CNS Pharmacology Notes PDF - 2022

CNS PHARMACOLOGY 4 4) Evaluating Exam Preparatory Course...

CNS PHARMACOLOGY 4 4) Evaluating Exam Preparatory Course 06 :9 (ID di ah M 1 fa ta LEGEND us M Ach: Acetylcholine GABA: Gamma-Aminobutyric Acid SAR: Structure-Activity Relationship AD: Alzheimer’s Disease GI: Gastrointestinal SC: Subcutaneous to ADHD: Attention Deficit Hyperactivity IBS: Irritable Bowel Syndrome SL: Sublingual Disorder IM: Intramuscular SNRI: Serotonin-Norepinephrine AV: Atrioventricular IR: Immediate Release Reuptake Inhibitor ed BBB: Blood Brain Barrier LDL: Low-Density Lipoprotein SR: Sustained Release BP: Blood Pressure MAO: Monoamine Oxidase SSRI: Selective Serotonin Reuptake ns CART: Cocaine-Amphetamine NE: Norepinephrine Inhibitor Regulated Transcript NMDA: N-Methyl D-Aspartate TAAR1: Trace Amine-Associated CHF: Congestive Heart Failure NNRTI: Non-Nucleoside Reverse Receptor 1 ce CNS: Central Nervous System Transcriptase Inhibitors TCA: Tricyclic Antidepressant COMT: Catechol-O-Methyltransferase NT: Neurotransmitter Transporter URTI: Upper Respiratory Tract Infection COPD: Chronic Obstructive Pulmonary N/V: Nausea/ Vomiting VMAT2: Vesicular Monoamine Li Disease OCD: Obsessive Compulsive Disorder Transporter 2 CR: Controlled Release PHN: Postherpetic Neuralgia XR: Extended Release CV: Cardiovascular PMDD: Premenstrual Dysphoric DA: Dopamine Disorder D/C: Discontinue PTSD: Post-Traumatic Stress Disorder EPSP: Excitatory Postsynaptic Potential PUD: Peptic Ulcer Disease Copyright © 2022 PharmAchieve Corporation Ltd. Private and Confidential. 2 Copyright © 2022 PharmAchieve Corporation Ltd. Private and Confidential. 1  CENTRAL NERVOUS SYSTEM DRUGS Opioid analgesics Antipsychotics Antidepressants Psychostimulants Anti-Parkinson’s Antiepileptics Anti- Alzheimer’s/dementia Copyright © 2022 PharmAchieve Corporation Ltd. Private and Confidential. 3 CENTRAL NERVOUS SYSTEM DRUGS Morphine, hydromorphone, hydrocodone, oxycodone, codeine, tramadol, tapentadol, fentanyl, methadone, meperidine, heroin, Opioid analgesics buprenorphine, Antipsychotics Antidepressants Psychostimulants Anti-Parkinson’s Antiepileptics Anti- Alzheimer’s/dementia Copyright © 2022 PharmAchieve Corporation Ltd. Private and Confidential. 4 Copyright © 2022 PharmAchieve Corporation Ltd. Private and Confidential. 2  OPIOID RECEPTORS 3 types of receptors: μ, δ, κ μ (mu) δ (delta) κ (kappa) Analgesia, sedation, Analgesia, control of Analgesia, respiratory inhibition, 4) Agonistic hormone and psychotomimetic slowed GI movement, effects? neurotransmitter effects, slowed GI 4 control of hormone and release movement 06 neurotransmitter release :9 Enkephalin > Endogenous Endorphin > enkephalin Dynorphin >> endorphin = opioid affinity? > dynorphin endorphin = enkephalin (ID dynorphin di Note, an opioid is defined as any compound acting on an opioid receptor ah Copyright © 2022 PharmAchieve Corporation Ltd. Private and Confidential. M 5 fa ta TYPES OF OPIOID ALKALOID ANALGESICS us M to PHENANTHRENES PHENYL- HEPTYLAMINES ed Morphine Methadone Hydromorphone ns Heroin PHENYL- Codeine MORPHINANS ce PIPERIDINES Li Fentanyl Levorphanol Sufentanil Alfentanil Copyright © 2022 PharmAchieve Corporation Ltd. Private and Confidential. 6 Copyright © 2022 PharmAchieve Corporation Ltd. Private and Confidential. 3  MORPHINE Indication? Acute or chronic severe pain MOA? Full agonist at μ, mimicking endorphin Phenol OH, aromatic ring, and 3o amine: essential for activity (position relative to each other is crucial – resembles tyrosine residue of met-enkephalin) 4) N-methylation blocks peptidase hydrolysis, amine is protonated and ionized for binding 4 Exists as single stereoisomer – altering stereochemistry significantly reduces activity 06 SAR? Tyrosine :9 (ID Morphine Met-enkephalin di Considerations? Administration: PO, IV ah Copyright © 2022 PharmAchieve Corporation Ltd. Private and Confidential. M 7 fa ta MORPHINE DERIVATIVES (HYDROMORPHONE, HYDROCODONE) us M Indication? Acute or chronic severe pain (hydromorphone), hydrocodone is used in cough syrups to Full agonist at μ; hydromorphone is x5 more potent than morphine; hydrocodone MOA? depresses the cough centers ed Hydromorphone’s acetyl group increases potency whereas hydrocodone’s methylation reduces potency ns ce SAR? Li Morphine Hydromorphone Hydrocodone Hydromorphone administration: PO tablets (XR, SR, IR), IV, IM, SC, rectal Considerations? Hydrocodone administration: PO tablets (IR) and syrup Copyright © 2022 PharmAchieve Corporation Ltd. Private and Confidential. 8 Copyright © 2022 PharmAchieve Corporation Ltd. Private and Confidential. 4  CODEINE AND OXYCODONE Indication? Codeine (mild/moderate pain and diarrhea), oxycodone (acute or chronic severe pain) MOA? Full agonist at μ; codeine is less potent whereas oxycodone is x2 as potent as morphine 4) Codeine’s phenol methylation reduces potency, oxycodone’s acetaldehyde increases potency 4 06 SAR? :9 (ID Morphine Codeine Oxycodone Codeine administration: PO tablets, SC, IM injections di Comments? Oxycodone administration: PO tablets (SR/IR), rectal ah Copyright © 2022 PharmAchieve Corporation Ltd. Private and Confidential. M 9 fa ta TRAMADOL/TAPENTADOL us M Indication? Acute or chronic severe pain to Full agonist at μ with weak inhibition of NE (both) and 5-HT (tramadol) MOA? reuptake; similar potencies ed 3° amine aids in binding to various neurotransmitter reuptake receptors Are synthetic codeine analogs ns ce SAR? Li Morphine Tapentadol Tramadol Tramadol: PO tablets (IR, XR, SR) Comments? Tapentadol: PO tablets (CR and IR) Copyright © 2022 PharmAchieve Corporation Ltd. Private and Confidential. 10 Copyright © 2022 PharmAchieve Corporation Ltd. Private and Confidential. 5  FENTANYL AND METHADONE Unresponsive severe/chronic/palliative pain, drug abuse withdrawal Indication? (methadone) MOA? Full agonist at μ; fentanyl is x100 more potent than morphine Agents are NOT structurally related to morphine 4 4) 06 SAR? :9 (ID Fentanyl Methadone Fentanyl: transdermal, SL, IM, IV, epidural Comments? di Methadone: PO tablets (IR/SR), PO diluted solution ah Copyright © 2022 PharmAchieve Corporation Ltd. Private and Confidential. M 11 fa ta MEPERIDINE AND HEROIN us M Indication? Acute or chronic severe pain to MOA? Full agonist at μ Heroin’s acetylated groups increase its potency ed Dual acetyl groups of heroin are cleaved, forming morphine ns SAR? ce Li Morphine Heroin Meperidine Meperidine: PO tablets (IR, XR, SR), rectal Comments? Heroin: drug of abuse (IM/IV) Copyright © 2022 PharmAchieve Corporation Ltd. Private and Confidential. 12 Copyright © 2022 PharmAchieve Corporation Ltd. Private and Confidential. 6  BUPRENORPHINE Indication? Acute or chronic severe pain (patch), opioid use disorder (SL tablet containing naloxone) Buprenorphine: partial agonist at μ, antagonist at κ MOA? Naloxone: antagonist at μ, δ, κ 4) Buprenorphine has 2 unique subgroups Naloxone’s alkene group causes antagonistic effects 4 06 SAR? :9 (ID Morphine Naloxone Buprenorphine Buprenorphine: transdermal patch, SL tablet (contains naloxone) di Comments? If SL tablets are crushed and injected, naloxone with antagonize buprenorphine’s ah euphoric effects (naloxone has no effect PO) Copyright © 2022 PharmAchieve Corporation Ltd. Private and Confidential. M 13 fa ta CENTRAL NERVOUS SYSTEM DRUGS us M Opioid analgesics to 1st generation (dopamine receptor inhibitors): low potency (chlorpromazine, methotrimeprazine), medium potency (loxapine, perphenazine, ed zuclopenthixol), high potency (haloperidol, fluphazine, flupenthixol) Antipsychotics 2nd generation (dopamine and serotonin receptor inhibitors): clozapine, ns asenapine, lurasidone, risperidone, ziprasidone, olanzapine, quetiapine, aripiprazole ce Antidepressants Li Psychostimulants Anti-Parkinson’s Antiepileptics Anti- Alzheimer’s/dementia Copyright © 2022 PharmAchieve Corporation Ltd. Private and Confidential. 14 Copyright © 2022 PharmAchieve Corporation Ltd. Private and Confidential. 7