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Pharmacological Approaches in Pain Management. Ryan J. Bickel, Pharm.D., BCPS updated by David G. Curry, PhD, APRN for NUR344, Fall, 2009 Used with permission. Learning Objectives. Review common non-opioid, opioid, and adjuvant analgesic medications

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Pharmacological Approaches in Pain Management

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Pharmacological approaches in pain management l.jpg

Pharmacological Approaches inPain Management

Ryan J. Bickel, Pharm.D., BCPS

updated by

David G. Curry, PhD, APRN for

NUR344, Fall, 2009

Used with permission


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Learning Objectives

  • Review common non-opioid, opioid, and adjuvant analgesic medications

  • Discuss and apply equianalgesic dosing concepts to selected case studies


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WHO Pain Ladder

http://erlewinedesign.com/end-of-life-care/gfx/who_ladder.gif


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Non-Opioid Medications

  • “Ceiling effect” to analgesia

  • Do not produce tolerance or physical dependence

  • Exhibit antipyretic properties

Ref. 1


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Acetaminophen (APAP)

  • Mechanism of action unclear

  • No anti-inflammatory effects

  • Causes liver toxicity at high doses

    • Max dose: 4 gm/day, if no liver disease

    • Newest recommendation 2.6 gm/day

  • Decreases opioid requirements

Ref. 1,2


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Aspirin (ASA)

Effective as APAP for acute pain at similar doses

Worse side effect profile than APAP

Salicylate Salts

Safer than ASA

No platelet effects

Examples:

Diflunisal (Dolobid)

Magnesium salicylate (Doan’s)

Salicylates

Ref. 1,3


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NSAIDs

  • Efficacy is similar amongst NSAIDs

  • Differences in potency, time of onset, & duration of action

  • Side effects:

    • GI bleeding

    • renal dysfunction

    • platelet dysfunction

Ref. 1,3


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NSAIDs

Ibuprofen (Motrin)

  • initial choice for acute pain due to cost & safety

  • GI safety profile similar to placebo in doses of <1200 mg/day

  • Maximum daily dose ~ 3200 mg/day

  • Now available in IV form (Caldolor)

    Ketorolac (Toradol)

  • first parenteral NSAID available in U.S.

  • use limited to <5 days due to side effects

Ref. 2,3


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COX-2 Inhibitors

  • Selectively inhibit cyclooxygenase-2

    • less GI irritation; less platelet effects

    • other side effects similar to NSAIDs

  • Celecoxib (Celebrex)

    • Role: patients with low cardiovascular risk who require NSAID therapy & are at increased risk for GI toxicity

Ref. 4


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Opioids

  • Originally derived from poppies

  • Body possesses endogenous opioids

    • enkephalins

    • endorphins

  • Opiate Receptors

    • mu ()

    • delta ()

    • kappa ()

    • sigma ()

Papaver somniferum

Ref. 2,5


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Pharmacology of Opioids

  • 1: inhibit transmission of pain

  • 2: respiratory depression, euphoria,

    constipation, physical dependence

  • : inhibit transmission of pain

  • : inhibit transmission of pain

  • : autonomic effects, dysphoria,

    hallucinations

Ref. 5


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Common Side Effects of Opioids

Constipation

  • very common, tolerance is unlikely

  • stool softeners + stimulant +/- metoclopramide

    Nausea/Vomiting

  • tolerance usually develops

  • pretreat with prochlorperazine

Ref. 6


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Common Side Effects of Opioids

Urticaria/Pruritis

  • due to histamine release

  • treat with antihistamine

    Sedation

  • tolerance usually develops

    Delirium

  • rare in patients with normal renal function

Ref. 6


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Side Effects of Opioids

Respiratory Depression

  • preceded by somnolence

  • tolerance develops

  • use caution in patients with underlying pulmonary dysfunction

  • if RR <8 bpm, consider naloxone (Narcan)

Ref. 6


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Morphine

  • Gold standard of opioid therapy

  • Half-life: 1.5 -2 hrs

  • Duration: 3 - 5 hrs

  • Metabolized to a renally excreted active metabolite

    • dose adjustment may be needed in renal failure

Ref. 7


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Morphine

  • Multiple dosage forms available

    • extended-release cap/tab

      • Avinza: once daily dosing

      • Kadian: daily or q12h dosing

      • MSContin, Oramorph SR: q8-12h dosing

    • Immediate-release tab

    • oral suspension (Roxanol)

    • suppository (RMS)

    • parenteral injection (Duramorph, Infumorph)

Ref. 7,8


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Hydromorphone (Dilaudid)

  • Alternative to morphine

    • safe in renal failure

    • more soluble than morphine

  • Good choice when opioid volume is an issue

    • opioid tolerant patients

    • cachectic patients

  • Forms: parenteral, tab, suppository

Ref. 7,9


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Oxymorphone (Opana)

  • Highly selective for mu receptor

  • More potent than morphine

  • Forms:

    • immediate release tab

      • do not take with meals

    • extended-release tab

      • do not take with meals or alcohol

    • parenteral

Ref. 8,9


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Codeine

  • Indicated for mild-moderate pain

    • weak opioid activity itself

    • usually combined with acetaminophen

  • Metabolized to morphine by the liver (2D6)

    • poor metabolizers (lack 2D6)

    • ultra-rapid metabolizers (2D6 gene duplication)

  • Side effects limit use

    • Primarily nausea/vomiting or constipation

Ref. 2,10


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Codeine Derivatives

  • Used in moderate-severe pain

  • Hydrocodone

    • combined with acetaminophen (Lorcet, Lortab, Norco, Vicodin, Zydone)

    • watch amount of acetaminophen (max: 4 gm/day)

  • Oxycodone

    • extended-release tabs (OxyContin)

    • immediate release caps/tabs (OxyIR, Roxicodone)

    • oral solution (Oxyfast, Roxicodone)

    • combination products (Percocet, Percodan, Tylox)

Ref. 1,2,8


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Meperidine (Demerol)

Not a first line agent!

  • Variable oral bioavailability

  • Short duration of action

  • Relatively low potency

  • Neurotoxic metabolites

    • Normeperidine has very long half-life!

  • Multiple drug interactions

Ref. 11,12


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Meperidine

  • Borgess Usage Guidelines

    • Do not use for over 48 hrs

    • Maximum dose: 600 mg/24 hr period

    • Avoid in patients with renal dysfunction or a history of seizures

  • Oral use discouraged


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Fentanyl

  • Highly lipophilic

  • Causes less histamine release than other opioids

  • Unique dosage forms/delivery devices

    • buccal tablet (Fentora)

    • lozenge (Actiq)

    • transmucosal film (Onsolis) – restricted use in US at the present time

    • transdermal patch (Duragesic)

Ref. 7-9


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Fentanyl Transdermal Patch

Advantages:

  • sustained-release opioid

  • good in patients with poor compliance

  • good choice if concerned about drug abuse

    Disadvantages

  • delay in onset

  • residual activity after patch removed – must remove old patch!!

  • expensive

    Note: Heat increases rate of release from patch

Ref. 2,13


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Methadone (Dolophine)

  • Not a first-line opioid

  • Non-opioid actions provide additional analgesia

  • Half-life: 22 hrs

  • Duration: 3-6 hrs (initial);8-12 hrs (chronic)

  • Pros: cheap; good for refractory pain

  • Cons: unpredictable; difficult to dose; drug interactions

Ref. 12,14


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Propoxyphene (Darvon)

  • Not a first line agent!

  • Neurotoxic metabolite

  • Long half-life

  • Propoxyphene-APAP (Darvocet)

    • not much more efficacious

      than APAP alone

Ref. 2,3


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Not a first line agent

causes withdrawal in patients on opioids

ceiling effect on analgesia

psychotomimetic adverse effects

Lower abuse potential

Examples:

Butorphanol (Stadol)

Pentazocine (Talwin, Talwin NX)

Buprenorphine (Buprenex)

Mixed Agonist-Antagonists

Ref. 7


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Tramadol (Ultram)

  • Dual mechanism of action

  • Used for moderate pain

  • Less respiratory depression than opioids

  • May enhance risk of seizures

    • max dose: 400 mg/24 hrs

    • decrease dose in elderly & renally impaired

Ref. 5,8


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Adjuvant Pain Medications

“drugs that are used primarily for treating conditions other than pain, but may be analgesic in selected circumstances”

-AMA

Ref. 1


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Common Adjuvant Medications

  • Antidepressants

  • Anticonvulsants

  • Corticosteroids

  • Topical Anesthetics

  • Calcitonin

  • Bisphosphonates

Ref. 1


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Pharmacokinetics of Routes

Ref. 6


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Equianalgesic Table

Ref. 8,15


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Equianalgesic Dosing Methodology

  • Total the 24-hour dose of current opioid usage including prn doses

  • Convert for drug & route using table

  • Reduce calculated dosage 30-50%

  • Calculate breakthrough pain dose, if converting long-acting opioids

    • 5 – 15% of total daily opioid dose

Ref. 15,16


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Equianalgesic Case 1

MJ is a 56 YOM with prostate cancer admitted to hospital for pain control. He was started on a morphine PCA. In the last 24 hours the patient has received 34 mg and his pain has been adequately control. The physician discontinued the PCA and started the patient on MSContin 30 mg PO BID. Is this an equivalent regimen?


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Equianalgesic Case 1

Table IV dose

Table PO dose

=

Pt 24 hr IV dose

X amount of PO


Equianalgesic case 136 l.jpg

Equianalgesic Case 1

Ref. 8,15


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10 mg IV

10 mg IV

30 mg PO

30 mg PO

=

=

34 mg IV

34 mg IV

X

X

Equianalgesic Case 1

Set up proportion

Cross multiply


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Equianalgesic Case 1

10X = 1020

Divide each side by the number in front of X:

10X 1020

10 10

Select Reasonable Regimen

MS Contin 45 mg PO BID

=

X = 102


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Equianalgesic Case 1

Calculate the oral morphine dose needed for breakthrough pain

Answer: Morphine 5 – 15 mg PO every 4 hours prn pain


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Equinalagesic Case 2

PJ is a 47 YO female who is receiving morphine 2-6 mg IV q2h prn post-op. In the last 24 hours, the patient has received 24 mg IV morphine. Surgery just dc’d the morphine & ordered Lortab 5/500 mg 1-2 tabs PO q6h PRN pain. What do you think of this regimen?


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10X = 720

X = 72 mg PO morphine

Equinalagesic Case 2

Convert to oral morphine:

10 mg IV

30 mg PO

=

24 mg IV

X


Equinalagesic case 242 l.jpg

30X = 1440

X = 48 mg hydrocodone

Equinalagesic Case 2

Convert to hydrocodone:

30 mg MS

20 mg HC

=

72 mg MS

X


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Equinalagesic Case 2

Dose Reduction

  • Suggested daily hydrocodone dose for BR 24 – 36 mg/day

    Assessment

  • BR’s current hydrocodone dose if given q6h scheduled = 20 – 40 mg


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Questions


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References

1.Pain Management Part 1: Overview of Physiology, Assessment, and Treatment. Chicago, IL, American Medical Association, 2003.

2.Li JM. Pain management in the hospitalized patient. Med Clin N Am 2002; 86: 771-95.

3.Sachs CJ. Oral analgesics for acute nonspecific pain. Am Fam Physician 2005; 71: 913-18.

4.Frampton JE, Keating GM. Celecoxib: A review of its use in the management of arthritis and acute pain. Drugs 2007; 67: 2433-72.

5.Trescot AM, Datta S, Lee M, Hansen H. Opioid pharmacology. Pain Physician 2008; 11: S133-53.

6.Emanuel LL, von Gunten CF, Ferris FD, eds. The Education for Physicians on End-of-life Care (EPEC) Curriculum. EPEC Project, The Robert Wood Johnson Foundation, 1999, Module 4.

7.Inturrisi CE. Clinical pharmacology of opioids for pain. Clin J Pain 2002; 18 : S3-S13.

8.Lexi-Drugs (Comp + Specialty) [computer program]. Lexi-Comp. October 24, 2008.

9.Nickel EJ, Smith T. Analgesia in the intensive care unit: pharmacologic and pharmacokinetic considerations.Crit Care Nurs Clin North America 2001; 13: 207-17.

10.Gardner-Nix J. Principles of opioid use in chronic noncancer pain. Can Med Assoc J 2003; 169:

38- 43.

11.Baker DE. Meperidine: a drug past its prime. Hosp Pharmacy 2001; 36: 1131-32.

12.Auret K, Schug SA. Underutilization of opioids in elderly patients with chronic pain. Drugs Aging 2005; 22: 641-54.

13.Walsh D. Pharmacological management of cancer pain. Semin Oncol 2000; 27: 45-63.

14.Toombs JD, Kral LA. Methadone treatment for pain states. Am Fam Physician 2005; 71: 1353-8.

15. Rapp CJ, Gordon DB. Understanding equianalgesic dosing. Orthop Nurs 2000; 19: 65-72.

16. Cleary JF. Pharmacokinetic and pharmacodynamic issues in the treatment of breakthrough pain. Semin Oncol 1997; 24: S16-13 – S16-19.


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