CNS Pharmacology Exam Prep

Study Notes

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

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

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
- 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
- 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
- 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
- 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)

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

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