Pain management

Question 1

Sulindac [Clinoril]

Answer 1

 Preferred with reduced renal function and in patients on Lithium who require an NSAID

Question 2

Phenanthrenes

Answer 2

• Codeine (Mild to moderate)
• Hydrocodone
• Oxycodone
• Pentazocine
• Butorphanol
• Nalbuphine
• Buprenorphine
• Tramadol
• Tapentadol
• Morphine
• Hydromorphone
• Oxymorphone
• Levorphanol

Question 3

Phenylpiperidines

Answer 3

• Meperidine [Demerol]
• Fentanyl [Duragesic, Sublimaze, others]

Question 4

Diphenylheptane

Answer 4

• Methadone [Dolophine]
  
  •  Avoid dose titrations more frequently than weekly due to unpredictable potency and variable half-life among patients

 Life threatening QTc prolongation (and Torsades de Pointes) have occurred during treatment. ECG should be done at baseline to make sure QTc interval is < 450 ms

 Avoid CYP3A4 inducers and inhibitors

 Effective in severe chronic pain

Question 5

Codeine

Answer 5

• Mild to Moderate Pain
• 15-30 mg PO/IM q 4-6h
• Prodrug -must be converted by CYP2D6 to morphine to produce pain relief (rapid 2D6 metabolizers can have morphine toxicity while poor metabolizers may have no analgesia)
• Take with food to reduce nausea

Question 6

Hydrocodone

Answer 6

• available with combination products with APAP [Norco, Lortab, Vicodin] and ibuprofen [Vicoprofen]; ER [Zohydro, Hysingla ER)
• Black Box Warning: Initiation of CYP3A4 inhibitors (or stopping 3A4 inducers) can lead to fatal overdose
• Ok for Renally impaired

Question 7

Oxycodone

[Roxicodone, OxyContin CR, Xtampza ER];

combination products with APAP [Endocet, Percocet, Roxicet]

Answer 7

 Black Box Warning: Initiation of CYP3A4 inhibitors (or stopping 3A4 inducers) can lead to fatal overdose

 Do not use or decrease dose with renal impairment; if using ER formulation, decrease dose by 1/2 to 1/3

Question 8

abuse-deterrent formulations

Answer 8

• Oxycontin
• Hysingly ER
• Exalgo
• Opana ER
• Xtampza ( opened can administered with soft food or in G tube)

Question 9

Agonist-Antagonist Derivatives

(moderate to severe)

Answer 9

 Increased risk of hypoxemia with underlying respiratory diseases such as COPD, pneumonia, and sleep apnea

 Due to substantial interpatient variability, should underestimate a patient’s 24-hour requirements when converting to or from another opioid

 Caution with using in patients on chronic opioid therapy because antagonist properties may induce symptoms of withdrawal

• Pentazocine (Talwin)
• Butorphanol (stadol)
• Nalbuphine
• Buprenorphine

Question 10

Butrans patch:

Answer 10

• Initial dosing (opioid naïve)
• Butrans patch: apply one patch (5 mcg/hr) once weekly (max 20 mcg/hr)
• Apply to hairless skin on flat surface (upper arm, chest, back, flank) and press in place for 15 seconds;
• Do not apply to same site for at least 3 weeks;
• If patch falls off during the 7-day dosing interval, apply a new patch to a different skin site;
• Avoid exposing patch to external heat sources;
• Dispose of patch by flushing it down the toilet

Question 11

Belbuca film:

Answer 11

• 75 mcg daily or q 12h (max 900 mcg q 12h)
• Insert between gum and cheek; do not eat or drink for 30 minutes after placement

Question 12

Buprenex injection

Answer 12

0.4 mg IV/IM q 6h

Question 13

Ketorolac [Sprix, Toradol]

Answer 13

• COX non-selective NSAID
•  Contraindicated in advanced renal impairment or risk due to volume depletion

 Decrease dose if ≥ 65 yo, < 50 kg, and increased SCr

Boxed Warning: For short-term moderate-severe acute pain only as continuation of IV or IM ketorolac (max combined duration of IV/IM/PO is 5 days in adults)

• Sprix nasal spray: 1 spray in each nostril q 6-8h (if ≥ 65 yo or < 50 kg, then 1 spray in one nostril)

Question 14

Tramadol [Ultram, Conzip]; combination product with APAP [Ultracet]

Answer 14

 If CrCl is < 30 mL/min, reduce dose of IR formulation and do not use ER formulation

 Lower severity of GI side effects compared to strong opioids (but still present)

 Seizure risk – avoid in patients with seizure history or head trauma

 In addition to mu opioid receptor agonist properties, tramadol also inhibits the reuptake of serotonin and norepinephrine – risk of serotonin syndrome when mixed with other serotonergic agents

 Prodrug -requires conversion to active metabolite by CYP2D6 – variable effects seen when used in patients who are slow or fast 2D6 metabolizers and when 2D6 inhibitors or inducers are used concomitantly (similar to codeine)

Question 15

Tapentadol [Nucynta, Nucynta ER]

Answer 15

 If CrCl < 30 mL/min, use is not recommended

 Lower severity of GI side effects compared to strong opioids (but still present)

 Seizure risk – avoid in patients with seizure history or head trauma

Question 16

(TIRF REMS) ACCESS Program

Answer 16

• Transmucosal Fentanyl (Abstral(R), Actiq(R), Fentora(R), Onsolis(R)), Lazanda(R))
• restricted distribution program called the Transmucosal Immediate-Release Fentanyl Risk Evaluation and Mitigation Strategy
• All ER and long-acting opioids are part of a Risk Evaluation and Mitigation Strategy (REMS) Program as of July 2012

Question 17

Morphine [MS Contin, Kadian, Roxanol, Avinza]

Answer 17

 Drug of choice in severe pain

 Do not crush or chew ER/CR formulations, but Kadian or Avinza capsules can be opened and sprinkled on applesauce or soft food; Avinza can also be put down a G-tube

 Avoid if CrCl < 30 mL/min

 Produces vein and artery dilation which can cause hypotension

Question 18

Hydromorphone [Dilaudid, Exalgo ER]

Answer 18

 Potent opioid – start at low dose and convert carefully to reduce overdose risk

 Exalgo is an ER abuse-deterrent formulation

 May cause less pruritus compared to other phenanthrenes

• Initial dosing (opioid naïve) PO: 2-4 mg q 4-6 h
• ER: Available at 8 mg, 16 mg, 12 mg, or 32 mg tablets; if switching from hydromorphone IR, use total daily dose and give daily; if switching from any other opioid, calculate total daily dose in hydromorphone IR and initiate Exalgo with half the dose (see below for more information)
• IM: 1-2 mg q 2-3h
• IV: 0.2-1 mg q 2-3h
• PR: 3 mg q 6-8h

Question 19

Oxymorphone [Opana, Opana ER]

Answer 19

• Initial dosing (opioid naïve)
• IR: 5-10 mg PO q 4-6h
• ER: 5 mg PO q 12h
• IV: 0.5 mg q 4-6h

 Take on ER on empty stomach (1 hr before or 2 hrs after eating)

 Do not use with moderate-to-severe liver impairment and use only low doses in elderly or with renal or mild liver impairment

Question 20

Meperidine [Demerol]

Answer 20

50-150 mg PO/IM q 3-4h

 Short duration of action (pain controlled for max of 3 hours)

 Risk for CNS toxicity including seizures with elderly and renal impairment (normeperidine metabolite is renally cleared and can accumulate- do not use with renal failure)

 Because of above 2 bullet points, it is only used short-term or for single use (not often used)

Question 21

Fentanyl [Duragesic, Sublimaze, others]

Answer 21

 Apply to hairless skin on flat surface (chest, back, flank) and press in place for 30 seconds

 Analgesic effect seen within 8-16 hours after application – do not immediately stop other opioid analgesic (just decrease dose by 50% for first 12 hours)

 Do not expose patch to heat and remove prior to MRI

 Do not use soap, alcohol, or other solvents to remove transdermal gel, only large amounts of water

 Dispose of patch in toilet

 Transmucosal preparations of Fentanyl [sublingual (SL)] should only be used in the management of breakthrough pain in cancer patients already requiring around-the-clock opioid therapy for their underlying, persistent cancer pain and should not be and should not be used in patients who are opioid-non-tolerant

Question 22

Methadone [Dolophine]

Answer 22

 Avoid dose titrations more frequently than weekly due to unpredictable potency and variable half-life among patients

 Life threatening QTc prolongation (and Torsades de Pointes) have occurred during treatment. ECG should be done at baseline to make sure QTc interval is < 450 ms

 Avoid CYP3A4 inducers and inhibitors

 Effective in severe chronic pain

Question 23

Antispasticity agents

Answer 23

• work on the spinal cord or directly on the skeletal muscles to improve muscle hypertonicity and involuntary spasms.
• Spasticity is defined as the increased muscle tone or stiffness that leads to undesirable and uncontrolled movements.
• These medications are used for spastic conditions such as cerebral palsy, multiple sclerosis, and spinal cord injuries
• Baclofen [Lioresal] ; Tizanidine [Zanaflex] Diazepam [Valium]

Question 24

Antispasmodics

Answer 24

• decrease muscle spasms through alterations of CNS conduction
• divided into benzodiazepines, which inhibit transmission on the postsynaptic GABA neurons, and nonbenzodiazepine agents, which act at the brain stem and spinal cord.

Question 25

muscle relaxants

Answer 25

• may cause excessive sedation, dizziness, and confusion, so caution should be used with activities requiring mental alertness.
• Patients should avoid alcohol, sleeping medications, antihistamines, and other sedatives while taking muscle relaxants

Question 26

Baclofen [Lioresal]

Answer 26

• Antispasticity agent with analgesic properties
• 5-20 mg PO TID-QID prn
• May be administered intrathecally for severe spasticity

Question 27

Tizanidine [Zanaflex]

Answer 27

• Antispastic + Antispasmodic with analgesic properties
• Central alpha 2 agonist so may cause hypotension, dry mouth, QT prolongation

Question 28

Diazepam [Valium]

Answer 28

• 2-10 mg PO q 6-8h prn
• Antispastic + Antispasmodic with analgesic properties
• Reduce dose by half if significant hepatic impairment
• Benzodiazepine – controlled substance due to risk of misuse/ dependence

Question 29

Cyclobenzaprine [Flexeril]

Answer 29

 May cause dry mouth

 Serotonergic agent – caution for serotonin syndrome if combined with other serotonergic agents

 May precipitate or exacerbate cardiac arrhythmias – caution in elderly and those with heart disease

Question 30

Carisprodol [Soma]

Answer 30

Antispasmodics which exert effects primarily through sedation (no analgesic effect)

 Controlled substance due to dependence, withdrawal symptoms, and diversion/misuse potential

 Poor and rapid CYP2C19 metabolizers may have increased sedation due to increased carisoprodol plasma levels (poor metabolizer) or increased metabolite levels (fast metabolizer)

Question 31

Metaxalone [Skelaxin]

Answer 31

Antispasmodics which exert effects primarily through sedation (no analgesic effect)

 Hepatotoxic – monitor hepatic function

Question 32

Methocarbamol [Robaxin]

Answer 32

• Antispasmodics which exert effects primarily through sedation (no analgesic effect)
• Hypotension – monitor BP

Question 33

Capsaicin 0.025% and 0.075% Cream

Answer 33

Apply to affected area TID or QID (gently rub in until fully absorbed)

 Causes topical burning which dissipates with continued use

 Best results typically after 2-4 weeks of continuous use

 DO NOT apply prn or it will not work

 Wash hands immediately after application, unless using to treat hands then wait 30 minutes before washing hands

 Do not touch eyes, mouth, nose, or genitals as it will burn sensitive skin

 Do not cover with bandages or external heating sources

Question 34

Diclofenac [Voltaren gel, Flector patch]

Answer 34

Flector patch: apply 1 patch (180 mg) to most painful area BID

Voltaren gel: Apply 2 grams (for hands, wrists, or elbows) or 4 grams (for feet, ankles, or knees) topically QID

 For Flector patch: remove if bathing/showering and for MRIs

 For Voltaren gel: patients should use the dosing card to correctly measure out 2 or 4 g; Apply the gel to clean, dry skin without cuts or open wounds and do not shower or wash treated areas for at least 1 hour after application

Question 35

Methyl salicylate topical OTCs [BenGay, Icy Hot, SalonPas]

Answer 35

Apply prn for pain – varies among products

 Do not apply over wounds or damaged skin

 Do not cover with bandages or external heating sources

Question 36

peripherally-acting mu opioid receptor antagonists (PAMORAs)

Answer 36

• block opioid receptors in the gut to reduce constipation without affecting analgesia. PAMORA options include the following :
  
  • Methylnaltrexone (Relistor)
  • Naloxegol (Movantik)
  • Almovapan (Entereg)

Question 37

Methylnaltrexone (Relistor)

Answer 37

o Dosing: OIC with chronic non-cancer pain – 12 mg SC daily or 450 mg PO daily; OIC with advanced illness – weight-based dose SC every other day; if CrCl < 30 mL/min, reduce dose

o Contraindicated with GI obstruction

o Warnings: Risk of GI perforation (rare, but monitor for severe abdominal symptoms), risk of opioid withdrawal

o Notes: Discontinue if opioid is discontinued; administer SC in upper arm, abdomen, or thigh; stop all laxatives prior to use; stay close to toilet after injecting SC

Question 38

Naloxegol (Movantik)

Answer 38

o Dosing: 25 mg PO once daily in the morning on an empty stomach; if CrCl < 60 mL/min, reduce dose to 12.5 mg daily

o Contraindicated with GI obstruction and strong CYP3A4 inhibitors

o Warnings: Risk of GI perforation (rare, but monitor for severe abdominal symptoms), risk of opioid withdrawal

o Notes: Discontinue if opioid is discontinued; stop all laxatives prior to use; do not use with strong CYP3A4 inhibitors (most protease inhibitors, itraconazole, ketoconazole, clarithromycin, telithromycin) and avoid or reduce dose to 12.5 mg with moderate CYP3A4 inhibitors (protease inhibitors, fluconazole, miconazole, diltiazem, verapamil, grapefruit juice, amiodarone, erythromycin)

Question 39

Almovapan (Entereg)

Answer 39

o Dosing: 12 mg PO daily or BID; not recommended with severe hepatic impairment or end stage renal disease

o Contraindicated with GI obstruction

o Warnings: Risk of GI perforation (rare, but monitor for severe abdominal symptoms), risk of opioid withdrawal; increased incidence of myocardial infarction with prolonged use (do not use more than 15 doses)

o Notes: Discontinue if opioid is discontinued; stop all laxatives prior to use

Question 40

Lubiprostone (Amitiza)

Answer 40

• can also be used for OIC.
• It belongs to a class of drugs known as chloride channel activators and works by increasing the amount of fluid within the intestines, making the passage of stool easier.
• dosed 24 mcg PO BID
• contraindicated with a GI obstruction.

Question 41

Overdose (Opioid)

Answer 41

• CNS depressants (i.e. alcohol and benzodiazepines) amplify CNS depression when used with opioid analgesics and use of these combinations should be discouraged when possible.
• When the combinations are used, patients should be monitored closely for respiratory depression.
• Additional risks for respiratory depression and overdose death include underlying respiratory diseases such as COPD, pneumonia, and sleep apnea; reduced clearance of opioid due to renal or hepatic disease or older age; high doses or a cumulative stacking effect from frequent dosing.
• Signs and symptoms of opioid overdose include excessive somnolence, respiratory depression or shallowed breathing, constricted (pin point) pupils, and cold or clammy skin.

Question 42

naloxone

Answer 42

• It is an opioid antagonist and replaces opioid on the m receptor
• Dosing: 0.4-2 mg IV/IM/SC q 2-3 minutes or 2-4 mg intranasally q 2-3 minutes; Repeat dosing may be required especially if a long-acting opioid contributed to overdose

 If naloxone is being used to reverse opiate side effects in a patient still requiring analgesia, it should be diluted and titrated (dose 0.1-0.2 mg q 2-3 minutes) to prevent reversal of the analgesia

o Notes: Naloxone will cause acute withdrawal symptoms potentially including pain, anxiety, diaphoresis, tachycardia, or tachypnea

Question 43

Acetaminophen (APAP) [Tylenol, Ofirmev]

Answer 43

 Reduces pain and fever, but does NOT reduce inflammation

 May cause severe hepatotoxicity with excessive intake (MAX 4000 mg/day); Make sure to account for all sources of APAP when calculating daily dose

 Avoid or limit alcohol use due to the risk of hepatotoxicity

 Commonly given with opioid analgesics to reduce the amount of opioid needed

Question 44

• Aspirin/ Acetylsalicylic acid (ASA) [Ecotrin, Durlaza]
• Diflunisal [Dolobid]
• Ibuprofen [Motrin, Advil, Caldolor IV]
• Naproxen [Naprosyn, Anaprox]; Naproxen sodium [Aleve]
• Celecoxib [Celebrex] - COX 2
• Meloxicam [Mobic, Vivodex] – COX 2

Answer 44

 Reduce pain, fever, and inflammation

 GI risk including bleeding, ulceration, and perforation (check for dark, tarry stool, stomach upset, and coffee ground emesis) – Risk is lower with COX-2 selective NSAIDs, but still present

 Take with food or use EC/buffered product to reduce nausea

 Caution for additive bleeding risk when taken concomitantly with other agents that increase bleeding risk

 All non-aspirin NSAIDs increase risk of serious thrombotic events (myocardial infarction and stroke) – Risk is higher with COX-2 Selective, avoid with cardiovascular disease risk, high doses, and long durations

 NSAIDs should not be used during pregnancy

 May be given with opioid analgesics to reduce the amount of opioid needed

Question 45

Acute Pain Algorithm

Mild-Moderate Pain (1-3)

Answer 45

• APAP +/or NSAIDs ( if no renal or hepatic failure)
• Titrate to max dose
• Recognize side effects of all analgesics prescribed and taking OTC; Use the most effective analgesic with the fewest side effects

Question 46

Acute Pain Algorithm

Moderate to Severe Pain

Answer 46

• Opioid + APAP /or NSAIDs
• may use NSAID ATC + opioid (prn) when risk does not outweigh benefits
• Use as needed (prn) regimens for breakthrough pain or when pain displays great variability (i.e. only hurts in the morning after waking) or has greatly subsided (i.e. some days are better than others)

 If the opioid medication is effective but the effects wear off too quickly, do not increase the dose because this will put the patient at risk for respiratory depression; instead, decrease the dosing interval (i.e. decrease from 6 hours to 4 hours).

Question 47

Algorithm for Acute Pain

Severe Pain (Score of 8-10 out of 10)

Answer 47

• Opioids ( may use ER and IR for breakthrough pain)
• Prn for BTP
• If the opioid medication is effective but the effects wear off too quickly, do not increase the dose because this will put the patient at risk for respiratory depression; instead, decrease the dosing interval (i.e. decrease from 6 hours to 4 hours).
• Properly titrate (assess and re-assess) the dose and chosen medications for each individual patient
• Use the oral route whenever possible

Question 48

Algorithm for Chronic Pain

Answer 48

• patient goals often include an increase in functionality rather than complete pain control (low pain rather than no pain).
• Opioids should not be considered first-line for chronic pain
• Immediate release opioids should be used first with the lowest effective dose and slow titration. patient should be tapered off the opioid to prevent withdrawal sypmtoms
• Benzodiazepines, GABAergic agents (gabapentin, pregabalin), and alcohol should be avoided when a patient is prescribed an opioid, especially if they are elderly.
• Adjunctive medications such as acetaminophen, NSAIDs, and neuropathic pain agents (TCAs, SNRIs, anticonvulsants) should be used as appropriate to reduce the opioid dose needed.

Question 49

chronic low-back pain

Answer 49

1. exercise, multidisciplinary rehabilitation, acupuncture, mindfulness-based stress reduction, tai chi, yoga, motor control exercise, progressive relaxation, biofeedback, low-level laser therapy, cognitive behavioral therapy, or spinal manipulation ⇒ should be used initially for most patients who have chronic low back pain.
2. For patients who do not respond to nonpharmacologic therapy, NSAIDs should be used.
3. Tramadol or duloxetine (SNRI) should be considered for those patients who do not respond to or do not tolerate NSAIDs.
4. Opioids should only be considered if other treatments are unsuccessful and when the potential benefits outweigh the risks for an individual patient.

Question 50

Algorithm for Pain Management in Oncology Patients

Mild-Moderate Pain (Score of 1-3 out of 10)

Answer 50

1. APAP and/or NSAID when risk does not outweigh benefits
2. If cannot tolerate GI effects with NSAID, take with food/milk/antacid or switch to APAP (unless bone pain is present)
3. If oral route not available, use APAP suppository

Question 51

Algorithm for Pain Management in Oncology Patients

Moderate-Severe Pain

Answer 51

1. Combination of opioid plus APAP or NSAID
2. Adjunct options: tricyclic antidepressant (amitriptyline or imipramine), anticonvulsant (gabapentin), or radiation/radiopharmaceutical (only for bone pain)
3. If cannot tolerate GI effects of opioid or NSAID, take with food/milk/antacid or switch NSAID to APAP (unless bone pain is present)
4. Dose to the maximum of each agent (if possible) before switching to the next step, unless pain is completely out of control

 If pain is constant or recurring, around the clock (ATC) dosing should be used

Question 52

Algorithm for Pain Management in Oncology Patients

Severe Pain

Answer 52

1. Morphine is a common choice
2. if myoclonic jerking occurs, try an opioid from another class
3. Opioid dosing should be around the clock (ATC) at this point with a constant ER formulation and IR formulation prn for breakthrough pain
4. A fentanyl patch placed q 72h may provide a more convenient dosing regimen when patient is on a stable oral dose
5. Adjunct options: tricyclic antidepressant (amitriptyline or imipramine) or anticonvulsant (gabapentin)

Question 53

Steps for converting from one opioid to another (except fentanyl patch):

Answer 53

(1) You must first calculate the total daily dose of opioids (or the total amount of opioid taken in 24 hours).
(2) Next, use the below table to convert from one opioid to another. Make sure the units and routes of administration match.
(3) This conversion will give you the new 24 hour dose.
(4) Reduce the new total daily dose by 25% to minimize the risk of overdose from converting to a new opioid with different properties.

o If switching to morphine and the patient has renal insufficiency, there should be a 50% reduction in the total daily dose due to morphine’s active metabolite that is renally cleared.

o If switching to hydromorphone, there should be a 50% reduction in the total daily dose due to hydromorphone’s higher potency

(5) Finally, divide the new daily dose to attain an appropriate interval for the new medication (i.e. is this a daily medication or dosed q4h?).

Question 54

Converting to Fentanyl Patch

Answer 54

1. first find the total daily dose in mg and then convert to mcg (multiply by 1,000).
2. divide by 24 to get the dose of fentanyl per hour (which is how the patch dose is supplied).