Opioids

Differentiate between Narcotic, Opiate and Opiod

• Narcotic

  • a drug with addictive properties that can produce analgesic and sedative effects.

• Opiate 

  • a drug naturally derived from opium (morphine and codeine)

• Opioid 

  • a drug, natural or synthetic, with morphine- like qualities

List the indications for opiods

Indications for Opioids

• Analgesic

• Anesthetic

• Antitussive

• Antidiarrhea

1. List the Strong Opioid Agonists

2. List the Moderate Opioid Agonist

3. List the Combination Meds

4. List the Weak Opioid Agonists

5. Other?

6. List the Mix Acting opioids

7. List the Opioid Antagonists

Strong Opioid Agonists

• Fentanyl (Sublimaze, Duragesic)

• Alfentanil, Remifentanil, Sufentanil

  • related to Fentanyl but use for anesthesia

• Hydromorphone (Dilaudid)

• Meperidine (Demerol)

• Methadone (Methadose, Dolophine)

• Morphine sulfate (MS Contin)

• Oxycodone (Oxycontin)

• Heroin

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Moderate Opioid Agonists

• Codeine (Robitussin AC)

• Hydrocodone

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Combination Meds

• Tylenol #2, 3, 4

  •  (acetaminophen/codeine)

• Vicodin, Lortab

  •  (acetaminophen/hydrocodone)

• Vicoprofen 

  • (ibuprofen/hydrocodone)

• Percocet 

  • (acetaminophen/oxycodone)

  • ***class II schedule***

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Weak Opioid Agonists

• Loperamide (Imodium)

• Diphenoxylate – (Lomotil) 

  • Combined with atropine

• Propoxyphene (Darvon)

  • Combined with acetaminophen

  • marketed as Darvocet 

    • (acetaminophen/propoxyphene)

• Dextromethorphan (Delsym, Robitussin DM)

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Other

• Tramodol (Ultram)

• Tapentadol (Nucynta)

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Opioid Agonist / Antagonist (Mixed-Acting)

• Pentazocine (Talwin)

• Nalbuphine (Nubain)

• Butorphanol (Stadol)

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Opioid Antagonist

• Naloxone (Narcan)

• Naltrexone (Revia)

List the Opioid receptors and their functions

Opioid Receptors

• mu “REAP”

  • Respiratory depression

  • Euphoria

  • Analgesia

  • Physical dependence

• kappa “SAM”

  • Sedation

  • Analgesia

  • Miosis

• Others:

  • delta

  • (epsilon)

  • (sigma)

List the Endogenous Opioids and their functions

Endogenous Opioids

• Endorphins

  • neurohormones (ACTH)

  • Function:

    • mediates pain

    • Appetite

      • (thirst, hunger, sex)

    • memory

    • mood

• Dynorphins

  • neurotransmitters

• Enkephalins

  • neurotransmitters

1. List the Opioid Receptor locations in the CNS (most to least [])

2. List Opiod’s 3 Sites of Actions and their function:

3. What is the MOA of opioids

Opioid Receptor locations in the CNS (most to least [])

1. cerebral cortex

2. amygdala

3. septum

4. thalamus

5. hypothalamus

6. midbrain

7. spinal cord

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Opiod’s 3 Sites of Actions and their function:

• SC:

  • inhibit release of NTs from afferents

• Thalamus and limbic system

  • Block pain perception/reaction

• Brain Stem

  • Act. descending inhibitory systems to modulate pain

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MOA of Opioids

• Gi -> ↓ cAMP -> Inhibition of pre/post synaptic firing in SC and brain (respectively) -> Hyperpolarization  -> Diminished/blocked pain perception

Describe Morphine

• Clinical Uses

• CI

• AE

  • Psycho?

  • eyes?

  • CV?

  • skin?

  • Pulmonary?

  • GI?

  • Biliary tract

  • Bladder?

  • Uterus

• Metabolism/Excretion

Morphine

Clinical Uses

• PAIN

  • Severe

  • Chronic

• acute pulmonary edema

• Palliative measures

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Contraindications

• respiratory compromise

• asthma

• intracranial injuries 

  • (increased ICP)

• paralytic ileus

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AE:

• Psychological:

  • euphoria and dysphoria

  • Anxiety

  • Sedation

• Miosis

• CV

  • Vasodilation, 

  • Decreases BP 

  • Negative inotropic response

• Skin

  • Histamine -> Itchy

• Pulmonary 

  • Bronchospasm

  • respiratory depression

• GI

  • decreases secretions + gut motility 

  • Nausea

  • Constipation

• biliary tract

  • 10 fold increase of pressure

    • b/c contraction of Sphincter of Odi

• urinary bladder

  • detrusor muscle tone increased

  • Increased Urgency

  • Urinary retenion 

    • increased muscle tone where sphincter closed off

• Uterus

  • Reduced uterine tone

    • -> prolong labor

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Metabolism:

• Conjugation -> Active Metabolites

  • morphine 6β glucoronide 

  • morphine 3β glucoronide

Excretion:

• Renally

Describe Fentanyl (Sublimaze, Duragesic)

• Comparison to Morphine

• Drug course

• Clinical Usages/Forms

Fentanyl (Sublimaze, Duragesic)

• Comparison to Morphine

  • 80 to 100 times more potent 

• Drug Course:

  • Rapid Onset ((peaks in 5 min))

  • Short Acting ((30 min))

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Clinical Usage

• preoperative medication

  • IV Form

• Epidurals

• Chronic Pain

  • Transdermal form 

    • – Onset of action is 12 hours

    • – replace patch every 72 hours

Describe Meperidine (Demerol)

• What does it synthesized into? Consequence of this?

• Avoid in?

Meperidine (Demerol)

• Synthesized -> normeperidine 

  • Seizures

    • Excessive accumulation

  • Serotonin syndrome

    • inhibits serotonin reuptake 

• Avoid in:

  • renal dysfunction patients

Describe Methadone (Methadose, Dolophine)

• Comparison to Morphine

• Clinical Usage

• Course

• Absorption

Methadone (Methadose, Dolophine)

• Comparison to morphine:

  • pharmacological activity + potency similar

  • less addiction liability

• Clinical usage:

  • maintenance program for narcotic dependence treatment

  • powerful pain reliever

• Course:

  • long duration of activity, 

    • half life of up to 24 hours

• Absorption:

  • absorbed well orally

Describe Heroin:

• Comparison to Morphine

• Clinical Usage

• Absorption

Heroin

• Comparison to Morphine:

  • diacetyl derivative

  • 3x more potent 

• Clinical Usage:

  • No medicinal value

    • recreational drug 

• Absorption:

  • Most lipophilic -> enhanced capability to enter brain

Describe Codeine

• Comparison to Morphine

• Clinical Usage

• Synergy

• Abuse

Codeine

• Comparison to Morphine:

  • 1/10th the potency

• Clinical Usage:

  • excellent antitussive

  • good analgesic

• Synergy:

  • usually combined with acetaminophen

• Abuse:

  • low potential for abuse and rarely produces dependence

Describe Propoxyphene

• Derivative of?

• Comparison to Morphine?

• Clinical Usage

• Synergy

Propoxyphene

• Derivative of?

  • methadone

• Comparison to Morphine:

  • 1/20th potency

• Clinical Usage:

  • analgesic effect similar to aspirin

    • If given alone 

• Synergy:

  • Usually combined with acetaminophen (Darvocet)

Describe Dextromethorphan

• AKA

• MOA

• Clinical Usage

• Other Opioids for cough treatment

• AKA:

  • (Delsym, Robitussin DM)

• MOA:

  • mu, kappa, sigma receptor activity

• Clinical Usage:

  • Antitussive

• Other Opioids for cough treatment:

  • codeine

  • hydrocodone

  • hydromorphone

Describe Antidiarrheals

• Drugs and effects

• AE

Antidiarrheals

• Drugs:

  • Loperamide 

    • (Imodium)

    • GI effects only

  • Diphenoxylate 

    • (Lomotil)

    • Combine w/ atropine

      • GI and CNS effects

• AE

  • Little analgesic properties @ therapeutic dose

  • no antitussive effect

  • respiratory depression + euphoria 

    • at high doses

1. List the Opioid Agonist / Antagonist and Partial Agonist

2. What are their clinical usage and benefits

• Opioid Agonist / Antagonist

  • Pentazocine (Talwin)

  • Nalbuphine (Nubain)

  • Butorphanol (Stadol)

• Partial Agonist

  • Buprenorphine (Subutex )

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• Clinical Usage:

  • Outpatient opioid detoxification

• Benefits:

  • Does not cause serious respiratory depression

Describe Opioid Antagonists

• Drugs

• MOA

Opioid Antagonists

• Drugs:

  • Naloxone (narcan)

  • Naltrexone (Revia)

• MOA:

  • high affinity Binding to opioid receptors

  • Displaces opioids

  • Completely + dramatically reverses opioids effects

Describe Naloxone (Narcan)

• Administration

• MOA

• Clinical Usage

• Why do repeat doses have to be used?

Naloxone (Narcan)

• Administration:

  • IV push

• MOA:

  • Rapidly displaces all bound opioid molecules

  • Binds to mu, kappa, and delta receptors

    • 10 fold affinity to mu 

• Clinical Usage:

  • Respiratory depression + sedation reversed

    • <30sec

• Repeat doses may have to be used:

  • b/c of longer durations of opioid agonists

    • Narcan duration = short (1-2 hrs)

Describe Naltrexone

• Comparison to Naloxone

• Clinical usage

• AE

Naltrexone (Revia)

• Comparison to naloxone

  • Same pharmacodynamics; Slightly different pharmacokinetics

  • Longer Half Life

    • ***One 100mg dose -> block heroin effects -> 48 hours.***

• Clinical Usage

  • negative reinforcement for Heroin

    • Patient gets no euphoric effect from heroin 

  • alcoholism

• AE:

  • Highly hepatotoxic

List the Pain Management Treatment Options

Pain Management Treatment Options

• Non-opioids

• Opioids

• Antidepressants

• Anticonvulsants

• Cognitive Behavioral Therapy

• CAM

Describe Fibromyalgia

• Symptoms

• Pathogenesis

• Management

Fibromyalgia

• Symptoms:

  • Widespread pain: > 3 months

  • Location:

    • Bilat

    • above + below waist

    • Axial skeletal pain

• Pathogenesis:

  • CNS neuroplastic changes -> Stimuli hypersensitivity -> ↓Serotonin levels + impaired serotonin metabolism -> ↓IGF 1 & function of hypothalamic-pituitary axis -> ↓ Serum androgen

• Management:

  • Pregabalin

  • Duloxetine/Gabapentin

  • Tizanidine

  • Trazodone (sleep disturbance)

  • Amitriptyline/Nortriptyline

Describe Migraine

• Symptoms

• Management

• List out the triptans

Migraine

• Symptoms:

  • Pressure in frontal region  -> periorbital and retroorbital region

  •  Nausea and light sensitivity

  • Nasal stuffiness

• Management:

  • Antiemetic

  • Triptains

  • NSAIDS

• Triptans:

  • Zolmitriptan

  • Naratriptan

  • Almotriptan

  • Rizatriptan

  • Sumatriptan

Describe Neuropathic Pain

• What is it?

• Description of Pain

• Management

  • Diabetic peripheral neuropathy:

  • Post-herpetic neuralgia:

  • Trigemnial neuralgia

Neuropathic Pain

• What is it?

  • Pain initiated by lesion or neural dysfunction:

    • Peripheral neuropathy

    • Trigemnial neuralgia

    • Central post-stroke pain

    • Spinal cord injury

• Description of pain:

  • Burning sensation

  • Cold

  • Tingling/Prickling

  • Shooting/Stabbing

  • Itching

• Management

  • Diabetic peripheral neuropathy:

    • Pregabalin/Duloxetine

  • Post-herpetic neuralgia:

    • Gabapentin/Pregabalin

  • Trigemnial neuralgia

    • Carbamezapine

how do you manage cancer pain

Management:

• Modifying source of pain

• Altering pain perception

• Blockade of pain transmission