Sara Qaradeh

Therapeutic Decision Making for

Pain
Dr. Amani Samir
 Learning Objectives
• Assess a patient in pain.
• Design a pharmacotherapy plan for individuals
with acute or chronic nociceptive or
neuropathic pain for both prescription and
OTC agents.
• Counsel patients on the appropriate use of
pain medications.
 Pain Case
• CC: I have so much pain, I can’t think straight
• HPI: YM is a 48 yo female admitted to the palliative care service for pain
management with triple negative, stage IV breast cancer with metastases
to the pelvis and spine. YM was diagnosed 8 months ago and has
completed 6 cycles of carboplatin/paclitaxel and has chosen not to see any
more chemotherapy. She has pain in her lower back and hips which make
it painful for her to stand or sit for long periods of time. She finds herself
spending most of her time on the couch or in bed laying down. YM also
states that the pain radiates down both of her legs and make it feel as
though she has shocks of pain that shoot down to her knees. Patient also
reports pain in finger tips and in feet that feels like her extremities are ‘on
fire’. States extremities are also numb so tasks sometimes take longer and
she is known to trip since she cannot feel her feet. Currently treated with
ibuprofen with little relief. Pain was mostly in the 6-8/10 range, but
patient fell this morning and now pain is much worse. Patient wishes to
have better pain control, but needs to be more functional so she can care
for her 3 young children.
 Pain Case
• PMH: breast cancer, depression, anxiety, lower back pain x 6 months, hip
pain x 8 months, insomnia
• SH: Married, lives with husband, has 3 young children (12, 10 , 8 years of
age), was a receptionist but is no longer working due to cancer diagnosis
• FH: Mother deceased from breast cancer, age 50, father alive age 75 with
CAD, 1 maternal aunt and 1 sister with breast cancer
• Outpatient medications: ibuprofen 600mg PO TID, acetaminophen 500mg
2 tablets PO TID, paroxetine 20mg PO daily, alprazolam 0.5mg PO TID prn
anxiety, trazodone 25mg PO daily at bedtime for insomnia, vitamin C
500mg PO daily, MVI PO daily
• Allergies: NKDA
• ROS: +wincing with movement, sweating, lower back pain, hip pain (worse
on L side), limited ROM in hips, numbness in feet and hands, + radiation of
pain both legs, tenderness on lumbar spine, denies N/V/D, GI upset,
coughing, fevers, syncope, falls
 Pain Case

PE:
Gen: Tearful, cachetic female in noticeable pain
VS: BP 156/92, P 110, RR 14 bpm, T 37C, Pain 10/10, Ht
163cm, Wt 52 kg
HEENT:PERRLA, EOMI
Neck: No lymphadenopathy
Resp: CTAB
CV: No m/r/g, normal S1, S2
Abd: NTND
Ext: Warm, + pulses
Neuro: CN II- XII grossly intact
 Pain Case
Labs (non-fasting):
Na 140 mEq/L
K 3.8 mEq/L
Cl 102 mEq/L
CO2 22 mEq/L
SCr 0.8 mg/dL
BUN 9 mg/dL
Gluc 78 mg/dL
RBC 4.5 x 106/mm3
WBC 6.0 x 103/mm3
Platelets 212 x 103/mm3
Hgb 11.2 g/dL
Hct 34.5 %

CT of pelvis: metastases in ileac crest and sacroileac joint

 What type of pain is this patient
experiencing?
• Acute on chronic, nociceptive, cancer pain
– Acute: worse today since fall
– Chronic: lower back and hip pain > 3 months
– Nociceptive: lower back pain, hip pain from bone
mets
– Cancer pain: pain from bone mets
• Chronic, neuropathic pain
– Pain radiates down legs
– Hands and feet ‘on fire’
 What is the reason for the patient's
pain?
• Nociceptive pain
– Cancer → bone mets
• Neuropathic pain
– Prior chemotherapy
– Bone mets → radiation of pain
 Is the pain mild, moderate or severe?
• Severe
– > 7/10

• Moderate
– 4, 5, 6/10

• Mild
• <3/10
 What autonomic symptoms is this
patient experiencing from her pain?
• Elevated blood pressure
• Tachycardia
• Diaphoresis
 What is the goal of therapy for this
patient’s pain management?
• Improve QOL
• Restore functional status
– Physical, emotional, social
• Pain relief < 3/10
– Need to counsel patients that no pain may not be
achievable
• Minimize use of pain medications
• Minimize adverse effects of pain medications
 Is this patient’s pain controlled?
• NO!
– Severe pain

• Need to consider each type of pain

– Nociceptive
• Site of pain: LBP, hip
– Neuropathic
• Burning, shooting, numbness
 What is your pharmacotherapy plan
for this patient’s pain?
• Acute, nociceptive pain
– Patient hospitalized → IV therapy for rapid relief
– Severe pain → opioid therapy acceptable
– Patient is opioid naïve
• Morphine IV 3-5 mg Q 3-4 hours
After the first dose of morphine, what
and when do you assess?
• Assess
– Pain relief
• What level is the pain reduced to and how long it takes?
• Should see relief within a few minutes
– Sedation
• Is the patient overly sedated?, minutes to hours
– Respiratory status
• Monitor for hypoventilation at initiation or dosage increases
– Cognition
• Is the patient cognitively intact, are any signs of delirium present?
– Itching or rash
• Histamine release, minutes to hour
– Constipation
• May occur within days
– Functional status
• When pain becomes more controlled
 Assessing Response to a Pain
Medication
• What do you rate your pain BEFORE taking a dose
of medication?
• What do you rate your pain AFTER taking a dose
of medication?
– If pain relief is not present with 1 dose, may need to
increase dose
• When do you get relief from your pain
medication?
• When do you need to take a PRN dose of pain
medication?
– May help alert you to end of dose failure
 Assessing Response to a Pain
Medication
• Are you woken up at night from pain?
– May alert you to end of dose failure or severity of pain
• What is your average pain?
– May alert you to overall pain control
• Are you able to do the things you want to do
while on this pain medication?
– Alert you to level of pain control or level of sedation
• Are you satisfied with your pain regimen?
 The patient is administered 3mg of IV
morphine. In 30 minutes, the pain is
still a 9/10.
• What is your assessment of the morphine
dose given?
– Inadequate
– Peak effect seen in 15-20 minutes
– Generally want to see a 30-50% reduction in pain
• How will you modify treatment to get better
pain control?
– Titrate dose 25 – 50% to achieve a 50% reduction
in pain
The patient’s pain management is bearable at a dose of
10mg IV Q4H, but she consistently requests a PRN dose
after 3 hours of therapy. What is your assessment of
the pain at this point?
• End of dose failure or wearing off

• What can be done to solve this issue?

– Shorten dosing span (instead of Q4H change to
Q3H)
– Change to continuous IV infusion
– Administer a longer acting product
• Only after dose has stabilized
• Longer-acting products are harder to titrate
Opioid dose has stabilized, but patient
still reports burning pain in hands and
feet.
• What type of pain is the patient experiencing?
– Neuropathic pain

• What can be done to optimize this patient’s

pharmacotherapy plan since he is already on
an opioid?
– Add an adjunctive agent
– May consider duloxetine in this patient with
concomitant anxiety
 Neuropathic Pain
• Gabapentin
– Start 100-300mg daily at bedtime and titrate up
• Largest dose most often given at bedtime due to sedation
• Long acting product may be better tolerated
• Given at bedtime → less daytime sedation
– SE: sedation, weight gain, edema
– May take 2 months to see full effect
• Pregabalin
– Similar to gabapentin but may be beneficial in patients
that do not respond to gabapentin
 Neuropathic Pain
• Duloxetine/Venlafaxine
– SNRIs
– Beneficial if patient also has anxiety and/or depression
– Side effects: change in appetite, sexual dysfunction,
sedation/insomnia
• TCAs
– Start low and titrate dose up
– Need a trial of 6-8 weeks with a 2 week optimal dosing
period to determine efficacy
– Avoid in elderly if possible
– May be helpful if patient needs adjunctive agent for
insomnia
• Risk of serotonin syndrome
 Neuropathic Pain
• Lidocaine patch
– Usually used in combination
– Useful for localized pain
– Can only be applied to intact skin
– Apply patch for 12 hours and then remove for
next 12 hours
– Caution with use of other class I antiarrhythmics
 The patient has considerable bone pain
from her metastases. What options maybe
considered to target bone pain?
• NSAIDs
• Corticosteroids
• Bisphosphonates

• Often used in conjunction with other agents

 Bone Pain
• NSAIDs
– Before using, must consider
• Renal function
• GI distress/PUD/GERD
• HTN
• CHF
• Bleeding risk
– May consider celecoxib if patient has GI precautions
• Avoid in sulfa-allergic patients
– Counsel patient to take on a scheduled basis with food
 Bone Pain
• Corticosteroids
– Given in low doses
– Before using, must consider:
• Concurrent DM and glucose control
• GI distress/PUD
• Bleeding risk
• HTN
• CHF
– May be beneficial for those with poor appetite
– Adverse events: irritability, hyperglycemia, insomnia,
weight gain
– Counsel patient to take with food
 Bone Pain
• Bisphosphonates
– Reduce skeletal events due to bone metastases
– IV or PO formulations are effective
– Ongoing medication administration needed
– Before prescribing, must consider
• GI effects
• Renal toxicity
• Osteonecrosis of the jaw
 What patient counseling would you
provide to a patient prescribed an
opioid medication?
• How to take medication
• Avoid use with other CNS depressants
• Adverse effects
 Opioid Counseling
• How to take medication
– Long acting:
• Take on a scheduled basis
• Most likely CANNOT crush
– Short acting: as needed
• Only take as needed
• Record how many doses per day
• Record when taken
• Any triggers for needing a PRN dose?
 Opioid Counseling
• Avoid use with other CNS depressants
– Benzodiazepines
– Barbiturates
– Alcohol
– Skeletal muscle relaxants
 Opioid Counseling
• Adverse effects:
• Sedation
– May resolve in a week, continue to take medication to see how
your body reacts
• Constipation
– Will not resolve
– Treat with stimulant laxative or PEG 3350
– Monitor how frequently BM’s occur
• Dizziness/risk of falls
• Incoordination
– Do not operate heavy machinery
Questions?
Pharmacotherapeutics of Opioids

Dr. Amani Samir

 Learning Objectives
• Discuss approach to opioid conversions.
• Describe dosage forms for each opioid.
• Discuss how side effects may guide the choice
of opioid.
 Required Reading
• Trescot AM. Review of the Role of Opioids in
Cancer Pain. JNCCN 2010;8:1087-1094.
• Gammaitoni AR, et al. Clinical application of
opioid equianalgesic data. Clin J Pain
2003;19:286-297.
http://pharmacologycorner.com/updated-sign-clinical-guideline-pain-management-in-adults-with-cancer/;
 Pain Management
• Not an exact science
• Acute pain
– Initial stages
• Short acting agents around the clock (ATC)
– Intermittent
• Produces variability in analgesia and sedation
• If starting with prn IR formulations → pain progresses
→ change to around the clock (ATC) dosing
– Used for ‘dose finding’
 Pain Management
• Chronic pain
– Around the clock (ATC) dosing
• ATC dosing prevent pain from occurring and then
having to treat it
• Let’s you “get ahead” of the pain
• Can use short or long acting agents
– Start with short and convert to long acting for ease of use

• Breakthrough pain
– Short acting agents
 Pain Management
• Try to maximize dose of first pain medication
before adding another pain medication
• Consider adjuvant therapy whenever possible
Opioids
 Opioids
• Best for moderate to severe pain
• Available in many formulations
– PO
• Tablets, capsules, liquids
• Short acting
– “Rescue dosing”
– Use for breakthrough pain
– May cause more sedation due to peak levels
• Long acting
– Maintenance of pain
– Added after dose stabilized on IR products
– “Standard or maintenance dosing”
 Opioids
• Available in many formulations
– IV
• Provides most rapid effect
• Flexible dosing
– Transdermal
• Not recommended for unstable pain
• Should be controlled on a regimen before being put on
a patch
– Transbuccal
– Intranasal
 Opioids: Things to Consider
• Age
– Elderly are very sensitive to the class of opioids
• History of previous response
– Likely will be the same with future use
• Current or history of substance abuse
• Renal function
– Active metabolites: morphine, meperidine
– Best choices: methadone, fentanyl
 Opioids: Things to Consider
• Hepatic function
– ALL opioids are hepatically metabolized
– May accumulate with severe hepatic impairment
• Adverse effects
– True allergies are rare
• Must correctly classify an ‘allergy’ to determine what
agents can be used
• If allergic to morphine; can use methadone,
meperidine, or fentanyl
 Opioids: Things to Consider
• Adverse effects
– Nausea/vomiting
• May be transient
• Most likely with codeine
– Pruritus
• Due to release of histamine
• Most likely with morphine and codeine
• Least with fentanyl and methadone
 Opioids: Things to Consider
• Adverse effects
– Sedation
– Tolerance may develop with chronic opioid use
 Opioids: Things to Consider
• Adverse effects
– Constipation
• Tolerance does NOT occur for constipation
• Recommended to use a stimulant laxative +/- stool
softener
– Respiratory depression
• Risk greatest with initiation of therapy and ↑ dose
• Tolerance usually develop within 1 week
– Mental status changes
• Delirium
 Opioids: Things to Consider
• Adverse effects
– Hypotension
• Orthostasis
– Bradycardia
– QTc prolongation:
• Methadone

• Titrate opioids up for optimal pain control

 Opioids: Things to Consider
• Physical dependence
– State of dependence that will produce a
withdrawal syndrome upon abrupt drug
discontinuation or drug antagonist
• Tolerance
– State that comes about with diminished effect
over time
• Pseudo-addiction
– Drug seeking behavior seen in patients with
inadequate pain control
 Opioid Antagonists
• Naloxone
– Antidote
• Naltrexone
– Maintenance of opioid-free state
• Can cause opioid withdrawal if given with
opioids
 Morphine
• Onset of action
– IR: 30 minutes
– ER: 90 minutes
• Metabolites
– Accumulate in renal impairment
– M6G
• More potent that parent drug
• Produces analgesia
• Responsible for respiratory depression
– M3G
• Lack of affinity for opioid receptors

Trescot AM. JNCCN 2010;8:1087-1094.

 Morphine
• Histamine release
– Bronchospasm
– Hypotension
• Respiratory depression
• Nausea/Vomiting
• Reduced testosterone levels

Trescot AM. JNCCN 2010;8:1087-1094.

 Morphine
• Decreased intestinal mobility
• Urinary retention
• PO
– IR
• Tablet and oral solution
– ER:
• SR tablets: Q12H to Q8H
• Capsules: Q12H to Q24H
• Rectal suppository
• IV
Trescot AM. JNCCN 2010;8:1087-1094.
 Codeine
• Weak analgesic
• Metabolized to morphine by CYP 2D6
– Drug-drug interactions
– Fast and slow metabolizers
• Useful for cough suppression
• Nausea
– Lower doses have higher nausea potential
– More problematic than other opioids
• Dosed Q4H

Trescot AM. JNCCN 2010;8:1087-1094.

 Hydrocodone
• Available only in combination with APAP or
ibuprofen
• Metabolized by CYP 2D6 to hydromorphone
• IR: Dosed Q4-6H
• LA: Q12 – Q24H

Trescot AM. JNCCN 2010;8:1087-1094.

 Oxycodone
• Available in combination with acetaminophen
or alone
• Metabolized by CYP2D6
• IR: oxycodone/APAP or oxycodone and
solution
– Dosed Q4-6H
• ER:
– Dosed Q12H
Trescot AM. JNCCN 2010;8:1087-1094.
 Oxymorphone
• 10 times more potent that morphine
• Not affected by CYP2D6 or 3A4
• Little histamine release
• IR : Dosed Q4-6H
• ER: Dosed Q12H

Trescot AM. JNCCN 2010;8:1087-1094.

 Hydromorphone
• Preferred over morphine for patients in renal failure
• High first pass effect
• PO
– IR: dosed Q4-6H
– ER: dosed Q24H
• IV PCA
• SQ
• Rectal suppository

Trescot AM. JNCCN 2010;8:1087-1094.

 Methadone
• Racemic mixture
– R form
• More potent; accounts for analgesic effect
– S form
• NMDA receptor antagonist
• May be useful for neuropathic pain
• Inhibits reuptake of 5HT and NE

Trescot AM. JNCCN 2010;8:1087-1094.

 Methadone
• Synthetic
– Useful in patients with true morphine allergies
• Hepatically metabolized
– Primarily by 3A4, but also by 2D6
– May induce 3A4 for 5-7 days which can lead to
overdosing if titration is not slow
– Useful in patients with renal dysfunction
• Half-life: 12-150 hours
• Used to treat heroin addiction and pain
• Most beneficial opiate for neuropathic pain
Trescot AM. JNCCN 2010;8:1087-1094.
 Methadone
• Known for lack of euphoric effect
• Duration of action
– 3-6 hours initially
– 8-12 with repeated dosing
– Dosed Q8H to Q12H
• QTc prolongation
– Usually at high doses > 100mg/day

Trescot AM. JNCCN 2010;8:1087-1094.

 Methadone
• Equianalgesic doses vary from person to
person and depend on how much morphine a
patient is taking
• Reference morphine to methadone conversion
chart
• Titrate no more than 1 time per week

Trescot AM. JNCCN 2010;8:1087-1094.

 Fentanyl
• IV
• Transdermal
– Lag time of 8-12 hours for analgesic effect
– May take 24 hours after removal for drug clearance
– Apply patch Q72H
– Need fat for absorption, may not be effective for cachectic
patients
• Transbuccal
– Lollipop
– Buccal tablet
– Buccal film
Trescot AM. JNCCN 2010;8:1087-1094.
 Fentanyl
• Transbuccal and intranasal
– Used for breakthrough pain for severe cancer pain
• 80 times more potent than morphine
• Metabolized by 3A4 to inactive metabolites
• Can be used in morphine allergic patients

Trescot AM. JNCCN 2010;8:1087-1094.

 Tramadol
• Centrally acting analgesic
• Weak μ agonist
– Indicated for moderate to severe pain
• Not a controlled substance
• IR: dosed Q4-6H; max of 400mg/day
• ER: dosed Q24H; max of 300mg/day
• Has 5HT and NE activity
– Risk of serotonin syndrome with antidepressants
Trescot AM. JNCCN 2010;8:1087-1094
 Tapentadol
• Centrally acting analgesic
• μ agonist
– Moderate to severe acute pain
• Controlled II substance
• IR: dosed 50-100mg Q4-6H; max of
600mg/day
• ER: dosed Q12H
• Risk of respiratory depression
Trescot AM. JNCCN 2010;8:1087-1094
 Ketamine
• NMDA receptor antagonist
– Analgesic
– Anesthetic
• IV, IM, or PO administration
• AEs:
– CNS and respiratory depression, physical
dependence, emergence reactions
– ↑ HR, BP
Patient Controlled Analgesia (PCA)
• Patient-controlled parenteral medication
administration
– Demand dosing
• Dose is administered on demand from patient
– Continuous infusion with demand dosing
• Continuous infusion
– Can programmed by a healthcare professional
• Bolus
– Controlled by the patient
Patient Controlled Analgesia (PCA)
• Initial loading dose
– Controlled by healthcare professional
– Used for titration
• Demand dose
– Controlled by patient
– Activated by demand button
– Intent is to produce sufficient analgesia with 1
demand
Patient Controlled Analgesia (PCA)
• Lockout interval
– Length of time after a demand dose that the PCA
will NOT deliver another dose
– Intent is to prevent overdose
• Background infusion rate
– Constant rate infusion
– Given without regard to on demand dosing
• 1-hr or 4-hr limits
– Limits the cumulative dose over a time period
Patient Controlled Analgesia (PCA)
• Candidates for PCA
– Cognitively intact patient
– Able to understand concept
• Common use of PCA
– Post-op patients
– Sickle-cell patients
Opioid Conversion
 Steps to Convert Opioids
• Assess the patient's pain
– Pain score before and after medications
– Adverse effects of medications
– Assess frequently: acute and post-op pain
– Assess less frequently: chronic pain
• P – palliative factors: what makes it better or worse?
• Q – quality: describe the pain
• R – radiation: where is the pain
• S – severity: is it better or worse than previous pain?
• T – timing: does the pain change with time?

Gammaitoni AR, et al. Clin J Pain 2003;19:286-297.

 Steps to Convert Opioids
• Determine the total daily dose
– Long acting + short acting
– If on more than 1 opioid, convert all to morphine
equivalents

Gammaitoni AR, et al. Clin J Pain 2003;19:286-297.

 Steps to Convert Opioids
• Choose a new opioid
– Consider
• Pain level
• Previous opioid use
• Route of administrations
• Dosage forms (IR or XL)
• Cost

Gammaitoni AR, et al. Clin J Pain 2003;19:286-297.

 Steps to Convert Opioids
• Individualize the new therapy to the patient
– Conservative
• Reduce “new” dose by ~33% to account for lack of complete cross-tolerance
between opioids
• Good option for those patients whose pain is controlled to prevent AEs
• ONLY when converting between different opioids
– Dosage reduction is NOT used if converting SAME opioid to another dosage form
• Used most often, especially for older adults
– Aggressive
• Give 100% or 125-150% of calculated dose of new opioid to treat uncontrolled
pain (i.e. pain 8,9, or 10/10)
– Decision is based
• Degree of pain
• Environment
• Opioid tolerance

Gammaitoni AR, et al. Clin J Pain 2003;19:286-297.

 Steps to Convert Opioids
• Monitor and reassess the patient
– Therapeutic response to new opioid
– Adverse effects
– May need to adjust dose within first few days of
new opioid therapy

Gammaitoni AR, et al. Clin J Pain 2003;19:286-297.

 Rescue Dosing
• Used to treat
– End of dose wearing off
– Acute pain
– Breakthrough pain
• Use short acting opioids
• Most dosed Q4H; may see Q1H to Q 4-6H PRN

Gammaitoni AR, et al. Clin J Pain 2003;19:286-297.

 Rescue Dosing
• Usually 10-20% of total daily dose OR 25-30%
of single long-acting opioid dose
• Best to have the same opioid for
standard/long acting and rescue dosing
• If using ~ >3 doses of rescue medications
continuously, then add in to standard dosing

Gammaitoni AR, et al. Clin J Pain 2003;19:286-297.

Equianalgesic Opioid Dosing
 Opioid Route Equianalgesic Dosing

200mg
Codeine PO

123mg
IM

30mg
Hydrocodone PO

7.5mg
Hydromorphone PO

1.5mg
IV/IM/SubQ

4mg
Levorphanol PO

2mg
IV

300mg
Meperidine PO

75mg
IV

30mg
Morphine PO

10mg
SubQ/IV/IM

20mg
Oxycodone PO

10mg
Oxymorphone PO

1mg
IV/IM/SubQ
Oral Morphine Equivalent Daily Dose (mg/day) Methadone Conversion Ratio (accounts for 25% dosing reduction)

0-30 mg 2:1

30-99mg mg 4:1

100-299 mg 8:1

300-499 mg 12:1

500-999 mg 15:1

> 1000 mg 20:1

 Fentanyl Dosing Conversion

Product Information; Duragesic; Ortho-McNeil-

Janssen Pharmaceuticals; Raritan, NJ®; 2009.
Questions