) Use: treatment of bipolar illness Copyright © 2020 Wolters Kluwer • All Rights Reserved Mood-Stabilizing Drugs #2 Mechanism of action o Lithium normalizes reuptake of certain neurotransmitters. o Valproic acid and topiramate increase the levels of GABA. o Valproic acid and carbamazepine inhibit the kindling process. Copyright © 2020 Wolters Kluwer • All Rights Reserved Mood-Stabilizing Drugs: Side Effects #1 Lithium o Nausea, diarrhea, anorexia, fine hand tremor, polydipsia, polyuria, metallic taste in the mouth, fatigue, lethargy; weight gain, acne (later in therapy) o Toxicity: severe diarrhea, vomiting, drowsiness, muscle weakness, lack of coordination Carbamazepine and valproic acid: drowsiness, sedation, dry mouth, blurred vision Copyright © 2020 Wolters Kluwer • All Rights Reserved Mood-Stabilizing Drugs: Side Effects #2 Carbamazepine: rash, orthostatic hypotension Valproic acid: weight gain, alopecia, hand tremor Topiramate: dizziness, sedation, weight loss Copyright © 2020 Wolters Kluwer • All Rights Reserved Mood-Stabilizing Drugs: Client Teaching Periodic monitoring of blood levels o 12 hours after last dose taken Taking medication with meals Safety measures Copyright © 2020 Wolters Kluwer • All Rights Reserved 4. Question #4 Is the following statement true or false? A client who takes an SSRI with an MAOI is at risk for a hypertensive crisis. Copyright © 2020 Wolters Kluwer • All Rights Reserved 4. Answer to Question #4 False Rationale: A client who takes an SSRI with an MAOI is at risk for serotonin syndrome. o Hypertensive crisis can occur if the client is taking an MAOI and ingests foods containing tyramine. Copyright © 2020 Wolters Kluwer • All Rights Reserved Antianxiety Drugs Use: treatment of anxiety and anxiety disorders, insomnia, OCD, depression, posttraumatic stress disorder, alcohol withdrawal Benzodiazepines, buspirone (see Table 2.6) Mechanism of action o Mediation of GABA (benzodiazepines) o Partial agonist activity at serotonin receptors (buspirone) Copyright © 2020 Wolters Kluwer • All Rights Reserved Antianxiety Drugs: Side Effects Benzodiazepines o Physical, psychological dependence o CNS depression o Hangover effect o Tolerance Buspirone o Dizziness, sedation, nausea, headache Copyright © 2020 Wolters Kluwer • All Rights Reserved Antianxiety Drugs: Client Teaching Safety measures Avoidance of alcohol Avoidance of abrupt discontinuation Copyright © 2020 Wolters Kluwer • All Rights Reserved Stimulants #1 Amphetamines (methylphenidate, amphetamine, dextroamphetamine) Use: treatment of ADHD in children and adolescents, residual attention-deficit disorder in adults, narcolepsy Copyright © 2020 Wolters Kluwer • All Rights Reserved Stimulants #2 Mechanism of action o Cause release of norepinephrine, dopamine, serotonin presynaptically o Block reuptake of neurotransmitters Dosage o Divided doses; higher doses for narcolepsy in adults o Doses for treating ADHD vary widely (see Table 2.7). Copyright © 2020 Wolters Kluwer • All Rights Reserved Stimulants: Side Effects and Client Teaching Side effects o Anorexia, weight loss, nausea, irritability o Growth and weight suppression Client teaching o Dose after meals o Avoidance of caffeine, sugar, chocolate o Proper storage out of reach of children Copyright © 2020 Wolters Kluwer • All Rights Reserved Disulfiram #1 Use: aversion therapy for alcoholism Mechanism of action: inhibition of enzyme involved with alcohol metabolism o Adverse reaction with alcohol ingestion Side effects: fatigue, drowsiness, halitosis, tremor, impotence Copyright © 2020 Wolters Kluwer • All Rights Reserved Disulfiram #2 Drug interactions with phenytoin, isoniazid, warfarin, barbiturates, long-acting benzodiazepines Client teaching: avoidance of alcohol, including common products that may contain it o Shaving cream, deodorant, OTC cough preparations Copyright © 2020 Wolters Kluwer • All Rights Reserved 5. Question #5 Which of the following drugs would the nurse expect to administer to a client with ADHD? A. Disulfiram B. Methylphenidate C. Buspirone D. Lithium Copyright © 2020 Wolters Kluwer • All Rights Reserved 5. Answer to Question #5 B. Methylphenidate Rationale: Methylphenidate is a stimulant used to treat ADHD. o Disulfiram is used to treat alcoholism. Buspirone is used to treat depression. Lithium is used to treat bipolar illness. Copyright © 2020 Wolters Kluwer • All Rights Reserved Cultural Considerations #1 More rapid response to antipsychotic medications and tricyclic antidepressants for African Americans than white people o Higher risk of side effects Slower metabolism of antipsychotics and tricyclic antidepressants for Asians than white people o Lower doses to produce the same effects Copyright © 2020 Wolters Kluwer • All Rights Reserved Cultural Considerations #2 Increased frequency of herbal medicine use o St. John’s Wort o Kava o Valerian o Ginkgo biloba Increased risk for interactions with herbal medicine Copyright © 2020 Wolters Kluwer • All Rights Reserved Self-Awareness Issues Clients and families need more than factual information; they need simple and thorough explanations. View chronic mental illness as having remissions and exacerbations, just as chronic physical illnesses do. Remain open to new ideas that may lead to future breakthroughs. Understand that medication noncompliance is often part of faulty thinking and reasoning related to the illness, not willful misbehavior. Copyright © 2020 Wolters Kluwer • All Rights Reserved