1. DEBBIE DONELSON, MD Opioid use for nonmalignant pain management

2. Objectives Describe the pharmacokinetics Give opioid prescribing guidelines  Identify when to use long-acting and short-acting opioids  Titration for breakthrough pain  List dosing equivalents for common opioids  Urine drug testing Identify resources for information on opioid prescriptions

3. Opioid use for pain management Opioids are natural or synthetic compounds that produce morphine-like effects when bound to receptors in the CNS. Opioids mimic the analgesic effects of endorphins and enkephalin. The anxiolytic and euphoric effects of opioids help to lead to their abuse.

4. Pharmacokinetics Opioids undergo extensive first pass metabolism in the liver Are conjugated in the liver to a much more potent analgesic morphine-6-glucuronide and the less analgesic morphine-3-glucuronide Both are excreted in the urine w/ small amounts in the bile Hepatic & renal dysfunction prolong the 4-6 hour duration when administered systemically.

5. Pharmacokinetics Morphine is poorly absorbed orally and readily enters all tissues, except the brain and is the least lipid soluble of the opiates ( fentanyl, methadone and heroin enter the CNS quickly) Codeine is more effective orally Inhalation is effective but this route is favored with non-medicinal administration

6. Overview The initial evaluation should include a through pain assessment (acute, chronic non-malignant pain) Titrate the dose incrementally Individualize dosing (renal, hepatic) Use immediate release for breakthrough pain Stay in the same class for long-acting and short-acting opioids

7. Overview Evaluate for respiratory depression especially in naive patients Patients treated with codeine will have both codeine and morphine in urine samples. If too much morphine is present, the patient may be taking heroin or ingesting morphine in addition to codeine

8. Opioid dosing equivalents OPIOID AGONISTPARENTERAL DOSE ORAL DOSE PO:IVDURATION OF ACTION Morphine (IR) 10 mg30 mg3:13-4 hrs. Morphine (controlled release) NA30 mg12 hrs. HYDROmorphone (Dilaudid) 1.5 mg7.5 mg5:12-3 hrs. OXYcodone (long-acting OxyContin) NA20 mgNA12 hrs. HYDROcodone (Lortab/Vicodin) NA30-45 mgNA3-5 hrs. CodeineNA180-200 mgNA4 hrs.

9. Prescribing Guidelines Dosing should be done incrementally and titrated to the desired effect Individualize dosing based on risks for adverse outcomes, prior effective doses, comorbidities, and response to therapy Use the same class of opioid analgesic for long-acting and short-acting pain relief

10. Prescribing Guidelines Always calculate the total daily dose needed in 24 hrs. Patent X’s daily dose of long-acting Morphine, totals 60mg with good pain control during hospital stay.

11. For breakthrough pain give 10-20% of the 24 hr. dose orally. On follow-up in the clinic, Patient X complains of having worsening of pain throughout the day, she currently takes 60 mg of long-acting Morphine daily. What type and how much additional Morphine would be needed?

12. Conversion of Opioid Analgesic to Fentanyl Transdermal Patch Current Opioid Analgesic Daily Dosage (mg/d) Morphine PO60-134135-224225-314315-404 Morphine IV/IM10-2223-3738-5253-67 Oxycodone PO30-6767.5-112112.5-157157.5-202 Oxycodone IV/IM 15-3333.1-5656.1-7878.1-101 Hydromorphone PO Dilaudid 8-1717.1-828.1-3939.1-51 -Recommended fentanyl transdermal dose (q72h) Fentanyl transdermal (Duragesic) 25 mcg/h50 mcg/h75 mcg/h100 mcg/h

13. Methadone and fentanyl are generally safe and considered good options in patients with renal insufficiency. Enzyme-linked immunoassays are reliable for detecting morphine and codeine in urine samples, but it misses hydrocodone, oxycodone, hydromorphone, methadone, fentynyl and buprenorphine, which are detected by gas chromatography and mass spectrometry..

14. Objectives Describe the pharmacokinetics Give opioid prescribing guidelines  Identify when to use long-acting and short-acting opioids  Titration for breakthrough pain  List dosing equivalents for common opioids  Urine drug testing Identify resources for information on opioid prescriptions

15. References Physicians’ Desk Reference www.empr.com/opioid-equianalgesic- doses/article/125879/ www.empr.com/opioid-equianalgesic- doses/article/125879/ Opioid equivalents, Retrieved from: http://emedicine.medscape.com http://emedicine.medscape.com Rational Use of Opioids for Management of Chronic Nonterminal pain, Retrieved 9/27/2013 from: http://www.aafp.org/afp/2012/0801/p252.html?pri ntiable=afp http://www.aafp.org/afp/2012/0801/p252.html?pri ntiable=afp

16. AMERICANPAINSOCIETY.ORG AAFP.ORG IAFP.COM AAPAINMANAGE.ORG NCBI.NLM.NIH.GOV Resources