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1、特殊人群的癌痛治疗特殊人群的癌痛治疗 华中科技大学同济医学院华中科技大学同济医学院 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 华中科技大学同济医学院华中科技大学同济医学院 附属同济医院药学部附属同济医院药学部 桂桂 玲玲 概念的转换概念的转换 Cancer pain VS noncancer pain 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 Patients with cancer with pain VS Patients with cancer pain Patients with cancer with p
2、ain 80% of patients with cancer have 2 types of pain. 1.Twycross R. Pain treatment in cancer patients.Schmerz 1990;4:6574. 33% have 4 types of pain. 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 33% have 4 types of pain. 2. Massaccesi M.Incidence and management of noncancer pain in cancer patients referr
3、ed to a radiotherapy center. Clin J Pain.2013;29:944947. It was more likely that the noncancer pain be uncontrolled than the cancer pain. Type of PainDescriptionAssociations Acute Short durationa course of treatment, surgery , disease Chronic Persistent pain, often diffuseSecondary to the disease or
4、 its treatment Type of Pain 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 or its treatment Neuropathic Sharp,shooting,burning pain “pins and needles” Chemotherapy, progressive disease Nociceptive Somatic: dull ,aching pain Visceral:difficult to localize Inflammatory pain Analgesic gap Severe sudden-onset
5、 pain, often be confused Occur at the end of a dose of pain medication Breakthrough Occur spontaneously or be incident severe pain Movement-related , sudden exacerbation Multidisciplinary oncology team Neuologist PalliativistPharmacist 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 Palliativist Radio- the
6、rapist General practitioner Pharmacist oncolo -gist What is the Pharmacists focus? Pharmacodynamics Pharmacokinetics Adverse drug reaction Individual 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 Adverse drug reaction Drug interaction Comorbidities Administration route Cost Individual Treatment l Opioids
7、 Individual Treatment 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 NSAIDs + Acetaminophen The Elderly Opioids 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 The Children Patients with Comorbidities The Elderly I.Older patients with caner dont appear to feel more pain than younger patients. II. Older patients
8、with cancer appear to feel more 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 Older patients with cancer appear to feel more depression than younger patients. III.Prescription advice for strong-acting opioids in frail elderly patients IV. Starting Opioid Doses for Frail elderly patients Differences in MS
9、AS Summary Scores Across the Four Older Age Groups I.Older patients with caner dont appear to feel more pain 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 MSAS =Memorial Symptom Assessment Scale; NS = not significant. 3. Christine R. Differences in the Symptom Experience of Older Oncology Outpatients. Jo
10、urnal of Pain and Symptom Management. 2014;47:697709. I.Older patients with caner dont appear to feel more pain QoL and fatigue scores of hospitalized cancer patients. 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 4. Eyigor S. Assessment of pain,fatigue, sleep and quality of life (QoL) in elderly hospita
11、lized cancer patients. Arch Gerontol Geriatr. 2010;51:e57e61. 1. The rate of depression in geriatric cancr patients was found to be 67.4%. 2. Depression was related to Severe cognitive II.Older patients with caner appear to feel more depression 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 impairment. 3.
12、 Cognitively impaired patients made pain assessment become more difficult. 5. Mystakidou K. Geriatric depression in advanced cancer patients: the effect of cognitive and physical functioning. Geriatr Gerontol Int. 2013;13:281288. General Gidelines for Managing Cancer Pain in Elderly Patients Route o
13、f adminsitration Use the least-invasive route possible Consider dysphagia when recommending oral analgesics Formulation Sutstained-release formulations are preferred when possible although dosing may be initiated with an immediate-release preparation and then converted to a sustained-release formula
14、tion Short-acting or ultra-short-acting analgesics may be appropriate for rescue medication Start low andslow 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 Dose Start low and go slow Monitor the patient closely and adjust dose promptly to improve efficacy Assess pain levels regularly and as appropriate a
15、t every follow-up Polypharmacy Polypharmacy is a fact of life for most elderly patients with cancer; introduce one agent at a time and allow sufficient interval between drugs to assess Rotate agents, if necessary, to avoid potential drug-drug interactions Regimen In most cases, administer at least o
16、ne analgesic round-the-clock(not on an as-needed basis) Educate patient and caregivers about adherence Reduce the pill burden as much as possible General Gidelines for Managing Cancer Pain in Elderly Patients Regimen Monitor the patient carefully and make prompt changes to manage potential side effe
17、cts Start opioid therapy with a bowel regimen Educate the patient and caregivers about opioid-associated side effects Manage side effects when appropriate, for example, using antiemetics 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 antiemetics Opioid Selection Select an appropriate opioid; for instance,
18、 methadone is not appropriate for many patients with cancer If it should be necessary to switch opioids, start with 50% to 75% of the published equianalgesic dose of the mew opioid or less to accommodate any corss-rolerance or individual variations 6.American Geriatrics Society Panel on Pharmacologi
19、cal Management of Persistent Pain in Older Persons. Pharmacologicalmanagement of persistent pain in older persons. J Am Geriatr Soc. 2009;57:13311346. 1. Multiple organ functions decline(renal /hepatic /cardiac). 2. Increased body fat and Decreased total volume of III. Prescription advice for strong
20、-acting opioids in frail elderly patients 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 2. Increased body fat and Decreased total volume of water in the body. 3. Compromised immune system. 4. Advanced disease III. Prescription advice for strong-acting opioids in frail elderly patients 华中科技大学同济医学院附属同济医院药学
21、部华中科技大学同济医学院附属同济医院药学部 7.Annette L. van Ojik.Treatment of Chronic Pain in OlderPeople： ：Evidence-Based Choice of Strong-Acting Opioids. Drugs Aging 2012; 29 (8): 615-625. IV. Starting Opioid Doses for Frail elderly patients Agent FormulationRecommended Starting Dose HydrocodoneOral2.5 to 5 mg every 4
22、 to 6 hours HydromorphoneOral1 to 2 mg every 3 to 4 hours MorphineImmediate release, oral2.5 to 10 mg every 4 hours MorphineSustained release, oral158 to 24 hours 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 MorphineSustained release, oral15 mg every 8 to 24 hours OxycodoneImmediate release, oral2.5 to
23、5 mg every 4 to 6 hours OxycodoneControlled release, oral10 mg every 12 hours OxymorphoneImmediate release, oral5 mg every 6 hours OxymorphoneExtended release, oral5 mg every 12 hours FentanylTransdermal12ug/hourpatchevery72 hours BuprenorphineTransdermal5ug/hour I.Therapeutic principles is as the s
24、ame in adults The Children 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 II. Starting Opioid Doses for children III.Multimodal(opioid sparing) analgesia I.Therapeutic principles is as the same in adults WHO principles: 1. Using a two-step strategy (“by the analgesic ladder”) 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医
25、学院附属同济医院药学部 2. Dosing at regular intervals (“by the clock”) 3. Using the appropriate route of administration (“by the appropriate route”) 4. Adapting treatment to the individual child (“with the child”). I.Therapeutic principles is as the same in adults 1. Using a two-step strategy Mild pain:acetami
26、nophen and/or ibuprofen Medium- to-severe pain:morphine, fentanyl, hydromorphone, 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 oxycodone, or methadone 3. Using the appropriate route of administration Recommend:intravenous, oral, rectal, PCA/NCA,transdermal NOT Recommend: Transmucosal II. Starting Opioid
27、 Doses for children 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 8. Stefan J Friedrichsdorf .Management of breakthrough pain in children with cancer. Journal of Pain Research 2014:7 117123 III.Multimodal(opioid sparing) analgesia 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 General Pharmacological Considera
28、tion for Various Types of Comorbidities Patients with Comorbidities Comorbidity Drug Therapy Effects on Patient Recommendations Renal May prolong Buprenorphine or tramadol may be good choices; 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 Renal impairment, Chronic kidney disease May prolong circulation,
29、uptake, and distribution. Can advance renal toxicity Buprenorphine or tramadol may be good choices; monitor creatinine clearance. Buprenorphine needs no dose adjustment for renally impaired patients. Avoid NSAIDs, especially ketorolac. Morphine may result in delayed opioid toxicity and neurotoxicity
30、; start low and extend dosing intervals. Hemodialysis will remove morphine metabolites but not fentanyl. Do not commence therapy with a fentanyl patch. Oxycodone is contraindicated in patients with severe renal impatient General Pharmacological Consideration for Various Types of Comorbidities Comorb
31、idity Drug Therapy Effects on Patient Recommendations Cardiac conditions, heart failure, arrhythmias, May promote hypertension; NSAIDs appear to increase risk of Avoid NSAIDs. Avoid propoxyphene. Avoid steroids. Consider buprenorphine, which does 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 arrhythmias,
32、 valve disease, coronary artery disease increase risk of cardiovascular events, including myocardial infarction Consider buprenorphine, which does not significantly prolong the QT interval NOTE: This Table is intended to provide a high-altitude overview which does not replace clinical judgment based
33、 on an individual patients needs General Pharmacological Consideration for Various Types of Comorbidities Comorbidity Drug Therapy Effects on Patient Recommendations Gastrointestinal disorders If gastric PH is altered, it may reduce the absorption of drugs. Nonselective NSAIDs Start low and monitor
34、closely. Patientswithgastrointestinal bleeding should avoid nonselective NSAIDs 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 Nonselective NSAIDs may promote bleeding NSAIDs gastrointestinal tract May reduce absorption of drugs Start low and monitor closely ObesityMay result in longer effective drug half
35、-life Start low and allow longer time intervals between doses NOTE: This Table is intended to provide a high-altitude overview which does not replace clinical judgment based on an individual patients needs General Pharmacological Consideration for Various Types of Comorbidities Comorbidity Drug Ther
36、apy Effects on Patient Recommendations Hypertension Acetaminophen and corticosteroids may induce or exacerbate Avoid acetaminophen (paracetamol). Avoid steroids 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 exacerbate hypertension Neurological disorders Can enhance anticholinergic effects Rotate opioids
37、or manage side effects. Avoid meperidine and normeperidine which may lead to seizures Diabetes The effect of opioids on diabetes is not well understood Buprenorphine appears less likely to contribute to development of diabetes than methadone General Pharmacological Consideration for Various Types of
38、 Comorbidities Hepatic disease, cirrhosis May disrupt oxidation but not usually conjugation Buprenorphine may be a good choice and needs no dose adjustment for mild to moderate hepatic impairment; it is not recommended in patients with severe hepatic impairment. Avoid acetaminophen (paracetamol). Co
39、nsider tramadol. Morphine may have increased bioavailability but the half-life is not substantially affected; start at a lower-than-normal 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 is not substantially affected; start at a lower than normal dose but maintain dosing cirrhosis. Do not use extended-rele
40、ase opioids in patients with advanced cirrhosis. Fentanyl has reduced clearance in hepatic disease; delayed toxicity is possible.Do not use fentanyl patch. Oxycodone may be prescribed at 50% of usual dose in patients with mild to moderate hepatic cirrhosis(but is contraindicated in patients with mod
41、erate-to-severe hepatic impairment) General Pharmacological Consideration for Various Types of Comorbidities Comorbidity Drug Therapy Effects on Patient Recommendations Pulmonary disease, chronic obstructive May put patient at elevated risk for potentially life-threatening respiratory depression If
42、therapy at the opioid level is required, start low and monitor the patient closely 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 obstructive pulmonary disorder respiratory depression 9. Joseph V. Pergolizzi .Treatment Considerations for Cancer. Pain Practice,2015 Opioids Individual Treatment 华中科技大学同济医学院附
43、属同济医院药学部华中科技大学同济医学院附属同济医院药学部 NSAIDs + Acetaminophen Degrees of COX selectivity Recommendations to reduce risk NSAIDs+Acetaminophen 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 Recommendations to reduce risk Approaches to mitigating risk Degrees of COX selectivity 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部
44、 10.Joseph V Pergolizzi Jr.Evolution to low-dose NSAID therapy. Pain Manag:2016 (Epub ahead of print) Degrees of COX selectivity 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 1. Lowest dose for the shortest conditions 2. GI toxicity:cox-2 inhibitors ibuproten 1800mg/d=indomethacin1800mg/d=indomethacin50m
45、g/d = naproxen500mg/d 3. CV toxicity: ibuproten/naproxen 4.drug-drug interaction(Aspirin):Diclofenac/ Etoricoxib /Ketorolac 1.Consider topical NSAID 2.Consider adding misoprostol or proton Approaches to mitigating risk 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 pump inhibitors 3.Consider NSAID prodrug
46、s 癌症患者疼痛控制现状癌症患者疼痛控制现状 A vertical comparison 1994：the rate of undertreated cancer pain is 40% 2012：the rate of undertreated cancer pain is 33% 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 2012：the rate of undertreated cancer pain is 33% There isnt obvious change in the past 20 years! 11. Cleeland CS. Pa
47、in and its treatment in outpatients with metastatic cancer. N Engl J Med. 1994;330:592596. 12. Fisch MJ. Prospective,observational study of pain and analgesic prescribing in Medical oncology outpatients with breast, colorectal, lung,or prostate cancer. J Clin Oncol. 2012; 30:19801988. A prospective
48、study 3,123 oncology outpatients Initial assessment：33% had inadequate pain control 癌症患者疼痛控制现状癌症患者疼痛控制现状 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部 Initial assessment33% had inadequate pain control One month later： 34% had inadequate pain control 12. Fisch MJ. Prospective,observational study of pain and analgesic prescribing in Medical oncology outpatients with breast, colorectal, lung,or prostate cancer. J Clin Oncol. 2012; 30:19801988. Pharmacist can give help for outpatients ! THE END 华中科技大学同济医学院附属同济医院药学部华中科技大学同济医学院附属同济医院药学部