PharmacologicalApproachesinPainManagement在疼痛治療藥物的方法課件

1、Pharmacological Approaches inPain ManagementRyan J. Bickel, Pharm.D., BCPSupdated byDavid G. Curry, PhD, APRN for NUR344, Fall, 2009Used with permission第1頁，共46頁。Learning ObjectivesReview common non-opioid, opioid, and adjuvant analgesic medicationsDiscuss and apply equianalgesic dosing concepts to s

2、elected case studies第2頁，共46頁。WHO Pain Laddererlewinedesign/end-of-life-care/gfx/who_ladder.gif第3頁，共46頁。Non-Opioid Medications“Ceiling effect” to analgesiaDo not produce tolerance or physical dependenceExhibit antipyretic propertiesRef. 1第4頁，共46頁。Acetaminophen (APAP)Mechanism of action unclearNo anti

3、-inflammatory effectsCauses liver toxicity at high dosesMax dose: 4 gm/day, if no liver diseaseNewest recommendation 2.6 gm/dayDecreases opioid requirementsRef. 1,2 第5頁，共46頁。SalicylatesAspirin (ASA)Effective as APAP for acute pain at similar dosesWorse side effect profile than APAPSalicylate SaltsSa

4、fer than ASANo platelet effectsExamples:Diflunisal (Dolobid)Magnesium salicylate (Doans)Ref. 1,3第6頁，共46頁。NSAIDsEfficacy is similar amongst NSAIDsDifferences in potency, time of onset, & duration of actionSide effects:GI bleedingrenal dysfunctionplatelet dysfunction Ref. 1,3第7頁，共46頁。NSAIDsIbuprofen (

5、Motrin)initial choice for acute pain due to cost & safetyGI safety profile similar to placebo in doses of 1200 mg/dayMaximum daily dose 3200 mg/dayNow available in IV form (Caldolor)Ketorolac (Toradol)first parenteral NSAID available in U.S.use limited to 5 days due to side effectsRef. 2,3第8頁，共46頁。C

6、OX-2 InhibitorsSelectively inhibit cyclooxygenase-2less GI irritation; less platelet effectsother side effects similar to NSAIDsCelecoxib (Celebrex)Role: patients with low cardiovascular risk who require NSAID therapy & are at increased risk for GI toxicityRef. 4第9頁，共46頁。OpioidsOriginally derived fr

7、om poppiesBody possesses endogenous opioidsenkephalinsendorphinsOpiate Receptorsmu ()delta ()kappa ()sigma ()Papaver somniferum Ref. 2,5第10頁，共46頁。Pharmacology of Opioids1: inhibit transmission of pain2: respiratory depression, euphoria, constipation, physical dependence: inhibit transmission of pain

8、: inhibit transmission of pain: autonomic effects, dysphoria, hallucinationsRef. 5第11頁，共46頁。Common Side Effects of OpioidsConstipationvery common, tolerance is unlikelystool softeners + stimulant +/- metoclopramideNausea/Vomitingtolerance usually develops pretreat with prochlorperazineRef. 6第12頁，共46

9、頁。Common Side Effects of OpioidsUrticaria/Pruritisdue to histamine releasetreat with antihistamineSedation tolerance usually developsDeliriumrare in patients with normal renal functionRef. 6第13頁，共46頁。Side Effects of OpioidsRespiratory Depressionpreceded by somnolencetolerance developsuse caution in

10、patients with underlying pulmonary dysfunctionif RR 8 bpm, consider naloxone (Narcan)Ref. 6第14頁，共46頁。MorphineGold standard of opioid therapyHalf-life: 1.5 -2 hrsDuration: 3 - 5 hrsMetabolized to a renally excreted active metabolitedose adjustment may be needed in renal failureRef. 7第15頁，共46頁。Morphin

11、eMultiple dosage forms availableextended-release cap/tabAvinza: once daily dosingKadian: daily or q12h dosingMSContin, Oramorph SR: q8-12h dosingImmediate-release tab oral suspension (Roxanol)suppository (RMS)parenteral injection (Duramorph, Infumorph)Ref. 7,8第16頁，共46頁。Hydromorphone (Dilaudid)Altern

12、ative to morphinesafe in renal failure more soluble than morphineGood choice when opioid volume is an issueopioid tolerant patientscachectic patients Forms: parenteral, tab, suppositoryRef. 7,9第17頁，共46頁。Oxymorphone (Opana)Highly selective for mu receptorMore potent than morphine Forms:immediate rele

13、ase tabdo not take with mealsextended-release tabdo not take with meals or alcoholparenteralRef. 8,9第18頁，共46頁。Codeine Indicated for mild-moderate painweak opioid activity itselfusually combined with acetaminophen Metabolized to morphine by the liver (2D6)poor metabolizers (lack 2D6)ultra-rapid metab

14、olizers (2D6 gene duplication)Side effects limit usePrimarily nausea/vomiting or constipationRef. 2,10第19頁，共46頁。Codeine DerivativesUsed in moderate-severe painHydrocodonecombined with acetaminophen (Lorcet, Lortab, Norco, Vicodin, Zydone)watch amount of acetaminophen (max: 4 gm/day)Oxycodoneextended

15、-release tabs (OxyContin)immediate release caps/tabs (OxyIR, Roxicodone) oral solution (Oxyfast, Roxicodone)combination products (Percocet, Percodan, Tylox)Ref. 1,2,8第20頁，共46頁。Meperidine (Demerol)Not a first line agent!Variable oral bioavailabilityShort duration of actionRelatively low potencyNeurot

16、oxic metabolitesNormeperidine has very long half-life!Multiple drug interactionsRef. 11,12第21頁，共46頁。MeperidineBorgess Usage GuidelinesDo not use for over 48 hrsMaximum dose: 600 mg/24 hr periodAvoid in patients with renal dysfunction or a history of seizuresOral use discouraged第22頁，共46頁。FentanylHigh

17、ly lipophilic Causes less histamine release than other opioids Unique dosage forms/delivery devicesbuccal tablet (Fentora)lozenge (Actiq)transmucosal film (Onsolis) restricted use in US at the present timetransdermal patch (Duragesic)Ref. 7-9第23頁，共46頁。Fentanyl Transdermal Patch Advantages:sustained-

18、release opioidgood in patients with poor compliance good choice if concerned about drug abuseDisadvantagesdelay in onsetresidual activity after patch removed must remove old patch!expensiveNote: Heat increases rate of release from patchRef. 2,13第24頁，共46頁。Methadone (Dolophine)Not a first-line opioidN

19、on-opioid actions provide additional analgesiaHalf-life: 22 hrsDuration: 3-6 hrs (initial) ;8-12 hrs (chronic)Pros: cheap; good for refractory painCons: unpredictable; difficult to dose; drug interactionsRef. 12,14第25頁，共46頁。Propoxyphene (Darvon)Not a first line agent!Neurotoxic metaboliteLong half-l

20、ifePropoxyphene-APAP (Darvocet)not much more efficacious than APAP aloneRef. 2,3第26頁，共46頁。Mixed Agonist-AntagonistsNot a first line agentcauses withdrawal in patients on opioidsceiling effect on analgesiapsychotomimetic adverse effectsLower abuse potentialExamples:Butorphanol (Stadol)Pentazocine (Ta

21、lwin, Talwin NX)Buprenorphine (Buprenex)Ref. 7第27頁，共46頁。Tramadol (Ultram)Dual mechanism of actionUsed for moderate painLess respiratory depression than opioidsMay enhance risk of seizuresmax dose: 400 mg/24 hrsdecrease dose in elderly & renally impairedRef. 5,8第28頁，共46頁。Adjuvant Pain Medications “dr

22、ugs that are used primarily for treating conditions other than pain, but may be analgesic in selected circumstances”-AMARef. 1第29頁，共46頁。Common Adjuvant MedicationsAntidepressantsAnticonvulsantsCorticosteroidsTopical AnestheticsCalcitoninBisphosphonatesRef. 1第30頁，共46頁。Pharmacokinetics of RoutesRef. 6

23、第31頁，共46頁。Equianalgesic TableOpioidIM/IV (mg)Oral(mg)Morphine1030OxycodoneNot Available20Oxymorphone110Hydromorphone1.57.5Fentanyl0.1Not AvailableMeperidine75300HydrocodoneNot Available20Codeine120200Ref. 8,15第32頁，共46頁。Equianalgesic Dosing MethodologyTotal the 24-hour dose of current opioid usage in

24、cluding prn dosesConvert for drug & route using tableReduce calculated dosage 30-50%Calculate breakthrough pain dose, if converting long-acting opioids5 15% of total daily opioid doseRef. 15,16第33頁，共46頁。Equianalgesic Case 1 MJ is a 56 YOM with prostate cancer admitted to hospital for pain control. H

25、e 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?第34頁，共46頁。Equianalgesic Case 1Table IV dosePt 24 hr IV dos

26、eTable PO doseX amount of PO=第35頁，共46頁。Equianalgesic Case 1OpioidIM/IV (mg)Oral(mg)Morphine1030OxycodoneNot Available20Oxymorphone110Hydromorphone1.57.5Fentanyl0.1Not AvailableMeperidine75300HydrocodoneNot Available20Codeine120200Ref. 8,15第36頁，共46頁。Equianalgesic Case 1Set up proportionCross multiply

27、10 mg IV34 mg IV=30 mg POX10 mg IV34 mg IV=30 mg POX第37頁，共46頁。Equianalgesic Case 1 10X = 1020Divide each side by the number in front of X: 10X 1020 10 10Select Reasonable RegimenMS Contin 45 mg PO BID X = 102=第38頁，共46頁。Equianalgesic Case 1Calculate the oral morphine dose needed for breakthrough pain

28、Answer: Morphine 5 15 mg PO every 4 hours prn pain第39頁，共46頁。Equinalagesic Case 2PJ 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 dcd the morphine & ordered Lortab 5/500 mg 1-2 tabs PO q6h PRN pain

29、. What do you think of this regimen?第40頁，共46頁。Equinalagesic Case 2Convert to oral morphine:10 mg IV24 mg IV=30 mg POX10X = 720X = 72 mg PO morphine 第41頁，共46頁。Equinalagesic Case 2Convert to hydrocodone:30 mg MS72 mg MS=20 mg HCX30X = 1440X = 48 mg hydrocodone 第42頁，共46頁。Equinalagesic Case 2Dose Reduct

30、ion Suggested daily hydrocodone dose for BR 24 36 mg/dayAssessmentBRs current hydrocodone dose if given q6h scheduled = 20 40 mg第43頁，共46頁。Questions第44頁，共46頁。References1.Pain Management Part 1: Overview of Physiology, Assessment, and Treatment. Chicago, IL, American Medical Association, 2019.2.Li JM.

31、 Pain management in the hospitalized patient. Med Clin N Am 2019; 86: 771-95.3.Sachs CJ. Oral analgesics for acute nonspecific pain. Am Fam Physician 2019; 71: 913-18.4.Frampton JE, Keating GM. Celecoxib: A review of its use in the management of arthritis and acute pain. Drugs 2019; 67: 2433-72.5.Trescot AM, Datta S, Lee M, Hansen H. Opioid pharmacology. Pain Physician 2019; 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, 2