A Primer on Pain Medications

Howard P. Levy, M.D., Ph.D.Assistant Professor,

Johns Hopkins UniversityJuly 21-22, 2011

Ehlers Danlos National Foundation2011 National Learning Conference

Baltimore, MD

Pain

Miracle Chocolate Pill

• Brings you back from almost dead

• Take as needed• Works fast• No side effects

“You can’t always get want you want”

-Mick Jagger, 1969

“But if you try sometimes, you might find,

you get what you need” -Mick Jagger, 1969

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

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

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

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”

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

needed

NSAIDsSide 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

NSAIDsGeneric name Brand name Typical 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® Patch 1 patch twice daily

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

Cox-2 InhibitorSide 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

Cox-2 InhibitorGeneric name Brand name Typical Adult Dosing

celecoxib(Rx) Celebrex® 100-200 mg 1-2 times/day

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

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

Skeletal Muscle RelaxersGeneric name Brand name Typical 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

Neuropathic Pain• Antiseizure medications• Tricyclic (& tetracyclic) antidepressants• SNRI antidepressants

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

Antiseizure MedicationsGeneric name Brand name Typical 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

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

Tricyclic AntidepressantsGeneric name Brand name Typical 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

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

SNRI AntidepressantsSide 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

SNRI AntidepressantsGeneric name Brand name Typical 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

Opioids (narcotics)• Most potent painkillers available• Treat both myofascial & neuropathic• Many risks & side effects• Best to minimize use

1st 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

Opioids (narcotics)Side Effects • Severe sedation• Clouded thinking• Disrupted sleep• Urinary retention• Dry mouth• Dizziness• Itching, sweating• Constipation, nausea (worsens IBS)

“Mostly Dead”

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 name Brand name Typical Adult Dosing

tramadol(Rx) Ultram® 50-100 mg 1-3 times/day

tramadol(Rx) Ultram ER® 100-300 mg daily

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

Opioids (narcotics)Generic Short/Long Typical Adult Dosing

oxycodone short 5-15 mg 3-4 times daily

oxycodone long-Oxycontin® 10-60 mg twice daily

morphine short 10-30 mg 4-5 times daily

morphine long-MS contin® 15-100+ mg twice daily

morphine long-Avinza®, Kadian® 10-100+ mg once daily

fentanyl short-Actiq® 0.2-0.6+ mg 4-5 times daily

fentanyl patch long-Duragesic® 12-100 mcg/hr every 3 days

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

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

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