Pain 2 - Oops, All Opioids Flashcards
What are the 3 main opioid receptor subtypes? What does activation of each do?
- mu (µ):
- Analgesia, euphoria, physical dependence, respiratory depression, reduced GI motility ( –> constipation), sedation - delta (ẟ):
- Analgesia, euphoria, physical dependence - kappa (ϰ):
- Analgesia, sedation, ? mood, does NOT contribute to physical dependence
What are the “big 5” opioids?
- Morphine
- Codeine
- Hydromorphone
- Oxycodone
- Fentanyl
What is the MOA of opioids?
Opioid molecules bind to opioid receptors in the central and peripheral nervous system, suppressing neuronal firing from the presynaptic neuron and also inhibition of postsynaptic nerves in some areas, which ultimately alters the transmission and perception of pain
Opioid use in acute pain:
What is the usual oral starting dose and frequency of codeine IR? (tylenol + codeine + caffeine)
15-30mg q4h prn
Opioid use in acute pain:
What is the usual oral starting dose and frequency of hydromorphone IR?
1-2mg q4-6h prn
Opioid use in acute pain:
What is the usual oral starting dose and frequency of morphine IR?
5-10mg q4h prn
What should we be taking into consideration when using opioids in acute pain? (3)
- Lowest dose (should not need >50 MEQ), shortest duration
- Use clinical judgement re: quantity (consider limit to 3-5 days to start)
- Education about adverse effects including toxicity, take home naloxone
What are 3 advantages of opioid use in chronic non-cancer pain? (3)
- Potent analgesic effect
- Fast onset
- Relatively low risk of major organ toxicity
- Renal, hepatic, cardiac
What are the adverse effects of opioid use in chronic non-cancer pain? (7)
- CNS depression
- Falls/fractures
- Constipation
- Apnea
- Hypogonadism
- Opioid-induced hyperalgesia
- Dependence, opioid use disorder
What are some disadvantages (4) to opioid use in chronic non-cancer pain?
- Adverse effects (discussed in another card)
- Risk of diversion
- Tolerance –> withdrawal-mediated pain, escalating dose
- Long term evidence of benefit (>3 months) lacking
Opioid use in osteoarthritis, chronic low back pain, and neuropathic pain. Yay or nay?
Nay. Only unless exhausted all other possible options
When are oral IR opioids used?
Used for acute pain, breakthrough pain, or when initiating someone on chronic therapy
What are the non-oral opioid formulations available? (4)
- Buccal/sublingual
- Suppository
- Transdermal
- Injection
What is the initial dosing for controlled-/extended-release morphine tabs?
How about caps? (both 12h and 24h)
Tab: 10-15mg q12h
Cap (12h): 10mg q12h
Cap (24h): 10mg q24h
What is the inital dosing for oral IR morphine? What is the maximum?
5-10mg q4h prn, maximum 40mg/day
What is the mimumum time interval for dose increase of CR/ER morphine?
How about for IR morphine?
CR/ER: Minimum 2 days. Recommended 14 days
IR: 7 days
Which two opioids are “opiates”?
Morphine and codeine
Morphine is metabolized into two primary compounds (excreted in urine). What are they?
- Morphine-6-glucuronide
- Active analgesic - Morphine-3-glucuronide
- Not active as an analgesic, CNS stimulation
Morphine use should be monitored closely (or avoided) if CrCl <__-__mL/min
20-30
Morphine is the “reference” opioid. Meaning?
Use for conversion factor calculations
The MEQ of codeine is?
0.15
Codeine is a _______. Converted to morphine in the body via CYP___
prodrug; 2D6
What are 2 CIs for codeine?
- ≤12 years old
- ≤ 18 years old post op tonsillectomy and/or adenoidectomy
Codeine antitussive dose is?
≥15mg q4-6h
What is the initial dose of codeine CR?
50mg q12h
What is the initial dose of codeine IR?
15-30mg q4h prn
What is the minimum time interval for increasing a dose in:
Codeine CR
Codeine IR
AND, what is the suggested dose increase?
CR: 2 days - 50mg/day increase
IR: 7 days - 15-30mg/day increase
What is the maximum dose/day of codeine CR?
IR?
CR: 300mg q12h
IR: 600mg/day or acet 4g/d (since often in combo product)
MEQ of oxycodone is?
1.5 (meaning 1.5x more potent)
Oxycodone is metabolized by CYP___ and ___ to active metabolites
3A4 (major); 2D6 (minor)
What is the initial dose of oxycodone CR?
10mg q12h
What is the inital dose of oxycodone IR? What is the maximum?
5-10mg q6h prn, maximum 30mg/day
What is the minimum time interval for increase of oxycodone CR?
IR?
AND, what is the suggested dose increase?
CR: Minimum 2 days. Recommended 14 days - 10mg/day increase
IR: 7 days - 5mg/day increase
Hydromorphone MEQ is?
5 (5x more potent than morphine)
Hydromorphone is a good option if someone requires an opioid in _____ __________
renal impairment
What is the inital dose of hydromorphone CR?
PR?
Should know the max/day for them too.
CR: 3mg q12h. Max 9mg/day
PR: 4mg q24h. Max 8mg/day
What is the initial dose of hydromorphone IR? What is the maximum?
1-2mg q4-6h prn. Maximum 8mg/day
What is the minimum time interval for increasing dose for hydromorphone?
CR
PR
IR
What is the suggested dose increase?
CR: Minimum 2 days - 3 mg/day increase
PR: Minimum 4 days. Recommended 14 days - 4 mg/day increase
IR: 7 days - 1-2mg/day increase
Tapentadol vs. Tramadol. Which is more potent?
Tapentadol (less potent than morphine though)
Fentanyl is much more potent than morphine –> ___x
100x
Fentanyl __mcg/hour patch ≅100mg of oral morphine
25
Fentanyl patch is a good option for what pts? (2)
- For those who cannot take oral medications and who are opioid-tolerant
- Option for pts with renal impairment since no known active metabolites
Fentanyl patch dosing schedule is Q__h
72
Fentanyl patch may not be suitable in the following conditions: (4)
- Diaphoresis (too sweaty for patch to stick)
- Morbid obesity
- Ascites
- Cachexia (wasting of the body)
What are some fentanyl patch counseling points we should touch on? (10)
- Do not apply in front of children
- Remove old patch before applying new patch
- Apply to a clean, dry, non-hairy skin area on the chest, back, flank, or upper-arm
- If required, clip hair as close as possible to the skin
- Do NOT shave the area - Avoid sensitive areas or areas of excessive movement
- Do not use an external source of heat on top of the area while patch is on (e.g., heated blanket/pad)
- When placing patch on skin, hold firmly for at least 30 seconds – if it falls off, discard it and use a new patch on a different site
- If gel from the patch contacts your skin (e.g., hands) during the application procedure, wash with water only and not soap, as soap will increase the absorption of the patch through the skin - Remove the patch after 3 days
- New patch should be applied to a different place on the skin
- When disposing, fold patch in half so sticky sides stick together and dispose in a child-proof container and return to pharmacy for disposal
What is the MOA of methadone (for pain)?
Potent mu opioid receptor agonist and an NMDA (N-methyl-D-aspartate) receptor antagonist
- NMDA mechanisms play a role in prevention of opioid tolerance, potentiation of analgesic effects and neuropathic pain treatment
The observed duration of methadone analgesia is _-__ hours. Usually dosed q_h for pain. Differs from once daily dosing for opiod use disorder
6-12; 8
Caution using methadone in: (3)
- Severe hepatic failure
- Hepatitis
- Concurrent antiretroviral use
Why is methadone useful in renal impairment?
Because inactive metabolites are excreted in the urine and feces
What are 2 risks involved with methadone?
- Risk of QTc prolongation
- Increases risk of serotonin syndrome when combined with serotonergic drugs
What are 3 considerations when switching someone from morphine to methadone?
- Conversion guides refer to the expected final stable methadone dose
- Starting dose should be much lower as the first step of a gradual cross rotation or “start low, go slow” method of initiation, and gradually increased until better pain and function control is achieved
- Extreme caution must be exercised (esp if on high dose of previous opioid)