Narcotic Analgesics - Fitzpatrick Flashcards
DOR
KOR
MOR
What are they?
Delta, kappa, mu opiod receptor
GPCRs
Opioid FULL AGONISTS used for analgesia
Fentanyl, Heroin, Hydromorphone, Meperidine, Methadone, Morphine, Oxycodone, Oxymorphone, Tramadol
Opioid (Mu) receptor ANTAGONISTS
Used for what?
Naloxone, Naltrexone, Methylnaltrexone
Management of opiod OD/addiction/side effects
Opioid (Mu) PARTIAL AGONIST
Buprenorphine, Codeine, Hydrocodone
Opioid Mixed AGONIST/ANTAGONIST
Buprenorphine-Naloxone
Poorly-absorbed opioid receptor AGONISTS
Used for what?
Loperamide, Diphenoxylate
Diarrhea
Common opioids w/ anti-tussive (cough) agents
Codeine, Dextromethorphan, Hydrocodone
Mu receptor ligands
Endorphins
Kappa receptor ligands
Dynorphins
Delta receptor ligands
Enkephalins, Endorphins
Sites of opioid action
Peripheral 1º afferent nociceptor
Dorsal horn Pre-synaptic CALCIUM channels
2º afferent post-synaptic POTASSIUM channels
5 steps of pain impulse propagation at SYNAPSE
- Afferent sensory signal (painful stimuli)
- Ca++ influx into pre-synaptic terminal
- Glutamate discharge
- Post-synaptic NMDA receptor activation
- Na+ influx-induced 2º neuron action potential
Binding of opioids at the 3 sites of action affect which steps of the process?
Function at post-synaptic terminal?
ALL STEPS
K+ efflux –> hyperpolarization (prevent action potential)
Are opioid agonists more for tissue injury or nerve injury?
Similarly to what drugs?
Tissue injury
NSAIDs, Acetaminophen
Opioid drugs to use for MODERATE, persisting or uncontrolled pain
Codeine, Codeine-related, Tramadol
Opioid drugs to use for SEVERE, persisting or uncontrolled pain
Morphine, Fentanyl, etc.
Morphine acts at which receptor?
Mu
Mu AGONISTS act MOSTLY where?
Thus, additional effects of morphine use? (4)
Brain and brainstem
SUPRA-SPINAL analgesia
Euphoria
CNS and respiratory depression
Drug-dependence
Which clinical effects of morphine use do NOT show tolerance (decrease in effect) over time?
Miosis (eyes ALWAYS pin-point)
Constipation (will continue to be constipated)
Which clinical effects of morphine use DO show tolerance over time?
Analgesia, Euphoria, Sedation, Pruritis, Nausea, Respiratory Depression
Common side effect of morphine use
So?
Constipation/Biliary pressure
Sometimes will need to choose a less-potent analgesic (like post-GI surgery) to reduce the constipation
Can the analgesic effect of morphine be elicited without the other effects?
NO
When you say respiratory depression, what does this mean?
Disruption of CO2 sensitivity
Contraindications to morphine use based on respiratory depression effects
Brain injury, emphysema
Clinical indications for morphine use
Post-op pain
Cancer pain
Other pain (sickle cell, trauma)
SEVERE DIARRHEA (w/ risk for electrolyte imbalances)
Mu FULL AGONISTS given parenterally or orally
Morphine, Methadone, Meperidine
Hydromorphone, Oxymorphone, LEvorphanol
“Three M’s go in or around the HOLe (Mouth)”
Mu FULL AGONISTS that are short-acting
Fentanyl, Sufentanil, Remifentanyl
“Three Fentanyl’s die Fast”
Mu Receptor agonists - codeine-related drugs
Codeine, Hydrocodone, Oxycodone
A patient needs an oral Mu FULL AGONIST drug. What are her options?
Why?
Methadone, Levorphanol
Good bioavailability
A patient needs a Mu FULL AGONIST drug, but is “NPO” in the hospital. What can be given parenterally?
Morphine, Hydromorphone, Oxymorphone, Meperedine
Contrast the potencies of the 6 different Mu FULL AGONISTS
Morphine = Methadone
Meperedine is WEAK (6x weaker than morphine)
HOLe (all 3) are STRONG (5x stronger than morphine)
Oral, STRONGER (lower dose) Mu full agonist
Levorphanol
Oral version of morphine
Methadone
Stronger parenteral morphine-like drugs
Hydromorphone, Oxymorphone
WEAKER (higher dose) version of morphine
Meperidine
Why is morphine poor when taken orally?
What does this?
First-pass effect
CYP3A4 in the liver
Why can people react differently to morphine?
Different ACTIVE metabolites, some of which are even MORE active than morphine (hydromorphone)
Inactive metabolite of morphine
Via what?
Normorphine
CYP3A4
Why might methadone be chosen over morphine?
Much longer 1/2 life = only give ONCE per day
Other clinical uses of methadone?
Why?
Withdrawal/detoxification, maintenance
Stays in body longer, allows for slow decrease rather than constantly falling towards zero after morphine dose
A patient is on long-term methadone treatment for detoxification from heroin. What is a potential side effect developed over time?
Why?
Long QT syndrome (on EKG)
Acts directly on inward rectifying K+ (IRK) channels, thus could cause delayed ability of heart cells to re-polarize
A patient is as a common opiate narcotic abuser with a recent history of seizures. He admits to using it at work and has never been caught.
What is he using?
Why has he never been caught?
Why is he having seizures?
Meperidine
Only opiate to cause pupillary DILATION (can’t detect using the standard pin-point pupil test)
Normeperidine = TOXIC METABOLITE that accumulates and causes SEIZURES
A patient is having a bad opioid withdrawal episode and needs an IMMEDIATE IV drug dose to calm the symptoms before he can be slowly withdrawn from the drugs.
What are your best options?
Why?
Fentanyl, Sufentanil, Remifentanyl
Act VERY FAST, then have SHORT DURATION
- Good for stabilizing the patient
COMPARE and CONTRAST the 3 short-acting IV Mu receptor agonists
ALL 3 = Short duration (
A pregnant woman needs immediate analgesia during childbirth, but she cannot have typical regional anesthesia. What are her options?
Which is the best option?
- Why?
Fentanyl, Sufentanil, Remifentanil
Remifentanil (VERY rapid onset, metabolized by plasma/tissue esterases - so baby does not need hepatic enzymes to break it down)
A patient needs an immediate analgesic for whatever reason. However, the pain needs to be kept off for a while after the near-immediate effect. What is a good combo to give?
Fentanyl + Morphine
Benefit of a transdermal skin patch for Fentanyl delivery
Slows onset, prolongs delivery
Danger of Fentanyl skin patches
Can be heated –> ABUSE POTENTIAL
Benefits to Codeine use for pain relief (3)
- Partial Mu Agonist, so less abuse or resp. depression
- Better oral bioavailability than morphine (50% > 20%)
- Anti-tussive (cough) effect
A patient has a bad acute cough and needs a medication. However, they have a history of drug abuse. What is the best medication?
Why?
Dextromethorphan
NOT analgesic (opioid-receptor independent), so not addictive
You suspect an opioid overdose, specfically of the codeine group (codeine, hydrocodone, oxycodone). What must be taken into consideration when treating the OD?
Some forms of codeine-type drugs come along with ACETAMINOPHEN, so must be careful of drug-drug interactions
Contrast the 3 codeine-related drugs
Codeine - Partial Mu agonist, less potent, better orally
Hydrocodone - Partial agonist, more potent than codeine
Oxycodone - FULL agonist, more potent than codeine
Why is it bad to give codeine to an opioid addict?
Metabolized to MORPHINE via CYP2D6, as well as to other active metabolites
A patient is trying to take codeine for a cough, but the effects wear off much quicker than they should. Additionally, she constantly feels “high” shortly after taking it. However, her friend also takes it, but does not seem to feel these narcotic effects at all.
Why?
Patient = ULTRAFAST metabolizer –> morphine
- Extra CYP2D6 allele(s)
Friend = SLOW metabolizer (gene deletion for CYP2D6)
A patient needs an analgesic for a post-op period. However, they have a history of drug abuse. What are the best options?
Why?
Hydromorphone, Oxymorphone, Fentanyl
Have NO active or toxic metabolites
A patient is a chronic heroin abuser. Why is the drug so potent?
Why do the effects of heroin last so long?
2 ACETYL groups on morphine –> rapidly penetrates BBB to cause EXAGGERATED euphoria
Metabolized into morphine
A patient has chronic bad diarrhea. The normal autonomic drugs do not seem to work. You think of opioid options.
What are your best options?
Why are these good for the gut?
Why are they OTC?
Loperamide, Diphenoxylate
Interact w/ Mu receptors in the gut
Poor solubility in blood, poor penetration of BBB
- Limited risk of abuse, dependence, or toxicity
What is Tramadol?
What is it like?
What is unique about it?
Cautions? (2)
Moderate/Partial Mu agonist (like codeine)
Good oral availability (like codeine)
Active metabolite (like codeine)
INHIBITS CATECHOLAMINE RE-UPTAKE
- Careful when using w/ patients on anti-depression meds
- Metabolite build-up –> SEIZURES
Buprenorphine action
Used for what?
Mu PARTIAL agonist + Kappa/Delta ANTAGONIST
OUTPATIENT withdrawal maintenance in abusers
Death by morphine (Mu agonist) overdose?
Respiratory depression
3 cardinal signs of opioid use/overdose
- Slow respiratory rate (
2 Mu receptor ANTAGONISTS
Function?
- Used when?
Contrast them
Naloxone, Naltrexone
Competitive antagonists of Mu receptor
- ANTIDOTE FOR OPIOID OVERDOSE
Naloxone = IV, use FIRST (immediate effect) Naltrexone = oral, use AFTER NALOXONE (48 hr duration)
Why do opioid agonists cause nausea and vomiting?
Increased GI smooth muscle tone, but INHIBITED coordination of peristalsis
A patient is taking morphine for post-op analgesia (pain relief), but is having severe trouble with constipation. The patient wants to continue with the analgesia, but not the constipation. What is a good cure?
Methylnaltrexone
Quaternary (charged), so cannot cross BBB. Acts as PERIPHERAL opioid antagonist, so does NOT affect the analgesic (CNS) effects of morphine.
