Central Nervous System (CNS) Drugs Part II PDF

Central Nervous System (CNS) Drugs PART II Dr. Lee PHAR 672 FALL 2024 36 Anxiety Disorders 37 38 What neurotransmitters are involved in GENERALIZED ANXIETY DISORDER (GAD)? 1. Norepinephrine 2. Serotonin...

Central Nervous System (CNS) Drugs PART II Dr. Lee PHAR 672 FALL 2024 36 Anxiety Disorders 37 38 What neurotransmitters are involved in GENERALIZED ANXIETY DISORDER (GAD)? 1. Norepinephrine 2. Serotonin 39 The Excitatory-Inhibitory Neurotransmitter Theory Related to Anxiety Disorders Locus Coeruleus Neurons ↑NE ↑Anxiety Symptoms 40  The Excitatory-Inhibitory Neurotransmitter Theory Related to Anxiety Disorders A Simplified Model GABA Neurons Locus Coeruleus ↓Anxiety Neurons ↓NE Symptoms Serotonin Neurons Serotonin (5HT3) NE reuptake 41 Serotonin reuptake Treatment Strategy for Generalized Anxiety Disorder (GAD) Psychotherapy What drugs should we consider? Pharmacotherapy SSRI ___ SNRI ___ TCA ___ (why? They block NE and ___ 5HT activities) 42  Some Antidepressants (ALL TAKEN by PO route) are ALSO USED FOR Generalized Anxiety Disorders 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 43 Pharmacotherapy for General Anxiety Disorder Antianxiety Effects Start SSRI or SNRI or TCA Time (weeks) 44 Pharmacotherapy for General Anxiety Disorder Agitation Paradoxical Anxiety Symptoms 8-12 weeks Antianxiety Effects Start SSRI or SNRI or TCA Time (weeks) 45  Anxiolytic medication = Anti-anxiety medication Pharmacotherapy for General Anxiety Disorder Solution: Start a temporary “anxiolytic” drug therapy Agitation Paradoxical Anxiety Symptoms 8-12 weeks Antianxiety Effects Start SSRI or SNRI or TCA Time (weeks) 46  “Temporary” Anxiolytics (ALL TAKEN by PO route) Drug Brand Name Drug Class Alprazolam Xanax Clonazepam Klonopin Benzodiazepine Diazepam Valium, Diastat, Valtoco - Subclass: Anxiolytics Lorazepam Ativan Buspirone Buspar Anxiolytics Hydroxyzine Atarax, Vistaril Antihistamine (Histamine 1 receptor antagonist)-Anxiolytics 47 Benzodiazepines CNS Active Drugs Onset Duration Penetration Metabolite Midazolam (Versed) IV ONLY Fast Short Fast YES Remimazolam (Byfavo) IV only Fast Short Fast Probably NO Triazolam (Halcion) Fast Short Fast NO Alprazolam (Xanax) Fast Short VERY Fast Some Clonazepam (Klonopin) Fast Intermediate Fast YES Lorazepam (Ativan) Fast Intermediate Fast NO Flurazepam (Dalmane) Fast Long Fast YES Diazepam (Valium) Fast Long-Very Long Fast YES Estazolam (Prosom) Intermediate Intermediate Fast YES Temazepam (Restoril) Intermediate Intermediate Fast NO Quazepam (Doral) Intermediate Long Fast YES Chlordiazepoxide (Librium) Intermediate Long Fast YES Oxazepam (Serax) SLOW Intermediate Fast NO 48  Anxiolytics (ALL TAKEN by PO route) Drug Brand Name Adverse Drug Reactions Counseling Points Alprazolam Xanax Black Box Warning: DEA SCHEDULE IV, so limited Sedation, respiratory refills Clonazepam Klonopin depression, coma or death DO NOT TAKE with opioids or when taken at the same time alcohol at the same time Diazepam Valium, Diastat, Valtoco as opioids or alcohol Take with grapefruit or grapefruit juice consistently, Lorazepam Ativan Drowsiness, dizziness, ataxia or not at all May take 2-4 weeks to work Avoid taking with alcohol Nausea, headache, dizziness, Buspirone Buspar Take with grapefruit or excitedness grapefruit juice consistently, or not at all Nausea, headache, dry Inform prescriber if there is past mouth medical history of asthma, Atarax (hydroxyzine hydrochloride) glaucoma (eye) or benign prostate Hydroxyzine Vistaril (hydroxyzine pamoate) hypertrophy (enlarged prostate) QTc prolonga on (↑ risk of Avoid taking with alcohol arrhythmia) Same issues with grapefruit juice 49 50  Neurotransmitters/Chemicals of Sleep Excitatory (Awake) Inhibitory (Asleep) 51 https://drsnoozz.com/neurotransmitters-of-sleep/ Accessed 8/20/2024 “Z-Drugs” and Benzodiazepines for Sleep: Activities on GABA-A (GABAA) receptor 52  Hypnotics (All taken by PO route) Drug Brand Name Drug Class Adverse Drug Reactions Counseling Points Black Box Warning: Sleep- TAKE on EMPTY STOMACH Eszopiclone Lunesta walking, sleep-driving, sleep- Hypnotics (Sleep DEA SCHEDULE IV, so limited eating, sleep-shopping, etc Ambien drugs) refills Zolpidem Edluar, “Z-drugs” Drowsiness, dizziness, Intermezzo tiredness Take right before bedtime, and Black Box Warning: Sedation, expect sleep time > 6 hours respiratory depression, coma or death when taken at the DO NOT TAKE with opioids or Benzodiazepine same time as opioids or alcohol at the same time Temazepam Restoril - Hypnotics alcohol Take with grapefruit or Drowsiness, dizziness, ataxia, grapefruit juice consistently, confusion or not at all 53 54 What neurotransmitters are involved in ADHD? 1. Norepinephrine 2. Dopamine 55 ADHD Drugs Drugs/Generic Names Brand Names Drug Class Amphetamine-Dextroamphetamine Adderall, Mydaylis Lisdexamfetamine Vyvanse CNS Stimulants Methylphenidate Ritalin, Concerta, Metadate ER Dexmethylphenidate Focalin Norepinephrine-dopamine Atomoxetine Strattera reuptake Inhibitor 56  ADHD Drugs Drugs/Generic Names Brand Names Adverse Drug Reactions Counseling Points Amphetamine- Black Box Warnings: High DEA Schedule II, so very Adderall, Mydaylis Dextroamphetamine potentials for misuse & abuse limited refills Lisdexamfetamine Vyvanse Ritalin, Concerta, Seizure Take only if you need Methylphenidate Metadate ER Loss of appetite, weight LOSS, symptom control and as Dexmethylphenidate Focalin restlessness, nausea prescribed Black Box Warnings: Risk of Report any chest pain, suicide ideation in children & palpations (fast heart beat) adolescents or dyspnea (shortness of Atomoxetine Strattera breath) (capsule) Dry mouth, fatigue, mood swings, loss of appetite, weight DO NOT CHEW, CRUSH or LOSS, irregular menses in women open capsule 57 SEIZURE & EPILEPSY 58  Seizure and Epilepsy Epilepsy: 2 or more episodes of UNPROVOKED seizures Seizure: Common Presentations Convulsion 59 Pathophysiology of Seizure/Epilepsy (What went wrong?) (NOT ENOUGH neuron inhibition) For example: NOT ENOUGH GABA activity (TOO MUCH neuron firing) For example: MANY neurotransmitters 60 HOW TO FIX? (NOT ENOUGH neuron inhibition) For example: NOT ENOUGH GABA activity FIX: ↑ GABA (TOO MUCH neuron firing) For example: MANY neurotransmitters FIX: ↓ FIRING 61  DRUGS for Seizure and Epilepsy Seizure Epilepsy (Anti-epileptic Drugs (AED), “Anticonvulsants” Drug of Choice: Benzodiazepines GENERIC BRAND Activity GENERIC BRAND Drug Class Divalproex sodium Depakote, Depakene previous notes Lorazepam Ativan Please see Carbamazepine Tegretol, Carbatrol, Epitol, Equetro Benzodiazepine Diazepam Valium Oxcarbazepine Trileptal OTHERS GABA activity Lamotrigine Lamictal REDUCE Keppra, Elepsia XR, Roweepra, Neuron Firing Levetiracetam Spritam Phenytoin Dilantin, Phenytek Topiramate Topamax, Qudexy XR, Trokendi XR Gabapentin Neurontin, Gralise GABA-like Pregabalin Lyrica 62  Uses of AED for Other Medical Conditions GENERIC BRAND Activity Bipolar Epilepsy Migraine Pain (some) Divalproex Depakote, Depakene X X X - sodium Tegretol, Carbatrol, REDUCE Carbamazepine X X - X Epitol, Equetro Oxcarbazepine Trileptal Neuron X X - - Lamotrigine Lamictal Firing X X - - Keppra, Elepsia XR, Levetiracetam - X - - Roweepra, Spritam Many mechanisms Phenytoin Dilantin, Phenytek - X - - Topamax, Qudexy XR, Topiramate - X X - Trokendi XR Gabapentin Neurontin, Gralise GABA-like - X - X Reduce neuron Pregabalin Lyrica - X - X firing X, commonly recommended 63  DRUGS for Epilepsy (AED) GENERIC BRAND Adverse Drug Reactions Counseling Points Divalproex sodium Depakote, Depakene Tegretol, Carbatrol, Carbamazepine Epitol, Equetro AS DISCUSSED PREVIOUSLY Oxcarbazepine Trileptal Lamotrigine Lamictal 64  DRUGS for Epilepsy (AED) GENERIC BRAND Adverse Drug Reactions Counseling Points Report worsening Keppra, Elepsia XR, depression Levetiracetam Somnolence, dizziness, asthenia (feeling weak) Roweepra, Spritam Do not stop drug abruptly IV only: Black Box Warning: MAX infusion LESS THAN 50 mg/min – cardiac arrhythmia risk Capsules and tablets Phenytoin Skin reactions – Occasionally fatal are DIFFERENT, DO (Capsules & Dilantin, Phenytek Somnolence, gingival hyperplasia, hirsutism NOT INTERCHANGE Tablets) (hair growth) THEM Monitor drug level in BLOOD for toxicities MANY drug-drug interactions Metabolic acidosis Decreased sweating and HYPERthermia Drink plenty of water Topamax, Qudexy Risk of birth defect in pregnant women every day Topiramate XR, Trokendi XR Kidney stone formation Tell your doctor if you Weight Loss, abnormal vision, difficulty with become pregnant memory and concentration, fatigue 65  DRUGS for Epilepsy (AEDs) GENERIC BRAND Adverse Drug Reactions Counseling Points Do not take aluminum or Drowsiness, dizziness, somnolence magnesium (e.g. antacids) for at least 2 hours BEFORE & AFTER Nystagmus (abnormal eye movement); taking the drug ataxia Neurontin can be taken with or Neurontin (IR) Gabapentin without food, Gralise MUST be Gralise (ER) MONITOR patient’s renal function taken with food (e.g. changes in blood serum Avoid taking at the same time creatinine, SCr) because ADRs are with alcohol or opioids or other more prominent with impaired renal sedating drugs function Avoid stopping drug abruptly! DEA Schedule V Report any unexplained muscle Peripheral edema pain, tenderness, or weakness Muscle pain Pregabalin Lyrica Avoid taking at the same time Weight gain, blurred vision, dry mouth, with alcohol or opioids or other constipation, somnolence sedating drugs Avoid stopping drug abruptly!66 Neurodegenerative Disorders Alzheimer’s Disease Parkinson’s Disease 67 Neurodegenerative Disorders Movement Disorder Memory, direction distortion Loss of motor function control Lost of cognition (Dementia) Parkinson’s Disease Alzheimer’s Disease LOSS of dopamine neurons LOSS of acetylcholine neurons INSUFFICIENT glutamate receptor activities 68 Neurodegenerative Disorders Generic Name Brand Name Sinemet, Sinemet CR Carbidopa-levodopa Duopa, Rytary Generic Name Brand Name Pramipexole Mirapex Ropinirole Requip Donepezil Aricept Memantine Namenda 69  Drugs for Parkinson’s Diseasec (All P.O.) Generic Names Brand Names Adverse Drug Reactions Counseling Points Do NOT stop drug abruptly Nausea The drug effects may wear off at the Dizziness, orthostasis (dizziness from end of the dose over time Carbidopa- Sinemet, Sinemet CR standing up due to blood pressure ↓) The drug may discolor the urine, levodopa Duopa, Rytary Confusion saliva, or sweat to a dark New movement disorder red/brown/black color Hallucination/psychosis Do NOT take with iron or high- protein diet Pramipexole Mirapex Nausea, drowsiness, dizziness, Take with food (nausea) orthostasis Do NOT take with opioid, alcohol or Ropinirole Requip New movement disorder other depressants Hallucination/psychosis 70  Drugs for Alzheimer’s Disease (all P.O.) Generic Names Brand Names Adverse Drug Reactions Counseling Points Nausea/Vomiting, diarrhea Take tablet in the evening to reduce Loss of appetite dizziness DIZZINESS Donepezil Aricept QTc prolongation (risk of arrhythmia) Be careful taking with Bradycardia (slow heart rate) (Reduce ACETYLCHOLINE ibuprofen/naproxen due to ↑ risk of Worsening of asthma or obstructive BREAKDOWN) stomach ulcers pulmonary disease (e.g. COPD) Memantine Namenda Confusion Each dose should not exceed 5 mg; so a (Increase GLUTAMATE Dizziness, headache patient that needs 10 mg will need to receptor activities) take the drug BID Fatigue 71  Eye Drops Ophthalmic Agents for Glaucoma 72  Glaucoma A condition when there is TOO MUCH PRESSURE inside the eye Generic Brand Store REFRIGERATED in the Pharmacy? Bimatoprost Lumigan Brimonidine Alphagan P Dorzolamide-timolol Cosopt Latanoprost Xalatan, Xelpros MUST be stored REFRIGERATED Timolol Timoptic, Betimol, Istalol Travoprost Travatan Z 73 The END QUESTIONS? 74