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Developing an Effective Oral Analgesic Regimen. Theresa Kristopaitis, MD Department of Internal Medicine, Division of General Medicine Associate Medical Director, Loyola Hospice. General Principles. Assess pain thoroughly Know your patient Know the medications

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Developing an effective oral analgesic regimen

Developing an Effective Oral Analgesic Regimen

Theresa Kristopaitis, MD

Department of Internal Medicine, Division of General Medicine

Associate Medical Director, Loyola Hospice


General principles
General Principles

  • Assess pain thoroughly

  • Know your patient

  • Know the medications

  • Dose to reduce pain by at least 50%

  • Reassess frequently


Developing an effective oral analgesic regimen
Pain

  • Pain is a personal, complex experience with 3 components

    • Sensory

    • Emotional

    • Cognitive


Review
Review

Neuroscience lectures on pain physiology!

P&T lectures on NSAIDs and opiates!


Pain pathophysiology
Pain pathophysiology

  • Acute pain

    • identified event, resolves days–weeks

    • usually nociceptive

  • Chronic pain

    • cause often not easily identified, multifactorial

    • indeterminate duration

    • nociceptive and / or neuropathic

Nociceptive pain – results from actual or potential tissue damage. Result

of ongoing activation of nociceptors on primary afferent nerves by

noxious stimuli

Somative vs visceral


Who 3 step ladder
WHO 3-Step Ladder

Step 3 - Severe

Step 2 - Moderate

Morphine

Hydromorphone

Methadone

Oxycodone

Fentanyl

Codeine/…

Hydrocodone/…

Oxycodone/…

…/acetaminophenor NSAID

Tramadol

Step 1 - Mild

Aspirin

Acetaminophen

NSAIDs

Always consider adding an adjuvant Rx


Adjuvant analgesic
“Adjuvant Analgesic”

  • Drug which has a primary indication other than pain management

  • Acts as analgesic in some painful conditions

    • Antidepressants

    • Corticosteroids

    • Anticonvulsants

    • Local anesthetics

    • Osteoclast inhibitors

    • Radiopharmaceuticals

    • Muscle relaxants

    • Benzodiazepenes


Our case
Our Case

  • Continuous pain

  • Moderate intensity

  • Chronic, non-neuropathic

  • Worsens with certain activites


Where to begin
Where to begin?

  • Begin low dose immediate release oral opioid

    • Examples

      • Hydrocodone 5mg

      • Morphine 5mg

      • Oxycodone 3mg

      • Hydromorphone 1mg

Hospice and Palliative Care Training for Physicians: UNIPAC 3

Assessment and Treatment of Physical Pain Associated with Life-

Limiting Illness, CP Storey et al, ed

EPERC, Fast Facts



Opioids vs narcotics
Opioids vs Narcotics

  • Opioid

    • Naturally occurring, semisynthetic, and synthetic drugs which produce effects by combining with opioid receptors and antagonized by nalaxone

  • Narcotic

    • “numbness” or “stupor”

    • Describes morphine like drugs and drugs of abuse (including coca/cocaine derivates)


Opioids vs narcotics1
Opioids vs Narcotics

“Who’s got the narc keys?”

“Who’s got the opioid keys?”


Immediate release oral opioid
Immediate Release Oral Opioid

  • Administered as

    • single agents

    • combination products

  • Peak analgesic effect occurs in 60-90 minutes

  • Expected total duration of analgesia of 2-4 hours.

  • Standard reference sources generally cite a 4 hour dosing interval for the single-agent opioids

    • 4-6 or 6 hour intervals for combination products

      • Agency for Health Care Policy and Research (AHCPR) Clinical Practice Guideline (1994) recommends dosing intervals for all short-acting opioids at an interval or every 3-4 hours, an interval more consistent with patient reports of pain relief and the half-life of oral opioids.


Combination opiate nonopiate
Combination opiate/nonopiate

-50 different opioid combination products

  • Contain either acetaminophen, aspirin or ibuprofen, with an opioid

  • range of tablet strengths and liquids

  • typically used for moderate pain that is episodic

    • For persistent pain administered on around-the-clock basis


Step 2 opioid combos
Step 2 Opioid Combos

  • Potency

    • Oxycodone > hydrocodone > codeine

      • Propoxyphene = aspirin or acetaminophen

  • The dose limiting property of all the combination products is?

    • aspirin, acetaminophen or NSAID


Who step 2 tramadol
WHO Step 2Tramadol

  • Centrally acting synthetic analgesic

    • m-opioid receptor binding

    • Weak inhibition of serotonin uptake

    • Weak inhibition of norepinephrine uptake

      • Cautions:

        • Serotonin syndrome

        • Lowers seizure threshold


Our patient
Our patient

  • On Percocet

    • Combination opioid/nonopioid

      • Oxycodone/acetaminophen

      • Strengths

        • 2.5/325

        • 5/325

        • 7.5/325

        • 7.5/500

        • 10/325

        • 10/650


Initial plan
Initial Plan

  • Oxycodone/acetaminophen

    • 2.5/325 q 6 hours

  • Not helping - still 5-6/10 pain

    • Titration

      • Increase 25-50% for mild-moderate pain

      • Increase 50-100% for moderate – severe pain

        • Most short acting opiates can be safely titrated every 2 hours

      • Side effect evaluation

        • Sedation


Epic in box
EPIC In-Box

  • Oxycodone/acetaminophen

    • 5/325 tab

      • 1-2 tabs every 6 hours as needed


Case options
Case Options?

  • Increase dose of oxycodone/acetaminophen?

    • 10/325 tabs – take 1 ½, not relieved, take 2

  • Change dosing interval?

    • Q 4 hours

  • Scheduled vs PRN dosing?

    • Scheduled

  • Change to another opiate combo?

    • Oxycodone most potent

  • Change to non-combo opiate?

    • Soon - reaching acetaminophen max

  • Add breakthrough dose of opiate?

    • Yes, but will need an agent without acetaminophen

  • Add an adjuvant?

    • Re-evaluarte characteristics of pain

  • Begin long acting opiate?

    • When stable daily dosage requirements determined


Developing an effective oral analgesic regimen
Plan

  • Oxycodone 10/325

    • 1 1/2 tabs q 4 hours scheduled

    • 2 days later, a little better, not sleepy

    • 2 tabs q 4hours scheduled

    • Titrated oxycodone from 40mg /24 hours to 120mg/24 hours

      (acetaminophen 3900mg/24 hours)

      Relief!!



Extended release opiate preparations
Extended-release opiate preparations

  • Improve compliance, adherence


Extended release opiates
Extended Release Opiates

NEVER!!!!!

In opiate naïve patients!!!!!


Extended release preparations
Extended Release Preparations

  • Extended Release Oral Morphine

  • Extended Release Oral Oxycodone

  • Transdermal Fentanyl


Extended release opiate preparations1
Extended-release opiate preparations

  • Morphine

    • Morphine ER, MS Contin, Kadian, Avinza

  • Oxycodone

    • Oxycodone ER, Oxycontin

  • Fentanyl

    • Transderm patch (Duragesic)


Extended release opioid preparations
Extended-release opioid preparations

  • Dose q 8, 12, or 24 h (product specific)

    • Don’t crush or chew capsules

    • No capsules down feeding tubes

      • may flush time-release granules (Kadian) down feeding tubes

  • Adjust dose q 2–4 days (once steady state reached)

  • Fentanyl transderm q 72 hours

    • Adjust dose at 6 days (once steady state achieved)


Extended release opioid preparations1
Extended-release opioid preparations

  • Should not be used for rapid titration in patients with severe pain


Case how
Case - How?

  • Oxycodone 10/325

    • 2 tabs q 4 hours

      • 120mg oxycodone/24 hours

  • Oxycodone ER 60mg q 12 hours


Developing an effective oral analgesic regimen


Fentanyl
Fentanyl

  • Lipid soluble

    -Crosses skin and oral mucosa

  • Transdermal fentanyl

    • 25 mg patch » 45–135 (likely 50–60) mg PO morphine / 24 h

      • 12 mg patch is available now


Fentanyl transdermal patch
Fentanyl Transdermal Patch

  • onset after application  24 hours

  • effect 72 hours (some patients 48 hours)

  • ensure adherence to skin

  • increased absorption with increased body temp

  • may not be as effective in cachexia (minimal adipose tissue)


Our patient1
Our patient

  • Convert to Fentanyl

    • Oxycodone 120mg/24 hours


Equianalgesic doses of opioid analgesics
Equianalgesic dosesof opioid analgesics

po / pr (mg) Analgesic SC / IV / IM (mg)

100 Codeine 60

15 Hydrocodone -

4 Hydromorphone 1.5

15 Morphine 5

10 Oxycodone -


Conversion
Conversion

  • Oxycodone 120mg x Morphine 15mg

    Oxycodone 10mg

    =180mg morphine equivalent

    • 25 mg patch » 50 mg PO morphine / 24 h

      Fentanyl 75mcg/hr patch q 72 hrs


Breakthrough pain
Breakthrough Pain

  • Incident

    • Activity related, identifiable precipitant

      • Anticipate and premedicate with short acting agents

  • Idiopathic, spontaneous

    • Unpredictable

    • PRN opiate, consider adjuvant

  • End-of-dose failure

    • Increase dose or shorten time between doses of long-acting agent


Breakthrough pain1
Breakthrough Pain

  • Use immediate-release opioids

    • 10%–15% of 24-hr dose

    • offer after Cmax reached

      • po  q 1hr

        • or 50% regular 4 hour dose

  • Do NOT use extended-release opioids


Our case1
Our Case

  • Oxycodone 120mg/24 hours

    • 10-15%

  • Oxycodone 15mg PO q 1 hour PRN breakthrough pain


Follow up
Follow-up

  • Oxycodone ER 120mg q 12 hours

  • Oxycodone 15mg breakthrough

    • 3 weeks later EPIC in-box

    • Has taken 4 breakthrough doses daily x 2 days

      • Re-evaluate pain

  • 60mg additional oxycodone

  • Increase oxycodone ER to

    • 150mg q 12 hours

  • New breakthrough dose?

    • Oxycodone 30mg q 1 hours PRN



Final thoughts
Final Thoughts

  • Physical pain is the most common source of “suffering”


Total pain
Total Pain

  • Dame Cicely Saunders

    • Physical

    • Emotional

    • Social

    • Spiritual