Opioid Analgesic Drugs

Front 1

Transmitters Involved in Descending Pain Modulation

Back 1

1. Limbic System: Enkephalins, endorphins, endomorphins

2. Periaqueductal Grey matter projections to:
a. Medulla (Raphe Magnus) - Serotonin.
b. Midbrain (Locus Cerules) - Norepinephrine.

3. Spinal Cord: Enkephalins and Dynorphins.

Front 2

Beta-endorphin Endogenous Source

Back 2

Derived from Pro-Opio-Melanocortin (POMC gene)

Front 3

Enkephalins Endogenous Source

Back 3

Derived from pro-enkephalin.

Met-Enkephalin & Leu-Enkephalin.

Front 4

Dynorphins Endogenous Source

Back 4

Derived from Pro-Dynorphin.

Front 5

Endomorphins & Nociceptin

Back 5

Ligands for orphanin receptor?

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Name the Opioid Receptors

Back 6

Mu - major opioid receptor of brain.

Kappa, Delta - homology along with Mu.

Orphanin - nociceptin binds.

Sigma - not related structurally.

Front 7

Mu Receptor

Back 7

Beta-endorphine (ME) is ligand.

Primary opioid receptor.

Effects: Supraspinal analgesia, sedation, reduced GI motility, Euphoria, Hormone release, Respiratory depression, Tolerance and physical dependence.

Front 8

Kappa Receptor

Back 8

Less important than Mu, more important than Gamma.

Dynorphins (KD) are the ligand.

Effects: Spinal analgesia, miosis, sedation

Front 9

Gamma Receptor

Back 9

Less important than Mu and Kappa.

Enkephalins (GEn) are the ligand.

Effects: Spinal analgesia, supraspinal analgesia.

Front 10

Sigma Opioid Receptor

Back 10

NMDA glutamate receptor complex.

Not related to Mu, Kappa, or Gamma structurally.

Effects: Dysphoria, Halluncinations, Psychosis.

Front 11

Orphanin Receptor

Back 11

First called OLR1 (opioid-like receptor 1)

Nociceptin is the ligand.

Endomorphins also ligand.

Do NOT respond to many traditional opioid agonist and antagonists.

Front 12

Post-Synaptic Opioid Receptor Mechanism

Back 12

An opioid (like morphine) binds to opioid receptor and through a G-protein and Adenylate Cyclase, it decrease cAMP. This decrease Calcium and causes a K (potassium) efflux. This hyperpolarizes the cell and decreases release of the neurotransmitter. Thus pain is decreased.

Front 13

Pre-Synaptic Opioid Receptor Mechanism

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Opioid binds to pre-synaptic receptor and causes a depolarization of the presynaptic membrane with the INflux of K through K-channels. This action decreases Calcium (Ca) influx during a Action Potential. With less calcium, there is decreased transmitter release in response to the action potential.

Front 14

Full Agonists

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Opioid Drugs: morphine, meperidine, methadone. (Remember the 3 Ms)

Morphine is the prototype.

Effects: Euphoria, analgesia, sedation, respiratory depression.

High degree of tolerance and dependence.

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Partial Agonists

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Opioid Drugs: Propoxyphene, Codeine, Oxycodeine. (remember PCO)

Milder analgesia and dependence.

Orally ACTIVE.

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Methadone

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Full Agonists with High intrinsic activity.

Front 17

Mixed Agonists/Antagonists

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Drugs: Buprenorphine, Pentazocine. (Remember BP or blood pressure is mixed)

Effects: Analgesia, sedation, psychotomimetic effects, nightmares, anxiety

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Antagonists

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Used to reverse opioid overdose.

Drugs: Naloxone, Naltrexone.

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Meperidine

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Full Agonist.

High Intrinsic Activity.

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Methadone

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Agonist.

High Intrinsic Activity.

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Busprenorphine

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Mixed Agonsist/Antagonist

Agonist: Mu
Antagonist: Kappa, Gamma

High Intrinsic Activity

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Oxycodone

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Partial Agonist

Moderate Intrinsic Activity

Front 23

Pentazocine

Back 23

Schedule IV, mild to moderate pain.

5x less potent than morphine.

Mixed Agonsist/Antagonist with Moderate Intrinsic Activity.

Agonist: Kappa, Delta
Antagonist: Mu

Abuse potential.

Talacen, Talwin.

Front 24

Codeine

Back 24

Schedule III for mod to severe pain.

Orally Active & 10-12x less potent than morphine.

Partial Agonist with Low Intrinsic Activity.

Found in Tylenol with acetaminophen.

Front 25

Naloxone

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Opioid Antagonist.

Poor oral availability, short duration.

Front 26

Naltrexone

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Opioid Antagonist.

Good oral availability, 10-12 hr duration.

Used to treat addicts due to its long half life.

Also used for Alcoholics.

Front 27

What optometric medications contain Hydrocodone?

Back 27

Lortab, Hydrocept

Both with acetaminophen.

Front 28

What optometric medications contain Pentazocine?

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Talwin (with asprin).

Talacen (with acetaminophen).

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What optometric medications contain Propoxyphene?

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Darvon.

Darvocet (with acetaminophen).

Front 30

What optometric medications contain Tramadol?

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Ultram

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Hydrocodone

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Schedule III for moderate to severe pain.

Similar potency to Codeine.

Found in Lortab, Hydrocet, and Hycodan.

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Propoxyphene

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Schedule IV for mild to moderate pain. (Partial Agonist)

Related to methadone, but similar potency to codeine.

Significant abuse potential.

Darvon, Darvocet-n 50, Darvocet-n 100.

Front 33

Pharmacokinetics: average half life and duration?

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Half lives are typically 2-4 hours except Propoxyphene which is 12 hours.

Duration: all range from 4-8 hours.

Front 34

Tramadol

Back 34

Unique unscheduled drug. It is a cross between a opioid and an antidepressant.

Weak Opioid agonist.

Inhibits uptake of Serotonin and Norepinephrine.

Limited adverse effects.