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Neuro II Final > Opioid Narcotic Analesics And Related (Fitz) > Flashcards

Opioid Narcotic Analesics And Related (Fitz) Flashcards

1
Q

List generic names of soluble, bioavailable, opioid narcotic agonists used for analgesia/other indications

A 
Codeine
Fentanyl
Heroin
Hydrocodone
Hydromorphone
Meperidine
Methadone
Morphine
Oxycodone
Oxymorphone
Tramadol
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2
Q

List generic names for opioid narcotic mu receptor antagonists used for management of opioid narcotic overdose/addiction/side effects

A

Naloxone
Naltrexone
Methyl naltrexone (GI specific)

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3
Q

List generic names of opioid partial agonists or mixed agonists/antagonists

A

Buprenorphine
Buprenorphine-naloxone
Pentazocine

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4
Q

List generic names of insoluble, poorly absorbed opioid receptor agonists used for diarrhea

A

Loperamide

Diphenoxylate

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5
Q

List generic names of most common opioid related anti-tussive agents (cough suppression)

A

Codeine
Dextromethorphan
Hydrocodone

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6
Q

What are the types of opioid receptors and their physiological ligands?

A

Ligands are peptides

Mu MOR: endorphins
Kappa KOR: dynorphins
Delta DOR: enkephalins, endorphins

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7
Q

Where are the opioid sites of action in the CNS/PNS?

A

Cortex and limbic system: thalamus and hypothalamus
Midbrain: periaqueductal gray
Medulla: reticular formation, locus ceruleus, raphe nuclei
Spinal cord: spinothalamic (mescencephalic, reticular tracts)

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8
Q

Describe the pain impulse at pre and post synaptic neurons. Describe opioid agonist-mediated signaling

A

Opioid receptors unoccupied

  1. Afferent sensory signal
  2. Increases Ca2+ influx (presynaptic)
  3. Increases glutamate discharge (presynaptic)
  4. Increases NMDA receptor-Na+ influx (postsynaptic)

Opioid agonist occupies opioid receptors

  1. Blunts afferent signal
  2. Blunts Ca2+ influx
  3. Blunts glutamate discharge
  4. Increases K+ efflux
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9
Q

Of the drugs that bind to mu opioid receptors, which are full agonists, partial agonists, and antagonists?

A

Full agonists:
Fentanyl
Morphine

Partial agonist/mixed
Buprenorphine

Mu/kappa mixed:
Pentazocine

Antagonist
Naloxone
Naltrexone

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10
Q

In detail, describe opioid binding and receptors

A

Opioids bind to G-protein-linked membrane receptors: mu, kappa, delta. Subtypes, splice variants confer diversity

Receptors are widely distributed throughout human body, including brain, spinal cord, gut, uterus, etc. Majority of clinically useful opioid analgesic drugs have significant agonist activity at mu receptors

Opioid receptors bind endogenous peptides and drugs

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11
Q

Describe the pain treatment ladder based on opioid-sparing rationale

A

Mild pain:
-NSAID, acetaminophen

Moderate/persisting/uncontrolled:

  • Codeine
  • Codeine-related +/- acetaminophen
  • tramadol

Severe/persisting/uncontrolled:

  • Morphine
  • Fentanyl
  • extended release forms
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12
Q

List analgesic mechs and clinical utility

A

Acetaminophen,NSAIDS
COX-1,-2
Tissue injury»acute or nerve injury

Opioids, prototype morphine
Mu receptor agonists
Tissue injury=acute stimuli>nerve injury

Anticonvulsant (gabapentin)
Ca2+ channel antagonists
Nerve injury>tissue injury=acute

Antidepressants (amitryptilene)
Reuptake inhibitor
Nerve injury>tissue injury»acute stimuli

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13
Q

What is the prototype mu agonist?

A

Morphine

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14
Q

Describe clinical effects of agonists acting on mu receptor MOR

A 
Analgesia (supra-spinal)
Euphoria
CNS and respiratory depression
Drug dependence
Miosis (pupil contraction)
GI, uterine motility
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15
Q

Describe clinical effects of agonists acting on kappa receptor KOR

A

Analgesia (spinal)
Sedation
Miosis
GI, uterine motility

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16
Q

Describe tolerance to morphine (mu agonist)

A

Tolerance: over time, for a given dose, response deteriorates, necessitating increase in dose or rotation to different opioid
-analgesia, euphoria, sedation, nausea, respiratory depression

No tolerance to
-miosis, constipation

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17
Q

Patient was recovering from surgery in post-anesthesia care unit (PACU). He had been receiving morphine IV for 2 hr for postsurgical pain. His resp rate was 7 per minute with shallow breaths. He did not respond to any stimuli

pH=7.15 (normal 7.4)
HCO3=22 (normal 24)
PaCO2=68 (normal 40).

Describe what happens with opioid and respiratory depression

A
  1. At baseline, pH7.4=normal
  2. Hypoventilation. Lungs retain CO2=retain acid
    - CO2 contributes to H+ to blood
  3. Rise in PaCO2=rise in H+
    PH=7.15

Increase in CO2 + H2O H2CO3 Increase in H+ + HCO3

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18
Q

Describe morphine-induced respiration depression. Contraindciations to morphine?

A

Morphine (mu agonist) depress sensitivity to CO2
Dose-related drop of respiration rate (3-4/minute in severe toxicity), minute volume, tidal exchange

Contraindications:

  • Brain injury
  • Emphysema
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19
Q

What are clinical indications for morphine?

A

Post-operative pain
-procedures and surgery

Cancer pain
-primary and metastatic malignancy

Other pain
-Sickle cell crisis, trauma, severe diarrhea, dyspnea caused by pulmonary edema from left ventricular failure

20
Q

What are the group 1 mu agonist opioid drugs?

A

Full agonists
Parenteral and oral

*Morphine
Methadone
Meperidine

Hydromorphone
Oxymorphone
Levorphanol

21
Q

What are the group 2 mu agonist opioid drugs?

A

Full agonists
Short acting

*Fentanyl
Sufentanil
Remifentanyl

22
Q

What are the group 3 mu agonist opioid drugs?

A

*Codeine-related
Hydrocodone
Oxycodone

23
Q

In group 1, potency and bioavailability are important when switching from parenteral to oral dosing or rotating between opioids. They also dictate some of the clinical uses of these drugs.

Compare and contrast their equivalent dose and oral/parenteral potency ratios

A 
Morphine: 10 mg dose and Low oral/parenteral potency ratio
Methadone: 10 and high
Meperidine: 60 and medium
Hydromorphone: 1.5 and low
Oxymorphone: 1.5 and low
Levorphanol: 2-3 and high

Meperidine, hydromorphone, oxymorphone, and levorphanol differ from morphine in efficacy

Methadone and levorphanol have good oral bioavailability

24
Q

Parenteral (IV, IM, SC, Patch, buccal) opioids have high bioavailability.
Oral morphine. First-pass metabolism. Poor bioavailability. Describe morphine’s metabolism breakdown

A

Morphine->UGT 1A1, UGT 2B7-> M-3-glucuronide, M-6-glucuronide (active metabolites)

Morphine->dehydrogenase->hydromorphone (active)

Morphine->CYP3A4->Normophine (inactive)

25
Q

Describe characteristics of methadone

A

Mu agonist (full agonist)
Longer half-life (27 hrs vs morphine’s 2 hrs)
Better oral absorption/bioavailability (90% vs 20% morphine)
Useful for withdrawal/maintenance and detoxification

26
Q

Describe cardiac effect of methadone

A

Can affect cardiac electrical conduction, producing QT-interval prolongation in acute overdose or during long-term methadone treatment

This effect is unrelated to its interaction with mu receptors
It delays cardiac repolarization by blocking flow of K+ ions through HERG channels (K+ channels)

27
Q

Describe meperidine distinctions as mu agonist

A

Eye: pupil dilation (mydriasis)
Abuse difficult to detect via pinpoint pupils
Accordingly, those who abuse this drug can escape detection

Normeperidine, a toxic metabolite, accumulates and causes seizures

28
Q

Describe group 2 mu agonists: short acting, high potency, full agonists

A

Sufentanil: kappa, delta, and mu agonists

Fentanyl, sufentanil, alfentanil, remifentanil are 100x more potent than morphine, methadone

Remifentanil: very short-acting

29
Q

Describe remifentanil popularity

A

Group 2 mu, short acting, full agonist

Gaining popularity for analgesia for childbirth if regional analgesia is either contraindicated or not desired

It is metabolized by plasma and tissue esterases

Although it transfers across placenta, its rapid metabolism in fetus lowers risk for neonatal depression

Its rapid onset of action, within 1 minute following intravenous injection, is another advantage

30
Q

Describe fentanyl: anesthesia and breakthrough pain

A 
Strong group 2 mu agonist (meperidine analog)
Used in anesthesia
*Rapid onset & distribution (lipophilic)
*Short duration of action (procedures)
*Transmucosal (lollipop)
Breakthrough pain (with morphine)
*Transdermal patch delivery
Slows onset and prolongs delvery

Caution: respiratory depression
*Abuse potential via heating patches

31
Q

Describe codeine; moderate pain & cough

A

As a partial agonist at mu receptors, codeine has less potential for drug dependence & respiratory depression
Reliable oral absorption/bioavailability (50% vs 20% morphine)
*Analgesia - moderate pain
Some formulations contain acetaminophen
Anti-tussive: cough relief (mu-independent)

32
Q

What drug is a safer antitussive agent than codeine?

A

Dextromethophan
It relieves cough independently of opioid receptors
Not analgesic
Not addictive

33
Q

Why has codeine for pain relief following a tonsillectomy and/or adenoidectomy caused death in children with obstructive sleep apnea?

A

Codeine->CYP2D6->morphine

Ultrafast metabolizer: CYP2D6 gene duplication & ultrafast allele
-leads to life-threatening or fatal amounts morphine in body

Intermediate metabolizer: CYP2D6 heterozygous

Poor metabolizer: CYP2D6 gene deletion & slow allele

34
Q

List drugs and their active metabolites

A 
Morphine: M6G and M3G, hydropmorphone
Heroin: Morphine
Codeine: Morphine
Oxycodone: oxymorphone
Meperidien: normeperidine (toxic)
Hydromorphone: None
Oxymorphone: None
Fentanyl: none
35
Q

Describe opioids and the gut

A

Loperamide
Diphenoxylate

Anti-diarrheals
Interact with mu opioid receptors in gut
Poor solubility (limited risk of parenteral abuse)
Poor penetration of BBB (limited risk of dependence/toxicity)

36
Q

Describe tramadol

A

*Moderate mu agonist
N-desmethyl active metabolite
Reliable oral absorption/bioavailabilty (70% vs 20% for morphine)
*Analgesia: moderate pain
*Inhibits catecholamine reuptake
Caution in patients in tricyclic or SRI anti-depressants
*Associated with seizures

37
Q

Describe pentazocine

A

Mixed: kappa agonist plus mu partial agonist and delta antagonist
Supra-spinal analgesia
Can precipitate withdrawal (in abusers)
Side effects: tachycardia, hallucinations

38
Q

Describe buprenorphine

A

Partial/mixed
Mu partial agonist plus kappa & delta antagonist
Analgesia
Can precipitate withdrawal (in abusers)
*office-based detox/maintenance in combination with naloxone

39
Q

Describe heroin (illegal substance)

A

Di-acetylmorphine

Penetrates BBB rapidly->exaggerated euphoria->addiction liability

40
Q

Describe addiction program compliance: % retention - 1 year

A

Methadone maintenance: 50-80%
Buprenorphine-naloxone: 40-50%
Naltrexone Maintenance: 10-20%
“Drug free”: 5-20%

41
Q

What are signs of opioid analgesic overdose?

A

Respiratory rate

42
Q

Describe mu receptor antagonists

A 
Occupy but do not activate mu receptors
Competitively inhibit (displace) heroin, morphine, fentanyl, etc (other mu agonists) from mu receptors
*Antidote for opioid overdose
43
Q

Describe naloxone

A

Can reverse coma and respiratory depression ~1 min after IV bolus
Depends on what opioid and what dose
Initial .04mg. If no response, then incremets to 15 mg
Short duration of action 1-2 hrs can lead to apparent relapse of overdose symtpoms
Antidotes for overdose can precipitate withdrawal

44
Q

Describe naltrexone

A

Has a long duration of action (48 hrs for single dose orally) in overdose

45
Q

Opioids increase smooth-muscle tone and inhibit coordinated peristalsis required for propulsion, which contributes to nausea and vomiting as well as constipation.
What strategies might work for opioid-induced side effects as constipation?

A

Methylnaltrexone

46
Q

What is methylnaltrexone?

A

Quaternary derivative of naltrexone with restricted ability to cross BBB
It functions as a peripheral acting opioid antagonist, including actions on GI tract to inhibit opioid-induced decreased GI motility and delay in GI transit time, thereby decreasing opioid-induced constipation
Does not affect opioid analgesic effects or induce opioid withdrawal symptoms

Neuro II Final (17 decks)

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