1. A Primer on Pain Medications Howard P. Levy, M.D., Ph.D. Assistant Professor, Johns Hopkins University July 21-22, 2011 Ehlers Danlos National Foundation 2011 National Learning Conference Baltimore, MD

2. Pain

3. Miracle Chocolate Pill Brings you back from almost dead Take as needed Works fast No side effects

4. “You can’t always get want you want” -Mick Jagger, 1969

5. “But if you try sometimes, you might find, you get what you need” -Mick Jagger, 1969

6. Pain Med Principles Easier to prevent than get rid of pain   Scheduled, preventive medication more effective than as-needed Goal is to limit, not eliminate pain Cocktail of multiple medications   Incremental benefits   Synergies   Maximize safer meds   Minimize riskier meds

7. Tylenol® (acetaminophen) Relatively weak by itself Can provide incremental pain reduction Augments other meds Regular standing dose, not just as needed Very well tolerated, few side effects

8. Tylenol® (acetaminophen) OTC: 3 strengths   Regular = 325 mg (3 tabs = 975 mg)   Extra = 500 mg (2 tabs = 1000 mg)   Arthritis = 650 mg (2 tabs = 1300 mg) Max safe dose 4000 mg/day   975 mg or 1000 mg 4 times/day   1300 mg 3 times/day

9. Tylenol® (acetaminophen) I thought 2000 mg was the max? White lies: up to 4000 mg/day is safe Found in many OTC meds Accidental overdose is too common READ ALL LABELS   acetaminophen   APAP   paracetamol   “non-aspirin”

10. NSAIDs Non-Steroidal Anti-Inflammatory Drugs Reduce pain (incremental effect) Reduce inflammation Regular standing dose, not just as needed

11. NSAIDs Side effects Gastritis:   Take w/food and/or antacids Bruising: Usually just cosmetic   Rarely significant bleeding Blocks cardiac benefit of aspirin   Wait 2 hours Heart attack, kidney disease   Rare, mainly w/high dose & prolonged use

12. NSAIDs Generic nameBrand nameTypical Adult Dosing ibuprofen (OTC)Advil®, Motrin®200-800 mg 4 times/day ibuprofen (Rx)600-800 mg 4 times/day naproxen (OTC)Aleve®220-440 mg 3 times/day naproxen (Rx)500 mg 3 times/day meloxicam (Rx)Mobic®7.5 mg twice daily OR 15 mg once daily nabumetone (Rx)Relafen®500 mg 3 times/day OR 750 mg twice daily diclofenac (Rx)Flector® Patch1 patch twice daily

13. Cox-2 Inhibitor CycloOXygenase 2 inhibitor   More targeted than NSAIDs Reduce pain (incremental effect) Reduce inflammation Regular standing dose, not just as needed No stronger or weaker than NSAIDs Different side effect profile

14. Cox-2 Inhibitor Side effects Gastritis: Less common than NSAIDs Bruising: Less common than NSAIDs Blocks cardiac benefit of aspirin   Wait 2 hours Heart attack   More common than NSAIDs, but still rare   Mainly w/high dose & prolonged use

15. Cox-2 Inhibitor Generic nameBrand nameTypical Adult Dosing celecoxib(Rx)Celebrex®100-200 mg 1-2 times/day

16. Topical Lidocaine (Lidoderm®) Anesthetic: local pain control Few side effects   Local rash/skin irritation Up to 12 hours/day Up to 3 patches at a time Can cut patches

17. Skeletal Muscle Relaxers Reduce spasm   Less pain   Possible  laxity Sedation is most common side effect   metaxolone may be least sedating Standing or as-needed dosing   Especially bedtime

18. Skeletal Muscle Relaxers Generic nameBrand nameTypical Adult Dosing metaxolone (Rx)Skelaxin®400-800 mg 1-3 times/day cyclobenzaprine (Rx)Flexeril®5-10 mg 1-3 times/day orphenadrine (Rx)Norflex®100 mg twice daily baclofen (Rx)Lioresal®5-10 mg 1-3 times/day carisoprodol (Rx)Soma®350 mg 3-4 times/day

19. Neuropathic Pain Antiseizure medications Tricyclic (& tetracyclic) antidepressants SNRI antidepressants

20. Antiseizure Medications Suppress undesired nerve signaling Can prevent/reduce migraines Side effects   Sedation   Dizziness   GI upset Gradual dose increase minimizes side effects Regular standing dose

21. Antiseizure Medications Generic nameBrand nameTypical Adult Dosing gabapentin (Rx)Neurontin®300-1200 mg 3 times/day pregabalin (Rx)Lyrica®25-100 mg 2-3 times/day topiramate (Rx)Topamax®25-100 mg 1-2 times/day lamotrigine (Rx)Lamictal®25-100 mg 1-2 times/day

22. Tricyclic Antidepressants Reduce nerve pain Can prevent/reduce migraines Helps treat stress, anxiety, depression Regular standing dose or as-needed Sedation is common   Can help treat insomnia   Take at bedtime Other side effects:   constipation, dry mouth

23. Tricyclic Antidepressants Generic nameBrand nameTypical Adult Dosing trazodone (Rx)Desyrel®25-150 mg at bedtime nortriptyline (Rx)Pamelor®25-100 mg at bedtime amitriptyline (Rx)Elavil®10-75 mg at bedtime Listed in order of increasing likelihood of side effects These doses are less than used for primary treatment of depression

24. SNRI Antidepressants Serotonin-Neurepinephrine Reuptake Inhibitors Cousins of SSRIs   (e.g. fluoxetine/Prozac®) Also treat stress, anxiety, depression   Full antidepressant dosing May also help prevent migraines Regular standing dose

25. SNRI Antidepressants Side Effects (most common) Increased appetite Sexual dysfunction May increase suicide risk, esp in teens Venlafaxine (Effexor®): Requires higher doses for pain benefit May  blood pressure (good for NMH?) Only one currently available as generic

26. SNRI Antidepressants Generic nameBrand nameTypical Adult Dosing venlafaxine (Rx)Effexor XR®150-225 mg daily desvenlafaxine (Rx)Pristiq®50 mg daily duloxetine (Rx)Cymbalta®30-90 mg daily milnacipran (Rx)Savella®25-100 mg twice daily

27. Opioids (narcotics) Most potent painkillers available Treat both myofascial & neuropathic Many risks & side effects Best to minimize use   1 st maximize cocktail of all other meds   Add occasional opioids as-needed If daily doses required, switch to long- acting form   Use short-acting version of same drug for breakthrough pain

28. Opioids (narcotics) Side Effects Severe sedation Clouded thinking Disrupted sleep Urinary retention Dry mouth Dizziness Itching, sweating Constipation, nausea (worsens IBS) “Mostly Dead”

29. Opioids (narcotics) Tramadol works the same way, with fewer side effects & problems Available in combination with acetaminophen (Ultracet®) Caution when combining with TCA or SNRI antidepressants Generic nameBrand nameTypical Adult Dosing tramadol(Rx)Ultram®50-100 mg 1-3 times/day tramadol(Rx)Ultram ER®100-300 mg daily

30. Opioids (narcotics) If tramadol fails, switch to true opioid Short acting form as needed   available in combination with acetaminophen Use long acting forms if taking daily   Add short acting version of same drug as needed for breakthrough pain

31. Opioids (narcotics) GenericShort/LongTypical Adult Dosing oxycodoneshort5-15 mg 3-4 times daily oxycodonelong-Oxycontin®10-60 mg twice daily morphineshort10-30 mg 4-5 times daily morphinelong-MS contin®15-100+ mg twice daily morphinelong-Avinza®, Kadian®10-100+ mg once daily fentanylshort-Actiq®0.2-0.6+ mg 4-5 times daily fentanyl patchlong-Duragesic®12-100 mcg/hr every 3 days

32. Opioids (narcotics) Other problems Stigma/suspicion of abuse Target of crime Written Rx only Narcotic bowel syndrome   Pain stimulation exceeds pain reduction   Especially abdominal, possibly other areas   Hard to distinguish from IBS/other GI prob’s

33. Opioids (narcotics) Addiction? Tolerance: need  dose for same effect Dependency: withdrawal sx’s if stopped Addiction:   take for reasons other than pain (“I just feel better”)   modify actions to get more drug

34. Summary Cocktail of multiple meds Incremental effects Maximize safer, less potent drugs Regular schedule to keep pain controlled Use opioids as last resort & try to limit use to no more than a few years