Pharmacology of Opioids 2025 D2L

What is an opioid?

Anything acting at an opioid receptor?

What is an opiate?

Naturally occurring opiods

Opiates examples?

• Morphine

• Codeine

Common Clinical Uses of Opioids?

• Severe acute pain mgmt

• Chronic pain

  • cancer

  • palliative care

Cough suppression opiod?

codeine

Diarrhea control opiod?

Loperamide

Opioid use disorder tx?

Buprenorphine

Opioid dependent constipation tx?

methylnaltrexone

Opioid overdose tx?

naloxone, naltrexone

How to opioids modulate pain?

• In SC by decreasing signal from peripheral to central pain pathways

• Perception of pain

• Mimic:

  • endorphins

  • enkephalins

  • dynorphins

Opioid receptors?

 µ, κ, δ

• decrease neurotransmission of sensory neurons

Opioids pre or post synaptic receptor effects?

• Both

  • ◦ Pre-: decreases Ca++ influx
    ◦ Post-: increases K+ efflux

μ
(mu) receptor functions

• Supraspinal and spinal analgesia

• Respiratory depression

• Slows GI transit (constipation)

• Sedation

• Miosis

• Euphoria (e.g., runner’s high)

• Physical dependence

δ
(delta receptor functions

• Supraspinal and spinal analgesia

Κ
(kappa) functions?

• Supraspinal and spinal analgesia

• Dysphoria

Most of opioids actions at what receptor?

mu

Dysphoria primarily at what receptor?

kappa

Morphine MOA?

mu receptor agonist

• others too but mu primarily

Morphine effects

• Analgesia

  • no LOC

  • Sedation (chill not sleep)

• Euphoria

  • cuts brake on reward pathway

• Diarrhea relief

• Miosis

  • increased PNS

  • contracted pupil

• FROW UP

Role of opioids in brain reward pathway?

• Endogenous enkephalins (or exogenous
  opioids) INHIBIT the GABA-ergic
  neurons, releasing the “brake” on the
  reward system

Adverse effects of opioids?

• Respiratory depression

• Urinary retention

• Hypotension and Bradycardia

  • FALL RISK

• histamine release

• Hyperalgesia and Androgen deficiency

  • chronic use

Opioid effects on Pregnancy?

• Cross placenta

  • ◦Morphine, Codeine, Oxycodone, Fentanyl, Buprenorphine: all cross readily

    ◦Naloxone: crosses if given IV; minimal oral bioavailability

 Neonatal Opioid Withdrawal Syndrome (NOWS):

• High pitched excessive crying

• Respiratory depression

• Neurodevelopment concerns

Strong full agonists?

• Fentanyl

• Morphine

• Hydrocodone

Mod/Mild agonists

• Oxycodone

• Codeine

• Tramadol

Partial agonist/Mixed

Buprenorphine

Opioid antagonists?

• Naloxone

• Naltrexone

Most potent opioid?

Fent

Why is codeine special?

• PRODRUG

  • liver metabolizes it into morphine

Why is Tramadol special?

• Weak mu agonist

• + SNRI

• Look for serotonin syndrome

Dextromethorphan?

Centrally acting anti tussive

Dextromethorphan MOA?

LOOK AT ADDED SLIDE

Buprenorphine special uses?

• Binds way better than morphine, so it kicks it off receptor

• Opioid use disorder

Naloxone use?

Reverse opioid overdose FAST

• short ½ life so may need a second dose eventually

• duration of action 1-2 hrs

Naltrexone use?

• Management of opioid/alcohol use disorder

Opioid withdrawal

• SNS rebound

  • piloerection

  • tachycardia

  • HTN

  • Diaphoresis

  • Mydriasis

Peripheral sensitization

• Physical damage at peripheral site

• Pain greater than stimulus

Segmental central sensitization

• neuroplastic Changes in dorsal horn

Suprasegmental central sensitization

• Physical or no damage

• Neuroplastic changes in thalamus and cortex

• NO STIM

What are the two gabapentinoids?

• Gabapentin

• Pregabalin

How do gabapentinoids work?

• Quiet hyperactive neurons

• Diabetic and nerve pain

What kind of drug is Amitriptyline?

TCA/Tricyclic antidepressant

TCA actions and adverse?

• Increase serotonin and NE

  • Inhibit pain transmission

• Anticholinergic effects

Duloxetine?

SNRI

Venlafexine?

SNRI

SNRI action?

• Enhance seretonin and NE

• better for elderly

SNRI SLIDE

SNRI SLIDE

Gabapentin MOA?

• modulates neuronal hyperexctibility

• Enhance descending noradrenergic inhibition

What is gabapentin useful for?

• Diabetic neuropathy

• postherpetic neuralgia

• SCI pain

• Others

  • sleep quality

  • not metabolized by liver so chronic liver problems or drug interactions

Adverse effects of gabapentin?

• dizziness,

• somnolence,

• ataxia,

• peripheral edema

• cognition decline

Pregabalin

• More potent

• longer ½ life

• weight gain

Indications for tricyclic antidepressants

◦MDD refractory to SSRIs, SNRIs

◦Amitriptyline: migraine

◦Chronic pain, neuropathic pain

Adverse effects of TCAD?

• Anticholinergic

  • dry mouth

• Antihisaminic

  • sleepy

• Postural hypotension

  • a1 receptor block

• Sexual dysfunction

• enhances other CNS depresants

• MORE OVERDOSE LETHALITY

  • usually fatal arrhythmias

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