Clinical Assessment and

Management of Pain

Gina C. Biglane, Pharm. D.

Spring 2010
Learning Objectives
 At the conclusion of the lectures, the student should be
able to:
 Primary Objectives
 Recognize the various types of pain:

 Acute

 Chronic

 Somatic

 Visceral

 Neuropathic
Learning Objectives
(con’t)
 Understand the meanings of commonly used terms:
 Allodynia

 Hyperalgesia

 Addiction

 Pseudoaddiction

 Tolerance

 Physical dependence
Learning Objectives
(con’t)
 Recommend appropriate pain therapy based upon
guidelines established by the World Health Organization
 Select an agent from the appropriate category (Step 1,
Step 2, Step 3) utilizing the following information:
 Patient characteristics (renal fx, allergies, etc)

 Drug specific characteristics (MOA, dosing,

contraindications)
 Calculate appropriate conversion doses between
opioids.
 Recommend appropriate management of side effects.
Learning Objectives
(con’t)
 Secondary Objectives
 Explain the pathophysiology involved in pain

 Recognize the impact of pain on other area of the

patient’s life
 Conduct a pain assessment using commonly accepted

tools:
 PQRSTU mnemonic

 Pain scales

 Recognize physical or non-verbal indicators of pain.

 Identify barriers to pain control.

Learning Objectives
(con’t)
 Recommend appropriate adjuvant medications.
 Recommend non-pharmacologic options for pain
management such as:
 Imagery

 Distraction

 Biofeedback

 Relaxation

 Physical therapy

 Chiropractic care

 Acupuncture
Introduction

 Pain is #1 reason patients see their primary

care physicians
 Affects everyone
 Remains undertreated
Pharmacist’s Role
in Pain Management
 Range of involvement
 Brief counseling when prescriptions are filled
 Extensive role in assessing and managing pain
 Consultation with prescribing physician
 Assessment of patient’s drug use and effect

 Patient education is key; how to use the

medication properly
New Guidelines

 Opioids in non-cancer pain

 American Pain Society
 American Academy of Pain Medicine

 Journal of Pain, Vol 10, No 2, 2009: pp 113-

130.
Types of Pain (cont.)
Acute vs Chronic
 Acute pain  Chronic nonmalignant pain
 Lasts hours to weeks  Lasts months to years

 Caused by surgery,  Can be severe and

trauma, medical disabling

procedures  Arthritis, headache, back
 Prognosis is predictable pain

 Primary treatment =
 Prognosis is
analgesics unpredictable
 Can have profound
complications
 Treatment is multimodal
Types of Pain (cont.)
Malignant vs Non-malignant
 New definition of malignant pain extends to pain
caused by conditions other than cancer, i.e., any
progressive disease that is potentially life limiting
Types of Pain (cont.)
Nociceptive or Neuropathic
 Nociceptive pain
 Somatic pain: Arises from skin, bone, joint,
muscle or connective tissue
 Visceral pain: Arises from internal organs
 Neuropathic pain: Caused by nerve damage
 Postherpetic neuralgia, trigeminal neuralgia,
diabetic neuropathy
The Language of Pain
Terms Related to Abuse

 Using improper terminology creates

confusion
 Proper terms:
 Physical dependence (withdrawal)
 Addiction
 Tolerance
 Pseudoaddiction
Terms Related to
Addiction (cont.)
 Addiction or appropriate use?
 Addicted individuals lose function
 Non-addicted individuals regain function
 Physical dependence is neuropharmacologic
 Addiction is also behavioral
 Physical dependence is to be expected in
patients on long-term opioid therapy
Treatment Goals
 Prevent, reduce or eliminate pain
 Improve quality of life, functional capacity,
ability to retain (or regain) independence
 Patients should set their own goals
 Example of goals:
 Pain score 3 or less at rest
 Pain score 5 or less with movement
 Able to have 6 hours of uninterrupted sleep
Routes of
Administration
Oral Preferred

 Ease of use & cost-effective
Rectal  Periods of N/V or fasting
 Begin w/same dose as oral
Transdermal  For pts stabilized on dose
 Provide for breakthrough
IM  Avoid: pain, inconvenience,
unreliable absorption
Routes of Administration
(con’t)
IV/SQ  For those unable to use oral route
 For rapid titration
 SC dose=IV dose
PCA  Patient controlled
 Usually given IV or SQ
Spinal  Minimizes systemic SE
 Epidural: use 1/10 IV dose
 Intrathecal: 1/10 epidural dose
Pharmacologic
Treatment Options (cont.)
Step 1 Products

 NSAIDS
 ASA
 Acetaminophen
Step 2 Products

 Usually combination products that have a

ceiling dose
 +/- adjuvant
Step 3 Products

 Pure opioids
 +/- anti-inflammatory (step 1)
 +/- adjuvant
Morphine

 Gold Standard
 Used for severe pain
 Hepatic metabolism
 45% to 55% to morphine-3-glucuronide, which
produces hyperalgesia, allodynia, hyperactivity
 10% to 15% to morphine-6-glucuronide, which
has greater analgesic properties, fewer adverse
effects
Codeine

 Metabolized to morphine
 ~10% of patients lack enzyme (CYP2D6) to
convert to morphine and will not experience
analgesia
 Causes nausea and constipation more than
other opioids
Hydromorphone
(Dilaudid)
 Available only as immediate release
Hydrocodone

 Metabolized to hydromorphone
 Available only in combinations
Oxymorphone (Opana)

 ER formulation recently released

 No metabolite data
 Caution: mod-severe hepatic disease
Oxycodone (Oxycontin)

 Metabolized to oxymorphone
 No more “efficacious” than other products
 P’kinetics appear independent of age, renal
statues, or albumin levels
Fentanyl

 Approximately 100 times more potent than

morphine
 Significant first-pass metabolism, reducing
effect of oral administration
 available as lozenge and transdermal patch
 Lozenge – 2-3hr duration
 Patch provides effective relief over 48 to 72
hours
Meperidine

 Potent analgesic
 Normeperidine
 CNS excitation → seizures (not reversed by
naloxone)
 Patients develop tolerance quickly
 Should not be used for more than 1 or 2 days
 Avoid use in elderly, renal impaired
Methadone
 A mainstay of treatment for opioid addiction
 Growing use for treating pain
 Accumulates with repeated dosing; may require
dosage reduction or increased dosing intervals
 Recent FDA advisory regarding QT prolongation
and Torsades de Pointes
 An estimated 2,452 overdose deaths were attributed to
methadone in 2003, up from a reported 623 in 1999.
Propoxyphene

 Greater risk of inducing seizures than other

opioids
 No proof of greater effectiveness
 May be associated with cardiac conduction
abnormalities (not reversible by naloxone)
 Should not be used in the elderly
 No longer used in United Kingdom
 1/30/09: FDA Advisors voted to recommend
banning propoxyphene.
Tramadol

 A weak opioid agonist effective in moderate

to moderately severe pain
 Also inhibits reuptake of 5HT and NE
 Reduced risk of respiratory depression,
physical dependence, and abuse
 Most common adverse events are dizziness,
nausea, constipation, somnolence
Tapentadol (Nucynta)

 Approved by FDA 11/08

 Mu agonist and NE reuptake inhibitor
 Dosing: 50-100mg q4-6hr
Buprenorphine (Subutex)

 MOA: exerts its analgesic effect via high

affinity binding to μ opiate receptors in the
CNS; displays both agonist and antagonist
activity
 Possible advantages:
 It has a lower abuse potential
 is less dangerous in an overdose
 causes fewer withdrawal symptoms when it's
stopped.
Buprenorphine (Subutex)

 Analgesic activity
 0.3 mg of parenteral buprenorphine =10 mg of
parenteral morphine
 Prescribing restrictions
 MDs with special training to use for opioid addiction
outside of a clinic: DEA # starts with “X”.
 MDs using for pain do not need “X” in DEA.
 Encourage them to write “for pain” on rx.
Buprenorphine (Subutex)

 Dosing:
 Once daily for addiction
 3-4 x daily for pain

 Dosage forms:
 Injection, solution: 0.3 mg/mL
 Tablet, sublingual: Subutex®: 2 mg, 8 mg
Opioids—Drug Selection
 Choice of agent based on pain intensity,
pharmacologic factors, coexisting condition,
economic factors
 Moderate pain: Combination of opioid and
acetaminophen or an NSAID
 Severe pain: Single-agent products
 Drug interactions – consider metabolic
pathways
Opioids—Adverse Effects

 Common: Constipation, nausea and

vomiting, sedation, pruritus
 Delirium less frequent
 Risk of respiratory depression
 Risk of abuse and diversion are important
considerations
Minimizing Adverse
Effects
 Titrate gradually
 Determine cause of symptoms
 Change dosing route or regimen
 Switch to another opioid
 Add an adjuvant and reduce dosage
 Eliminate other nonessential agents
 Assume that constipation will occur and provide
preemptive treatment
Constipation

 Common effect due to opioids’ slowing

peristalsis
 Usual treatments do not relieve opioid-
induced constipation
 Recommend stool softener plus stimulant
laxative.
 Ex: Senokot-S plus docusate
 Monitor incidence; adjust agent or dose
Constipation -
Peripheral Opioid
Antagonists
 Alvimopan (Entereg)
 Potent peripheral mu antagonist localized to GI
system
 Small, dipolar molecule
 Not absorbed in GI system
 Doesn’t cross BBB
 Approved for management of postoperative ileus
 Dosing 12mg BID
Constipation - POA
 Alvimopan (con’t)
 2 studies looking at use
in OBD
 Dosing 0.5mg to 1mg
QD or BID
 AE: n/v, diarrhea,
flatulence
 NOTE:
 [U.S. Boxed Warning]: For
short-term (≤15 doses) hospital
use only. Only hospitals that
have registered through the
ENTEREG Access Support
and Education (E.A.S.E.™)
Program and met all
requirements may use.
 Alvimopan is contraindicated in
patients receiving therapeutic
doses of opioids for more than
7 consecutive days
immediately prior to alvimopan
initiation
Constipation - POA

 Methylnaltrexone (Relistor)
 Methyl group added to the aine of naltrexone
 Increases polarity
 Decreases lipid solubility and ability to cross BBB
 Humans are unable to demethylate
 Approved Use: Opioid-induced constipation
 Sub-q dosing according to body weight
Respiratory Depression

 Serious potential adverse event; can be fatal

 Opioids depress all phases: Rate, minute
volume, tidal exchange
 Lower risk in severe pain
 Higher risk in opioid-naïve patients
 Rare in patients whose dose has been
carefully titrated upward
Sedation

 Common adverse event

 May be due to poor sleep prior to starting
opioid therapy
 Usually abates within first days to weeks
 Initially caution against driving; in time,
patients can resume normal activities
Less Common Adverse
Effects
 Cognitive impairment
 Manifested as confusion or delirium
 Usually abates soon after initiation of therapy
 If persists, consider changing dose or agent
 Pruritus
 Can be particularly bothersome
 More frequent with parenteral agents than oral
 Tolerance occurs quickly
 Antihistamine may help (caution – sedation)
Allergic Reactions

 True allergy to opioids is rare

 Have been reports of anaphylactic-type
reactions with some agents
 Fentanyl, morphine, meperidine
 Can be partially attenuated with naloxone
and/or antihistamines
 Change to different class
Dosing

 Start with short acting product at dosage

sufficient to alleviate pain and interval q4h.
 Convert to long acting product.
 Continue to allow same short acting dose for
“breakthrough” or “incident” pain.
 May dispense smaller amount
Titration

 Use amount of short acting product used

daily to determine how much to increase long
acting product.
 Example:
MS Contin 30mg q12h (60mg/day)
MSIR 15mg q4h prn. Pt is using 4 doses each day
for last 5 days. (60mg/day)
Example (con’t)

 Pt is tolerating 120mg / day. Increase MS

Contin to 60mg q12hr.
 If 15mg dose continues to alleviate
breakthrough pain, leave dose as is. If not,
increase to 30mg q4h.
Opioids—Dosing Errors

1. PRN dosing for constant pain.

2. Long acting product without short acting
product.
3. Not using prophylactic dose for incident
pain.
4. Use of multiple opioids or formulations
5. Underuse of adjuvant products
Opioids—Dosing Errors

6. Insufficient rescue dose titration.

7. Using “incident” doses to titrate SR product.
8. Pharmacologically incorrect dosing.
9. Changing > 1 drug at a time.
10. Incorrect calculations of equianalgesic
dosing.
11. Inadequate follow-up.
Calculating Equianalgesic
Dosing
 Refer to your handout for accepted
equianalgesic doses
 Step 1
 Calculate total daily opioid intake
 Regular and breakthrough doses
 Step 2
 Convert to morphine equivalents
Calculating Equianalgesic
Dosing
 Step 3
 Convert from morphine equivalent to new opioid
 Step 4
 Start new product at 75% of calculated dosage
 Step 5
 Evaluate frequently for uncontrolled pain and
retitration, if needed.
 Step 6 – Rule of thumb
 Breakthrough dose – 10-20% of total daily dose
Adjuvant and Other
Medications
 Many chronic pain conditions respond well to
adjuvant medications
 Neuropathic pain: Anti-epileptic drugs, and
tricyclic antidepressants recommended as
first-line treatment in addition to opioid
analgesics
 Responses vary among different agents and
within classes
Tricyclic Antidepressants
 Effective in treating a variety of pain states
 Block the reuptake of norepinephrine (and
5HT), which modulates pain
 Analgesia at lower doses than anti-
depressant effect
 Use limited by side effects (anti-cholinergic)
 Amitriptyline vs desipramine
 Caution: coronary disease
Antiepileptics
 Demonstrated effectiveness in variety of
neuropathic pain states
 Reduce firing of sensory neurons
 Agents: Carbamazepine, phenytoin, gabapentin,
lamotrigine
 No ceiling dose: Start low and titrate upward
until adverse effects appear
 Adverse effects vary
 Most common are sedation, mental clouding,
dizziness, nausea, unsteadiness
Local Anesthetics

 Often used to manage neuropathic pain

 2 available agents
 EMLA cream, contains lidocaine and prilocaine
 5% lidocaine patch or cream
Cases
Case #1
You receive a call from a local physician with whom you have a
good working relationship. She is asking about one of her
patients, a 79 year old white male who is taking Lortab 10/500 for
lower back pain (pt diagnosed with degenerative disc disease).
The problem is that the physician had written a prescription for
Lortab 10/500 q6h prn pain with a quantity of 120. Her
expectation was that this would last the patient for one month.
The patient is now requesting a refill about 10 days early. He
states he has been taking 2 tabs q4h because “the pain is so bad
I just can’t stand it!”. She also tells you that the Lortab does
relieve his pain, but one tablet just isn’t working for him
Case #1 (con’t)

 Is this patient exhibiting signs of

addiction?

 What is the problem with this order?

 What would you recommend?

Case #1 (con’t)
Need continuous product for continuous pain
 Long acting product with short acting for
breakthrough. Ex: morphine
Calculate conversion from hydrocodone to
morphine
1. Calculate TDD of hydrocodone.
2 tabs q4h = 12 tabs/day or 120mg of
hydrocodone (6gms APAP!)
2. Calculate morphine equivalent.
Hydrocodone:morphine are 1:1.
120mg hydrocodone = 120mg of morphine.
3. Convert to morphine SR dose.
Morphine 120mg daily divided into two doses.
Calculate 75% of dose
4. 90mg daily (45mg q12h). This would be 3 of the 15mg
MS Contin tabs
Recommend breakthrough 10-20% of TDD
 IDEAL: 90mg/6 doses (q4h) = 15mg / dose.
Therefore, MSIR 15mg q4h.
 Lortab 10/500 1-2 q4h (Do not exceed 6/day
[previously 8/day]. This is in line with calculated
breakthrough – 10-20mg q4h.
Case #1 (con’t)

Follow up…
The next week, the physician calls you again.
The patient reported to have had much better
relief with the new tablets, but he is still taking
at least 4 lortabs each day.
How would you titrate?
Case #1 (con’t)

1. Pt is taking 40mg lortab (=40mg morphine)

plus 90mg morphine daily = 130mg TDD of
morphine
2. Increase to MS Contin 60mg q12h = TDD
120mg
3. Continue lortab as is for breakthrough.
Case #2
FN is a 60 year old black female with a diagnosis of lung
cancer. She was recently admitted to hospice, who
contacts you to arrange for a sub-q PCA pump for the
patient, as she is no longer able to swallow. Her current
pain medications are as follows:
Duragesic 75mcg patch
Darvocet N 100 – 2 tabs po q4h
Percocet 5/325 – 1 q4h
The nurse states the patient has been taking all allowed
doses.
How do you proceed?
Case #2 (con’t)
1. Calculate all morphine equivalents.
a. Duragesic (100mcg/hr = 2-4mg/hr [use 3mg/hr]) = 2.25mg/hr
morphine = 54mg/day [this is IV morphine].
b. Propoxyphene (130mg=30mg morphine)=1200mg propy =
~280mg/day morphine (oral dosing)=93mg/day IV
c. Percocet (20-30mg=30mg morphine)= 30mg oxycodone =
30mg/day morphine (oral) = 10mg/day morphine IV
d. TDD morphine = 54+93+10=~160mg/day morpine IV.
2. Start PCA pump with continuous dose of 160mg * 75% =
120mg/24hrs = 5mg/hr.
3. Calculate bolus dosing: for q15 minutes, allow ¼ of hourly
dose: 1.25mg q15 min. This allows pt to double hourly dose
via patient activated dosing.
Case #3
35 yo CF was admitted to the hospital with severe back
pain which started after she lifted a heavy object at
work 2 months ago. She had been having this pain
constantly for the last 2 months without a significant
improvement. Pain was in the lower back, 10/10, like
"electricity", shooting down her right buttock. Her back
also felt very stiff. Patient was tearful, admitting to
feeling depressed.
Her medications include:
Ibuprofen 800mg tid
Hydrocodone/APAP 5/500 (Vicodin) 2
tabs q6h
Ultram 50mg q6h prn
Case #3 (con’t)

What type of pain does pt have?

Neuropathic pain – “electricity”
Somatic – stiff back
What medications would you choose now?
Opioid - for pain
Muscle relaxant – for stiff back/spasm
AED/TCA/local anethetic – neuropathic
SSRI – depression
Stim laxative/SS - constipation
Case #4

MD takes MS Contin 60mg q12h with good

control of baseline pain. He has incident pain
when he works in his garden for more than a
few minutes. His incident pain is controlled
with 30mg of IR morphine premedication,
usually 1 dose per day.
Would you recommend an increase in his
SR dose?
Case #5

KR is on 240mg of MS Contin q12h. He is

admitted to the hospital for intractable
vomiting and needs an opioid route change.
How much IV morphine should he receive?
240mg q12hr = 480mg TDD (po)~160mg IV.
If dosed q4h, the IV dose is 26mg ~ 20mg
q4h.
FDA

 2/6/09 FDAsent letters to manufacturers of

certain opioid drug products, indicating that
these drugs will be required to have a Risk
Evaluation and Mitigation Strategy (REMS) to
ensure that the benefits of the drugs continue
to outweigh the risks.
 Link:
http://www.fda.gov/Drugs/DrugSafety/Informa
tionbyDrugClass/ucm163647.htm