Pain and Cancer Pain and Cancer Pain ManagementPain Management

Dr.Staporn LeelanuntakitDr.Staporn Leelanuntakit

Definition of PainDefinition of Pain““An unpleasant sensory and emotional An unpleasant sensory and emotional

experience associated with actual or experience associated with actual or potential tissue damage or described in potential tissue damage or described in terms of such damage. Pain is always terms of such damage. Pain is always subjective. Each individual learns the subjective. Each individual learns the application of the word through experiences application of the word through experiences related to injury in early life…. It is related to injury in early life…. It is unquestionably a sensation in a part or parts unquestionably a sensation in a part or parts of the body but it is also always unpleasant of the body but it is also always unpleasant and therefore an emotional experience”and therefore an emotional experience”

International Association for the Study of Pain,1979International Association for the Study of Pain,1979

The Perception of The Perception of PainPain

The processes involved in The processes involved in perception of pain are no perception of pain are no longer viewed as a simple hard longer viewed as a simple hard wired system with a pure wired system with a pure stimulus response stimulus response relationship.relationship.

Neurobiology and Neurobiology and Neurophysiology Neurophysiology of Painof Pain

Neurotransmitters Neurotransmitters Involved in Pain Involved in Pain PathwaysPathways

SerotoninSerotonin GABAGABA GlutamateGlutamate Substance PSubstance P Opioid peptidesOpioid peptides

Reisine T, Pasternak G. In: Goodman & Gilman’s. 9th ed. 1996;521-555.Ollat H, Cesaro P. Clin Neuropharmacol.1995;18:391-404.

Neurotransmitter that Neurotransmitter that play a role in Pain play a role in Pain ModulationModulation

Alpha-2-adrenergic agonistsAlpha-2-adrenergic agonists N-methyl-d-aspatate (NMDA) N-methyl-d-aspatate (NMDA)

antagonistsantagonists Sodium channel blockersSodium channel blockers Calcium channel blockersCalcium channel blockers Gamma-aminobutyric agonists Gamma-aminobutyric agonists

(GABA)(GABA)

Pain BehaviourPain Behaviour

Nociception

Pain

Suffering

Pain Behaviour

Physiological Pain ----Physiological Pain ---- PAIN PAIN ------- Pathological ------- Pathological Pain Pain (Functional) (Functional) (Nociceptive;Neuropathic)(Nociceptive;Neuropathic)

^̂ | | | |

Psychological PainPsychological Pain

Composition of PainComposition of Pain

Other symptoms adverse Other symptoms adverse effects of treatmenteffects of treatment

PhysicalPhysical

DepressionDepression AngerAngerLoss of social positionLoss of social position Bereaucratic bungling Bereaucratic bunglingLoss of job prestige and incomeLoss of job prestige and income Delays in diagnosis Delays in diagnosisLoss of role in familyLoss of role in family Unavailable doctors Unavailable doctorsInsomnia and chronic fatigueInsomnia and chronic fatigue Therapeutic failure Therapeutic failureSense of helplessnessSense of helplessness Friends who do not visit Friends who do not visitDisfigurementDisfigurement

AnxietyAnxietyFear of hospital or nursing homeFear of hospital or nursing homeFear of PainFear of PainWorry about family and financeWorry about family and financeFear of deathFear of deathSpiritual unrest, uncertainty about futureSpiritual unrest, uncertainty about future

Robert Taycross; 1944Robert Taycross; 1944

TOTAL PAINTOTAL PAIN

Pain related to CancerPain related to Cancer

Pain UnrelatedPain Unrelated PHYSICAL PAINPHYSICAL PAIN Pain related toPain related toto cancerto cancer cancer treatment cancer treatment

PainPain + + - Pain - Pain Other physical symptom +Other physical symptom + - Other physical symptom - Other physical symptom Psychological problem +Psychological problem + - Psychological problem - Psychological problem Social difficultSocial difficult ++ - Social difficult - Social difficult Cultural issue +Cultural issue + - Cultural issue - Cultural issue Spiritual concern +Spiritual concern + - Spiritual concern - Spiritual concern

What the patient says it isWhat the patient says it is CLINICAL PAINCLINICAL PAIN What has to be What has to be treatedtreated

The Concept of Clinical PainThe Concept of Clinical Pain

Types of PainTypes of Pain Acute PainAcute Pain Chronic PainChronic Pain Cancer PainCancer Pain

Difference between Difference between Acute and Chronic PainAcute and Chronic Pain

Acute painAcute painTranscientTranscientActs as a warning signActs as a warning sign

Patients: Patients: DecreasesDecreasesObviously in painObviously in painComplains loudly of painComplains loudly of painUnderstand painUnderstand pain

Primarily affect patientsPrimarily affect patientsDoctors: Doctors: Treatment Treatment

straightforwardstraightforwardParenteral analgesicsParenteral analgesicsAnalgesic side effectsAnalgesic side effectsaacceptablecceptable

Chronic painChronic painPersistentPersistentServe no useful purposeServe no useful purposeTends to increaseTends to increaseMay only seem depressedMay only seem depressedMay only complain of May only complain of

discomfortdiscomfortSee pain as unending and See pain as unending and

meaninglessmeaningless

Pain overflows to affect Pain overflows to affect familyfamily

Treatment may be complexTreatment may be complexOral analgesics preferableOral analgesics preferableSide effects unacceptableSide effects unacceptable

Pain in Cancer PatientPain in Cancer Patient Direct tumor involvementDirect tumor involvement Complications of cancer treatment or of Complications of cancer treatment or of

antalgic therapyantalgic therapy Cancer related physiologic and biochemical Cancer related physiologic and biochemical

alterations, and those associated with alterations, and those associated with chronic illness, such as muscle weakness and chronic illness, such as muscle weakness and other disorder known as “paraneoplastic other disorder known as “paraneoplastic syndrome”syndrome”

Painful disorders unrelated to cancer and Painful disorders unrelated to cancer and cancer therapycancer therapy

A combination of theseA combination of these

What is Cancer Pain?What is Cancer Pain?

By nature cancer pain is:By nature cancer pain is: Recurrent acute pain because there is Recurrent acute pain because there is

continual tissue damage.continual tissue damage. If there is nerve damage, cancer pain can If there is nerve damage, cancer pain can

be very severe and persistent.be very severe and persistent. Rarely, there may be associated chronic Rarely, there may be associated chronic

pain.pain.Particularly when there is nerve damage and Particularly when there is nerve damage and

the patient has a long history.the patient has a long history.

Unique Aspects of Unique Aspects of Cancer PainCancer Pain

More than one site of painMore than one site of pain More than one syndromeMore than one syndrome More than one etiologyMore than one etiology Acute and/or chronicAcute and/or chronic Varied pattern, intensity, and Varied pattern, intensity, and

durationsdurations More than one treatmentMore than one treatment

Prevalence of Cancer Prevalence of Cancer PainPain

Approximately 25% of patients with Approximately 25% of patients with localized disease report painlocalized disease report pain

Prevalence of pain can be as high as Prevalence of pain can be as high as 90% in patients with advanced cancer90% in patients with advanced cancer

Adequate pain control can be achieved Adequate pain control can be achieved in as many as 88% of patients with in as many as 88% of patients with cancer-related pain, but in reality cancer-related pain, but in reality many patients have inadequate pain many patients have inadequate pain managementmanagement

Cause of Cancer PainCause of Cancer Pain Somatic (Bone)Somatic (Bone) VisceraViscera Nervous systemNervous system

Types of Pain : Types of Pain : Somatic PainSomatic Pain

When nociceptors are activated in When nociceptors are activated in cutaneous or deep tissues, somatic cutaneous or deep tissues, somatic pain results, typically characterized pain results, typically characterized by a dull or aching but well-localized by a dull or aching but well-localized pain. Metastatic bone pain, pain. Metastatic bone pain, postsurgical incisional pain, and postsurgical incisional pain, and myofascial and musculoskeletal pain myofascial and musculoskeletal pain are common examples of somatic are common examples of somatic pain.pain.

Types of Pain : Types of Pain : Visceral PainVisceral Pain

Visceral pain results from activation of nociceptors Visceral pain results from activation of nociceptors from infiltration, compression, extension or from infiltration, compression, extension or stretching of the thoracic, abdominal or pelvic stretching of the thoracic, abdominal or pelvic viscera. This typically occurs in patients with viscera. This typically occurs in patients with interperitoneal metastases and is common with interperitoneal metastases and is common with pancreatic cancer. This type of pain is poorly pancreatic cancer. This type of pain is poorly localized; is often described as deep, squeezing, and localized; is often described as deep, squeezing, and pressure-like, and when acute is often associated pressure-like, and when acute is often associated with significant autonomic dysfunction, including with significant autonomic dysfunction, including nausea, vomiting and diaphoresis. Visceral pain is nausea, vomiting and diaphoresis. Visceral pain is often referred to cutaneous sites that may be often referred to cutaneous sites that may be remote from the site of lesion (e.g. shoulder pain remote from the site of lesion (e.g. shoulder pain with diaphragmatic irritation). It may be associated with diaphragmatic irritation). It may be associated with tenderness in the referred cutaneous site.with tenderness in the referred cutaneous site.

Types of Pain : Types of Pain : Neuropathic PainNeuropathic Pain

Neuropathic pain result from injury to Neuropathic pain result from injury to the peripheral or central nervous the peripheral or central nervous system as a consequence of tumor system as a consequence of tumor compression or infiltration of peripheral compression or infiltration of peripheral nerves or the spinal cord, or from nerves or the spinal cord, or from chemical injury to the peripheral nerve chemical injury to the peripheral nerve or the spinal cord caused by surgery, or the spinal cord caused by surgery, radiation therapy or chemotherapy.radiation therapy or chemotherapy.

Types of Pain : Types of Pain : Neuropathic PainNeuropathic Pain

Pain from nerve injury is often severe and is Pain from nerve injury is often severe and is described as burning or dysesthetic, with a described as burning or dysesthetic, with a vice-like quality. The pain is typically most vice-like quality. The pain is typically most common in the site of sensory loss and may common in the site of sensory loss and may be associated with hypersensitivity to non-be associated with hypersensitivity to non-noxious (allodynia) and noxious stimuli. noxious (allodynia) and noxious stimuli. Intermittently patients complain of Intermittently patients complain of paroxysms or burning or electric shock-like paroxysms or burning or electric shock-like sensations. The latter symptoms result from sensations. The latter symptoms result from the phenomenon of central sensitization. the phenomenon of central sensitization.

Principle of Treating Principle of Treating Cancer PainCancer Pain Aim of treatmentAim of treatment

- relief and prevention of pain- relief and prevention of pain General principlesGeneral principles

- through assessment- through assessment- good communication- good communication- reassurance about pain relief- reassurance about pain relief- discourage acceptance of pain- discourage acceptance of pain- encourage patient participation- encourage patient participation

Principle of Treating Principle of Treating Cancer PainCancer Pain Principle of treatmentPrinciple of treatment

- integrated part of a multidisciplinary - integrated part of a multidisciplinary plan of careplan of care

- should be appropriate to the stage of - should be appropriate to the stage of the diseasethe disease

- use the appropriate treatment - use the appropriate treatment modalitiesmodalities- must be consistent, and variable- must be consistent, and variable- requires continuity of care- requires continuity of care- involves repeated reassessment- involves repeated reassessment

Examples of two females and one male actor showing neutral,

anger and pain faces (from left to right column). Five time points in the clip are displayed.

ASSESSMENT of ASSESSMENT of PAINPAIN

Clinical Evaluation Clinical Evaluation 1.Pain is what the patient says-so believe 1.Pain is what the patient says-so believe

and treat.and treat.2.Assess the pain carefully2.Assess the pain carefully

- history (especially result from the - history (especially result from the previous treatment)previous treatment)

- examination- examination- investigation- investigation

Clinical Evaluation Clinical Evaluation (cont..)(cont..)

3. Assess each pain (most cancer patients have more than one pain)

- type of pain- cause of pain- intensity of pain- characteristic of pain

Clinical Evaluation Clinical Evaluation (cont..)(cont..)4. Assess the extent of the patient’s disease4. Assess the extent of the patient’s disease

- The pain- The painSSiteite Where’s it? Where’s it?Radiation Radiation Does it spread to anywhere else? Does it spread to anywhere else?Present since Present since How long have you had it? How long have you had it?ProgressiveProgressive Has it got worse? Has it got worse?Severity How bad is it? (use tools)Severity How bad is it? (use tools)QualityQuality What is it like? What is it like?FrequencyFrequency How often does it occur? How often does it occur?DurationDuration How long does it last? How long does it last?Precipitating factorsPrecipitating factors What brings it on? What brings it on?Aggravating factorsAggravating factors What make it worse? What make it worse?Relieving factorsRelieving factors What helps the pain? What helps the pain?Impact on – activityImpact on – activity Does it stop patient doing things? Does it stop patient doing things?

- sleep- sleep Does it disturb patient sleeping? Does it disturb patient sleeping? - mood- mood Does it make patient unhappy or depressed? Does it make patient unhappy or depressed?

Clinical Evaluation Clinical Evaluation (cont..)(cont..)4. Assess the extent of the patient’s disease (cont..)4. Assess the extent of the patient’s disease (cont..)

- Effect of previous medication- Effect of previous medicationMedicationMedication What did patient take?What did patient take?DoseDose How much?How much?RouteRoute By mouth? or others?By mouth? or others?FrequencyFrequency How often?How often?DurationDuration For how long?For how long?EffectEffect Did it help?Did it help?Side effectsSide effects Did it upset patient?Did it upset patient?

5. Assess the other factors which may influence pain-physical, 5. Assess the other factors which may influence pain-physical, psychological, social, culture, spiritualpsychological, social, culture, spiritual

6. Reassessment especially for the new or more extensive pain.6. Reassessment especially for the new or more extensive pain.

MANAGEMENT MANAGEMENT OF OF

CANCER PAINCANCER PAIN

Modalities of Treatment Modalities of Treatment (I)(I)

Treatment of underlying cancerTreatment of underlying cancer AnalgesicsAnalgesics Adjuvant analgesicsAdjuvant analgesics Neurostimulatory treatmentNeurostimulatory treatment Anesthetic, neurolytic and Anesthetic, neurolytic and

neurosurgical proceduresneurosurgical procedures

Modalities of Treatment Modalities of Treatment (II)(II)

Physical therapyPhysical therapy Lifestyle modificationLifestyle modification Treatment of other aspects of Treatment of other aspects of

suffering which cause or suffering which cause or aggravate pain: physical, aggravate pain: physical, psychological, social, cultural, psychological, social, cultural, spiritualspiritual

““Analgesic drugs are Analgesic drugs are the mainstay for control the mainstay for control

cancer pain”cancer pain”

““All pain do not respond All pain do not respond equally to analgesic”equally to analgesic”

AnalgesicsAnalgesics Non-Opioid AnalgesicNon-Opioid Analgesic Opioid AnalgesicOpioid Analgesic

- Weak opioid- Weak opioid- Strong opioid- Strong opioid

Adjuvant DrugsAdjuvant Drugs

The Use of Analgesics The Use of Analgesics for Cancer Painfor Cancer Pain

Choice of DrugChoice of Drug- appropriate drug for choice of pain- appropriate drug for choice of pain- appropriate drug for severity of pain- appropriate drug for severity of pain- use of combinations of drugs not - use of combinations of drugs not combined drugscombined drugs- follow the analgesic ladder- follow the analgesic ladder- use adjuvant analgesics- use adjuvant analgesics- never use placebo- never use placebo

The Use of Analgesics The Use of Analgesics for Cancer Painfor Cancer Pain

AdministrationAdministration- give in adequate dosage- give in adequate dosage- titrate the dose for each individual patient- titrate the dose for each individual patient- schedule administration according to - schedule administration according to drug pharmacologydrug pharmacology- strict scheduling to prevent pain, not PRN- strict scheduling to prevent pain, not PRN- give written instructions for patients on - give written instructions for patients on

multiple drugsmultiple drugs

The Use of Analgesics The Use of Analgesics for Cancer Painfor Cancer Pain

AdministrationAdministration- warn of, and give treatment to prevent, - warn of, and give treatment to prevent,

side effectside effect- keep the analgesic program as simple as- keep the analgesic program as simple as

possiblepossible- use the oral route whenever possible- use the oral route whenever possible

Review and reassessReview and reassess

Help patient survives to Help patient survives to live with pain and inspite live with pain and inspite of painof pain

Type of Pain: Implications for Type of Pain: Implications for treatmenttreatment NociceptiveNociceptive

Bone, soft tissueBone, soft tissue mild,modulate mild,modulate non-opioidnon-opioid(opioid if required)(opioid if required) severe opioid + non-opioidsevere opioid + non-opioid

VisceralVisceral mild mild non-opioidnon-opioid(opioid if required)(opioid if required) severesevere opioid opioid ±± non-opioid non-opioid

Type of Pain: Implications for Type of Pain: Implications for treatmenttreatment Neuropathic Neuropathic

Nerve compressionNerve compression :opioid + corticosteroid:opioid + corticosteroidanticonvulsantanticonvulsantor tricyclic antidepressantor tricyclic antidepressantor oral local anesthetic or oral local anesthetic

drugdrug

Sympathetic-type painSympathetic-type pain :sympathetic nerve block :sympathetic nerve block

Type of Pain: Implications for Type of Pain: Implications for treatmenttreatment OtherOther

Raised intracranial pressureRaised intracranial pressure:corticosteroid:corticosteroid

Muscle spasmMuscle spasm :muscle :muscle relaxantrelaxant

Non-Opioid AnalgesicsNon-Opioid Analgesics AspirinAspirin ParacetamolParacetamol Nonsteroidal Anti-inflammatory Nonsteroidal Anti-inflammatory

DrugsDrugs (NSAIDs)(NSAIDs)

NSAIDsNSAIDs The realization that NSAIDs may The realization that NSAIDs may

have a central action.have a central action. The cyclo-oxygenase enzyme The cyclo-oxygenase enzyme

differentiates into two types, differentiates into two types, COX-1 and COX-2.COX-1 and COX-2.

Development of safer Development of safer NSAIDsNSAIDs

Preferential inhibitor of COX-2Preferential inhibitor of COX-2- nabumetone- nabumetone- etodolac- etodolac- meloxicam- meloxicam

Highly selective COX-2 inhibitorHighly selective COX-2 inhibitor- celecoxib, etoricoxib,valdecoxib, - celecoxib, etoricoxib,valdecoxib,

parecoxibparecoxib NSAIDs containing nitric oxideNSAIDs containing nitric oxide

The new classification of The new classification of NSAIDs as COX-2 NSAIDs as COX-2

conceptsconcepts1. Classical NSAIDs1. Classical NSAIDs2. Preferential COX-2 inhibitors2. Preferential COX-2 inhibitors (selective COX-2 inhibitor)(selective COX-2 inhibitor)3. Highly specific COX-2 inhibitors3. Highly specific COX-2 inhibitors (COX-2 inhibitor, specific COX-2 (COX-2 inhibitor, specific COX-2

inhibitors)inhibitors)

Selective (nonacidic) Selective (nonacidic) COX-2 inhibitorsCOX-2 inhibitors

- COX-2 and the gastrointestinal COX-2 and the gastrointestinal tracttract

- COX-2 and kidney functionsCOX-2 and kidney functions- COX-2 and the cardiovascular COX-2 and the cardiovascular

systemsystem- COX-2 and the other body COX-2 and the other body

functionsfunctions

OPIOIDSOPIOIDS

Classification of Classification of OpioidsOpioids

““Weak” or “Strong”Weak” or “Strong” Mechanism of actionMechanism of action The chemical derivation of drugThe chemical derivation of drug

- naturally occuring opium alkaloids- naturally occuring opium alkaloids- semisynthetic derivatives of opium- semisynthetic derivatives of opium

alkaloidsalkaloids- synthetic opioids- synthetic opioids

Effects of Activation of Effects of Activation of Opioid ReceptorsOpioid Receptors

µµ : Analgesia, supraspinal: Analgesia, supraspinal: Dependence (withdrawal signs, : Dependence (withdrawal signs,

drug-drug- seeking behaviour)seeking behaviour)

: Sedation: Sedation: Euphoria: Euphoria: Respiratory depression: Respiratory depression

Effects of Activation of Effects of Activation of Opioid ReceptorsOpioid Receptors

KK : Analgesia, spinal: Analgesia, spinal: Sedation: Sedation

SS : Dysphoria: Psychomotor stimulation

(not clinically useful): Hallucination

Opioid Analgesics IOpioid Analgesics I

Optimal use of opioid analgesics Optimal use of opioid analgesics requires a sound understanding of the requires a sound understanding of the general principles of opioid general principles of opioid pharmacology, the pharmacological pharmacology, the pharmacological characteristics of each of the characteristics of each of the commonly used drugs and principles commonly used drugs and principles of administration, include:of administration, include:

Opioid AnalgesicsOpioid Analgesics IIII

1. Drug selection1. Drug selection2. Routes of administration2. Routes of administration3. Dosing and dose titration3. Dosing and dose titration4. Adverse effects and their 4. Adverse effects and their

managementmanagement

NO SINGLE OPIOID IS NO SINGLE OPIOID IS RIGHT FOR ALL RIGHT FOR ALL

PATIENTS IN ALL PATIENTS IN ALL SITUATIONSSITUATIONS

Weak-OpioidsWeak-Opioids CodeineCodeine DextropropoxypheneDextropropoxyphene TramadolTramadol

Strong OpioidsStrong Opioids MorphineMorphine MethadoneMethadone PethidinePethidine

BuprenorphineBuprenorphine HydromorphineHydromorphine LevorphanolLevorphanol

PentazocinePentazocineNot a control drugNot a control drugIt is an agonist-antagonist of the nalophine It is an agonist-antagonist of the nalophine type. It has agonist properties at the kappa type. It has agonist properties at the kappa and sigma receptors but an antagonist and sigma receptors but an antagonist effect at the mu receptor, analgesics of this effect at the mu receptor, analgesics of this type produce psychomimetic side effects type produce psychomimetic side effects such as dysphoria, depersonalization, vivid such as dysphoria, depersonalization, vivid day- dreams, nightmares and hallucinations. day- dreams, nightmares and hallucinations. As a partial agonist it may attenuate the As a partial agonist it may attenuate the effects of pure agonist given concurrentally.effects of pure agonist given concurrentally.It has no place in the relief of cancer pain.It has no place in the relief of cancer pain.

BuprenorphineBuprenorphine

Sublingual and injectionSublingual and injectionNot controlled drugNot controlled drug6 to 8 hourly regimen6 to 8 hourly regimenPartial agonist at the mu-opioid receptorPartial agonist at the mu-opioid receptorAnalgesic celling dose of about 5 mg, Analgesic celling dose of about 5 mg, which which equivalent to about 50 mg of equivalent to about 50 mg of oral oral morphine 4 hourly.morphine 4 hourly.

PethidinePethidine Pethidine has no real place in cancer pain Pethidine has no real place in cancer pain

management.management. It often need to be given every two to It often need to be given every two to

three hour to maintain relief.three hour to maintain relief. It has a toxic metabolite, norpethidine, It has a toxic metabolite, norpethidine,

with a plasma half-life of some 17 hours with a plasma half-life of some 17 hours compared with 3.5 hours of pethidine compared with 3.5 hours of pethidine itself.itself.

Norpethidine is excitatory and causes Norpethidine is excitatory and causes tremor, twitching, agitation and tremor, twitching, agitation and convulsions of high plasma concentration.convulsions of high plasma concentration.

PethidinePethidine Appreciable cumulation occurs with Appreciable cumulation occurs with

doses of pethidine of 200-300 mg doses of pethidine of 200-300 mg particularly if taken by mouth when particularly if taken by mouth when the ratio of pethidine to norpethidine the ratio of pethidine to norpethidine in the blood shifts in favour of the in the blood shifts in favour of the latter.latter.

In patients with severe renal failure, In patients with severe renal failure, toxic effects are seen at much lower toxic effects are seen at much lower doses.doses.

MethadoneMethadone Methadone is slightly more potent than Methadone is slightly more potent than

morphine in single doses but use repeatedly; it morphine in single doses but use repeatedly; it is considerably more potent on account of is considerably more potent on account of cumulation.cumulation.

With chronic use, the plasma half-life increases With chronic use, the plasma half-life increases from 15 hours to two to three days, the use of from 15 hours to two to three days, the use of methadone is more complicated than the use methadone is more complicated than the use of morphine.of morphine.

It is not advisable to use methadone in the very It is not advisable to use methadone in the very elderly and severity debilitated, in patients with elderly and severity debilitated, in patients with appreciable liver, renal or respiratory failure or appreciable liver, renal or respiratory failure or in patients with intracranial tumours. in patients with intracranial tumours.

Morphine is generally the Morphine is generally the standard against which standard against which

other opioids are other opioids are compared and is compared and is

considered by many to be considered by many to be the analgesic of choice for the analgesic of choice for

severe pain associated severe pain associated with terminal illness.with terminal illness.

Opioid agonist drugsOpioid agonist drugsDrugDrug Dose (mg) Dose (mg) equianalgesic equianalgesic

to 10 mg IM Morphineto 10 mg IM Morphine

IMIM PO POHalf-life Half-life (hrs)(hrs)

Duration of Duration of action (hrs)action (hrs)

CodeineCodeine 130130 200200 2-32-3 2-42-4OxycodoneOxycodone 1212 3030 2-32-3 2-42-4PropoxyphenePropoxyphene 5050 100100 2-32-3 2-42-4MorphineMorphine 1010 3030(repeated (repeated

dose)dose)

6060(single (single dose) dose)

2-32-3 3-43-4

HydromorphoneHydromorphone 1.51.5 7.5 7.5 2-32-3 2-42-4MethadoneMethadone 1010 2020 15-19015-190 4-84-8MeperidineMeperidine 7575 300300 2-32-3 2-42-4OxymorphoneOxymorphone 1 10 1 10

(PR)(PR)2-32-3 3-43-4

HeroineHeroine 55 6060 0.50.5 3-43-4LevorphanolLevorphanol 2 42 4 12-1512-15 4-84-8Fentanyl transdermal Fentanyl transdermal systemsystem

NA NANA NA 48-7248-72

Morphine is not Morphine is not the Panaceathe Panacea

Morphine sulphateMorphine sulphate Strong narcotic of choiceStrong narcotic of choice Usual starting dose 10 mg 4 hourlyUsual starting dose 10 mg 4 hourly With frail elderly patients, it may be With frail elderly patients, it may be

wise to start on a suboptimal dose.wise to start on a suboptimal dose. If changing from alternative strong If changing from alternative strong

narcotic, a considerably higher dose narcotic, a considerably higher dose may be need may be need

Morphine sulphateMorphine sulphate Adjust upwards after first-dose if not Adjust upwards after first-dose if not

more effective than previous medication.more effective than previous medication. Adjust after 24 hours if pain not 90% Adjust after 24 hours if pain not 90%

controlledcontrolled Most patients are satisfactorily Most patients are satisfactorily

controlled on doses of between 5 and 30 controlled on doses of between 5 and 30 mg 4 hourlymg 4 hourly

Giving a larger dose at bed times (1.5 or Giving a larger dose at bed times (1.5 or 2xdaytime dose) 2xdaytime dose)

Oral-to-Parenteral Oral-to-Parenteral potency ratio of potency ratio of MorphineMorphine

1.2: 1.3 or 1.61.2: 1.3 or 1.6

MorphineMorphineDose (titrate up or down based on patient Dose (titrate up or down based on patient response)response)Initial doseInitial dose POPO 10-30 mg10-30 mg q 3-4 h.q 3-4 h.

IMIM 5-10 mg 5-10 mg q 3-4 h.q 3-4 h.IVIV 1-2.5 mg q 5 min PRN1-2.5 mg q 5 min PRNSRSR 15-30 mg15-30 mg q 12 h q 12 h CR 30-60 mg q 24 hCR 30-60 mg q 24 h

Use immediate-release product with SR or CR product to Use immediate-release product with SR or CR product to control “breakthrough” pain.control “breakthrough” pain.

Morphine sulphateMorphine sulphate Use co-analgesic medications as appropriateUse co-analgesic medications as appropriate Prescribe an antiemetic for regular use should Prescribe an antiemetic for regular use should

nausea or vomiting developnausea or vomiting develop Prescribe laxativePrescribe laxative Warm patient of possibility of initial drowsinessWarm patient of possibility of initial drowsiness Controlled release morphine sulphate, B.I.D. or Controlled release morphine sulphate, B.I.D. or

sustained release morphine sulphate, O.D. sustained release morphine sulphate, O.D. should be considered in long term treatment.should be considered in long term treatment.

Subcutaneous, intramuscular injection only in Subcutaneous, intramuscular injection only in patient who becomes difficult in swallowing or patient who becomes difficult in swallowing or vomiting persists.vomiting persists.

Route of Drug Route of Drug AdministrationAdministration

OralOral InternasalInternasalBuccalBuccal SubcutaneousSubcutaneousSublingualSublingual IntravenousIntravenousRectalRectal EpiduralEpiduralTransdermalTransdermal IntrathecalIntrathecal

and Intracerebroventricularand Intracerebroventricular

and alcohol

(Ethylene-vinyl acetate co-polymer)

silicone

Durogesic® : Fentanyl Transdermal System Delivers fentanyl direct to circulation

D-trans Matrix Durogesic

Mechanism of ActionMechanism of Action

D-TRANSD-TRANS®®

Layers :Layers : Backing layerBacking layer Solid drug-in-adhesive Solid drug-in-adhesive

matrix:matrix:– Contains and releases Contains and releases

fentanyl (in dissolved state)fentanyl (in dissolved state)– Simultaneously functions as Simultaneously functions as

adhesiveadhesive

Technology of Technology of D-TRANSD-TRANS®® Drug-in-Adhesive Matrix TechnologyDrug-in-Adhesive Matrix Technology

Reservoir SystemReservoir System

Layers :Layers : Backing layerBacking layer Reservoir with permeation Reservoir with permeation

membranemembrane– Fentanyl embedded in a gelFentanyl embedded in a gel– Contains ethanol to enhance Contains ethanol to enhance

permeationpermeation Adhesive layerAdhesive layer .....

.........................................Reservoir

Technology of Technology of D-TRANSD-TRANS®® SummarySummary

DurogesicDurogesic Reservoir Reservoir Durogesic Durogesic D-TRANS D-TRANS MatrixMatrix

Patch structurePatch structure Reservoir system with gel Reservoir system with gel Flexible matrix Flexible matrix

Patch sizePatch size 25 µg/h – 18.7 cm25 µg/h – 18.7 cm22

50 µg/h – 34 cm50 µg/h – 34 cm22

75 µg/h – 44.2 cm75 µg/h – 44.2 cm22

100 µg/h – 57.0 cm100 µg/h – 57.0 cm22

- 10.5 cm- 10.5 cm2 2

- 21 cm- 21 cm22 - 31.5 cm- 31.5 cm22

- 42 cm- 42 cm22

AdhesiveAdhesive Silicone-adhesiveSilicone-adhesive Polyacrylate polymerPolyacrylate polymerFentanylFentanyl Embedded in gel of Embedded in gel of

water/ethanol/water/ethanol/ hydroxyethyl cellulosehydroxyethyl cellulose

Dissolved in the adhesive Dissolved in the adhesive layerlayer

(diffusion through matrix (diffusion through matrix and skin = rate limiting)and skin = rate limiting)

Permeation enhancerPermeation enhancer Ethanol Ethanol NoneNone

Protective linerProtective liner Without slitWithout slit Provided with an S-shaped slitProvided with an S-shaped slit

PackagingPackaging Child-resistantChild-resistant

Matrix smaller

Comparison of PatchesComparison of PatchesCharacteristiCharacteristicscs

Fentanyl transdermal Fentanyl transdermal patchpatch

Fentanyl Matrix Fentanyl Matrix

Dosage Dosage StrengthsStrengths

25, 50, 75, and 100 25, 50, 75, and 100 mcg/hmcg/h

25, 50, 75, and 100 25, 50, 75, and 100 mcg/hmcg/h

Rate ControlRate Control Membrane and skin Membrane and skin stratum corneum stratum corneum provide drug delivery provide drug delivery rate control. rate control.

Ethanol included as Ethanol included as permeation enhancer.permeation enhancer.

No membrane. No membrane.

Skin stratum corneum Skin stratum corneum provides drug deliver provides drug deliver rate-control. rate-control.

No permeation No permeation enhancer.enhancer.

Side effects and Side effects and Complications of Opioid Complications of Opioid

AnalgesicsAnalgesics ConstipationConstipation Central nervous system side effectsCentral nervous system side effects

EuphoriaEuphoria ConfusionConfusionSedationSedation DizzinessDizzinessDrowsinessDrowsiness

Nausea, vomiting and puritusNausea, vomiting and puritus Respiratory depressionRespiratory depression ToleranceTolerance Physical DependencePhysical Dependence AddictionAddiction

Tolerance VS AddictionTolerance VS Addiction

TOLERANCETOLERANCE

≠≠ADDICTIONADDICTION (Psychological Dependence)(Psychological Dependence)

PHYSICAL PHYSICAL DEPENDENCEDEPENDENCE

≠

Signs and Symptoms of Signs and Symptoms of Opioid Intoxication and Opioid Intoxication and WithdrawalWithdrawal

IntoxicationIntoxicationEuphoriaEuphoriaDysphoriaDysphoriaApathyApathyMotor retardationMotor retardationSedationSedationAttention ImpairmentAttention ImpairmentMiosisMiosisSlurred speechSlurred speech

WithdrawalWithdrawalLacrimationLacrimationRhinorrheaRhinorrheaMydriasisMydriasisPiloerectionPiloerectionDiaphoresisDiaphoresisDiarrheaDiarrheaYawningYawningFeverFeverInsomniaInsomniaMuscle achingMuscle aching

Adjuvant Adjuvant AnalgesicsAnalgesics

Adjuvant use for Adjuvant use for Multipurpose SymptomsMultipurpose Symptoms

CorticosteroidsCorticosteroids AntihistaminesAntihistamines Muscle relaxantsMuscle relaxants NeurolepticsNeuroleptics

AnticholinergicsAnticholinergics PsychostimulantsPsychostimulants AntibioticsAntibiotics Etc.Etc.

Adjuvants used for Bone Adjuvants used for Bone PainPain

Anti-inflamatory drugs (NSAIDs, Anti-inflamatory drugs (NSAIDs, corticosteroids)corticosteroids)

BisphosphonatesBisphosphonates RadiopharmaceuticalsRadiopharmaceuticals CalcitoninCalcitonin

Adjuvants used for Adjuvants used for Neuropathic PainNeuropathic Pain

AntidepressantsAntidepressants Oral local Oral local

anestheticsanesthetics ClonidineClonidine CapsicineCapsicine Adjuvant drugs for Adjuvant drugs for

sympathetically sympathetically maintain painmaintain pain

AnticonvulsantsAnticonvulsants BaclofenBaclofen CalcitoninCalcitonin PimozidePimozide

Commonly used Adjuvant Commonly used Adjuvant Analgesics Analgesics (1/4)(1/4)

Class Class (example)(example)

Usual IndicationUsual Indication Approximate Approximate Adult Daily Adult Daily Dose RangeDose Range

Route of Route of AdministrationAdministration

AnticonvulsanAnticonvulsanttGabapentinGabapentinPhenytoinPhenytoinCarbamazepiCarbamazepineneOxcarbazepinOxcarbazepineeClonazepamClonazepam

Neuropathic Neuropathic painpain

ParticularlyParticularlyLancinating orLancinating orProxysmal painProxysmal pain

900-3600 mg900-3600 mg300-500 mg300-500 mg200-1600 mg200-1600 mg600-2400 mg 600-2400 mg

1-8 mg1-8 mg

POPOPOPOPOPOPOPOPOPO

AntidepressaAntidepressantsntsAmitryptyllineAmitryptyllineNortriptyllineNortriptyllineImipramineImipramineDesipramineDesipramineTrazodoneTrazodone

Neuropathic Neuropathic painpain

10-300 mg10-300 mg10-100 mg10-100 mg20-100 mg20-100 mg25-300 mg25-300 mg50-225 mg50-225 mg

POPOPOPOPOPOPOPOPOPO

Commonly used Adjuvant Commonly used Adjuvant Analgesics Analgesics (2/4)(2/4)

Class Class (example)(example)

Usual IndicationUsual Indication Approximate Approximate Adult Daily Adult Daily Dose RangeDose Range

Route of Route of AdministratiAdministrationon

Local Local AnestheticsAnestheticsMexiletineMexiletine Neuropathic painNeuropathic pain 450-600 mg450-600 mg POPOCorticosteroidCorticosteroidssDexamethasoDexamethasonenePrednisonePrednisone

Tumor invasion ofTumor invasion of neural tissue,elevatedneural tissue,elevated intracranial pressureintracranial pressure spinal cordspinal cord compressioncompression additional effect (mood additional effect (mood elevation, antiemesis, elevation, antiemesis, appetite stimulation)appetite stimulation)

16-96 mg16-96 mg40-100 mg40-100 mg

POPOPOPO

Commonly used Adjuvant Commonly used Adjuvant Analgesics Analgesics (3/4)(3/4)

Class (example)Class (example) Usual IndicationUsual Indication Approximate Approximate Adult Daily Adult Daily Dose RangeDose Range

Route of Route of AdministratiAdministrationon

AntihistamineAntihistamineHydroxyzineHydroxyzine Coanalgesic, Coanalgesic,

AntiemeticAntiemetic75-450 mg75-450 mg PO or IMPO or IM

Muscle relaxantsMuscle relaxantsOrphenadrineOrphenadrineCarisoprodolCarisoprodolMethocarbamolMethocarbamolChlorzoxazoneChlorzoxazoneCyclobenzaprineCyclobenzaprine

Occasional useful Occasional useful for for musculoskeletal musculoskeletal painpain

75-200 mg75-200 mg800-1400 mg800-1400 mg

4000-6000 4000-6000 mgmg

1500-3000 1500-3000 mgmg

20-60 mg20-60 mg

POPOPOPOPOPOPOPOPOPO

NeurolepticsNeurolepticsMethotrimeprazMethotrimepraziineneFluphenazineFluphenazine

Neuropathic painNeuropathic pain 15-100 mg15-100 mg1-10 mg1-10 mg

POPOPOPO

Commonly used Adjuvant Commonly used Adjuvant Analgesics Analgesics (4/4)(4/4)

Class (example)Class (example) Usual IndicationUsual Indication Approximate Approximate Adult Daily Adult Daily Dose RangeDose Range

Route of Route of AdministratiAdministrationon

Other drugs for Other drugs for Neuropathic painNeuropathic painBaclofenBaclofenClonidineClonidineCalcitoninCalcitoninCapsicine topicalCapsicine topical

Neuropathic painNeuropathic pain 20-120 mg20-120 mg0.1-0.6 mg0.1-0.6 mg50-100 mg50-100 mg

POPOPO or TDPO or TD

SC, IM, NSSC, IM, NS

AnticholinergicsAnticholinergicsGlycopyrolateGlycopyrolate Visceral pain Visceral pain

resulting from resulting from bowel obstructionbowel obstruction

2-6 mg2-6 mg POPO

PsychostimulantsPsychostimulantsCaffeineCaffeineMethylphenidateMethylphenidateDextroamphetaminDextroamphetaminee

Decreased Decreased sedations resulting sedations resulting from opioid from opioid analgesiaanalgesia

50-1000 mg50-1000 mg10-15 mg10-15 mg5-10 mg5-10 mg

POPOPOPOPOPO

Pharmacologic Pharmacologic Management of Management of

Neuropathic PainNeuropathic PainDrug class ExampleAntidepressants Amitriptyline, desipramine,

nortriptyline, imipramineAnticonvulsants Carbamazepine, Oxcarbezepine,

phenytoin, valproic acid, gabapentin, clonazapam

Antiarrhythmias and local anesthetics

Lidocaine, mixelitine

Topical formulations Capsaicin, EMLA cream, aspirinBaclofen

Dissociative anesthetics KetamineDextorphan Delsym

Anticonvulsants as Anticonvulsants as Adjuvant AnalgesicsAdjuvant Analgesics

DrugDrug Site of ActionSite of ActionCarbamazepineCarbamazepine Decreases sodium channel activity Decreases sodium channel activityPhenytoinPhenytoin Decreases sodium channel activityDecreases sodium channel activityValproateValproate Decreases sodium channel activity, Decreases sodium channel activity,

possibly increases GABApossibly increases GABAClonazepamClonazepam Increases GABA functionIncreases GABA functionGabapentinGabapentin Increases GABA levels, decreasing Increases GABA levels, decreasing

sodium channel functionsodium channel functionUpton N. Trends Pharmacol Sci. 1994;15:456-463.

Petroff O, et al. Ann Neurol. 1996;39:95-99.Am Fam Physician. 1996;55:2534. Family Practice International.

Gabapentin

Upton N. Trends Pharmacol Sci. 15;456-463.Chadwick D. Lancet. 1994;343:89-91.

Petroff O, et al. Ann Neurol. 1996;39:95-99.Goldlust A, et al. Epilepsy Res. 1995;22:1-11.

Pharmacologic Properties of Pharmacologic Properties of Second-Generation Second-Generation AnticonvulsantsAnticonvulsants

Increases GABA in brain, possibly by Increases GABA in brain, possibly by enhancing rate of synthesis from glutamateenhancing rate of synthesis from glutamate

Binds to specific site localized to brain regions Binds to specific site localized to brain regions associated with major excitatory inputsassociated with major excitatory inputs

Inhibits sodium currents by mechanism Inhibits sodium currents by mechanism distinct from phenytoin and carbamazepinedistinct from phenytoin and carbamazepine

Inhibits branched-chain amino acid Inhibits branched-chain amino acid transferase, possibly reducing glutamate transferase, possibly reducing glutamate concentrationconcentration

No effect on GABANo effect on GABAAA or GABA or GABABB receptors receptors

GABA

OxcarbazepineOxcarbazepineThe pharmacological activity of oxcarbazepine is

primarily exerted through the metabolite (MHD) of oxcarbazepine.

The mechanism of action of oxcarbazepine and MHD is thought to be mainly based on blockade of voltage-sensitive sodium channels, thus resulting in stabilisation of hyperexcited neural membranes, inhibition of repetitive neuronal firing and diminishment of propagation of synaptic impulses; and increased potassium conductance and modulation of high-voltage activated calcium channels may also contribute to the anticonvulsant effects of the drugs.

CAUTION ! ! CAUTION ! ! !!ADVERSE REACTIONSADVERSE REACTIONS

Examples of Examples of Nonpharmacologic Nonpharmacologic

Approaches to CancerApproaches to Cancer Physical methodPhysical method

- Acupuncture- Acupuncture- Acupressure- Acupressure- TENS (Transcutaneous Electrical - TENS (Transcutaneous Electrical

Nerve Stimulation)Nerve Stimulation)- Electrode Implantation- Electrode Implantation

Examples of Examples of Nonpharmacologic Nonpharmacologic

Approaches to CancerApproaches to Cancer SurgerySurgery

- Tumor debulking- Tumor debulking- Adrenalectomy- Adrenalectomy- Hypophysectomy- Hypophysectomy

NeurosurgeryNeurosurgery- Cordotomy- Cordotomy- Rhizotomy- Rhizotomy- Deep brain stimulation- Deep brain stimulation- Placement of dorsal column stimulators- Placement of dorsal column stimulators- Cingulotomy- Cingulotomy

Examples of Examples of Nonpharmacologic Nonpharmacologic

Approaches to CancerApproaches to Cancer Anesthesiology procedureAnesthesiology procedure

- Myofascial trigger point injection- Myofascial trigger point injection- Nerve blocks- Nerve blocks

Psychological procedurePsychological procedure- Relaxation- Relaxation- Hypnosis- Hypnosis- Biofeedback- Biofeedback- Brief psychotherapy- Brief psychotherapy

Palliative care for Palliative care for Cancer PatientsCancer Patients

Pain TeamPain Team PhysicianPhysician NurseNurse Social workerSocial worker PharmacistPharmacist Patient and FamilyPatient and Family VolunteerVolunteer TherapistTherapist

Case StudyCase StudyKnown case of 52-years-old Chinese Known case of 52-years-old Chinese

male patient with diagnosis of Ca floor of male patient with diagnosis of Ca floor of mouth stage IV, Left cervical LN size 3x6 mouth stage IV, Left cervical LN size 3x6 cm fixed post radiation and chemotherapy.cm fixed post radiation and chemotherapy.

SevereSevere burning, spontaneous shooting burning, spontaneous shooting pain at left side of neck, left cheek with pain at left side of neck, left cheek with radiated to left forehead.radiated to left forehead.Treatment on Oct19,2001Treatment on Oct19,2001

Codeine 60 mg PO q 4 h.Codeine 60 mg PO q 4 h.Paracetamol 2 tab q 4 h.Paracetamol 2 tab q 4 h.Neurontin 300 mg q 12 h.Neurontin 300 mg q 12 h.MO solution 5 mg PO p.r.n. q 1 h.MO solution 5 mg PO p.r.n. q 1 h.MOM 20 ml PO hs.MOM 20 ml PO hs.

Case StudyCase Study

Oct 20,01Oct 20,01 : Off Codeine: Off Codeine: MST 30 mg p.o. q 12 h.: MST 30 mg p.o. q 12 h.: : Neurontin to 600 mg p.o.q12 h.Neurontin to 600 mg p.o.q12 h.: MOM 30 ml p.o. hs: MOM 30 ml p.o. hs

Nov 09,01: Neurontin to 900 mg p.o.q12 h.Nov 09,01: Neurontin to 900 mg p.o.q12 h.: Paracetamol 2 tab q 6 h.: Paracetamol 2 tab q 6 h.

Nov 12,01: Neurontin to 1200 mg Nov 12,01: Neurontin to 1200 mg p.o.q12h.p.o.q12h.

Dec 07,01: Add Ativan 1 mg p.o. Dec 07,01: Add Ativan 1 mg p.o. morning&hsmorning&hs

CaseCase StudyStudy

Jan 08,02Jan 08,02 : Neurontin to 1800 mg : Neurontin to 1800 mg p.o.q12hp.o.q12h

Jan 17,02 : (severe headache)Jan 17,02 : (severe headache): MST to 90 mg q12h: MST to 90 mg q12h: Dexamethasone 1 mg p.o. : Dexamethasone 1 mg p.o.

q6hq6hJan 24,02 : MST to 120 mg p.o. q12hJan 24,02 : MST to 120 mg p.o. q12h

Last seen on Jan30,02 , No Pain at AllLast seen on Jan30,02 , No Pain at All

Case StudyCase Study

Feb 12,02Feb 12,02Readmission with history of Readmission with history of

severe burning pain at right side of severe burning pain at right side of the neck, face, and scalp after the neck, face, and scalp after developing some groups of small developing some groups of small vesicles and inflammatory vesicles and inflammatory appearance at the skin of the right appearance at the skin of the right side of the neck (harpes zoster to be side of the neck (harpes zoster to be diagnosed) for 3 days.diagnosed) for 3 days.

Case StudyCase Study

Treatment on Feb 12,02Treatment on Feb 12,02MST 150 mg p.o. q 12 hMST 150 mg p.o. q 12 hNeurontin 1800 mg p.o. q 12 hNeurontin 1800 mg p.o. q 12 hParacetamol 100 mg p.o. q 4 hParacetamol 100 mg p.o. q 4 hAmitryptylline 50 mg p.o. hsAmitryptylline 50 mg p.o. hsMO 10 mg p.o. prn q 1 hMO 10 mg p.o. prn q 1 hMOM 30 mg p.o. hsMOM 30 mg p.o. hsAcyclovir 800 mg p.o. q 4 h for 7 daysAcyclovir 800 mg p.o. q 4 h for 7 days(5 times/day)(5 times/day)

Case StudyCase StudyFeb 18,02Feb 18,02 : Amitryptylline to 75 mg p.o. hs: Amitryptylline to 75 mg p.o. hs

: MO to 20 mg p.o. prn q 1 h: MO to 20 mg p.o. prn q 1 hFeb 20,02Feb 20,02 : Amitryptylline to 100 mg : Amitryptylline to 100 mg

p.o.hsp.o.hsFeb 21,02: MST to 210 mg p.o. q 12 hFeb 21,02: MST to 210 mg p.o. q 12 h

: Dexamethasone to 2 mg p.oq6h: Dexamethasone to 2 mg p.oq6hFeb 25,02: MST to 270 mg p.o. q 12hFeb 25,02: MST to 270 mg p.o. q 12h

:: Neurontin to 2100 mg p.o.q12hNeurontin to 2100 mg p.o.q12hNo pain at all on Feb28,02; and developingNo pain at all on Feb28,02; and developingsome degree of dizziness and severe some degree of dizziness and severe drowsiness on Mar7,02 drowsiness on Mar7,02

Case StudyCase StudyMar07,02Mar07,02 : Neurontin to 1800 mg p.o. q12h: Neurontin to 1800 mg p.o. q12hMar12,02 : MST to 210 mg p.o. q12hMar12,02 : MST to 210 mg p.o. q12h

: Neurontin to 1500 mg p.o. q12h: Neurontin to 1500 mg p.o. q12hMar14,02 : Mar14,02 : Due to developing some clonus at Due to developing some clonus at

all extremities, MST q12h dosage and MO all extremities, MST q12h dosage and MO solution prn dosage were off, but all of the solution prn dosage were off, but all of the other adjuvant pain medications are still other adjuvant pain medications are still further on adjuvant pain medications are still further on adjuvant pain medications are still further onfurther on:Fentanyl patch 150 mcg/h q3days:Fentanyl patch 150 mcg/h q3days:MO 5 mg SC. Inj. prn q 1 h:MO 5 mg SC. Inj. prn q 1 hfor breakthrough pain were substitutedfor breakthrough pain were substituted

Case StudyCase Study

Patient tolerated well to the new Patient tolerated well to the new adjusted pain medication, and no any adjusted pain medication, and no any pain recurred.pain recurred.

Patient expired peacefully on Patient expired peacefully on Mar17,02Mar17,02

Thank you for Thank you for your attentionyour attention