CNS Pharmacology Exam Prep

CNS Pharmacology

• Evaluating exam preparatory course for CNS pharmacology

Opioid Analgesics

• Types of opioid receptors: μ, δ, κ
• Agonistic effects of opioid receptors:
  • μ: analgesia, sedation, respiratory inhibition, slowed GI movement
  • δ: analgesia, control of hormone release, slowed GI movement
  • κ: analgesia, psychotomimetic effects
• Endogenous opioid affinity: endorphin > enkephalin > dynorphin
• Definition of an opioid: any compound acting on an opioid receptor

Types of Opioid Alkaloid Analgesics

• Phenanthrenes: morphine, hydromorphone, heroin
• Phenylheptylamine: methadone
• Morphinans: levorphanol
• Piperidines: fentanyl, sufentanil, alfentanil

Morphine

• Indication: acute or chronic severe pain
• MOA: full agonist at μ, mimicking endorphin
• Structure-activity relationship (SAR): phenol OH, aromatic ring, and 3° amine are essential for activity
• Administration: PO, IV

Morphine Derivatives

• Hydromorphone
  • Indication: acute or chronic severe pain
  • MOA: full agonist at μ, x5 more potent than morphine
  • SAR: acetyl group increases potency
  • Administration: PO tablets (XR, SR, IR), IV, IM, SC, rectal
• Hydrocodone
  • Indication: mild/moderate pain and diarrhea
  • MOA: full agonist at μ, depresses the cough centers
  • SAR: methylation reduces potency
  • Administration: PO tablets (IR), syrup

Codeine and Oxycodone

• Codeine
  • Indication: mild/moderate pain and diarrhea
  • MOA: full agonist at μ, less potent than morphine
  • SAR: phenol methylation reduces potency
  • Administration: PO tablets, SC, IM injections
• Oxycodone
  • Indication: acute or chronic severe pain
  • MOA: full agonist at μ, x2 as potent as morphine
  • SAR: acetaldehyde increases potency
  • Administration: PO tablets (SR/IR), rectal

Tramadol and Tapentadol

• Tramadol
  • Indication: acute or chronic severe pain
  • MOA: full agonist at μ, weak inhibition of NE and 5-HT reuptake
  • SAR: 3° amine aids in binding to various neurotransmitter reuptake receptors
  • Administration: PO tablets (IR, XR, SR)
• Tapentadol
  • Indication: acute or chronic severe pain
  • MOA: full agonist at μ, weak inhibition of NE reuptake
  • SAR: 3° amine aids in binding to various neurotransmitter reuptake receptors
  • Administration: PO tablets (CR and IR)

Fentanyl and Methadone

• Fentanyl
  • Indication: unresponsive severe/chronic/palliative pain
  • MOA: full agonist at μ, x100 more potent than morphine
  • SAR: agents are NOT structurally related to morphine
  • Administration: transdermal, SL, IM, IV, epidural
• Methadone
  • Indication: unresponsive severe/chronic/palliative pain, drug abuse withdrawal
  • MOA: full agonist at μ
  • SAR: agents are NOT structurally related to morphine
  • Administration: PO tablets (IR/SR), PO diluted solution

Meperidine and Heroin

• Meperidine
  • Indication: acute or chronic severe pain
  • MOA: full agonist at μ
  • SAR: similar to morphine
  • Administration: PO tablets (IR, XR, SR), rectal
• Heroin
  • Indication: acute or chronic severe pain
  • MOA: full agonist at μ, acetylated groups increase potency
  • SAR: dual acetyl groups are cleaved, forming morphine
  • Administration: drug of abuse (IM/IV)

Buprenorphine

• Indication: acute or chronic severe pain (patch), opioid use disorder (SL tablet containing naloxone)

• MOA: partial agonist at μ, antagonist at κ

• Naloxone: antagonist at μ, δ, κ

• SAR: 2 unique subgroups, alkene group causes antagonistic effects

• Administration: transdermal patch, SL tablet (contains naloxone)### Central Nervous System Drugs

• Opioid analgesics are a type of CNS drug

Antipsychotics

• Classified into 2 generations
• 1st generation: dopamine receptor inhibitors with varying potency levels
  • Low potency: chlorpromazine, methotrimeprazine
  • Medium potency: loxapine, perphenazine, zuclopenthixol
  • High potency: haloperidol, fluphazine, flupenthixol
• 2nd generation: dopamine and serotonin receptor inhibitors
  • Examples: clozapine, asenapine, lurasidone, risperidone, ziprasidone, olanzapine, quetiapine, aripiprazole

Other CNS Drugs

• Antidepressants
• Psychostimulants
• Anti-Parkinson's
• Antiepileptics
• Anti-Alzheimer's/dementia