1. Providing Patient-Centered Analgesia
Scott Strassels, PharmD, PhD
Optum West Region Clinical Pharmacist
November 8, 2016

2. Disclosure
I have no relevant financial relationships with manufacturers of any commercial products and/or providers of commercial services discussed in this presentation.
This discussion will include the use of medications for off-label indications.

3. Acknowledgments Dan Carr, MD Dermot Fitzgibbon, MD
Optum Hospice Pharmacy Services team
Jillian Baer, PharmD, BCPS
Piper Black, PharmD, BCPS
Brandon Copeland, PharmD, BCPS
Christopher DiTomaso, PharmD
Natasha Jordan
Mike Lux, PharmD
Brian Monson, PharmD
Shannon Simpson
Amanda Weiland, PharmD, CGP
Sean Sullivan, PhD

4. Questions?
Scott Strassels
(224)

5. Objectives
After this presentation, participants will:
Understand important domains for assessing pain
Be able to choose an analgesic based on the type and severity of the patient’s pain
Understand roles of pharmacists in pain and palliative care practice

6. Lorraine and Ralph… Clinical issues Age: 66 years old
Part 1: Sources of pain
History of fibromyalgia, osteoarthritis
Cancer
Surgical repair of hip fracture
Part 2: Pharmacy/Rehab
Medications:
Opioid: oxycodone
Antiemetic: ondansetron (Zofran)
Antidepressant: duloxetine (Cymbalta)
NSAID: naproxen sodium (Aleve, Anaprox)
No bowel movement for 4 days
Patient thought laxatives were to be used “as needed”, not every day
Dry mouth
Adherence, persistence:
Hesitation to use opioids
Treating the family, not just the patient
Understanding of how to use medications
Clinical issues
Age: 66 years old
Renal and hepatic function not known
Major comorbidities are present
Risk of addiction?
Matching treatment to type of pain
Nociceptive
Tumor-related
Hip fracture
Postoperative
Osteoarthritis
Neuropathic
Tumor- and chemotherapy-related
Fibromyalgia

7. Assessing Pain

8. Numeric Rating Scale
Person rates their pain on a 0-10, , or scale, where 0 = no pain, and 10, 20, or 100 = worst pain imaginable
NRS and VAS measure pain similarly, but NRS is easier for some people and clinicians
Often categorized, but cutpoints may vary
0 = none
1-3 or 1-4 = mild
4-6 or 5-7 = moderate
7-10 or 8-10 = severe
Importance is to translate report of severe or unexpected pain to action

9. OLD CARTS
Onset
What was the initial aggravating factor?
Location
Etiology
Association with underlying disease
Diagnostic tests
Duration
How long are episodes?
How long has the pain been present?
Characteristics
Aggravating Factors
Relieving Factors
Temporal variation
During day
Breakthrough pain
Severity/Intensity
Functional status
Presence or risk of substance abuse disorder

10. Wong-Baker Faces Scale

11. Really Revised Faces Scale
9/20/2018

12. Really Revised Faces Scale
0:  Hi.  I am not experiencing any pain at all.  I don't know why I'm even here.
1:  I am completely unsure whether I am experiencing pain or itching or maybe I just have a bad taste in my mouth.
2:  I probably just need a Band Aid.
3:  This is distressing.  I don't want this to be happening to me at all. 4:
5:  Why is this happening to me??
6:  Ow.  Okay, my pain is super legit now
7:  I see [deity of your choice] coming for me and I'm scared.
8:  I am experiencing a disturbing amount of pain.  I might actually be dying.  Please help.
9:  I am almost definitely dying.
10:  I am actively being mauled by a bear.
11: Blood is going to explode out of my face at any moment

13. Really Revised Faces Scale
TSFN: You probably have Ebola. It appears that you may also be suffering from pinkeye.
Or 11: Afraid you’ll die from the pain
TSFN: Afraid you won’t die from the pain
9/20/2018

14. What is Lorraine’s risk of developing a substance abuse disorder?
A. None
B. Low
C. Moderate
D. High
E. I’m more worried about Ralph

15. Types of pain

16. Types of pain
Acute, chronic
Nociceptive
Somatic, Visceral
Neuropathic

17. Acute pain
Generally of recent duration, though not always
Often after injury or surgery
Typically limited duration
Tends to decrease with time

18. Chronic pain
Lasts for an undefined period
Longer than expected for injury to heal
Cellular & biochemical changes seen with chronic pain arise soon after an injury
Acute & chronic pain are points on the same continuum, rather than distinct phenomena
May be somatic, neuropathic, or both
Acute & chronic pain may also overlap
Arthritis (chronic) plus postoperative (acute)
Acute exacerbations of chronic pain disorders (overdoing it, etc)
Treatment duration is not determined by type of pain!

19. Chronic pain
“Not ordinary pain that endures, but a different condition, in the same way that an alcoholic’s drinking differs from that of a social drinker. It is not the duration of pain that characterizes chronic pain, but the inability of the body to restore normal functioning.” Thernstrom M. The Pain Chronicles (2010)

20. Nociceptive pain
Further described as
Somatic
Visceral
Somatic pain arises from body structures:
Skin, bones, joints, muscle, connective tissue
Is generally specifically located
Visceral pain arises from internal body structures
Is more generally located than somatic pain
Descriptors include:
Cramping, deep aching, and terms used for somatic pain

21. Neuropathic pain
Results from nerve lesions or other nervous-system dysfunction
Includes central & peripheral pain
Central: deafferentation (phantom pain), sympathetically-maintained processes, post-stroke
Peripheral: may result from poly- or mononeuropathies

22. Cancer pain
~75% from direct effect of neoplasm
Also from therapies to manage disease or unrelated issues
Nociceptive pain syndromes
Neoplastic invasion of bone, joint, muscle, connective tissue
Result is persistent somatic pain
Bone syndromes are most common, but not all are painful
Neuropathic pain syndromes
Infiltration or compression of nerve, plexus, roots
Remote effects of malignant disease on peripheral nerves
Syndromes are highly variable

23. Cancer pain
Post-treatment pain syndromes (most are neuropathic)
Postsurgical: syndromes after mastectomy, thoracotomy, radical neck dissection, nephrectomy, stump/phantom pain
Postchemotherapy: polyneuropathies (Taxanes)
Postradiotherapy: fibrosis
Nociceptive pain due to chemotherapy, radiation, or surgery is thought to be rare

24. What kind of pain is Lorraine’s biggest problem?
A. Nociceptive
B. Neuropathic
C. Cancer-related
D. We can’t tell without more information
E. It’s all equally bad.

25. Pharmacotherapy

26. Basic concepts
By mouth when possible
If injection is needed, not IM. Absorption is erratic and it hurts.
By the ladder
By the clock
For the individual, with attention to detail
Also, please look out for:
Multiple short-acting opioids (such as hydrocodone/apap and morphine oral concentrate)
Multiple long-acting opioids (such as methadone and MS ER or oxycodone ER)

27. WHO 3-step analgesic ladder
9/20/2018

28. What step is Lorraine on?
B. 2
C. 3

29. Step 1: Acetaminophen & NSAIDs

30. Acetaminophen (APAP, N-acetyl-para-aminophenol)
9/20/2018
Acetaminophen (APAP, N-acetyl-para-aminophenol)
Commonly used for mild pain, or in combination
Doesn’t affect platelet aggregation or inflammation
Often used first line for osteoarthritis
Role is incompletely understood
Ineffective for acute low back pain, unclear if effective for chronic back pain (Saragiotto et al 2016)
Daily dose limits: 3 g/day for healthy persons, less for persons with history of EtOH abuse, hepatitis, limited renal function
Lower dose limits are under debate (2 – 3 g/day in general)
APAP dosing recommendation--Anesthesiology 8/97, kinetics paper

31. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Widely used in US; highly effective
Also responsible for significant morbidity & mortality
Used alone for mild to moderate pain; drugs of choice for some types of bone pain
Opioid-sparing effect
Nonspecific COX vs. COX-2 specific inhibitor
Not used with corticosteroids

32. NSAIDs: Available agents
Celecoxib (Celebrex)
Diclofenac Sodium Delayed Release (Voltaren)
Diflunisal (Dolobid)
Etodolac (Lodine)
Fenoprofen (Nalfon)
Flurbiprofen (Ansaid)
Ibuprofen (Motrin, Advil, Nuprin)
Indomethacin (Indocin)
Ketoprofen (Orudis)
Ketorolac (Toradol)
Meclofenamate (Meclomen)
Meloxicam (Mobic)
Nabumetone (Relafen)
Naproxen (Naprosyn, Anaprox, Aleve)
Oxaprozin (Daypro)
Piroxicam (Feldene)
Sulindac (Clinoril)
Tolmetin (Tolectin)

33. Steps 2 and 3: Opioids

34. We’re off to see the Wizard!
9/20/2018
9/20/2018
9/20/2018 34 34

35. Where do we get Morphine?
Although morphine has been synthesized from scratch, the route is not cost efficient.
Opium is isolated from the latex from the poppy plant (Papaver somniferum).
Contains 10-15% morphine, 3-4% codeine, 0.1-2% thebane. Related drugs are also synthesized using natural products as starting materials.
In 2000, illicit production of enough opium concentrate to make 470 tons of heroin.
In general, plants are the source of approx. 25% of currently used pharmaceuticals.
PR Blakemore, JD White 2002 Chem Comm

36. “Opioid”, not “narcotic”
Opioids
“Opioid”, not “narcotic”
Cornerstone of treatment for moderate to severe pain
Often categorized by receptor activity, chemical structure
Receptors: mu, kappa, delta (many subtypes, too)
Agonists at each receptor produce analgesia
Kappa agonists were designed to produce less respiratory depression and have lower abuse potential, but adverse-effect profile is similar to mu agonists at equianalgesic doses
Kappa agonists and Mu antagonist/Kappa agonists have limited analgesic activity and clinical ceilings
May cause withdrawal in physically dependent patients
9/20/2018

37. Opioid structure
Phenanthrenes: codeine, hydrocodone, hydromorphone, morphine, oxycodone, oxymorphone
Phenylpiperidines: alfentanil, fentanyl, meperidine, remifentanil, sufentanil
Diphenylheptane: methadone
Phenylpropylamines: tapentadol, tramadol
In clinical practice, patients who are allergic to a phenanthrene are generally given methadone or fentanyl (cautiously)
9/20/2018

38. In general, mu agonists have similar ability to provide pain relief
Opioids
In general, mu agonists have similar ability to provide pain relief
Some important exceptions
Codeine, meperidine
Consider side effects, pharmacokinetics, pharmacodynamics
In dose range typically used, dose-response relation is consistent
As long as person is responding and side effects are manageable, dose can be increased if needed
9/20/2018

39. Morphine is the prototype, but
Opioid choice
Morphine is the prototype, but
Preference, experience, and adverse effects may also be important effects
~1:5 will have nausea or itching on a particular drug
Individual response is difficult to predict
9/20/2018

40. Lorraine reports itching with oxycodone. What do you do?
A. Change to morphine
B. Add an antihistamine, like diphenhydramine
C. Change to a fentanyl patch
D. Change to methadone
E. None of the above

41. Opioids by Receptor Type
Mu agonists
Kappa agonist/
Mu antagonists
Alfentanil
Opium
Buprenorphine (partial agonist)
Nalmefene
Codeine
Oxycodone
Butorphanol
Naloxone
Fentanyl
Oxymorphone
Nalbuphine
Naltrexone
Hydrocodone
Remifentanil
Pentazocine
Hydromorphone
Sufentanil
Levorphanol
Tapentadol
Meperidine
Tramadol
Methadone
Morphine

42. Active Opioid Metabolites
Major Metabolites
Major enzymes involved
Morphine
Morphine-3-Glucuronide,
Morphine-6-Glucuronide
UGT2B7
Hydromorphone
Hydromorphone-6-Glucuronide
UGT1A3
Oxycodone
Noroxycodone, Oxymorphone
3A4, 2D6
Codeine
Codeine-6-Glucuronide, Morphine,
Norcodeine
UGT2B7, 2D6, 3A4
Hydrocodone
Norhydrocodone, Hydromorphone
Oxymorphone
6-OH-Oxymorphone
Uncertain
Meperidine
Normeperidine
3A4, 2B6, 2C19
Buprenorphine
Norbuprenorphine
3A4
Tramadol
O-Desmethyl Tramadol (M1)
2D6
Smith HS. CJP 2011

43. Clinical Pearls for Select Opioids

44. Buprenorphine
Partial mu agonist, can antagonize full mu agonists
Has limited intrinsic activity, but high receptor affinity (dissociation half- life = 166 min vs. 7 min for fentanyl)
25-50 times more potent than morphine (0.4 mg B = ~10 mg morphine IM)

45. ~1/10 of dose is converted to morphine
Codeine
~1/10 of dose is converted to morphine
Some people lack the enzyme for conversion (CYP 2D6)
Bioavailability ~ %
30 mg codeine ~1 - 4 mg morphine
Extensive metabolizers make more morphine, slow metabolizers make less
Deaths in nursing infants have been reported
When codeine used by extensive metabolizer mothers
9/20/2018

46. Fentanyl transdermal system
~100x more potent than morphine (10 mcg fentanyl ~ 1 mg morphine), but varies by route of administration
Fentanyl transdermal system
Takes ~12 hours to build subcutaneous depot
Serum concentrations fall by 50% ~17 hours after removing patch
DO NOT CUT
Dosing effects of transdermal fentanyl are often misunderstood by both clinicians and patients
Only clinicians who are familiar with the dosing and absorption properties of transdermal fentanyl and are prepared to educate their patients about its use should consider prescribing it.
9/20/2018

47. Fentanyl Transdermal System
Typically changed every 72 hours
Some patients have end of dose failure after 48 hours (check need for increased dose, too)
Absorption from patch is increased across irritated skin (shaving) and with heat (hot tubs, heating pads, saunas, and so on)
Don’t use soaps, oils, lotions that could irritate skin
Concomitant use with 3A4 inhibitors (erythromycin, clarithromycin, telithromycin, fluoxetine, fluconazole, ketoconazole, itraconazole, protease inhibitors, for example) may result in increased fentanyl concentrations
DO NOT USE in opioid-naïve persons, in individuals whose analgesic need is not stable, and people who can take oral medications
9/20/2018

48. I prescribe transmucosal or iontophoretic fentanyl (Abstral, Actiq, Fentora, Ionsys, Onsolis, Lazanda, Subsys) in my practice
A. No
B. Yes

49. Diacetylmorphine (DAM) or diamorphine
Fun Fact: Heroin
Diacetylmorphine (DAM) or diamorphine
First synthesized in 1874, marketed by Bayer as a non-addictive morphine substitute, cough suppressant, and cure for morphine addiction (before discovering it is metabolized to morphine!)
Rapidly hydrolyzed to 6-monoacetylmorphine (6-MAM), then to morphine
DAM & 6-MAM are more lipid-soluble than morphine, so they enter the brain more readily
Available in other countries (Canada, UK), but is a C-I drug here
9/20/2018

50. Metabolized by CYP 2D6 to hydromorphone (4%) and others
Hydrocodone
Equipotency is not well understood, but is thought to be similar to morphine
Metabolized by CYP 2D6 to hydromorphone (4%) and others
Commonly used in combination with acetaminophen
Watch acetaminophen content
9/20/2018

51. Methadone Analgesic half-life ~8-12 hours
Elimination half-life ~35 ± 22 hours
Risk of toxicity due to accumulation
Dose change every 5 days
Methadone should not be the first choice for an ER/LA opioid.
Only clinicians who are familiar with methadone’s unique risk profile and who are prepared to educate and closely monitor their patients, including risk assessment for QT prolongation and consideration of electrocardiographic monitoring, should consider prescribing methadone for pain (CDC 2016).
9/20/2018

52. I am comfortable prescribing/monitoring methadone
A. Yes
B. No
C. Are you nuts?

53. Effective analgesic, especially when other opioids have failed
Benefits of Methadone
Effective analgesic, especially when other opioids have failed
Unique pharmacological properties
Most effective opioid for neuropathic pain
Decreased incidence of tolerance
Beneficial for neurotoxicity
Structurally different than other opioids
No toxic metabolites
Safe in renal and hepatic impairment
Methadone also has a multitude of benefits. As we discussed earlier, it’s unique mechanism of action allows methadone to be very effective in neuropathic pain, as well as neurotoxicity. It has a reduced incidence of tolerance, does not have a toxic metabolite and is safe for use in renal and hepatic dysfunction. In severe cases of hepatic or renal failure, CrCl <10, the dose of methadone might need to be reduced, but it is generally considered safe in these patients. While methadone dose have potential for your typical opioid side effects, the incidence is generally decreased compared to other opioids, even nausea and constipation. Making methadone a good option in someone having dose limiting side effects from other opioids.
It is available generically and is very inexpensive.
Multiple dosage forms are available that all maintain its long acting effects. It has a solution, tablet and injectable form. Methadone is the only long-acting opioid that can be crushed and still maintain its long duration of action. This allows for SL administration using the tablet. The liquid could also be used SL or rectally depending on the volume. And the tablets can be used rectally as well.
Even though it is long acting, methadone can still be used as your prn agent for breakthrough pain as well. This allows for one agent for pain relief in the home and less risk of confusion between the agents. And it allows less frequent administration than other short acting opioids, with q4h prn dosing.

54. Methadone Dosage Forms
Strengths
Comments
Solution, oral
5 mg/mL
10 mg/5 mL
10 mg/mL
May contain sodium benzoate or propylene glycol
Intensol contains 8% EtOH
Tablets
5 mg
10 mg
Tablet, dispersible
40 mg
Not approved in pain management
Injection
Methadone is available in numerous long acting dosage forms. This is particularly important in the pediatric setting. Methadone is available in 3 concentrations of oral liquid. So, you can easily choose the concentration that allows for measurable doses, as well as decreased volume for your patient. However, the solutions may contain sodium benzoate or propylene glycol, so this content must be monitored when used in the neonatal setting. Also, the intensol product (10 mg/mL) contains 8% alcohol, but is sugar free.
It is also the only tablet that can be crushed and still provide long acting effect. Of note, the 40 mg dispersible tablet is not recommended for pain management. It is also available as an injection.

55. Rationale for Use in Neuropathic Pain
Most effective opioid for neuropathic pain
Inhibits re-uptake of serotonin and norepinephrine
NMDA receptor antagonism
Reduces CNS amplification of pain sensation by reducing the release of excitatory amino acids
Reduces CNS sensitization to pain/hyperalgesia
Reduced development of analgesic tolerance
Methadone’s inhibition of serotonin and norepinephrine make it the most effective opioid for neuropathic pain. Similar to the mechanism behind the use of TCA for neuropathic pain.
Remember back to when we discussed the pathophysiology of pain, this inhibits the descending pathway of pain. While it’s NMDA receptor antagonism inhibits the ascending pathway. Tramadol (not recommended in peds) & tapentadol (no peds data)

56. Rationale for Use in Neurotoxicity
Structurally different from other opioids
No toxic metabolites
Safe in renal failure
NMDA receptor antagonist
Reduces CNS amplification of pain sensation by reducing the release of excitatory amino acids
Reduces CNS sensitization to pain/hyperalgesia
Inhibits serotonin and norepinephrine reuptake
Similarly, Activation of the NMDA receptor can produce central sensitization (i.e., lowering central nervous system pain thresholds), so blocking this receptor may help prevent the development of tolerance and hyperalgesia (Amplification of pain sensation (wind up)). Methadone is also structurally different from other opioids, allowing for appropriate opioid rotation in the setting of neurotoxicity. The major cause of neurotoxicity is the accumulation of toxic metabolites, which methadone does not have. And methadone is safe in renal dysfunction. All of these components make methadone a great option in the setting of neurotoxicity.
Few other known NMDA receptor antagonists:
Dextromethorphan
Ketamine
Memantine ?

57. When to Potentially Avoid Methadone
History of cardiac conduction abnormalities or arrhythmia
Use of other medications that can affect the QT interval
Rapid opioid titration is necessary to manage severely uncontrolled pain
Lack of clinician comfort level
Inability to monitor for safe use
Abuse, diversion in the home
Patient/family is not capable or willing
if they are not educated on methadone there is a higher risk of overdose if it is diverted since they may take higher doses trying to get that euphoric feeling. If there is any concerns of diversion in the home, a pain management agreement is highly recommended.
Obviously, I’ve stressed the risk of cardiac arrhythmias and it makes sense that we might avoid methadone in patients with a history of cardiac arrhythmia or if they are using other medications that can prolong the QT interval.
Hopefully through appropriate education we can overcome obstacles regarding clinician and family comfort with using methadone. But, if we aren’t able to appropriately monitor initiation and we aren’t confident that the caregivers are capable, then methadone should be avoided. So, while there are definitely patient’s that would benefit from methadone, unfortunately there are some patients that methadone might not be the most appropriate agent for.

58. Potential Drug Interactions
CYP Inhibitors:
↑ Methadone Levels
CYP Inducers:
↓ Methadone Levels
Drugs Affected
by Methadone
Cimetidine (Tagamet®)
Ciprofloxacin (Cipro®)
Clarithromycin (Biaxin®)
Doxycycline (Vibramycin®)
Erythromycin (Erytab®)
Fluconazole (Diflucan®)
Fluoxetine (Prozac®)
Fluvoxamine (Luvox®)
Grapefruit Juice
Ketoconazole (Nizoral®)
Paroxetine (Paxil®)
Sertraline (Zoloft®)
Verapamil (Isoptin®)
Carbamazepine (Tegretol®)
Chronic alcohol ingestion
Pentobarbital (Nembutal®)
Phenobarbital
Phenytoin (Dilantin®)
Risperidone (Risperdal®) Rifampin (Rifadin®)
Ritonavir (Norvir®)
Secobarbital (Seconal®)
Spironolactone (Aldactone®)
Tobacco
Amphetamines
Selected B-blockers
Dextromethorphan (Delsym®)
Fluoxetine (Prozac®)
Lidocaine
Mirtazapine (Remeron®)
Nefazodone (Serzone®)
Paroxetine (Paxil®)
Risperidone (Risperdal®)
Zidovudine (Retonavir®)
Thioridazine (Mellaril®)
Tricyclic antidepressants
Venlafaxine (Effexor®)
It’s important to be aware of medications that might interact with methadone, in addition to the agents that may increase the risk of torsades, because patients will need to be monitored and possibly have their dose adjusted if they are receiving these medications. This is very patient specific, though. Doses should not automatically be adjusted, only if the patient is experiencing symptoms of overmedication or withdrawal/pain.
The CYP inhibitors, will inhibit the metabolism of methadone, and therefore increase methadone levels. These patients may need their methadone dose decreased. Some antibiotics, such as cipro, are inhibitors.
On the other hand, CYP inducers, induce the metabolism of methadone, therefore decreasing methadone levels. These patients may need dose increases to provide adequate pain relief. Many anticonvulsants are inducers.
Of course, Avoiding interacting drugs is ideal, but not always possible.
Adapted from:

59. Short and long acting forms available
Oxycodone
Short and long acting forms available
About as potent as morphine, but more bioavailable (80% for oxycodone, 30% for morphine)
Half-life ~4-6 hours
No clinically important metabolites, so a good choice for people with poor renal function
Oral concentrate is expensive
9/20/2018

60. Adverse Events of Opioids

61. Appropriate movement or response
Sedation Scale
Score
How Sleepy?
How arousable?
Not sleepy
Easily arousable 1
Infrequently sleepy 2
Frequently sleepy 3
Not easily arousable S
Normal Sleep
Appropriate movement or response
S = 2 is similar to normal sleep, but implies an opioid-induced process
9/20/2018

62. Tolerance develops slowly, if at all
Constipation
Tolerance develops slowly, if at all
Treatment: prevention, using stool softeners and stimulant laxatives
Use of stool softeners alone is not recommended
May result in an uncomfortable patient who cannot move bowels
Evidence for docusate is thin and the taste is extremely bad!
Stimulants: senna, bisacodyl
Lubricants: glycerin suppositories
9/20/2018

63. Pain can also cause nausea
Nausea and vomiting
Common, least desirable postoperative adverse effect of opioids from patient’s perspective
Why: direct stimulation of chemoreceptor trigger zone, slowed GI motility
Pain can also cause nausea
Treatment: change route of administration, haloperidol, metoclopramide, 5-HT-3 antagonists for chemotherapy-induced nausea and vomiting
Consider comorbid conditions
Use of promethazine, prochlorperazine is common, but sedation can be a concern
9/20/2018

64. Drugs for Neuropathic Pain

65. Treatment of neuropathic pain (EFNS)
Etiology
1st line
2nd or 3rd line
Diabetic peripheral neuropathies
Duloxetine
Opioids
Gabapentinoids
Tramadol
TCAs
Venlafaxine ER
Postherpetic neuralgia
Capsaicin
Lidocaine plasters
Classical Trigeminal Neuralgia
Carbamazepine
Surgery
Oxcarbazepine
Central pain
Cannabinoids (MS)
Lamotrigine
Tramadol (SCI)
European Federation of Neurological Societies 2010
European Federation of Neurological Societies 2010

66. Treatment of Neuropathic Pain in Nonspecialist Settings (NICE)
Etiology
1st Line
2nd Line
3rd Line
Diabetic peripheral neuropathies
Duloxetine
Change to (or add TCA or gabapentinoid
While waiting for referral:
Consider Tramadol +/- 2nd line treatment
Topical lidocaine
Reserve opioids for specialist referral
TCA (generally amitriptyline, imipramine, or nortriptyline)
Other painful neuralgias
Gabapentinoids
Tan T, et al. BMJ 2010

67. Stepwise pharmacotherapy of neuropathic pain
(Canadian Pain Society 2007)
TCA or gabapentinoid
Add agents sequentially if partial by inadequate pain relief
SNRI or topical lidocaine
Tramadol or CR opioid
Cannabinoids, methadone, lamotrigine, topiramate, valproic acid
Moulin DE et al 2007

68. Pharmacological Treatment: SNRIs
Drug
Initial Dose
(Range)
Formulations
Half-life
Notes
Duloxetine*
(Cymbalta®)
30mg daily
(30-60mg)
Caps
12 hours
Avoid in hepatic impairment/heavy alcohol use
Risk of urinary retention
Higher incidence of constipation and dry mouth than venlafaxine
Desvenlafaxine
(Pristiq®)
50mg daily
(50-100mg)
ER tabs
10 hours
Active metabolite half-life 11 hrs.
Venlafaxine
(Effexor®, Effexor XR®)
37.5mg daily
( mg)
Tabs, ER tabs, ER caps
5 hours
Inhibits 5-HT at doses < 150mg and dopamine at doses > 450mg
Levomilnacipran
(Fetzima®)
20mg daily
(40-120mg)
ER caps
Risk of SIADH, seizures, urinary retention
Greater affinity for NE than 5-HT
Duloxetine and venlafaxine preferred
Duloxetine – fibromyalgia, GAD, MDD, musculoskeletal pain, diabetic neuropathy
Venlafaxine – GAD, MDD, panic disorder, SAD – more w/d symptoms and cardiac side effects
Desven and levomiln – MDD only
Short half lives – increased risk of discontinuation symptoms, need to anticipate and taper

69. Lorraine reports that duloxetine doesn’t help much. What would you do?
A. Assess for adherence and duration of therapy
B. Increase duloxetine dose to 40 mg daily
C. Change to venlafaxine 37.5 mg daily
D. A and C
E. A and B

70. Question: I work with pharmacists…
A. No
B. Sometimes, but not regularly
C. Regularly, but not daily
D. Daily
E. What’s a pharmacist?

71. Pharmacists’ Roles in Interdisciplinary Teams

72. Roles
Goals: reduce readmissions and never-events, improve patient outcomes, improve cost-effectiveness
Antibiotic stewardship
Reduction of adverse events
Development of infusion protocols

73. Pharmacists in Palliative and Hospice Care (AJHP 2016)
Essential services (Core processes)
Direct patient care
Symptom management and reduction
Medication use resource
Distribution, compounding
Anticipate transitions of care
Order review and reconciliation in patient care settings
Provide education and medication counseling
Administrative roles to ensure safe use of medications

74. Pharmacists in Palliative and Hospice Care (AJHP 2016): Desirable roles
Recommendations for hospice patients
Pain and symptom management
Medication stewardship
Avoidance and monitoring of adverse events
Consideration of cost and insurance coverage
Support of transitions of care
Medication discontinuation, deprescribing
Education and training
Scholarship and research
Clinical trials
Health outcomes

75. Questions?
Scott Strassels
(224)