EXAM 3 Chronic Pain Part I Dr. Thomason Flashcards
Recommendation 1 for opioid use for acute
maximize the use of non-pharmacologic (physical therapy, heat, icing; and non-opioids meds)
when we use opioids, assess the risks and benefits
Recommendation 2 for subacute pain or chronic pain
Nonopiods preferred
-set realistic expectations that the pain is not going to be eliminated by 100%
-may have to adjust the dose
-set goals to reestablish functioning
-may have to d/c if risks outweigh benefits
Which formulation should be used to initiate opioid therapy?
start with immediate release
-for acute, subacute and chronic pain
How should opioid therapy be initiated in opioid-naive patients?
start with the lowest dose
-> to prevent overdose
How should opioids be discontinued?
gradually taper to lower dose -> until d/c
-> to prevent withdrawal
-> patients may even want to take more opioids to relieve withdrawal symptoms
When may an abrupt discontinuation of opioids be considered?
life-threatening situation
-> should NOT d/c abrupt, but taper
use Naloxone?
-signs of overdose:
confusion, sedation, slurred speech
When should patients see their provider after initiating opioid therapy?
within 1-4 weeks to reevaluate de-escalation to non-opioids, dose adjustments
What should be offered to patients using opioids?
Naloxone
How can providers check if patients are receiving opioids from other sources?
using the state prescription drug monitoring program (PDMP)
Which drugs should not be used with opioids?
-CNS depressants: Pregabalin
-Antipsychotics: Seroquel
-Benzos
-> due to the risk of respiratory depression
BBW: don’t use this meds with opioids
Examples of conditions that are treated with NSAIDs
-pain associated with inflammation
-bone pain (broken bone, cancer in the bone)
-Dental
-post-operative pain (after labor)
Which patients should get NSAIDs, who soudlnt, risks
Conditions that can be treated with Antidepressants
-Neuropathic pain (after shingles)
-fibromyalgia
-low-back pain
-headache (migraines) -> TCA
Conditions that can be treated with Anticonvulsants
-Neuropathic pain
-fibromyalgia
What is the drug of choice for trigeminal neuralgia?
Carbamazepine
trigeminal pain is so severe that it has led patients to suicide
Conditions that can be treated with Skeletal muscle relexant
Adjuvant therapy for short-term relief
-> they actually don’t work on the muscles, they are sedative on put patients to sleep and thereby relax muscles
Conditions that can be treated with topical agents
Neuropathic pain and musculoskeletal disorders
-Capsaicin (need to be used for longer time to see the effect)
-Salicylates
How are pure agonists different from other opioids?
no ceiling effect
-> the more you give the higher the analgesic effect, but also the risk of side effects
Which of the opioids are considered opiates?
Codeine and Morphine
the rest are considered synthetic -> opioids
How is Codeine converted in its active form?
CYP 2D6 to Morphine
-> Codeine is not preferred due to metabolic variation (rapid metabolizer (toxicity), slow or non-metabolizer (low analgesic effect)
-> for chronic pain switch to long-acting version
bc in combo products we have a limit with tylenol dosing
How is a partial agonist different from a pure agonist?
ceiling effect for analgesia
-Buprenorphine
-Butorphanol (IV)
-Pentazocine (not seen)
BUT the affinity to the mu receptor is very strong and can kick off other opioids -> so it can cause withdrawal (vomiting, urinating, sweating, pain) in patients who use other opioids
What are the semi-synthetics and synthetics?
Semi:
-Hydrocodone
-Hydromorphone
-Oxycodone
Synthetic:
-Fentanyl -> need a specific test to detect fentanyl
-Methadone
What is the onset of transdermal fentanyl patch?
18-24h onset
-> so it takes time until it works (keep in mind for patients who need immediate pain relief)
-> keep in mind for people who are afraid to touch patches and think they get exposed
Brand name for Hydromorphone
IR: Dilaudid
XR: Exalgo
Hydromorphone is 6x more potent than morphine
NOT in opioid-naive patients
opioid tolerant
60 mg/day PO morphine
30 mg/day PO oxycodone
8 mg/day PO hydromorphone
25mcg/day transdermal fentanyl
25 mg/day PO oxymorphone
if less than that -> opioid-naive
How is Oxycodone metabolized?
active metabolite -> Oxymorphone
Hepatic metabolism
CYP3A4 and 2D6
patients with low enzymes will not benefit from the drug
What may impact the effect of Oxycodone
CYP2D6 inhibitors
-Fluoxetine
-Paroxetine
so they will only get the pain relief from Oxycodone but not from the metabolite Oxymorphone, so net less pain relief
CYP3A4 will prevent the metabolism to Noroxycodone (inactive)
When is fentanyl used?
breakthrough pain in opioid-tolerant
NOT opioid-naive!
Metabolism of fentanyl
CYP3A4
What is the onset of Fentanyl transdermal?
Duragesic
18-24h onset -> use IR for patients with breakthrough pain
if the patch is removed it is still active for 8-16h
Where should the fentanyl transdermal patch be attached?
on an area with fat tissue
bc the drug is released into fat tissue first, then into the blood
->doesn’t work in patients with cachexia or malignancies (lost fat and muscle mass)
What should be avoided when using a transdermal patch?
-cutting/lick/chew
-heat -> cause dose dumping (overdose)
-sauna
-heat lamps (tanning)
-electric blankets
How much should the dose be decreaed to account for incomplete cross-tolerance?
25%
if the patient has acute pain we may reduce by 25%
if the patient had adverse effects, renal or hepatic dysfunction with the first opioid reduce by 50% when converting
How much should the dose be reduced when converting to Methadone?
75%
What is Methadone used for?
-Neuropathic pain
-treating SUD -> it is not allowed to be dispensed for SUD treatment in the pharmacy only for pain
How is Methadone metabolized?
CYP3A4 and CYP2B6, CYP2C19
-> CAUTIOUS: DDI
How is methadone dosed?
for SUD: once a day to keep patients out from craving, also bc it is highly lipophilic (accumulates in adipose tissue and liver)
-> duration gets longer as it accumulates
for pain: needs multiple times a day!
CAUTION: tell patients not to take more frequently than prescribed bc of the danger of accumulation
BBW for Methadone
-respiratory depressant effect occurs later and persists longer
-Qtc prolongation (need regular EKG evaluation) !!!
Which patient population may benefit from Methadone?
-renal impaired (no active metabolites)
-Patients taking too many tablets
-patients who can’t tolerate other opioids
ADE for Methadone
-Respiratory depression
-QT interval prolongation & arrhythmias
-Hypotension
How is Transdermal Buprenorphine different from transdermal fentanyl?
it lasts for 7 days Vs fentanyl with 3 days
Conversion to transdermal Bupenorphine
if the Oral Morphine Equivalent is <30 mg:
go with 5 mcg/hr
if oral Morphien Equivalent is 30-80 mg:
go with 10 mcg/hr
-> may switch to 20 mcg/hr
What is the risk that is associated with transdermal buprenorphine?
Qtc prolongation
What is the risk associated with Tramadol?
combining with antidepressants (serotine syndrome)
-> it is a weak SNRI
-> codeine analog, binds to mu receptor
-used for osteoarthritis, fibromyalgia, neuropathic pain
Which opioids have risks for serotonin syndrome?
Tramadol
Tapentadol -> CAUTION in epilepsy (may cause seizure)
How should the dose of an opioid be increased?
25-50% of the total daily dose
be cautious with increasing at higher doses
What would be the best way to change from IR to ER?
try to use the same drug
Oxycodone IR -> Oxycontin ER
-same total daily dose
Oxycodone IR 30 mg (10 mg 3xd) to
Oxycontin ER 15 mg 2x day (=30mg)
How to dose for breakthrough pain
10-15% of the daily total dose q4-6h
-exception: much less with fentanyl patch and tablets
Opioid CNS side effects
-Sedation
-Hallucination
-euphoria, dysphoria
-Myoclonus (twitching, jerking of muscles)
Opioid GI side effects
-Nausea/vomiting
-Constipation (Lomotil®)
use Stimulant laxatives or stool softener
Opioid Hypersensitivity side effects
-Nausea
-Pruritis (itching)
-> Histamine release
->Natural opioids
Opioid CV and respiratory side effects
CV
-Bradycardia, hypotension
-QTc Prolongation with Methadone, transdermal bupenorphine
respiratory
-Too high bolus dose -> use Naloxone 0.4 mg IV and repeat as needed
To which side effects can patients develop tolerance?
-Sedation
-Nausea/vomiting
-Urinary retention
-Respiratory depression (risk is greatest with first therapy or in combo with antidepressants)
Which of the side effects do not develop tolerance?
-Hallucinations (change opioid)
-Pruritis (change opioid)
-Constipation (scheduled stimulant laxative)
use Methylnaltrexone if refractory (counteracts opioids in the gut)
Opioids to avoid in opioid-naive patients
Hydromorphone
Fentanyl
Physical Dependence is inevitable (no matter what) T/F?
True
it comes with chronic use and abrupt discontinuation
How to monitor for Pain Outcomes
!!!!
4 As
-Analgesia -> how has the pain improved, is the drug working?
-Adverse effects
-Activities (function)
-Aberrant drug-related behavior - is the patient developing a SUD (asking for early refills, urine drug test shows positive for something else, dropped pills in the sink)
When should a patient be tapered off?
Rapid taper
-Early refills despite adequate titrations
-Major adverse effects or intoxication
-Opioid – induced hyperalgesia
-Nonadherence to the treatment agreement
Gradually taper
-functional goals not met
-they are on high dose, Morphine equivalent > 100 mg without benefit
-still having side effects despite rotating opioids
How to taper off
stay with a single long-acting opioid
-reduce by 10% in 1-4 weeks -> until 20% of the original dose remains
-then reduce by 5% until d/c
-rapid taper: 25% decrease every 3-7 days
Opioids metabolized by CYP3A4
Oxycodone -> Oxymorphone
Fentanyl
Methadone
Hepatic glucuronidation of morphine
* Morphine-6-glucuronide (active)
* Morphine-3-glucuronide (inactive)
-> Morphine is not the best choice in renal-impaired patients because the metabolites are excreted really and they would accumulate
Bowel regimen in opioid use
-Sennokot: 2 tabs (17.6 mg) PO BID
-Bisacodyl: 5 – 10 mg PO BID
if refractory:
Methylnaltrexone 8mg or 12 mg (depending on weight)
