Neurobiology & Psychopharmacology Fall 2024 Lecture Notes PDF

Neurobiology & Psychopharmacology MARISA ASTIZ, MS, RN, CNE How many people have watched a cooking show? Objectives Explain the role of neurotransmitters in mental health symptoms and medication side effects Understand how the mechanism of action of various psychiatric medications (psychotropi...

Neurobiology & Psychopharmacology MARISA ASTIZ, MS, RN, CNE How many people have watched a cooking show? Objectives Explain the role of neurotransmitters in mental health symptoms and medication side effects Understand how the mechanism of action of various psychiatric medications (psychotropics) Apply understanding of neurobiology and psychopharmacology to case studies.  By the end of today’s lecture you should be able to answer the following questions… 1. Schizophrenia is characterized by psychotic symptoms. How are the mechanism of action of antipsychotics linked to the types o f side effects observed? 2. Depression symptoms can be impacted by low levels of serotonin, norepinephrine, and dopamine. How does each neurotransmitter impact which symptoms a person will experience? 3. Alcohol increases the concentration of GABA. We use a benzodiazepine taper to treat alcohol withdrawal. What are the possible complications of alcohol withdrawal? Explain why this treatment is effective. 4. Symptoms of mania often result when there is an excess of neuronal activity and elevated levels of serotonin. What symptoms w ill result from elevated serotonin? What neurotransmitter should be targeted to decrease neuronal firing? 5. Antihistamines are commonly used in psychiatry to treat insomnia (difficulty or inability to sleep) and movement disorders. W hat is the effect will an antihistamine have on the nervous system that make this possible? 6. Benzodiazepines are GABA agonists. Explain what this means. What will happen to the concentration of GABA? What are possible side effects? 7. Antipsychotics are a dopamine antagonist. Explain what this means. What will happen to the concentration of dopamine? What are possible side effects of dopamine? 8. MAO is an enzyme that degrades neurotransmitters. MAOIs (monoamine oxidase inhibitors, a type of antidepressant) is an enzyme inhibitor. What effect will MAOIs have on the concentration of neurotransmitters? 9. SSRIs (an antidepressant) is a selective serotonin reuptake inhibitor. Explain that this means. What will happen to the conce ntration of serotonin available in the synapse? What are possible side effects? Mood Fluctuations are Normal Frequency Intensity Impact Psychopharmacology It is important to understand the effect neurotransmitters have in the body. Most psychiatric symptoms are caused by changes in neurotransmitters or neuronal transmission. In practice we target symptoms and symptoms may cut across the drug/illness classes. Many drugs from one class treat disorders assigned to another class (e.g., antidepressants are used to treat anxiety, antipsychotics are used to treat depression) Mechanism of Action: Neurotransmitters & Electrical Impulses  Pre-Work: Recap Signal muscles to become alert; 1. Dopamine A. sleep/wakefulness Mood; Appetite; Sleep/Wake; Temp. Reg; Pain; 2. Norepinephrine B. Sexual Bx Movements; Motivation; Pleasure; 3. Acetylcholine C. Reward; Cognition; Emotional Response 4. Serotonin D. Inhibitory; Modulates other Neurotransmitters Attention; Learning; Memory; Sleep/Wake; 5. GABA E. Mood  Pre-Work: Recap - Answers Movements; Motivation; Pleasure; 1. Dopamine C. Reward; Cognition; Emotional Response 2. Norepinephrine E. Attention; Learning; Memory; Sleep/Wake; Mood Signal muscles to become alert; 3. Acetylcholine A. sleep/wakefulness Mood; Appetite; Sleep/Wake; Temp. Reg; Pain; 4. Serotonin B. Sexual Bx 5. GABA D. Inhibitory; Modulates other Neurotransmitters  Important Neurotransmitters in Psychiatry Neurotransmitter Function Disorders Medications Side Effects Dopamine Norepinephrine Serotonin Acetylcholine Glutamate GABA Histamine Neuropeptides  Dopamine Norepinephrine Serotonin GABA HIGH “drugs” “NEeurotic” Mania “grab a grey goose” Psychotic symptoms Flight or flight Antidepressant Side Elevated with benzos & (e.g., schizophrenia; Effects: alcohol: hallucinogenic drug “sleepy” Benzos - ffects similar use) “sick stomach” to Benzoalcohol “sex” intoxications “serious stuff” “don’t want to do it” “No Energy; no fun” “so, so sad” “I’m getting anxious” “don’t dance” Fatigue/lethargy, Low mood Benzos – potentiate Low motivation Concentration issues GABA (avolition) Anxiety (acute) Low pleasure Alcohol withdrawal (anhedonia) LOW Psychopharmacology Medication Primary NT MOA COMMON SE Antipsychotics D Antagonist Partial Agonist SUDs D Agonist Antidepressants D, NE, S Reuptake Inhibitor (e.g., SSRI) Enzyme Inhibitor e.g., MAOI) Benzodiazepines GABA Agonist Mood Stabilizers Electrical Salt Impulses GABA - agonist Psychosis & Antipsychotics st (1 Gen.) High Dopamine MOA Low Dopamine Psychosis Dopamine Movement Disturbed Antagonist Disorders (e.g., thought process Partial Agonist EPS) & perception (prevents full agonism) 2nd Generation: dopamine antagonist & serotonin agonist (more on this during psychotic disorders lecture) Substance Use & Addiction MOA Impact Continued Use Dopamine Increased Physical Agonist pleasure & Dependence Drugs, euphoric Psychological alcohol, sex, Motivates gambling, etc. future use Depression & Antidepressants SX: Low NT MOA Side Effects Low D Reuptake Inhibits High D Low NE (SSRI, SNRI, NDRI) High NE: nausea; F/F Low S *NE – paradoxical High S: sleepy, sick effect on anxiety stomach, sex, Enzyme Inhibition serious stuff (SI & (MAOI) SS)! *possible mania exacerbation Anxiety (acute) & Benzodiazepines Pathophysiology MOA Side Effects Active Potentiate High GABA Excitatory NTs GABA Risk for Overactive GABA is physical electrical inhibitory dependence impulses Elevated NE Alcohol Withdrawal & Management Low GABA MOA High GABA Overexcited nerves Benzodiazepines Relaxation Think “extreme” Potentiate GABA Cognitive and hangover physical inhibition Risk for delirium, Decreased seizure, coma, death coordination Increased lethargy OVERDOSE risk Mania & Mood Stabilizers Pathophysiology MOA Side Effects Overactive Lithium – Depends on electrical regulate salt the medication impulses Antiepileptics - More info High S potentiate when covering (opposite of GABA mood low mood) disorders Anxiety/Insomnia & Antihistamines Side Effects Sedation Tx: Anxiety & Insomnia Antihistamine – inverse Tx: Movement disorders agonist (does the caused by antipsychotics opposite) Histamines: Control Causes CNS depression alertness e.g., Benadryl, Vistaril, Atarax  Acetylcholine & Anticholinergic Effects Acetylcholine Acetylcholine – Receptor Blockade major chemical of = Anticholinergic ANS Toxicity Rexulti Commercial https://www.youtube.com/watch?v=_C3Ao9Dw4KU What is the MOA of Rexulti? What neurotransmitters are impacted by Rexulti? HINT: Listen to side effects Rexulti Commercial Antidepressants may cause suicidal thoughts Report fever, stiff muscles, and confusion and actions (NMS) Worsen depression in individuals under 18 Uncontrolled muscle movements (EPS), which may be permanent (TD) Unusual urgers Raise cholesterol, weight gain , high blood Falls sugar (metabolic syndrome) Seizures Low white blood cells (agranulocytosis) Trouble swallowing Dizziness on standing (orthostatic Sleepiness hypotension) Critical Thinking: Health Teaching A 32-year-old female client visits her primary health care provider for her annual physical examination. At the end of her visit, the provider determines the client has generalized anxiety disorder (GAD) and prescribes venlafaxine XR 37.5 mg (a serotonin- norepinephrine reuptake inhibitor) orally once a day as an initial dose. ❖What will this medication (SNRI) do to the levels of serotonin & norepinephrine? ❖Consider potential side effects when planning health teaching. Which health teaching about venlafaxine (SNRI) listed is appropriate for the nurse to provide for the client. Select all that apply. A. “Your drug dosage will likely be increased based on how well this dosage reduces your anxiety.” B. “Take the drug in the morning on an empty stomach to decrease the risk of nausea.” C. If you begin thinking about harming yourself let your primary health care provider know immediately.” D. “This drug may decrease your appetite, so monitor your weight.” E. “This drug can make you sleepy.” F. “Follow-up with your primary health care provider to check your blood pressure, which may increase.” Group Work: Case Studies Reese Bradley Copper Marky Mark Sarah Withoutherspoon Silverandgoldman Critical Thinking: Managing Side Effects Reese Withoutherspoon, insists on being prescribed the same anti- anxiety medication as her sister. The next day she comes to the nurses station feeling agitated and restless. She says “I don’t feel good. My head hurts and my heart feels like it’s going to beat out of my chest” ❖What course of action should you take? ❖Which medication do you suspect she is taking? Critical Thinking: Managing Side Effects Bradley Copper comes to the nurses station reporting feelings of nausea and a severe headache. His vital signs are all elevated and you notice a slight tremor as he raises the thermometer to his mouth. He reports that benzodiazepine the nurse gave him last shift helped relieve his symptoms. ❖What medical issues is he experiencing? ❖If you give him a benzodiazepine, what will you need to monitor for to know it was the appropriate dose? Critical Thinking: Managing Side Effects Marky Mark, your patient comes up to the nurses station a day after starting a new medication and says “I can’t get comfortable. I feel like I have ant in my pants.” Upon observation you notice muscle spasms, motor restlessness, rigidity, tremor, jerky movements. The doctor discontinues the medication and starts the patient on a new one. ❖What type of medication do you expect the doctor to prescribe? ❖Which symptoms would alert you that the new medication is not working? Critical Thinking: Managing Side Effects Sarah Silverandgoldman calls the doctors office and tells you, “I’m not feeling well. Ever since I started this new medication I feel nauseous and can’t eat. I’m tired all the time. I don’t feel better at all.” ❖What type of medication do you think she is on (hint: identify the neurotransmitter first)? ❖Which symptoms would alert you that the new medication is not working? Group Brainstorm What questions can you ask during clinical to better understand a patient’s experience with medication? Advocating for Patients Medication Compliance is the “act of taking medication on schedule or taking medication as prescribed” 1. Why might someone with chronic conditions like diabetes, high blood pressure, or high cholesterol not take their medications as prescribed? 2. Why might a patient not completely finish a course of antibiotics or steroids? 3. Why might an oncology patient postpone starting chemotherapy? Why might they decide to stop all together? Mr. Jay Mr. Jay has schizophrenia and was just prescribed an antipsychotic. His family wants to know the risk–benefits of the medication. How would you answer? Mr. Jay decided to stop taking his medication. How would you explore the topic of medication with Mr. Jay?  By the end of today’s lecture you should be able to answer the following questions… 1. Schizophrenia is characterized by psychotic symptoms. How are the mechanism of action of antipsychotics linked to the types o f side effects observed? 2. Depression symptoms can be impacted by low levels of serotonin, norepinephrine, and dopamine. How does each neurotransmitter impact which symptoms a person will experience? 3. Alcohol increases the concentration of GABA. We use a benzodiazepine taper to treat alcohol withdrawal. What are the possible complications of alcohol withdrawal? Explain why this treatment is effective. 4. Symptoms of mania often result when there is an excess of neuronal activity and elevated levels of serotonin. What symptoms w ill result from elevated serotonin? What neurotransmitter should be targeted to decrease neuronal firing? 5. Antihistamines are commonly used in psychiatry to treat insomnia (difficulty or inability to sleep) and movement disorders. W hat is the effect will an antihistamine have on the nervous system that make this possible? 6. Benzodiazepines are GABA agonists. Explain what this means. What will happen to the concentration of GABA? What are possible side effects? 7. Antipsychotics are a dopamine antagonist. Explain what this means. What will happen to the concentration of dopamine? What are possible side effects of dopamine? 8. MAO is an enzyme that degrades neurotransmitters. MAOIs (monoamine oxidase inhibitors, a type of antidepressant) is an enzyme inhibitor. What effect will MAOIs have on the concentration of neurotransmitters? 9. SSRIs (an antidepressant) is a selective serotonin reuptake inhibitor. Explain that this means. What will happen to the conce ntration of serotonin available in the synapse? What are possible side effects? ANTIPSYCHOTICS Schizophrenia is characterized by psychotic symptoms. How are the mechanism of action of antipsychotics linked to the types of side effects observed? DEPRESSION Depression symptoms can be impacted by low levels of serotonin, norepinephrine, and dopamine. How does each neurotransmitter impact which symptoms a person will experience? ETOH WITHDRAWAL Alcohol increases the concentration of GABA. We use a benzodiazepine taper to treat alcohol withdrawal. What are the possible complications of alcohol withdrawal? Explain why this treatment is effective. MANIA Symptoms of mania often result when there is an excess of neuronal activity and elevated levels of serotonin. What neurotransmitter should be targeted to decrease neuronal firing? BIPOLAR DISORDER In bipolar disorder, patients experience depression (the opposite of mania). What might happen if you give a patient with bipolar disorder an SSRI (antidepressant)? ANTIHISTAMINES Antihistamines are commonly used in psychiatry to treat insomnia (difficulty or inability to sleep) and movement disorders. What is the effect will an antihistamine have on the nervous system that make this possible? BENZODIAZEPINES Benzodiazepines are GABA agonists. What will happen to the concentration of GABA? What are possible side effects? ANTIDEPRESSANTS – Enzyme Inhibitor MAO is an enzyme that degrades neurotransmitters. MAOIs (monoamine oxidase inhibitors, a type of antidepressant) is an enzyme inhibitor. What effect will MAOIs have on the concentration of neurotransmitters? ANTIDEPRESSANTS – Reuptake Inhibitors SSRIs (an antidepressant) is a selective serotonin reuptake inhibitor. Explain that this means. What will happen to the concentration of serotonin available in the synapse? What are possible side effects? SUBSTANC USE What substances might people use to feel better if they have difficulty experiencing pleasure? What neurotransmitter is increased when people use a substance/experience to feel better? ATTENTION DEFICIT Is it harder or easier to pay attention to things that you do not enjoy? What neurotransmitter deficit might explain the mechanism of action of medications used to treat attention deficit disorders or anhedonia and concentration issues in depression?  Side Effects – Matching Question Side Effects Explanation 1. Anticholinergic A. Excessive activation of serotonergic receptors 2. Sedation B. Antagonism of dopamine (D2) receptors 3. Serotonin Syndrome C. Potentially lethal side effect of antipsychotics 4. Neuroleptic Malignant Syndrome D. Blockade of adrenergic receptors 5. Orthostatic Hypotension E. Blockage of histamine receptors 6. Sexual Dysfunction & GI Upset F. Hyper-serotonergic state 7. Movement Disorders (e.g., EPS) G. Blockade of muscarinic acetylcholine receptors Review Questions 1. The cerebrum consists of which of the 3. Which neurotransmitter is not an following? inhibitory neurotransmitter? A. Hemispheres A. Acetylcholine B. Basal ganglia B. Dopamine C. Hippocampus C. Gamma-aminobutyric acid D. Amygdala D. Serotonin 2. A nerve impulse originates in the 4. Neurotransmitter receptors are static synaptic cleft. (True or false?) and not subject to change. (True or False?) Cerebrum Your patient has “impaired executive functioning” from traumatic brain injury (TBI) causing damage to his frontal lobe. Consider what would be a reasonable follow-up schedule for this patient for counseling sessions. Would it be reasonable to schedule visits at 1:00 PM weekly? Is the patient able to keep to this schedule? Why or why not? What would be the best schedule? Limbic System ❖The limbic system, which includes the thalamus, hypothalamus, hippocampus, and amygdala, is responsible for regulating emotion, memory, and arousal. What psychiatric behaviors do you expect to see if there are problems with the limbic system? Basal Ganglia ❖The basal ganglia regulate motor functions. What neurotransmitter do you think you would find in the basal ganglia? ❖The nigrostriatal pathway is part of the extrapyramidal system (EPS). Antipsychotic medication causes EPS side effects which affect movement and mimic which neurological disease? Cerebellum ❖You are doing a shift as an ER nurse and a patient comes in stating he feels a little dizzy after getting hit in the back of the head with a baseball. What symptom(s) would alert you to the face that the swelling has worsened? Neuroplasticity Continuous process of modulation of neuronal structure and function in response to the changing environment. A woman who has experienced a “ministroke” continues to regain lost cognitive function months after the stroke. Her husband takes this as evidence that she never had a stroke. How would you approach patient teaching and counseling for this couple to help them understand this occurrence if the stroke did damage to her brain? High - Dopamine Schizophrenia & Antipsychotics ____ Dopamine Side Psychosis Hallucinogenic Drug Use (Dopamine _____nist) Effects Intoxication & TX & Withdrawal Depends on the Substance Use Addiction Management Substance dependent  Low - Dopamine Depression TX: SE: No motivation, ________ ADD/ADHD TX: SE: (anhedonia), or reward Drugs & Alcohol TX SE 1. What might people use to feel better if they have difficulty experiencing pleasure? 2. Is it harder or easier to pay attention to things that you do not enjoy?  High - Norepinephrine How do you think Benzodiazepines: people feel after they antianxiety - increase take anti-anxiety GABA (inhibitory) What symptoms do medicine? you associate with Anxiety “fight or flight”? SNRI (NE reuptake Agitation & inhibitor has a restlessness, increase paradoxical effect on blood pressure & anxiety) heart rate  Low - Norepinephrine Lethargy; difficulty concentrating; Depression TX SE  Low - Serotonin GI distress, sexual side effects low mood; SSRI Antidepressant Hyper-Serotonergic neurovegetative Depression (Serotonin State symptoms Reuptake) Mania – in bipolar patients  High - Serotonin Mood Stabilizers: elevated mood, Mania (opposite of Lithium or SE: flat, low mood impulsive, hypersexual depression) Antiepileptics (e.g., Depakote)  Low - GABA Mania Mood Stabilizers What does alcohol Anxiety Low GABA Benzodiazepines intoxication look (acute/panic) like? ETOH w/d (r/f) CIWA & Benzo Taper Seizures  High - GABA Decrease anxiety, poor coordination, poor Alcohol Intoxication Physical Dependence Withdrawal judgement, sedation. Neurotransmitters Function Disorders Medications Mechanism of Action Side Effects Serotonin Mood & Appetite Anxiety – Low Non-Benzo Anxiolytics Increases S Sedation Schizophrenia- Low Antipsychotics (2nd Increases S Metabolic Syndrome Gen) Depression – Low Antidepressants: MAOIs – Inhibit enzyme Sedation; GI Upset; MAOIs – S, NE, & D TCAs & SSRIs – Inhibit Weight Gain; Increased TCAs – S, NE, & D Reuptake SI; Serotonin Syndrome SSRIs - S Norepinephrine Fight/Flight & Arousal Depression – Low Antidepressants: SNRIs Inhibit Reuptake – Incr. Hypertension; S & NE Agitation; GI Upset (N) Dopamine Pleasure & Reward Depression – Low Antidepressants: NDRIs Inhibit Reuptake – Incr. Agitation; Increased NE & D Seizure Risk ADHD – Low Stimulants Increase Dopamine Appetite Suppression, Weight Loss, Irritability Schizophrenia - High Antipsychotics (1st & Dopamine Antagonist – Movm’t d/o (EPS &TD); 2nd Gen) Decrease Dopamine Anticholinergic; NMS Addiction depends on substance see SUDS lecture n/a GABA Inhibition & Relaxation Anxiety – Low Benzodiazepines Increase GABA Sedation Mania - Low Anticonvulsants Increase GABA Sedation Liver Toxicity Action Potential Electrical Impulses Mania – Seizure Lithium Unknown – Slow/stop Lithium Toxicity Activity seizure activity GI Update ADHD – Slow Stimulants Speed up - CNS Weight Loss Irritability