Medications in Pain ManagementBLAIR LANSFORD, MSN, RN, APRN, NP-C

Introduction

u Up to 50% of patients seen in primary care report chronic pain

u “In 2016 an estimated 20.4% (50.0 million) of U.S. adults had chronic pain and 8.0% of U.S. adults (19.6 million) had high-impact chronic pain” (CDC, 2018)

u Cost of pain $560 billion/year (CDC, 2018)

Types of pain

u Treatment is determined by evaluation and determination of cause/type of pain

u Acute (<3 months, implies tissue damage) vs Chronic (>3 months, implies pathological)

u Types

u Neuropathic (radiculopathy, peripheral neuropathy, MS, phantom limb)

u Nociceptive (arthritis, fracture, toe stub)

u Central (CRPS, fibromyalgia)

Pain Management

u Pain management focus is on maximizing function while minimizing symptoms

u Optimal outcomes when using multidisciplinary approach

Treatment of Pain

u Pharmacologic

u Physical Medicine

u Behavioral Medicine

u Neuromodulation

u Interventional

u Surgical approaches

u Medication should not be the sole focus of treatment, but can be used with other modalities to meet treatment goals

Medications

u Acetaminophen

u NSAIDs

u Opiates

u Ca2+ Channel modulators

u Adjunctive agents

u Herbals

u Cannabinoids

Acetaminophen

u Mechanism: Analgesic mechanism not fully understood

u 3000 mg maximum daily dose

u Onset of action <1 hour

u Duration 4-6 hours

u Toxicity

u overdose leads to hepatic dysfunction

u Contraindicated in the setting of pre-existing hepatic dysfunction. Caution with chronic alcohol use. If long term use caution with renal impairment.

u Monitor kidney (baseline Cr) and liver function with long term use

NSAIDs

u Anti-inflammatory, Antipyretic, Analgesic, Antiplateletu Inhibit the COX (cyclooxygenase) enzymes ultimately inhibiting the synthesis and release

of prostaglandins and thromboxane

u There are 2 COX enzymes targetedu Nonselective COX inhibitors- target both COX-1 and COX-2

u Selective COX-2 specific inhibitors

u Use of NSAID at lowest effective dose for the shortest amount of timeu Contraindications: severe renal disease, gastric ulcers, venous thrombosis

u Lead to fluid retention; caution in HTN, renal insufficiency, or heart failureu Avoid with anticoagulation use- capacity to inhibit platelet function, increasing bleeding

risk(So lo m o n , 2017)

Non-selective inhibitors

u NSAIDs inhibit both COX-1 and COX-2

u Aspirin

u aspirin inhibits platelet COX-1 in an irreversible manner; has proven benefits in reducing the risk of secondary thrombotic cardiovascular events

u Ibuprofen: 3200mg/day divided

u Naproxen: 1500mg/day divided

u Diclofenac: 18-35mg TID

u Ketoprofen: 300mg/day divided

u Indomethacin: 200mg/day divided

COX 2 inhibitors

u Celecoxib: 100-200mg daily

u Rofecoxib and valdecoxib no longer on marketu Benefits

u Selective inhibition of COX-2 results and anti-inflammatory action without disrupting the beneficial effects of COX-1 (maintaining gastric mucosa, regulating renal blood flow, and fluency and platelet aggregation)

u can be used in perioperative period because they do not affect platelet functionu No more efficacious in treating osteoarthritis the nonspecific COX inhibitorsu Decreased risk of bronchoconstriction

u Side effects

u Cardiac toxicity

Relatively selective COX-2

u Relatively selective for the cyclooxygenase (COX)-2 receptor at low doses. More effective inhibitors of COX-2 than COX-1.

u Nabumetone 1000-2000mg/day divided

u Meloxicam: 7.5-15mg daily

u Etodolac: 1000mg/day divided

Opiates

u Opioids produce analgesia by acting on central and peripheral mu-, kappa-, and delta-opioid receptors to inhibit the transmission of nociceptive input and the perception of pain

u Use in acute nociceptive pain. Use in chronic noncancer pain is controversial

u Goal: Increased function

Opiates

u PO forms: Short (IR) and long acting (ER), Abuse deterrent

u Hydrocodone, oxycodone, morphine, hydromorphone, fentanyl, codeine, methadone, buprenorphine

u Tapentadol and Tramadol- centrally acting analgesics, both mu receptor binding and monoamine (serotonin and norepinephrine) reuptake blockade

Opiates

u Risks of dependency, addiction, abuse, overdose, death

u In 2017 CDC: Guideline for Prescribing Opioids for Chronic Pain, guidelines for PCP to follow when treating chronic, noncancer pain

u Risk of opioid-related death in patients prescribed pregabalin or gabapentin with opioids

u concomitant prescription of pregabalin was associated with a dose-related increase in the risk of opioid-related mortality. Sim ilar results w ith gabapentin. Respiratory depression and abuse potential (Rosenquist, 2019)

u Concomitant use with benzos or other CNS depressants can lead to respiratory suppression or death (FDA, 2016)

Ca2+ channel modulators

u GABA agentsu D e c re a se tra n sd u c tio n o f p a in

u R e d u c e h yp e r-e xc ita b ility o f vo lta g e d e p e n d e n t C a ++ c h a n n e ls in a c tiva te d n e u ro n s

u C a u tio n w ith re n a l im p a irm e n t, a vo id a b ru p t w ith d ra w a l

u C o m m o n s/e : d izz in e ss, se d a tio n , e d e m a

u Risk of opioid-related death in patients prescribed pregabalin or gabapentin with opioidsu c o n c o m ita n t p re sc rip tio n o f p re g a b a lin w a s a sso c ia te d w ith a d o se -re la te d in c re a se in th e risk o f o p io id -re la te d m o rta lity . S im ila r

re su lts w ith g a b a p e n tin . R e sp ira to ry d e p re ssio n a n d a b u se p o te n tia l

u Gabapentin: 300-1200mg TIDu In d ic a tio n : p a rtia l se izu re a d u lts/c h ild re n a n d Po sth e rp e tic N e u ra lg ia (PH N )

u FM a n d n e u ro p a th ic p a in (o th e r th a n PH N ) a re o ff la b e l u se s

u Pregabalin: Max 600mg/day dividedu In d ic a tio n : d ia b e tic n e u ro p a th ic p a in , n e u ro p a th ic p a in a sso c w ith SC I, PH N , FM , p a rtia l se izu re s

u C a u tio n in C H F

Adjunctive Agents

u Antidepressants (TCA and SNRI)

u Pain may worsen concurrent depression. A 2014 review of 17 studies found consistent evidence suggesting that treatment of pain can improve response to treatments for depression. (Rosenquist, 2019)

u Muscle Relaxants

u Anticonvulsants

u Topical agents

u Lidocaine patch- PHN, diclofenac gel- OA, many OTC

Antidepressants

u SNRIs

u Duloxetineu In d ic a tio n s: p a in fu l d ia b e tic n e u ro p a th y , fib ro m ya lg ia ,

c h ro n ic lo w b a c k p a in , O A

u D o se 20-60m g /d a y

u Venlafaxine u a c u te a n d c h ro n ic n e u ro p a th ic p a in (o ff- la b e l)

u 37.5-375m g /d a y

u Milnacipranu F ib ro m ya lg ia

u 12.5-200m g /d a y

u Risks: Increase suicidality in youth <25 y/o, serotonin syndrome, HTN, avoid abrupt withdrawal

u TCAs

u None carry indication for pain managementu believed to have independent analgesic effects as well

as an ability to relieve the depressive symptoms associated with chronic pain.

u Amitriptyline and Nortriptyline: 10-75mg/dayu s/e anticholinergic, antihistaminergic, cardiac effects, u Contraindicated in cardiac conduction disturbance,

severe cardiac disease,u Caution in elderly

Muscle Relaxants

u Cyclobenzaprine – centrally acting, potentiates Norepi and binds to serotonin receptors

u 5-40mg/day divided TID/QID

u Caution with cardiac

u Tizanidine – centrally acting alpha-2 adrenergic receptors

u 2-36mg/day divided TID

u Caution with liver impairment

u Methocarbamol – centrally acting, unknown

u 750-4500mg/day divided TID

u Baclofen – centrally acting, inhibits spinal reflexes

u 5-80mg/day divided TID/QID

u Metaxalone – centrally acting, unknown

u 400-800mg QID

u Caution with renal and hepatic impairment

u Chlorzoxazone– centrally acting, inhibits spinal reflexes

u 250-2000mg/day divided TID/QID

Anticonvulsants

u Block voltage gated Na channels, stabilizing neural membranes, inhibiting repetitive firing

u Oxcarbazepine

u 300-2400mg/day divided BID

u Topiramate (Avoid with hx nephrolithiasis)

u 25-200mg/day divided BID

u Carbamazepine

u 200-1600mg/day divided BID/QID

Herbals

u Role in management of pain is uncertain.

u A 2014 systematic review evaluated randomized trials of acute, subacute, and chronic low back pain. Evidence for effectiveness was the best for:

u Topical cayenne, oral Devil's claw, oral white willow bark, topical comfrey root extract, and topical lavender essential oil

u Could have medication reactions or impurities in product

(Rosenquist, 2019)

Glucosamine

u Widely used for treatment of hip and knee OA, little data to support use in back pain

u glucosamine sulfate (1500 mg/day) or chondroitin (800 mg/day)

Cannabinoids

u Tetrahydrocannabinol (THC)u Psychoactiveu Rx: dronabinol (FDA approved for Chemo induced n/v), nabiximols (Not in US)

u Potentiates opioid analgesiau Federal: illegal (Schedule I), State: legal in 33 states and District of Columbia

u Indications: Chemotherapy induced n/v, HIV, neuropathy, MS spasticityu Cannabidiol (CBD)

u Non-psychoactiveu Schedule V

u Available online in several states, including MO u Suppresses auto-inflammatory conditions (MS, RA, colitis, hepatitis, certain cancers), neuroprotective in

chemo, TBI models

Medicinal Marijuana in MO

(MODHSS, 2019)

References

u CDC. (2018). Prevalence of chronic pain and high-impact chronic pain among adults — United States, 2016. Weekly / September 14, 2018 / 67(36);1001–1006 https://www.cdc.gov/mmwr/volumes/67/wr/mm6736a2.htm

u Chou, R. (2018). Subacute and chronic low back pain: Nonpharmacologic and pharmacologic treatment. Up to Date. Retrieved March 28, 2019 from https://www.uptodate.com/contents/subacute-and-chronic-low-back-pain-nonpharmacologic-and-pharmacologic-treatment?search=steroid%20pain%20treatment&topicRef=7768&source=see_link#H868722963

u FDA. (2016). FDA Drug Safety Communication: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. Retrieved March 29, 2019 from https://www.fda.gov/drugs/drugsafety/ucm518473.htm

u MO DHSS. (2019). Medical marijuana regulation. Retrieved March 30, 2019 from https://health.mo.gov/safety/medical-marijuana/index.php

u Rosenquist, E. (2019). Overview of the treatment of chronic non-cancer pain. Up to Date. Retrieved March 8, 2019 from https://www.uptodate.com/contents/overview-of-the-treatment-of-chronic-non-cancer-pain?search=pain%20management&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

u Rosenquist, E. (2019). Use of opioids in the management of chronic non-cancer pain. Up to Date. Retrieved March 8, 2019 from https://www.uptodate.com/contents/use-of-opioids-in-the-management-of-chronic-non-cancer-pain?search=opiates&topicRef=2785&source=see_link

u Solomon, D.H. (2017). NSAIDs: Pharmacology and mechanism of action. Up to Date. Retrieved March 8, 2019 from https://www.uptodate.com/contents/nsaids-pharmacology-and-mechanism-of-action?search=nsaids&topicRef=7993&source=see_link

u Solomon, D.H. (2018). Overview of selective COX-2 inhibitors. Up to Date. Retrieved March 8, 2019 from https://www.uptodate.com/contents/overview-of-selective-cox-2-inhibitors?search=cox%202%20inhibitors&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H9