ࡱ> @ JPbjbjFF (,,0H$$$$$$$8UUU8U4U<8L4W4W"VWVWVWVWVWVW$>R$VWVWVWVWVW$$VWVWfZfZfZVW$VW$VWfZVWfZfZ?t$$VW(W \z2UlW^G0L W 88$$$$ $HfZVWVWVW88D0|4!PZ88|4PAIN MANAGEMENT ANALGESICS PAC 16 Pharm II Overview Definition of Pain unpleasant sensory and emotional experience that normally serves to alert an individual to actual or potential tissue damage Causes of tissue damage which results in pain Exposure to noxious chemical (acid), mechanical (pressure), or thermal stimuli Pathological process- tumors, muscle spasm, inflammation, and nerve damage Classification of pain Duration (acute vs. chronic) Table 1 Acute vs. Chronic Pain Acute PainChronic PainIs there an obvious cause?Yes (well defined, recent onset)Not always (persist over time)Is it reversible?YesNoWhat other Signs and Sx occur?( HR, HTNDepression, withdrawal Relation to cancer (malignant vs. nonmalignant) Pathophysiology (Nociceptive, neuropathic, visceral) Nociceptive pain due to stimulation of nerve fiber by noxious stimulus (chemical, thermal, mechanical and/or ischemic) Somatic- well localized to specific dermal, subcutaneous, or muscular tissue; often described as aching or dull; treat with opiates or non-opiate derivatives Visceral- originate in thoracic or abdominal structures, poorly localized, and distant from the source of the pain; described as deep aching or cramping; can be treated with opiates and non-opiates Neuropathic pain usually caused by nerve damage to CNS or PNS. Often described as burning or stabbing and may radiate down arms and legs. Treatment w/ all forms of analgesics variable and unpredictable. Diabetic neuropathy, post-herpetic neuropathy, nerve compression, nerve inflammation; can be treated with all forms of analgesics Idiopathic pain often due to psychological factors with no known cause or origin Pain prevention/relief General anesthetics inhalational or parenterally to cause the loss of consciousness and prevent awareness of pain during surgery Local anesthetics applied topically or locally to the site where the pain will originate to prevent transmission of pain impulse to spinal cord Analgesics opiod analgesics work in the central nervous system to inhibit neurotransmission of pain Non-opiod analgesics: Inhibitors of prostaglandin synthesis. Also exert antipyretic and anti-inflammatory properties. Work in peripheral tissue to inhibit formation of pain impulses by the nociceptive pain stimuli. Aspirin NSAIDS Acetaminophen no anti-inflammatory properties relatively safe Can cause liver toxicity with high doses, prolonged use or in alcoholics. Limit dose to 4 grams/day (8 extra strength Tylenol); 2 gm with conjunctive hepatotoxics Opiods & Opiod receptors Opium extracts of opium poppy. Morphine was isolated from morphine in 19th century Opiod Receptors members of G protein-coupled receptor family. Activation of receptor: Figure 1 Opiod receptor activation Activation of opiod receptor ( Inhibition of adenylyl cyclase ( Decrease in concentration of cAMP ( Increase in efflux of K+ and Ca2+ channels close ( Presynaptic inhibition of neurotransmitter release ( Postsynaptic inhibition of membrane depolarization Types of opiod receptors mu-1 and mu-2 ((1 and (2) mediates most of effects of morphine and strong opiod agonists sigma delta (() epsilon kappa (() mediates effects of mixed opiod agonist-antagonists Endogenous opiod peptides- can bind to receptors and produce pain-relieving experience enkephalins smaller peptides, release from neurons throughout entire pain axis endorphins larger peptides dynorphins larger peptides Opiod Drugs (Narcotics) Full agonists strong agonists mild-moderate agonists Full agonists can also be subdivided based on chemical structure class (useful to know in case patient has allergic-type reaction to one particular agent) Phenanthrenes; codeine, morphine, oxycodone, hydromorphone, levorphanol Phenylpiperidines: meperidine, fentanyl Diphenylheptanes: methadone, propoxyphene Mixed agonist-antagonists Pure antagonists Pharmacological effects of Opiod Agonists Table 2 Pharmacological Effects of Opiod Agonists CNS effects Analgesia alters perception of pain and patients reaction to pain Dysphoria/euphoria floating sensation, free from anxiety Inhibition of cough reflex useful as antitussive Miosis (except meperidine causes mydriasis)- classic sign (meperidine-opposite) Physical dependence Respiratory Depression often dose-limiting factor Sedation causes drowsiness and impairs thinking CVS effects ( myocardial oxygen demand vasodilation & hypotension GI/biliary effects Constipation due to decreased motility and decreased HCl secretion Increased biliary sphincter tone & pressure caution in pts w/ gall stones Nausea and vomiting (via stimulation of CTZ) Genitourinary effects Increased bladder sphincter tone Prolongation of labor Urinary retention Neuroendocrine system effects Inhibition of release of LH & FSH decreases ovarian and testicular function Stimulation of release of ADH and prolactin Immune system effects Suppression of function of natural killer cells Dermal effects Flushing Pruritis Urticaria (hives) or other rashAlso see table 4 at end of handout Therapeutic uses of Opiods analgesics acute myocardial infarction (for pain and anxiety) antitussives- best treatment Treatment of acute pulmonary edema antidiarrheals Adjunct to anesthesia (given in combo with anticholinergic prior to surgery. Anticholinergic will decrease tracheal and bronchial secretions) Relative Contraindications & Precautions to with Opiod Use Avoid mixed agonist/antagonist in pts on full agonists-precipitate withdrawal Do not use in patients with head injuries-depression Chronic use during pregnancy may result in a dependent offspring In pts with underlying respiratory dysfunction, respiratory failure can occur Half-lives increased in patients with hepatic or renal dysfunction Adverse effects of Opiods & Management Tolerance begins after 2-3 weeks of therapy, more drug needed for same effect Physical dependence - after few weeks w/ withdrawal symptoms if drug abruptly d/c; short lived Psychologic dependence Constipation give high fiber with stool softeners and laxatives to reduce effect Nausea & Vomiting Can use metoclopramide, prochlorperazine or trimethobenzamide short term. Respiratory depression patients usually develop tolerance. With overdose, pinpoint pupils occur. Treat with naloxone (opiod antagonist) Sedation, confusion usually occurs during initiation or with dose increases. May last 2-3 days or until dose decreased, tolerance should develop. Hypersensitivity reactions true hypersensitivity reactions are rare Strong Opiod Agonists (B/D)- become category D with long term use or high dose at term Used for moderate to severe pain Dosing no ceiling dose, no maximum dose, Can be given PO, PR, SL, Buccal, IV, IM, SC, spinally (epidural and intrathecal) and transdermal. Controlled Substance category CII Individual drugs Morphine (IV,PO, PR) Principal alkaloid of opium poppy Kinetics well absorbed PO, but undergoes significant first pass. The IV:PO ratio is 1:6 or 1:3 with chronic use (see Table 5) Indications drug of choice for cancer pain. Also used for severe pain associated with trauma and MI Dosage forms IV in several doses Epidural or intrathecal must use preservative-free IV solutions (Duramorph) to prepare PO (MS Contin, Kadian, Avinza) long acting PO (MSIR) immediate release, short acting, used PRN for breakthrough pain in combo with MS Contin around the clock PO solution It comes in generic in various concentrations (10mg/5ml, 20mg/5ml or 20mg/ml) and brand name Roxanol (20mg/ml or 100mg/5ml). Caution when prescribing and administering Suppository (RMS) 5mg, 10mg, 20mg, 30mg Dosing in cancer patient use around the clock (ATC) with long acting form and PRN for breakthrough pain with immediate release form. PRN total daily dose should be half the total daily dose of the ATC regimen. . (I.e. MS Contin 200mg Q 8 hrs (total dose 600mg/day) & Morphine Sulfate Immediate Release 60mg q 4h prn, MDD 5/day (300mg/day). Hydromorphone (Dilaudid) (PO, PR, INJ) Levorphanol (Levo-Dromoran) (PO,INJ) Methadone (PO, INJ) Low therapeutic index Used for pain but more so for detoxification and maintenance treatment of opiate dependence (heroin addiction). Oxycodone (PO) Available immediate release (OxyIR, Roxicodone), oral solution (Oxycodone) and controlled release (Oxycontin). When given alone, considered strong agonist, when combined with APAP as in Percocet, can be used for mild-moderate pain although still CII controlled drug Fentanyl (INJ) (transdermal patch - Duragesic) (PO-oral lozenge/lollipop Actiq) Used for pain control and as adjunct to regional and general anesthesia Oral Transmucosal Fentanyl Citrate (Actiq) Used for the management of breakthrough cancer pain in patients with cancer who already are receiving and who are tolerant to opiod therapy. Transdermal system; Start with 25mcg/hr patch if no previous opiate use, otherwise use conversion chart. Patch changed every 3 days. Some patients require every 2 days. Conversion from morphine to transdermal fentanyl (Table 3) Table 3 Corresponding doses of Oral/IM morphine and Duragesic patch PO 24 hr Morphine (mg/day)IM 24 hr morphine (mg/day)Duragesic dose (mcg/hr)45-1348-2225135-22428-2750225-31438-5275315-40453-67100405-49468-82125495-58483-97150585-67498-112175675-764113-127200765-854128-142225855-944143-157250945-1034158-1722751035-1124173-187300Meperidine (Demerol) (PO) (INJ) Not recommended for cancer patients b/c of short analgesic half-life of 3 hours and irritates tissue to the point that it may cause severe muscle fibrosis. Metabolite-Normeperidine has convulsant activity and may cause neurological adverse effects. Often combined with Phenergan to increase analgesia but is associated with increased renal effects. Meperidines use within 14 days of MAOI (Tranylcypromine, Phenelzine, Isocarboxazid, Pargyline) can produce life-threatening drug interaction encompassing: hypertensive crisis (severe headache, palpitations, neck stiffness, nausea, vomiting, sweating, choking sensation, temperature elevation, agitation, shivering, mydriasis, and/or visual disturbances such as photophobia) Tachycardia or bradycardia and chest pain may occur. Intracranial hemorrhage has also been reported. Moderate Opiod Agonists Less potent than strong opiod agonists Do not produce maximum analgesia at doses that are well tolerated, therefore they are given in submaximul doses for the treatment of mild-moderate pain and given in conjunction with non-opiod analgesic like aspirin or acetaminophen to enhance their effects. Remember to monitor total dose of non-opiod analgesic as well. (i.e. APAP should be less than 4 grams/day) Individual drugs Codeine (PO, INJ) (C-II) Better bioavailabilty than morphine Good choice for anti-tussive Codeine w/ APAP (PO) (CIII or CV if liquid form) Tylenol #2 15mg codeine Tylenol #3 30mg codeine Tylenol #4 60mg codeine (All have 300 or 325 mg APAP) Hydrocodone/APAP- Vicodin (C-III) Oxycodone/APAP Percocet (C-II) Oxycodone/ASA Percodan (C-II) Tramadol (Ultram) (PO) (C) used for mild to moderate pain. Manufacturer is aiming for the NSAID population. It has no anti-inflammatory activity. Not an opiod but binds to opiod receptors Abuse potential- must avoid in patients with previous opioid dependence Can cause seizures even in normal dosing. Even though structurally unrelated to opiates, this atypical opiate may cause anaphylactoid reactions in patients with a history of opiate allergy. Use is contraindicated in opiate allergy. Miscellaneous Opiod Agonists Propoxyphene Questionable analgesic efficacy DDI with CNS meds like sedatives and other psychotropic meds causing ADRs like hallucinations. Active metabolite - norpropoxyphene Used to treat mild to moderate pain Formulations by itself (Darvon, Darvon-N) (C-IV) (C/D) with APAP (Darvocet) (C-IV) (C) with ASA (Darvon Compound) (C-IV) (D) Dextromethorphan (DM in cough & cold preparations) little analgesic activity significant antitussive activity Diphenoxylate (with atropine = Lomotil) and Loperamide (Imodium) activate opiod receptors in GI smooth muscle used to treat diarrhea DO NOT USE IN PSEUDOMEMBRANOUS COLITIS Mixed Agonist/Antagonists & Partial Agonists Mixed agonists are Pentazocine (Talwin), Butorphanol (Stadol) and Nalbuphine (Nubain) Partial narcotic agonists include: Buprenorphine (Buprenex, Temgesic) and Dezocine (Dalgan) Unlike opiates, these drugs have an analgesic ceiling effect and all (with the exception of Butorphanol) are not controlled. May produce psychotomimetic reactions which include feelings of unreality, depersonalization, dysphoria, nightmares, vivid daydreams, hallucinations, delusions and panic. Butorphanol (CIV) is also available as a nasal spray for migraine headache sufferers. Indications Parenteral forms for preoperative and post operative analgesia and obstetric analgesia during labor and delivery. Oral forms for moderate to severe pain Opiod Antagonists Naloxone (Narcan) (IV) and Naltrexone (Revia) (PO) competitive antagonists that rapidly reverse effects of morphine Used for treatment of opiod overdose and prevention and treatment of opiod dependence and addiction. Naltrexone has also been used in the treatment of alcohol dependence Patient-controlled analgesia (PCA) use an IV narcotic with a setting for the patient IV administration where patient can self-administer preset amounts of analgesic via a syringe pump with a timed device. May not be suitable in elderly or immediately following surgery Can be given with or without local anesthetics (lidocaine-used to reduce amount of narcotic used) May cause infection and urinary retention Adjuvant drugs These drugs can enhance the analgesic efficacy of opiates, treat concurrent symptoms that exacerbate pain, and provide independent analgesia for specific types of pain. Can be used in all stages of the step wise approach to pain mgt They do not replace opiates for pain mgt. Examples of adjuvant pain meds Tricyclic Antidepressants (TCA) Amitriptyline - TCA of choice in treating neuropathic pain. HS dosing minimizes ADRs (dry mouth, blurred vision, etc). Also it produces sedation Benzodiazepines may be useful to treat anxiety. Short acting is best, such as Lorazepam or Alprazolam. Corticosteroids Decrease inflammation and edema, treating pain due to nerve compression and brain metastases and for bone pain. Prednisone and Dexamethasone are the most commonly used. Taper doses due to risk of hypothalamic-pituitary-adrenal (HPA) axis suppression. Anticonvulsants (Carbamazepine, Phenytoin, Clonazepam, Valproate and Gabapentin) are utilized for treating neuropathic pain. Psychostimulants include Dextroamphetamine (Dexadrine), Methylphenidate (Ritalin) and Pemoline (Cylert) May decrease sedation from narcotics and potentiate their analgesic effects. Low doses may enhance patients sense of well-being and may provide enough energy to increase food consumption. Avoid HS since it may produce insomnia. Biphosphonates (i.e., Pamidronate), Calcitonin, Gallium Nitrate and Strontium-89 Effective adjuvants for treatment of bone pain associated with malignancy. (Baclofen (Lioresal), Pimozide Orap) and Mexiletine (Mexitil) Used for the treatment of neuropathic pain such as trigeminal neuralgia and diabetic neuropathy. Pimozides ADRs include acute dystonia and akathisias. Capsaicin cream Activates peripheral nociceptors on primary sensory neurons Produces burning sensation initially then analgesic effect Pregabalin (Lyrica) (PO) GABA analogue Recently received FDA-approval for diabetic peripheral neuropathy and post herpetic neuralgia pain. 1st drug approved to treat both these conditions. Will be available for prescribing shortly. Currently under FDA review for adjunct treatment of partial seizures Ziconotide (Prialt) (Intrathecal) Non-opiod analgesics: N-type calcium channel blockers. Recently received FDA-approval for the management of severe chronic pain in patients for whom intrathecal (IT) therapy is warranted, and who are intolerant of or refractory to other treatment, such as systemic analgesics, adjunctive therapies or IT morphine MOA: targets and blocks N-type calcium channels on nerves that ordinarily transmit pain signals. Warnings: Can cause severe psychotic symptoms and neurological impairment and meningitis Approaches to Pain Management Factors affecting the choice of treatment location, cause and severity of pain risk of producing drug dependence Pain assessment cancer patients get whatever they want essential to adequately treat pain Various pain assessment tools/scales available Utilize step-wise approach Step 1 - Mild to moderate pain use non-opiate +/- adjuvant medication Step 2 - If pain persists after step 1, use moderate opiate +/- non-opiate+/- adjuvant medication Step 3 For moderate to severe pain use strong opiate +/- non-opiate+/- adjuvant medication Acute vs. Chronic pain Analgesic Strategies between Acute and Chronic Pain Treatment (McKee CD, US Pharmacist, 1997) ACUTE PAINCHRONIC PAINTherapeutic goalPain reliefPain preventionSedationOften desirableUsually undesirableRapid onset of effectImportantUnnecessaryDesired duration of effect2-4 hoursAs long as possibleTimingAs needed (prn)Regularly (in anticipation, ATC dosing)DoseUsually standardIndividually titratedRouteParenteral/OralOral/Transdermal/ParenteralAdjuvant MedicationsUncommonCommonTreatment of acute pain Usually effectively managed with an analgesic and appropriate treatment of underlying condition Risk of producing drug dependence is low Initial stages give analgesics ATC to avoid wide swings in pain and sedation, then switch to PRN basis Can use PCA as well Treatment of chronic pain Varies greatly with underlying cause Increased risk of opiod tolerance and dependence Use both opiods and non-opiods as well as adjuvant drugs If associated with peripheral nerve or nerve root sensitization use treatment with transcutaneous nerve stimulation (TENS) or local anesthetics Treatment of cancer pain usually requires administration of strong opiod agonist ATC with PRN breakthrough doses as well Non-opiates and adjuvants also utilized Patients should receive sufficient doses to control their pain, regardless of potential for dependence or tolerance PAGE  PAGE 9 /0K  + 7 J K _  w y 8 B QR?P67@KW \_bdm| h^hH*aJhHOJQJaJ haJh^h)aJ jh^haJh^hHaJ hHaJh^h5aJh^haJh^hOJQJaJ</09K  $Ifl  & F & FgdH & F & F$a$0PIP  A ` n^^^$Ifl kd$$IflFz,"v1  06    4 lapp ` a s w z ~nnn$Ifl kd$$IflFz,"v1 06    4 lapz { ~nnn$Ifl kd$$IflFz,"v1 06    4 lap " :  R~xssniinan & FgdH & F & F & Fp^pkd/$$IflFz,"v1 06    4 lap ?7,L\m  *,NP$a$T^T & F & F & F & F & F & F & F   *+,4NOPXno+Hrح؎h^h;OJQJaJh^hOJQJaJh^h5>*aJ h;aJ h;5aJ jkh^haJ jdh^haJ jmh^haJh^h5aJh^h)aJh^haJ jh^haJ0P`gqya~ & F   & F & F & F & F & F$a$7Hr1d.:UpA$Ifl $@&If^l  & F & F p^ & F p!^.:;pAW8N~HX"STU s !!!""y"}"(%%񬙬񬢬񬙬 h`aJ h`5aJ hK5aJh^h)aJh^h5aJh^haJh^h;5aJhKh;>*aJh^h;CJOJQJaJ jh^h;aJh^h;OJQJaJ hKaJh^h;aJ4AWx 8N~$Ifgda[Wl $Ifl $@&If^l   <Y|Ug & F & F & F$a$bkd$$Ifl4'"064 la!J h!!"&"R"""""##$$($$$(%% & F & F & F & F & F & F & F% &_'''''G(V((a)))*a++++,1,$$Ifa$l ^gd$ & Fa$ & F & F & F%&&)$*'**++++8.9...{0092Q233303B3I3%4P4a44[55788@8:':(:-:;,;J<n<o<<<===|| ha[WaJ ha[W5aJha[Wh,O5aJha[Wh5aJh^h)5aJh^h5aJh^h,OaJ h,OaJ haJh^h5OJQJaJh^h)OJQJaJh^hOJQJaJh^h)aJh^haJ01,2,9,>,A,yfff$$Ifa$l kdg$$IflF*   06    4 lapA,B,J,P,S,yfff$$Ifa$l kd$$IflF*   06    4 lapS,T,\,b,e,yfff$$Ifa$l kd$$IflF*   06    4 lape,f,n,t,x,yfff$$Ifa$l kd#$$IflF*   06    4 lapx,y,,,,yfff$$Ifa$l kd$$IflF*   06    4 lap,,,,,yfff$$Ifa$l kdK$$IflF*   06    4 lap,,,,,yfff$$Ifa$l kd$$IflF*   06    4 lap,,,,,yfff$$Ifa$l kds$$IflF*   06    4 lap,,,,,yfff$$Ifa$l kd$$IflF*   06    4 lap,,,,,yfff$$Ifa$l kd$$IflF*   06    4 lap,,,--yfff$$Ifa$l kd/ $$IflF*   06    4 lap-----yfff$$Ifa$l kd $$IflF*   06    4 lap--?--9..{000(292ytoggob]]] & F & F & Fgd) & F & FkdW $$IflF*   06    4 lap 92R2v22222303R3s33Q4445555/6T6x6666 & F$ & F$ & F$ & F$gd & F" ^  & F! & F  & F66+7E7f77778@888q9:s:;,;_;;J<<=[== & F# & F,gd & F$ & F* & F*gd & F$gd & F$ & F$ & F$===>> ?+?K???J@[@@A[AA@BBC)C{CCDgDD$ & F%a$$ & F%a$ & F% & F% & F$ & F$==+?J???J@Y@[@c@ZAkAAA@BCB)CzC{CCCDD DEEEEuFFFGGHH6H>HPHZHiHjHH I1IJJKKǺǺǺǺǺǬǛǛǛǛxh^h56aJ ha[WaJ!h^h)B*OJQJaJph!h^hB*OJQJaJphh^hH*OJQJaJh^h)OJQJaJh^hOJQJaJh^h>*OJQJaJh^h>*aJh^haJh^h5aJ/DDD%E>ELERFuFFGHjHHHHH2IUIIIIIJJJJK$h^ha$ & F$ & F$ & F$$ & F%a$$ & F%a$KK*K7K8KIKUKeKR??$$Ifa$l kd $$IflF,`'\  \ 0$    4 la<$$@&If^a$l $Ifl K7K0P1P7P8P9P;P@8 Title$a$ 5OJQJ4 @4 Footer  !.)@!. 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Rini,                           ! " # $ % & ' ( ) * + Oh+'0 ,8 T ` l xPAIN MANAGEMENT ANALGESICSAINcscuserscuscu Normal.dotMNicholas M. Rini AN2chMicrosoft Word 10.0@vA@HR@wz2@wz2 j=՜.+,0( hp  &St Vincent's Catholic Medical CentersE$ H PAIN MANAGEMENT ANALGESICS Title  !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWYZ[\]^_`bcdefghijklmnopqrstuvwxyz{|}~Root Entry F;oz2Data X1TableaWordDocument(SummaryInformation(DocumentSummaryInformation8CompObjj  FMicrosoft Word Document MSWordDocWord.Document.89q