2024+LEE+PHAR672+04+CNS+DRUGS+1.pdf

Central Nervous System (CNS) Drugs Dr. Lee PHAR 672 FALL 2024 1 An IMPORTANT FEATURE in the Human Body: 2 Central Nervous System (CNS) 3 4 Neuron Firing (action potent...

Central Nervous System (CNS) Drugs Dr. Lee PHAR 672 FALL 2024 1 An IMPORTANT FEATURE in the Human Body: 2 Central Nervous System (CNS) 3 4 Neuron Firing (action potential) 5 How do Neurons “Fire” (Produce Action Potentials)? Open Na+ Open K+ and Ca2+ Channels Channels 6  The Excitatory-Inhibitory Neurotransmitter Theory Excitatory Gamma-aminobutyric acid (GABA) Others Stimulatory (Excitatory) Inhibitory Glutamate Aspartate Norepinephrine Histamine 7 The Excitatory-Inhibitory Neurotransmitter Theory Gamma-aminobutyric acid (GABA) Others Excitatory Inhibitory Modulatory Stimulatory (Excitatory) Inhibitory Acetylcholine (Ach) Glutamate Serotonin (5-HT) Aspartate Norepinephrine Depends on the receptors engaged Histamine 8  MAJOR neurotransmitters’ Involvement in Functions Other Neurotransmitters Roles Histamine Arousal/Awake Movement Glutamate (GLU) Learning and memory Psychosis Acetylcholine (Ach) Thought, memory/learning Endorphins Pleasure, reduce pain 9  Drugs: Agonists, Antagonists, and Partial Agonists Drugs Drugs Drugs Partial Agonist Natural Ligand Inside the Body Full Response Full Response Partial Response No Response 10 So…………. When to use a drug that is ….. An agonist? The body does not have enough response from receptor A partial agonist? The body does not have enough AND TOO MUCH response from receptor, needing a re-balance USUALLY FUNCTION as an ANTAGONIST An antagonist? The body has TOO MUCH response from receptor 11 Psychiatric Disorders Major Depressive Order Autism spectrum disorder “Depression” (ASD) Post-Traumatic Stress Disorder (PTSD) 12 NOT SHOWN: ADHD 13  Psychiatric Disorders (Some Examples) Affective (“Mood”) Substance Use Thought Disorders Anxiety Disorders Others Disorders Disorders Major Depressive Disorders Generalized Anxiety Alcohol Disorder (GAD) Dysthymia Attention-Deficit- Flight of ideas Tobacco Panic Disorder (PD) Hypersensitivity Thought blocking Bipolar Disorders Disorder (ADHD) Incoherence Caffeine Phobias Paranoia Cyclothymic Disorder Addiction Echolalia Opioid (Cyclothymia) Separation Anxiety Word salad Disorders (SAD) Dissociative Identity Delusions “Street Drugs”/ Premenstrual Disorder (DID)/ Illicit Drugs: LSD, Dysphoric Disorder Social Anxiety Multiple Personality Psychosis cocaine, GHB, heroin, (PMDD) Disorders (SAD) Disorder ……… Schizophrenia Seasonal Affective Others Disorder, etc Schizoaffective Disorders 14 Schizophrenia 15 TOO MUCH DOPAMINE SEROTONIN DYSFUNCTION CAUSES NOT CLEAR MANY neurotransmitters 16  WHAT MAJOR neurotransmitters are involved in Schizophrenia? 1. Dopamine 2. Serotonin Psychosis 17  Antipsychotics (all have dopamine activities) Generation Drug Brand Name COUNSELING POINTS 1st HIGH risk of Parkinson-like Dopamine Haloperidol Haldol Black Box Warning: Increased risk of symptoms death in ELDERLY with dementia- Olanzapine Zyprexa related psychosis (cardiovascular or WEIGHT GAIN, hyperglycemia, infectious causes) Seroquel hyperlipidemia Quetiapine Antipsychotics) Seroquel XR Risk of QTc prolongation – Increased (Atypical risk of arrhythmia (heart racing, Take with food! 2nd Lurasidone Latuda pounding for not physical reasons) Be consistent with taking grapefruit or grapefruit juice (drug metabolism) Movement disorders: HIGH risk of Parkinson-like Risperidone Risperdal Extrapyramidal symptoms symptoms Dopamine & (Parkinson’s disease like HIGH risk of QTc prolongation Serotonin Ziprasidone Geodon symptoms, akathisia) Take with food Tardive dyskinesia (e.g. lip- 2nd Aripiprazole Abilify smacking) High Risk of akathisia (Atypical) 18 MOOD DISORDERS Depression Bipolar Disorder 19 ACTIVITIES 20 Depression 21  WHAT MAJOR neurotransmitters are involved in DEPRESSION? 1. Norepinephrine 2. Serotonin 3. Dopamine 22  Antidepressants (ALL TAKEN by PO route) Drug Brand Name Drug Class Citalopram Celexa Escitalopram Lexapro Fluoxetine Prozac, Sarafem Selective serotonin reuptake inhibitor (SSRI) Paroxetine Paxil Sertraline Zoloft Venlafaxine Effexor (tablet); Effexor XR (capsule) Serotonin-norepinephrine reuptake inhibitor Desvenlafaxine Pristiq (SNRI) Duloxetine Cymbalta Amitriptyline Elavil Tricyclic antidepressant (TCA) Nortriptyline Pamelor (Serotonin/Norepinephrine/dopamine/many) Vilazodone Viibryd SSRI/Serotonin-1a receptor partial agonist Bupropion Wellbutrin, Zyban Norepinephrine-dopamine reuptake inhibitor Mirtazapine Remeron Norepinephrine/histamine antidepressant 23  Antidepressants ADRs (ALL TAKEN by PO route) Drug Brand Name ADVERSE DRUG REACTIONS Citalopram Celexa Sleep disturbance (Somnolence, insomnia) Escitalopram Lexapro Anxiety SSRI Nausea, Dry mouth Fluoxetine Prozac, Sarafem Diarrhea Paroxetine Paxil Sexual dysfunction; Hyponatremia Sertraline Zoloft Increased risk of bleeding Venlafaxine Effexor (tablet); Effexor XR (capsule) Nausea, Dry mouth SNRI Desvenlafaxine Pristiq Constipation; Hypertension Duloxetine Cymbalta Sexual dysfunction; Hyponatremia May experience ANTICHOLINGERGIC side Amitriptyline Elavil effects: Dry mouth, blurred vision, constipation, TCA and/or urinary retention (difficulty urinating); Nortriptyline Pamelor drowsiness; hyponatremia; weight gain Increased risk of bleeding; nausea/vomiting Vilazodone Viibryd Hyponatremia Sexual Dysfunction 24  Antidepressants ADRs (ALL TAKEN by PO route) Drug Brand Name ADVERSE DRUG REACTIONS SEIZURE INSOMNIA Bupropion Wellbutrin, Zyban Dry mouth Tremors, headache Drowsiness, somnolence Increased appetite, weight gain Mirtazapine Remeron Dry mouth Constipation 25  Antidepressants (all have serotonin activities) Drug Brand Name COUNSELING POINTS Citalopram Celexa MAY INCREASE the RISK of May take 2-4 weeks to start seeing Escitalopram Lexapro bleeding, especially taking with the efficacy effects, and full effects Fluoxetine Prozac, Sarafem other blood thinners (e.g. in 4-6 weeks Paroxetine Paxil warfarin, apixaban, etc) Sertraline Zoloft Sexual dysfunction Black Box Warning: Increased risk of Effexor (tablet); Venlafaxine suicide in Children, adolescents, and Effexor XR (capsule) MAY INCREASE BLOOD YOUNG adults Desvenlafaxine Pristiq PRESSURE (and heart rate) Duloxetine Cymbalta Risk of QTc prolongation – Increased May experience ANTICHOLINGERGIC risk of arrhythmia (heart racing, Amitriptyline Elavil side effects: Dry mouth, blurred pounding for not physical reasons) vision, constipation, and/or urinary retention (difficulty urinating) Nortriptyline Pamelor Risk of HYPONATREMIA (headache, weakness, confusion) May cause drowsiness MAY INCREASE the RISK of bleeding, DO NOT STOP THE DRUG ABRUPTLY; especially taking with other blood Vilazodone Viibryd reduce dose over time (“taper the thinners (e.g. warfarin, apixaban, dose”) etc); SEXUAL Dysfunction; 26 TAKE WITH FOOD!  Antidepressants (Other Neurotransmitters) Drug Brand Name Counseling Points May take 2-4 weeks to start Carries the risk of SEIZURE; DO NOT seeing the efficacy effects, and TAKE if patient has a history of seizure; Wellbutrin, full effects in 4-6 weeks max. dose 450 mg per day Bupropion Zyban IF taken for smoking cessation (Zyban), Black Box Warning: Increased risk start 1 week before quit day of suicide in Children, Sedating – Take at bedtime adolescents, and YOUNG adults Mirtazapine Remeron Risk of QTc prolongation – Increased DO NOT STOP THE DRUG risk of arrhythmia (heart racing, ABRUPTLY; reduce dose over pounding for not physical reasons) time (“taper the dose”) 27 Bipolar Disorder 28 29 Bipolar Disorder Management MOOD STABILIZER +/- Antidepressant MUST HAVE one of the following: Lithium Valproate (Valproic acid) A MOOD STABILIZER MUST Carbamazepine already be used before starting an antidepressant Lamotrigene 2nd Generation Antipsychotics 30 Mood Stabilizers (for Bipolar) Drug/Generic Name Brand Name Drug Class Lithium Carbonate Lithobid Mood Stabilizer Valproic acid/ Depakote Valproate/divalproex Depakene Mood Stabilizer Lamotrigene Lamictal Antiepileptic Carbamazepine Tegretol Drugs (AEDs)/ Trileptal (IR) Anticonvulsants Oxcarbazepine Oxteller ER Different 2nd generation antipsychotics Antipsychotics 31  Mood Stabilizers (for Bipolar) Drug/Generic Name Brand Name Drug Class ADR Counseling Points Blackbox warning: Monitor drug Consume some level in BLOOD for toxicities SODIUM & drink 2-3 Lithium Carbonate Lithobid Mood Stabilizer Nausea, vomiting, thirst, liter of water daily dehydration, hypotension (e.g. sport drinks) Periodic Table 32  Mood Stabilizers (for Bipolar) Drug/Generic Name Brand Name Drug Class ADR Counseling Blackbox warnings: 1) Liver toxicity, 2) pancreatitis, 3) fetal toxicity (birth defects) Nausea-vomiting, abdominal pain, diarrhea Avoid during Headache, tremors (shakes), dry mouth pregnancy Valproic acid/ Drowsiness, fatigue Depakote Valproate/ Hair loss (alopecia) Report suicide Depakene divalproex Irregular/delayed periods in women of thoughts to Mood Stabilizer reproductive age healthcare WEIGHT GAIN professionals Antiepileptic Monitor drug level in BLOOD for toxicities Drug (AEDs) Suicidal thoughts or actions (1 in 500) Anticonvulsants Blackbox warning: Skin reaction (Stevens- Johnson Syndrome) – Higher risk in pediatrics Report suicide Dizziness, drowsiness, headache, ataxia, thoughts to Lamotrigene Lamictal abdominal pain, dry mouth healthcare Many drug-drug interactions professionals Monitor drug level in BLOOD for toxicities Suicidal thoughts or actions (1 in 500) 33  Mood Stabilizers (for Bipolar) Drug/Generic Name Brand Name Drug Class ADR Blackbox warning: Skin reaction Start with a low dose (e.g. (Stevens-Johnson Syndrome) 500 mg) at week 1, then – most common in Asians increase dose to 1000 mg Bone marrow failure (low WBC, red at week 2, and increase blood cells, platelets) again to 1500 mg at week Carbamazepine Tegretol Hyponatremia, drowsiness 3 Mood Stabilizer Fatigue, nausea-vomiting Monitor drug level in BLOOD for Report suicide thoughts to Antiepileptic toxicities healthcare professionals Drug (AEDs) Suicidal thoughts or actions (1 in 500) Anticonvulsants Skin reaction (Stevens-Johnson Syndrome) – most common in Asians ER formulation needs to Hyponatremia, drowsiness be taken with food Trileptal (IR) Oxcarbazepine Fatigue, ataxia, abdominal pain Oxteller ER Monitor drug level in BLOOD for Report suicide thoughts to toxicities healthcare professionals Suicidal thoughts or actions (1 in 500) 34 Mood Stabilizers (for Bipolar) Aripiprazole (Abilify) Olanzapine (Zyprexa) Quetiapine (Seroquel, Seroquel XR) Risperidone (Risperdal) Ziprasidone (Geodan) 35