Pharmacology & Therapy: Analgesic and Morphine in Palliative Care PDF

PHARMACOLOGY & THERAPY ANALGESIC and MORPHINE IN PALLIATIVE Endang CARE Isbandiati Soediono DR, Dr, MS, SpFK Medical Faculty, Widya Mandala Catholic University SURABAYA FKUKWMS7.5 01 02 AnalgMorphPal 1...

PHARMACOLOGY & THERAPY ANALGESIC and MORPHINE IN PALLIATIVE Endang CARE Isbandiati Soediono DR, Dr, MS, SpFK Medical Faculty, Widya Mandala Catholic University SURABAYA FKUKWMS7.5 01 02 AnalgMorphPal 1 lCarePharmacolTheEIS2023Nov PALLIATIVE CARE 01 ANALGESIC FKUKWMS7.5 01 02 AnalgMorphPal 2 lCarePharmacolTheEIS2023Nov  The goal of palliative care improve overall quality of life for pts., caregivers, and families while managing both general and disease-specific symptom … simultaneously while a pt. is receiving curative or life-prolonging tx. Knowledge of pain classification is important and necessary to determine the appropriate medication tx. for each pt. An interdisciplinary team approach is beneficial throughout the care of the pt. → evident whenFKUKWMS7.5 addressing more 01 02 AnalgMorphPal 3 lCarePharmacolTheEIS2023Nov PAIN & THERAPY 01 Effective plan for …. Assessment of pts. description : quality, precipitating or palliating factors, region affected, radiation, temporal/time, impact to function ability. Non-communicative pts. → nonverbal indicators : grimacing, agitation, restlessness, or resistance to personal care Identifying the cause and appropriate treatment FKUKWMS7.5 01 02 AnalgMorphPal lCarePharmacolTheEIS2023Nov 4 PAIN & THERAPY 02 Mechanism of pain based on Pathophysiology  A Nociceptive pain: Results from stimulation of pain receptors. Somatic: damage to body tissue, well localized Visceral: from viscera, poorly localized, may have n.  B Neuropathic pain: Results from dysfunctions or lesions in either the central or peripheral nervous systems.  C Mixed pain syndromes: multiple or unknown mechanisms (e.g. headaches, vasculitic syndromes).  D Psychogenic : FKUKWMS7.5 01 02 AnalgMorphPal lCarePharmacolTheEIS2023Nov 5 PAIN & THERAPY 03 A. NOCICEPTIVE. Achy, throbbing, and dull. Tx. :. non-opioid analgesic (acetaminophen) → not for severe hepatic impairment. NSAIDs → not for renal impairment, increase risk of CV & GI bleeding. Preferable → around the clock (not as needed). Palliative care : severity, or CIs to non-opioid → use of opioid ( morphine, oxycodone, hydromorphone) Tx. throughout the day : LA or ER opioid ; (+) short-acting opioid for “breakthrough” pain FKUKWMS7.5 01 02 AnalgMorphPal 6 lCarePharmacolTheEIS2023Nov PAIN & THERAPY 04 B. NEUROPATHIC. Tingling, sharp, burning, electric shock- like, or numbness. Cause by damage to the central or peripheral NS. First line tx. : adjuvant agents considered TCA, SNRIs, Ca channel alpha-2-delta ligands (gabapentin, pregabalin). Second – line tx.: traditional analgesic ( opioids, tramadol). Third-line tx.FKUKWMS7.5 : morphine, oxycodone 01 02 AnalgMorphPal 7 lCarePharmacolTheEIS2023Nov PAIN & THERAPY 05 More commonly tx. based on the type of pain : neuropathic, musculoskeletal, visceral, dysfunctional Multimodal tx. for all types of pain : pharmacologic, physical rehabilitation, and cognitive behavioral therapy → should be combined.. Interventional tx. should be considered if possible Tx. plan must always include evaluation of factors : age, comorbidities, ROA, concurrent medication, FKUKWMS7.5 01 02 AnalgMorphPal 8 laboratory abnormalities, and financial resources lCarePharmacolTheEIS2023Nov PAIN & THERAPY 06 Acute pain tx. : NSAID, acetaminophen, or opioids Chronic pain tx.:. First-line for neuropathic pain consist of :. antidepressants (SNRIs or TCA) → enhance the descending inhibitory pain pathway. Anticonvulsants (sodium-channel blockers, CCBs, or GABA agonists) → inhibit activation of sodium and calcium channels, block release of EAAs such as glutamate, or block the post synaptic receptors. Some anticonvulsants also enhance inhibitory effects of GABA. Localized pain : topical agents (eg. capsaicin, or local anesthetics). addition of tramadol, tapentadol, or another opioid if the former agents fail to provide analgesia.. Combination tx. more effective in some cases : TCA-anticonvulsant or opioid-anticonvulsant. Interventional tx. may be helpful for short-term relief → nerve blocks FKUKWMS7.5 01 02 AnalgMorphPal 9 lCarePharmacolTheEIS2023Nov  PAIN & THERAPY 07 Chronic musculoskeletal pain :. acetaminophen, salicylates, or NSAIDs,. in addition to non-pharmacologic tx. such as heat and ice or physical rehabilitation modalities Opioids → tx. in the acute pain setting (immediately after injury or surgery) Local pain → topical tx. (NSAIDs, capsaicin) Trigger points (taut muscle bands) → injections (SNRI) Duloxetin → tx. musculoskeletal pain (LBP or OA pain) Visceral pain (somatosensory pathways) → tx. antidepressant or opioid. Additionally : anticonvulsants (reduce central sensitization and hyperalgesia) FKUKWMS7.5 01 02 AnalgMorphPal 10 Monitored Efficacy and Toxicity lCarePharmacolTheEIS2023Nov PAIN & THERAPY 08 Multimodal tx. : essential Monitoring :. NSAIDs → dyspepsia, PU, GI bleeding, elevated BP, declining renal function. Antidepressants → dry mouth, constipation, urinary retention and drowsiness. All anticonvulsants → drowsiness, dizziness, and cognitive dysfunction, w. short-term memory loss and word-finding difficulty. Some anticonvulsants → laboratory for liver toxicity, electrolyte imbalance, or bone marrow abnormalities. Opioids → laboratory monitoring long-term ADR (osteoporosis, hypogonadism, and end-organ impairment, pt. ask about constipation, drowsiness, n, v, ). Interactions PK interaction (eg. Hepatic enzyme interactions) PD interaction (eg. Additive sedation) FKUKWMS7.5 01 02 AnalgMorphPal 11 lCarePharmacolTheEIS2023Nov Age related changes 01 1 Reduction in number and function of peripheral nociceptive neurons. 2 Sensory threshold for thermal and vibratory stimuli increase w. age. 3 Pain receptors: 50% decrease in Pacini's corpuscles, 10%-30% decrease in Meissner's/Merkle's disks 4 Diminished endogenous analgesic response (endorphins) in the older pts. FKUKWMS7.5 01 02 AnalgMorphPal 12 lCarePharmacolTheEIS2023Nov Age related changes 02 A. Peripheral nerves : a) Myelinated nerves Decreased density Increase abnormal/degenerating fibers Slower conduction velocity b) Unmyelinated nerves Decreased number of large fibers (1.2- 1.6 mm No change in small fibers (0.4 mm) Substance P content decreased FKUKWMS7.5 Geriatric medicine: An evidence based approach01 4th 02 AnalgMorphPal edition 2003 13 lCarePharmacolTheEIS2023Nov Age related changes 03 B Central nervous system Loss in dorsal horn neurons Altered endogenous inhibition, hyperalgesia Loss of neurons in cortex, midbrain, brainstem 18% loss in thalamus Altered cerebral evoked responses Decreased catecholamines, acetylcholine, GABA, serotonin Endogenous opioids: mixed changes Neuropeptides: no change Geriatric medicine: An evidence based approach 4th edition 2003 FKUKWMS7.5 01 02 AnalgMorphPal 14 lCarePharmacolTheEIS2023Nov Factors affecting perception of pain 01 a) Pain affects quality of life far beyond the local region of injury b) Feeling of loneliness is predictor of psychological distress c) Lack of intimate relationships, dependency, and loss increase loneliness d) Loneliness has been shown to lower pain threshold e) Loneliness is a risk factor for depression Deane G et.al., Overview of pain management in older persons. Clin Geriatr Med 24,185- 201,2008. FKUKWMS7.5 01 02 AnalgMorphPal 15 lCarePharmacolTheEIS2023Nov Factors affecting perception of pain 02  f) Depression: lack of energy, avoidance of diversional activities, decreased engagement in treatment  g) Anxiety: may inhibit participation in rehab efforts  h) Sleep disturbance: pain is best predictor of sleep disturbance.  i) Increased health care needs  j) Isolation and reduced independence: Involvement w. family and friends can provide pleasurable experience FKUKWMS7.5 01 02 AnalgMorphPal 16 lCarePharmacolTheEIS2023Nov Factors affecting perception of pain 03  k) Focusing one's attention on pain makes the pain worse.  l) Patients who have low levels of pain remember it as being worse than they originally reported.  m) Pain can be a learned response, rather than a purely physical problem.  n) Psychosocial issues like patient’s belief about their pain , their coping skills, their involvement in the “sick role”, all have an impact on how much pain patients feel, and how it affects them. FKUKWMS7.5 01 02 AnalgMorphPal 17 lCarePharmacolTheEIS2023Nov Challenges of pain assessment in older patients  Myths that having pain is “natural” with aging  Fears about addiction to pain medications  Sensory and cognitive impairments  Under-reporting  Co-morbidities complicating the clinical picture and caregivers' beliefs and the reliability of patients' pain.  Lack of congruence between patients' and caregivers' perceptions of pain  Caregiver may misinterpret pain perception Stein, W.M. Pain in the nursing home. Clinics in Geriatric Medicine 17, 575-94,2001 Stewart, K. et. al. Assessment approaches for older people receiving social care: content and coverage. International Journal of Geriatric Psychiatry 14, 147-56,1999. Horgas, A.L. et. al. Pain in nursing home residents. Comparison of residents' self-report and nursing assistants' perceptions. Journal of Gerontological Nursing 27, 44-53, 2001. Weiner, D., et. al. Chronic pain associated behaviours in the nursing home: resident versus caregiver perceptions. Pain 80, 577-88,1999. FKUKWMS7.5 01 02 AnalgMorphPal 18 lCarePharmacolTheEIS2023Nov Pain Treatment Age-Related Physiologic Changes Decreased renal function Decreased VD because of decreased lean body weight Decreased liver mass and HBF Decreased enzyme activity Decreased serum protein concentrations Decreased pulmonary function FKUKWMS7.5 01 02 AnalgMorphPal 19 lCarePharmacolTheEIS2023Nov FKUKWMS7.5 01 02 AnalgMorphPal 20 lCarePharmacolTheEIS2023Nov Pain Treatment 01 Nonopioid Analgesics for Older Adults 1 Acetaminophen: 1)Treatment of choice for Osteoarthritis 2)Exhibits an analgesic ceiling beyond which higher doses do not provide greater pain relief. 3) Maximum dose 4 gm/day FKUKWMS7.5 01 02 AnalgMorphPal 21 lCarePharmacolTheEIS2023Nov Pain Treatment 02 2 Nonselective NSAIDs Inhibit PG synthesis Appropriate for short term use All have ceiling effect Risk of GI bleed, renal impairment, platelet dysfunction 3 Selective COX-2 inhibitors (celecoxib is only one currently available in U.S.) Reduced GI SE and platelet inhibition FKUKWMS7.5 01 02 AnalgMorphPal lCarePharmacolTheEIS2023Nov 22  A wide variety of medication classes are used for neuropathic, bone, and visceral pain. alone or in combination w. other pain management tx. (e.g., opioid) and. after opioid tx. has been optimized or the pts has demonstrated intolerance to an opioid Clinicians should be familiar w. the indications, common adverse effects, adverse reactions, PKs, and dosing guidelines of these medications for pain. Adjuvant … FKUKWMS7.5 01 02 AnalgMorphPal 23 lCarePharmacolTheEIS2023Nov Non-opioid medications for pain (adjuvant ) 01 a)TCA ( amytriptyline, desipramine) for neuropathic pain, depression, sleep disturbance. Not used often due to SEs. b)Duloxetine (Cymbalta ) is newer antidepressant FDA approved for neuropathic pain. c)Anticonvulsants ( gabapentin, pregabalin, carbamazepine) for neuropathic pain. FKUKWMS7.5 01 02 AnalgMorphPal lCarePharmacolTheEIS2023Nov 24 Non-opioid medications for pain (adjuvant ) 02  d)Muscle relaxants : for muscle spasm, monitor for sedation  e)Local anesthetics (lidocaine patch, topical voltaren gel, capsaicin). Capsaicin depletes substance P, take weeks to reach full effect, AE include burning and erythema.. Lidocain patch FDA approved for post herpetic neuralgia.  f)Placebos: unethical FKUKWMS7.5 01 02 AnalgMorphPal 25 lCarePharmacolTheEIS2023Nov ANALGESICs Adjuvant analgesics : medications w. primary indications other than pain but w. analgesic properties in pts w. certain pain syndromes Typical adjuvant are antidepressants (AD), anticonvulsants (AC), corticosteroids, and disease- modifying medications/therapies FKUKWMS7.5 01 02 AnalgMorphPal lCarePharmacolTheEIS2023Nov 26 Adjuvant Analgesics 1. Corticosteroids. MOA : PG synthesis inhibition; central action on mood and appetite; antitumor effects in lympho-proliferative disorders, breast and prostate cancer. Indication : pain related to raised ICP, extradural spinal cord compression, tumor compression and invasion of nerve roots or individual peripheral nerve. Indication as adjuvant analgesics : FKUKWMS7.5 01 02 AnalgMorphPal 27 lCarePharmacolTheEIS2023Nov 1. Corticosteroid (continued 01 ). Neurological : raised ICP, SC compress., nerve compress./ infiltration. Bone metastases. Capsular stretching : liver metast., visceral metast.. Soft tissue infiltration: head &neck tumors, abdominal & pelvic tu.. Vascular obstruction: vena cava obst., lymphedema. Metastase to joints (intra-articular inj.). Tenesmus (rectal suppository or enema). Effect of hematological malignancies FKUKWMS7.5 01 02 AnalgMorphPal 28 lCarePharmacolTheEIS2023Nov 1. Corticosteroid (continued 01 ‘). Preparation :. Prednisolone, Dexamethasone, Hydrocortisone. Choice :. Acute neurological (spinal cord impression, raised ICP) : dexamethasone16-24mg/D; weaned as soon as clinically feasible. Other indications : dexamethasone 2-4mg/D or prednisolone 15-30mg/D FKUKWMS7.5 01 02 AnalgMorphPal 29 lCarePharmacolTheEIS2023Nov 1. Corticosteroid (continued 02). SE (related to the dose and duration of treatment) :. Cushingoid facies and body habitus. Cataract. Oropharyngeal candidiasis. CV : HT, thrombosis. Dyspepsia (particularly pt. w. aspirin or NSAID): tx. antacids, H2-R antagonist, or misoprostol. Proximal myopathy, weakness (chronic adm.). Osteoporosis, arthralgia. Skin (atrophy, thining, striae, hirsutism, easy bruising, purpura). Production or aggravation of diabetes. Fluid retention, edema (Hi-Do.). Hypoadrenalism (abrupt withdrawal). Neuropsychological (improved sense of well-being, insomnia, frank psychosis). Neutrophilia, lymphopenia FKUKWMS7.5 01 02 AnalgMorphPal 30 lCarePharmacolTheEIS2023Nov Adjuvant Analgesics (2) 2. Progestogen. Medroxyprogesterone acetate, megestrol acetate : analgesic for metastatic breast, prostate, endometrial, renal cancer. (antitumor action). Dose : 200-500mg/D MPA or 160mg/D MA. SE : n, v, fluid retention, weight gain, edema, CF, HT, vaginal bleeding FKUKWMS7.5 01 02 AnalgMorphPal 31 lCarePharmacolTheEIS2023Nov Adjuvant Analgesics (3) 3. Anticonvulsants. Indication : neuropathic pain. Carbamazepine, sodium valproate, clonazepam (lack of cross-resistance). Tx. w. second AC sometime successful. SE : n, v, sedation, ataxia, dizziness, confusion carbamazepine → leucopenia FKUKWMS7.5 01 02 AnalgMorphPal 32 (check WBC)lCarePharmacolTheEIS2023Nov  Anticonvulsant for neuropathic pain starting increase usual effective dose by dose Carbamazepine 100mg/D 100mg each 3D 400- 800mg/D Sodium valproate 200mg/D 200mg each 3D 800- 2000mg/D Clonazepam 0,5mg/D 0,5mg each 3D 2- 4mg/D FKUKWMS7.5 01 02 AnalgMorphPal 33 lCarePharmacolTheEIS2023Nov Adjuvant Analgesics (4) 4. Antidepressants. Indication : neuropathic p., constant burning dyesthetic type p., (+) insomnia or depression p.. Analgesia by increasing night-time sedation, improving mood , relieving depression. Dose : lower than AD, 50-75mg/D amitriptyline ( effect occurs 2-3D). TCA (amitriptyline, imipramine, doxepin) → superior than the newer non-TCA. Amitriptyline started 25-50mg at night , increasing to 50-75mg at night (one week no response, stopped). SE: sedation, anticholinergic , postural hypotension34 FKUKWMS7.5 01 02 AnalgMorphPal lCarePharmacolTheEIS2023Nov Adjuvant Analgesics (5) 5. Neuroleptics. Chlorpromazine, haloperidol : no analgesic, reducing anxiety, improving night-time sedation. Specifically for tx. delirium, nausea 6. Anxiolytic Drugs. Benzodiazepine (diazepam, oxazepam, lorazepam) → advanced cancer → anxiolytic effect. Diazepam: tx. muscle spasm, acute musculoskeletal p.. SE : drowsiness, weakness, postural hypotension 7. Antihistamines. Hydroxyzine FKUKWMS7.5 → opioid sparing effect 01 02 AnalgMorphPal 35 (sedative, anxiolytic) lCarePharmacolTheEIS2023Nov Adjuvant Analgesics (6) 8. Psychostimulants. Cocaine : no analgesic effect. Amphetamines : augment post-op. pain control by opioids counteract severe sedation caused by opioid elderly → dysphoric. Methylphenidate : to counteract opioid induced sedation FKUKWMS7.5 01 02 AnalgMorphPal 36 lCarePharmacolTheEIS2023Nov Adjuvant Analgesics (7) 9. Oral Local Anaesthetics. Indication : refractair pain. MOA : neuronal membrane stabilization. Mexiletine, 150mg/D, increased each few days in the same amount up to max. 750mg/D; should not taken w. food. SE : n, sedation, tremor. Caution : IHD, cardiac arrhythmias. (flecainide , risk of sudden death) 10. Ketamine. Dissociative anaesthetic ( short surgical). NMDA –R antagonist. Indication : relieve unresponsive neuropathic p.. SC infusion, subanaesthetic: 0,1-0,5 mg/kg/H , titrated against FKUKWMS7.5 01 02 AnalgMorphPal 37 effect lCarePharmacolTheEIS2023Nov Adjuvant Analgesics (8) 10. Muscle Relaxants A. Skeletal muscle spasm :. Benzodiazepines (diazepam). Baclofen (reduced function), sedation. Dantrolene : directly on muscle, less sedation, hepatotoxic B. Smooth muscle :. nifedipine → tx. tenesmus p. , oesophageal spasm FKUKWMS7.5 01 02 AnalgMorphPal 38 lCarePharmacolTheEIS2023Nov Adjuvant Analgesics (9) Drugs for Neuropathic pain 1. Clonidine. Indication : refractair neuropathic p.. Starting Lo-Do, increasing to a max. 300 g/D. ROA (also epidural). SE : hypoT., sedation 2. Nifedipine. Indication : sympathetic type p.. Dose : 20mg 2dd. SE : edema, flushing, postural hypotension 3. Capsaicin. Topical : depletion of substance P neuron in the treated area. Applied at least 3 or 4 times /D. SE : initially transient stinging FKUKWMS7.5 01 or burning 02 AnalgMorphPal 39 lCarePharmacolTheEIS2023Nov Adjuvant Analgesics (10) Drugs for Bone pain 1. Bisphosphonates. Inhibit bone resorption. Indication : tx. Hypercalcaemia, metastatic bone dis.. (+) pamidronate → less pain 2. Radioisotopes. Stronium (99SR) : relieving bone pain, osteoblastic activity (response takes 2- 4weeks) FKUKWMS7.5 01 02 AnalgMorphPal 40 lCarePharmacolTheEIS2023Nov  Adjuvant Analgesics Medication Class Dosing Indication Antidepressants Amitriptyline TCA 10–150 mg daily Neuropathic pain syndromes Nortriptyline TCA 10–150 mg daily Neuropathic pain syndromes Paroxetine SSRI (AD) 10–40 mg daily Neuropathic pain syndromes Citalopram SSRI (AD) 10–40 mg daily Neuropathic pain syndromes Duloxetine SNRI 60 mg daily Neuropathic pain syndromes Anticonvulsants Carbamazepine 1th generation AC 400–800 mg daily Neuropathic pain syndromes Gabapentin 2nd generation AC 1,200–1,800 mg daily Neuropathic pain syndromes Pregabalin 2 generation AC nd 150–300 mg daily Neuropathic pain syndromes Corticosteroids Prednisone Corticosteroids 20–80 mg daily Bone pain Dexamethasone Corticosteroids 4–20 mg daily Bone pain Other Lidocaine Anesthetics dependent on dosage form Neuropathic pain syndromes Baclofen Muscle relaxant 40–80 mg daily Neuropathic pain syndromes Calcitonin PP hormone 100–200 IU/day IV/SQ Bone pain Pamidronate Bisphosphonates 30–90 mg IV Bone pain FKUKWMS7.5 01 02 AnalgMorphPal 41 lCarePharmacolTheEIS2023Nov  Antiemetic Drugs Antiemetic Site of Action Dosage/Route Major Adverse Effect. Metoclopramide D2 ( GIT) , 5HT3 (HiDo) 5–20 mg po/sc or IV ac ; BBT Dystonia, akathisia, esophageal spasm, colic GIT obstruction Haloperidol D2 (CTZ) 0.5–4 mg po /sc/IV every 6H Dystonia , akathisia Prochlorperazine D2 ( CTZ) 5–10 mg po /IV every 6H, or 25 mg rectally every 6H Dystonia, akathisia, sedation Chlorpromazine D2 (CTZ) 10–25 mg po every 4H, 25–50 mg IM or IV every 4H or 50–100 mg rectally every 6H Dystonia, akathisia, sedation, pos.hypotension Promethazine H1, mAChR, D2 (CTZ) 12.5–25 mg po/IV every 6H or 25 mg rectally every 6 h Dystonia, akathisia, sedation Source: Wood GJ, Shega JW, Lynch B, VonRoenn JH. Management of intractable nausea and vomiting. JAMA 2007;298:1196-1207. Copyright © 2007 American Medical Association. All rights reserved. FKUKWMS7.5 01 02 AnalgMorphPal 42 lCarePharmacolTheEIS2023Nov  Diphenhydramine H1 25–50 mg po/ IV/sc every 6H Sedation, dry mouth, ur. ret. Scopolamine mAChR 1.5 mg transd.patch every 3D Dry mouth, blur.vi., ileus, ur.ret., confusion Hyoscyamine mAChR 0.125–0.25 mg sl/po every 4H or 0.2–0.5 mg sc/ IV every 4H Dry mouth,blur.vi., ileus, ur.ret., confusion Ondansetron 5HT3 4–8 mg po by pill or dis. tab. or IV every 4–8 h Headache, fatigue, constipation. Mirtazapine 5HT3 15–45 mg po every night Somnolence at LoDo, dry mouth, increased appetite Source: Wood GJ, Shega JW, Lynch B, VonRoenn JH. Management of intractable nausea and vomiting. JAMA 2007;298:1196-1207. Copyright © 2007 American Medical Association. All rights reserved. FKUKWMS7.5 01 02 AnalgMorphPal 43 lCarePharmacolTheEIS2023Nov FKUKWMS7.5 01 02 AnalgMorphPal 44 lCarePharmacolTheEIS2023Nov PALLIATIVE CARE 02 MORPHINE FKUKWMS7.5 01 02 AnalgMorphPal 45 lCarePharmacolTheEIS2023Nov Opioids Treatment  Stimulates µ opioid receptor.  Used for moderate to severe pain.  Used for both nociceptive and neuropathic pain.  Opioid drugs have no ceiling to their analgesic effects and have been shown to relieve all types of pain.  Elderly people, compared to younger people, may be more sensitive to the analgesic properties.  Advanced age is associated w. a prolonged half-life and prolonged PKs of opioid drugs FKUKWMS7.5 01 02 AnalgMorphPal 46 lCarePharmacolTheEIS2023Nov FKUKWMS7.5 01 02 AnalgMorphPal 47 lCarePharmacolTheEIS2023Nov  Opioid peptide in both. The brain stem. The spinal cord specific opioid receptors reduce the activity of the dorsal horn relay neurones analgesia Opioid analgesics → mimic endogenous opioid peptides prolonged activation of opioid receptors FKUKWMS7.5 01 02 AnalgMorphPal 48 lCarePharmacolTheEIS2023Nov  Opioid analgesics. Strong. Moderate/weak. Morphine. codeine. Diamorphine (heroin). dihydrocodeine. Oxycodone. dextropropoxyphene. Pentazocine +. Methadone. Pethidine. Buprenorphine x. Fentanyl + partial agonist x mixed agonist / antagonist FKUKWMS7.5 01 02 AnalgMorphPal 49 lCarePharmacolTheEIS2023Nov  Opiod analgesic. Analgesia. Respiratory depression. Depression of vasomotor centre → postural hypotension. Euphoria. Sedation. Miosis (except pethidine → weak atropine- like activity). N, v (stimulation of chemoreceptor trigger zone) Pain act as an antagonist of respiratory depression FKUKWMS7.5 01 02 AnalgMorphPal 50 lCarePharmacolTheEIS2023Nov  The goal of palliative care improve overall quality of life for pts., caregivers, and families while managing both general and disease-specific symptom … simultaneously while a pt. is receiving curative or life-prolonging tx.. Knowledge of pain classification is important and necessary to determine the appropriate medication tx. for each pt.. An interdisciplinary team approach is beneficial throughout the care of the pt. → evident when addressing more psychologically based symptoms, such as delirium. FKUKWMS7.5 01 02 AnalgMorphPal 51 lCarePharmacolTheEIS2023Nov Strong opioid analgesics Morphine. Pe. → widely used to tx. severe pain. Po. → DOC in terminal care. May cause histamine release → vasodilatation , itching. Tolerance w. continuous adm.. Little tolerance : miosis and constipation. Physical and psychological dependence on opioid analgesics gradually developed. Sudden termination adm. → withdrawal syndrome FKUKWMS7.5 01 02 AnalgMorphPal 52 lCarePharmacolTheEIS2023Nov Morphine Opioid analgesic regimen :. Monitor and manage ADR → constipation, n, v, sedation, confusion. < ADR : pruritus, urinary retention, myoclonus. Careful monitoring sedation → respiratory depression : slow dose titration. Tolerance : after initial days of therapy or after an increase in dose → not for constipation : tx. (+) simultaneous stimulant laxative. ADR pts. experience unacceptable w. one opioid rotation to another agent FKUKWMS7.5 within 01 02 the class AnalgMorphPal lCarePharmacolTheEIS2023Nov 53 Morphine Cancer Pain Management Mo. is the DOC for moderate and severe cancer- related pain Wide tx. range Efficacy by many ROA Reliability Availability Low cost Pharmacology. HL : 2-3Hs; DOA 4 Hs. M6G : chronic adm. > analgesia than single dose. Elderly : increase plasma and CNS fluid of M6G → increase neurotoxcicity FKUKWMS7.5 01 02 AnalgMorphPal 54 lCarePharmacolTheEIS2023Nov  MOA: a (direct) spinal b Brain : modulating peripheral nociceptive input, activation the descending inhibitory system from the brain stem to the basal ganglia c Limbic system and higher centers → modify the emotional response to pain There is no standard dose of Mo. for the tx. of chronic cancer-related pain The correct dose of Mo. → controls the pain whilst tolerable SEs The dose must be titrated for each pts. Relative : opioid sensitive and opioid- insensitive pain FKUKWMS7.5 01 02 AnalgMorphPal 55 lCarePharmacolTheEIS2023Nov  Contraindications & Cautions :. renal impairment. severe hepatic dysfunction. Pulmonary dis., acute/ severe bronchial asthma. CNS depression from any cause. Mo. intolerance or allergy → alternative opioid. Explanation, reassurance, and antiemetic for the first few days FKUKWMS7.5 01 02 AnalgMorphPal 56 lCarePharmacolTheEIS2023Nov Morphine : side effects … induce CNS) adverse effects, divided into three groups.. The first group : effects that lower the level of consciousness–sedation, drowsiness and sleep disturbance.. The second group affects the thinking process and the ability to react–cognitive impairment, psychomotor impairment, delirium, hallucinations, dreams and nightmares.. The third group is of the direct toxic effects of opioids on neurons and includes myoclonus (perhaps), hyperalgesia and tolerance. FKUKWMS7.5 01 02 AnalgMorphPal 57 lCarePharmacolTheEIS2023Nov Morphine : side effects CNS : sedation, drowsiness, confusion, narcosis, coma, dysphoria, psychotomimetic effects (fear, panic, agitation, feeling unreality, depersonalisation, vivid dreams, nightmares, hallucinations, disorientation, delusion, psychosis), myoclonus, miosis GIT : n, v, delayed gastric emptying, constipation, dry mouth, biliary colic Respiratory : resp. depression, cough reflex suppression CV : postural hypotension Urinary : urgency, retention Skin : flushing, sweating, pruritus Tolerance Physical dependence Psychological dependence FKUKWMS7.5 01 02 AnalgMorphPal 58 lCarePharmacolTheEIS2023Nov Morphine : side effects Sedation. Occurs more frequently in pts.”. Elderly or frail. Renal impairment. Have other causes of CNS depression. Opioid naïve. Only mild pain. Have had pain acutely relieved by a procedure such a nerve block. Usually mild and last 2 to 5Ds. In a few cases → severe drowsiness and confusion occur → dose reduction. Persistent sedation : assessment of renal function, exclusion of other causes CNS depression → metabolic disturbances, infection, cerebral FKUKWMS7.5 01 02 AnalgMorphPal 59 metastase, DI -sedationlCarePharmacolTheEIS2023Nov Morphine : side effects Narcosis. Too La-Do → severe sedation or narcosis w. loss of consciousness and respiratory depression. Tx. :. Naloxone,. suspected OD 0,4 – 2,0mg iv. , q33min, up to 5 doses. Buprenorphine , 8-16mg to reverse narcosis FKUKWMS7.5 01 02 AnalgMorphPal 60 lCarePharmacolTheEIS2023Nov Morphine : side effects Dysphoria and psychotomimetic effects. May occur w. morphine or other opioid drugs. Tx. Tranquilizer (e.g haloperidol) GIT, nausea, vomiting. Constipation every pt. commencing therapy w. morphine requires dietary advice and prescrition of laxatives to px. constipation Tolerance does not develop to the constipating effects of morphine and dietary and laxative tx. are necessary for the duration of tx. Xerostomia. Tx. Symptomatic if severe → assessment of for other causes should be made → drugs w. anticholinergic SE (antidepressants) FKUKWMS7.5 01 02 AnalgMorphPal 61 lCarePharmacolTheEIS2023Nov Morphine : side effects Hallucinations, Dreams, and Nightmares. Hallucinations and nightmares associated w. opioid use, mainly in the post-operative rather than the palliative care setting.. In the terminally ill, nightmares, particularly about death, have been associated w. opioid use. little evidence to suggest opioid- induced dreams, nightmares or hallucinations in palliative care, other than as part of a delirium, perhaps as prodromal symptoms. FKUKWMS7.5 01 02 AnalgMorphPal lCarePharmacolTheEIS2023Nov 62  Toxic Effects on neurons. Neurotoxic effects : endocytosis of opioid receptors, and activation of NMDA-Rs.. Glutamate, activates NMDA-Rs and opioid-induced neurotoxicity regulation, at least in part, by spinal glutaminergic activity and NMDA-Rs.. NMDA-Rs w. antagonists (ketamine) → px., tx.. Modulating glutamate transporter activity in SC px. development of opioid- induced neurotoxic FKUKWMS7.5 01 02 AnalgMorphPal 63 lCarePharmacolTheEIS2023Nov  Toxic Effects on neurons. Opioid rotation → alleviation of neurotoxicity. Pt. who had a poor analgesic to Mo. and morphine-induced neurotoxicity, rotation to methadone, an NMDA antagonistic , aided analgesia and alleviated the neurotoxicity. FKUKWMS7.5 01 02 AnalgMorphPal 64 lCarePharmacolTheEIS2023Nov  MYOCLONUS. Chronic opioid, particularly Hi-Do.; risk increased in the presence of spinal cord lesions.. MOI of myoclonus :. glycine inhibition in dorsal horn neurons → decrease in the inhibitory effects of this neurotransmitter → myoclonus and hyperalgesia.. Glutamate activation of NMDA- Rs, or serotonergic and GABA- aminergic pathways in the brain stem. FKUKWMS7.5 01 02 AnalgMorphPal lCarePharmacolTheEIS2023Nov 65  MYOCLONUS. Dopamine antagonism in the basal ganglia → EP pathways.. Myoclonus associated w. Mo. → accumulation of the active metabolite M-6-G and the toxic metabolite M-3-G.. Tx. : a opioid rotation or dose reduction. b (+) benzodiazepines, or baclofen → alleviate myoclonus. FKUKWMS7.5 01 02 AnalgMorphPal 66 lCarePharmacolTheEIS2023Nov  HYPERALGESIA …. develop in conjunction w. opioid tolerance → a result of opioid-induced apoptosis of certain cells.. The loss of GABA neurons → changes in spinal neuronal circuits involved in pain and pain modulation → sensitivity to pain increased → hyperalgesia. … NMDA-R agonism also has a major role in the development of hyperalgesia, as does glycine, an inhibitory neurotransmitter that mediates the post synaptic inhibition of spinal neurons. …. Glycine is inhibited by Mo. → a reduction of postsynaptic inhibition at the spinal cord level and an increase in pain. …. The treatment of hyperalgesia is not well established. NMDA antagonists, ketamine, → prevented fentanyl-induced hyperalgesia. FKUKWMS7.5 01 02 AnalgMorphPal 67 lCarePharmacolTheEIS2023Nov  TOLERANCE. The same dose → less analgesia or an increase in dose fails to increase analgesia. Characterized → a shortened DOA and decreased extent of analgesia, euphoria, sedation and other effects caused by CNS depression, as well as by marked elevation of the average lethal dose Escalating dose of opioids may be indicative of pharmacological tolerance, it may also reflect escalating pain from disease progression. FKUKWMS7.5 01 02 AnalgMorphPal 68 lCarePharmacolTheEIS2023Nov  Tx. or px. of opioid tolerance :. NMDA receptor antagonism and nitrous oxide synthetase inhibition.. NMDA receptor antagonists, ketamine, px. and reverse tolerance and abolish hyperalgesia.. NMDA antagonism is specific for Mo. and not other opioids. Methadone, some NMDA antagonistic activity, decrease the development of tolerance. Tolerance minimized by opioid rotation → to methadone Tolerance to methadone less commonly than other opioid-tolerance FKUKWMS7.5 01 02 AnalgMorphPal lCarePharmacolTheEIS2023Nov 69 ROA of Morphine Immediate-release oral Controlled-release oral Subcutaneous infusion Intravenous Intramuscular Rectal Spinal Intraventricular FKUKWMS7.5 01 02 AnalgMorphPal 70 lCarePharmacolTheEIS2023Nov  Immediate-release oral Mo.. POC for pts w. moderate or severe pain who are able to take oral medication. 30mg PO equiv. to 10mg IM Mo. sulphate 30mg tabl., longer acting po. Oral Mo. Mixture. Mo. HCl 2mg/ml, 5mg/ml and 10mg/ml. Advantage : cheap, well absorbed, well tolerated, (self adm.), easy to take (30-100ml/24Hs) compare to imm.-rel. tab., effective in 85% pts, flexibility of dose, wide T range, frequent dose adjustment poss., no cummulative toxicity, Hi-Do. poss. in small volumes. No other drug should be included in a Mo. mixture 71 FKUKWMS7.5 01 02 AnalgMorphPal lCarePharmacolTheEIS2023Nov  Initial dose : estimated from the amount of opioid drugs the pt. is currently taking. Breakthrough pain : tx. w. extra doses of mixture taken as often as necessary Incident pain : occurs only in certain circumstances such as after a particular movement or on standing. Adjustment of dose: if pain relief is inadequate or more than occasional backup dose are required, the dose is titrated upwards watch the SE. If pain worse at night or troubled by sedation during the day →lower dose byFKUKWMS7.5 day and higher dose at night 01 02 AnalgMorphPal 72 lCarePharmacolTheEIS2023Nov  Controlled-release oral Mo.. Preparations given 12-hourly, TOC for pt. able to take oral Mo., once the general dose requirements have been established. Should be swallowed whole.. For pts. not currently receiving opioid drugs and those on tx. w. opioids other than Mo., the best methode of starting controlled-release Mo. is to stabilize the pt. on immed.-release oral Mo. mixture for one to a few days. FKUKWMS7.5 01 02 AnalgMorphPal 73 lCarePharmacolTheEIS2023Nov  Subcutaneous infusion Mo. compatible : tx. in home setting → effective and safe. Given 4-hourly injection or by continuous infusion, via a sc-butterly needle.. Sc infusion is the preferred method as it avoids fluctuating blood levels and requires drug preparation only once a day.. Compatible drug w. Mo.: metoclopramide, haloperidol, clonazepam, midazolam, buscopan FKUKWMS7.5 01 02 AnalgMorphPal 74 lCarePharmacolTheEIS2023Nov UNDERUTILISATION OF MO.: OPIOPHOBIA Professional :. Only be used when pts. are dying. Hasten death. Doesn’t work :. Incorrect admin.. Opioid-insensitive pain. Ignoring psychosocial aspect of care Causes respiratory depression Causes unacceptable SEs :. Constipation, nausea, somnolence Fear of :. Tolerance. Physical dependence. Psychological dependence FKUKWMS7.5 01 02 AnalgMorphPal lCarePharmacolTheEIS2023Nov 75  Patient opiophobia :. “ means I’am going to die soon”. Nothing left for when the pain gets worse. Fear of addiction. Allergy. Didn’t work :. Incorrect adm.. No instruction for breakthrough pain. Mo.-insensitive pain. Ignoring psychosocial issues. Couldn’t take the Mo. :. Somnolence. Confusion. Nausea. Constipation FKUKWMS7.5 01 02 AnalgMorphPal lCarePharmacolTheEIS2023Nov 76  Analgesic Morphine in palliative care : Given adequate explanation, good prescribing and individual titration dosage, most patients will achieve good pain relief without unacceptableside effects. FKUKWMS7.5 01 02 AnalgMorphPal 77 lCarePharmacolTheEIS2023Nov Other Opioid Analgesic Diamorphine (heroin, diacetylmorphine). More lipid soluble → more rapid OOA by injection. Higher peak level → more sedation. Diamorphine : tx. control severe pain Methadone. Long DOA; less sedation. Used orally for maintenance tx. for morphine, heroin addicts → px. “buzz” of iv. drugs FKUKWMS7.5 01 02 AnalgMorphPal 78 lCarePharmacolTheEIS2023Nov Other Opioid Analgesic Buprenorphine. Partial agonist, agonist, antagonist. PK : po well absorbed, liver metab., excretion in bile & urine, HL 3Hs. Slow OOA. Effective analgesic sublingual adm.. PD : DOA 6-9Hs. Indication : moderate to severe pain. SE : similar opioid; respiratorry depression LaDo. Naloxone (but difficult to reverse → dissociates very slowly from Rs).. Prolonged vomiting FKUKWMS7.5 01 02 AnalgMorphPal 79 lCarePharmacolTheEIS2023Nov Other Opioid Analgesic (2) Buprenorphine. Tx. Depression : naloxone > (2 -3 mg inj.). DDI :. if (+) second opioid prevent or delay the second drug. pts. w. HiDo Mo.(+) buprenorphine withdrawal sy.. Dose : 0,3 – 0,6mg IM, or 0,4 – 0,8mg SL, q8H. Dose equivalence : 0.3mg IM eq. to Mo. 10mg IM 0,4mg SL eq.to Mo. 30mg PO FKUKWMS7.5 01 02 AnalgMorphPal 80 lCarePharmacolTheEIS2023Nov Other Opioid Analgesic (3) Codeine (methylmorphine). Po. well absorbed, liver metab., urine excretion. HL 2,5 0 3H. DOA :4 – 6 Hs. Indication : mild to moderate pain, cough, diarrhoea. SE : similar to Mo., more constipating. Dose : 30 – 60 mg q4 – 6H. Dose eq. : 240mg PO eq. to Mo. 30mg PO. Preparation :. codeine tablet 30mg. codeine 8mg (+) aspirin / paracetamol. codeine 30mg (+) aspirin/ paracetamol FKUKWMS7.5 01 02 AnalgMorphPal 81 lCarePharmacolTheEIS2023Nov Other Opioid Analgesic (4) Dextromoramide. PK : po well absorbed. DOA : 2-3Hs. Indication : severe pain. SE : similar to Mo. more rapid tolerance devel.. Preparation : 5mg tablet. Dose equiv.: 10mg PO equiv. to 30mg PO Mo. (but may last only 2Hs) FKUKWMS7.5 01 02 AnalgMorphPal 82 lCarePharmacolTheEIS2023Nov Other Opioid Analgesic (5) Dextropropoxyphene. PK : po well absorbed, liver metab., urine excr., HL 12- 15Hs. DOA : 4-6Hs. Indication : mild to moderate pain. SEs :. generally less severe than Mo.. CNS depression & seizure in overdose. DDI :. Potentiates oral anticoagulant. Predisposing carbamazepine toxicity. Preparation :. D HCl 32,5 mg (+) paracetamol 325mg. D. napsylate 100 mg. Dose : D. HCl 65mg q4-6H FKUKWMS7.5 01 02 AnalgMorphPal 83 D. napsylate 100mg q4-6H lCarePharmacolTheEIS2023Nov Other Opioid Analgesic (6) Fentanyl , alfentanil, remifentanil. Synthetic opioid for perioperative pain : IV., IM., SC., ED., or transdermal. DOA : short (0,5 – 1H). Lo-Do fentanyl and alfentanyl → short- acting (rapid redistribution);. La-Do saturate tissues → more prolonged actions. Patch : DOA 72Hs (does not peak plasma level for 12- 24Hs ) → need other analgesia during this time. Dose equiv. : 0,1mg fentanyl equiv. to 10mg IM Mo.. Indication : transdermal fentanyl for pts intolerant of oral MO. /unable to take because dysphagia or drowsiness (particularly useful in renal failure). Pts. intolerant of Mo. and requiring PE tx. Continuous IV or SC infusion FKUKWMS7.5 01 02 AnalgMorphPal 84 lCarePharmacolTheEIS2023Nov Other Opioid Analgesic (7) Methadone. Synthetic opioid ; PO, PR., injection. Tx. severe pain, Mo. intolerance. CI or great caution : frail, elderly,, confused, significant hepatic or renal impairment. SE : similar to MO.; cumulative toxicity (+) → sedation confusion. Single dose HL 15Hs; continued tx. HL 2-3Ds → reduce both the dose and frequency of admin.. DOA : long DOA, 4-6Hs initially; 6-12Hs w. continued adm.. Dose : calculated from previous tx., adjusted for response and toxicity frequency : q 4-6H for first 1-3D; then q6-12Hs. Equiv. dose : 20mg PO equiv. to 30mg PO MO. 10mg IM equiv. to 10mg IM MO.. Preparation : 5mg,FKUKWMS7.5 01 02 AnalgMorphPal 10mg tablets; 10mg injection lCarePharmacolTheEIS2023Nov 85 Other Opioid Analgesic (8) Oxycodone. Semi-synthetic derv. of codeine; wider therapeutic range. Indication : LoDo. to tx. mild and moderate pain, HiDo. for severe pain. Well absorbed PO and rectal; liver metab., exc.urine. DOA : oral 4-6H, rectal 6-12Hs. Dose : oral 5-10mg q4-6Hs; rectal 30mg q6-12Hs. Dose equiv. : 30mg PO or PR equiv. to 30mg PO Mo.. Preparation : O. HCl 5mg tablet O. pectinate 30mg suppository 86 FKUKWMS7.5 01 02 AnalgMorphPal lCarePharmacolTheEIS2023Nov Other Opioid Analgesic (9) Pentazocine. Synthetic; absorbed slowly orally; HL 2-3H DOA : 3-4Hs; PO, PE. Indication : mild to moderate pain in pts not receiving other opioid drugs. SEs : similar to other opioid, (+) psychotomimetic SE. Not for chronic cancer - related pain because of the high incidence of psychotomimetic SE and the potential for DDIs w. opioid agonists (precipitated withdrawal sy. and pain). Dose : no standard do. for chronic cancer pain; freq. q3-4Hs. Dose equiv. : 180mg PO equiv. to 30mg PO Mo. 60mg IM equiv. to 10mg IM Mo. FKUKWMS7.5 01 02 AnalgMorphPal 87. Preparation : tablet 25mg, 50mg; injection 30mg lCarePharmacolTheEIS2023Nov Other Opioid Analgesic (10) Pethidine. Irregularly absorbed per oral; liver metab., urine excr.; HL 3-4H. Rapid OOA , Short DOA : 2-3H. Indication : severe acute pain. Tx.-ceiling related to CNS toxicity; not used to tx. chronic cancer- rel. pain. CI : pts taking MAO-I; caution : renal impairment. SE : less constipating, not antitussive, no miosis CNS toxic. (nor-pethidine accumulation): agitation, tremor, myoclonus, seizures. DDI :. phenobarbitone, phenytoin : diminish analgesia, increase CNS toxicity of pethidine. MAO-I : excitation, hyperpyrexia, seizures. Enhance toxicity of other CNS depressant drugs. No standard dose forFKUKWMS7.5 chronic 01 ca-pain, freq. q3H 02 AnalgMorphPal 88 lCarePharmacolTheEIS2023Nov  Pethidine (continued). Norpethidine : renal imparment ( frequent or high doses) agitation, tremor, myoclonus and seizures. Tx. myoclonus and seisures : BDZ and anticonvulsants Not responsive to naloxone FKUKWMS7.5 01 02 AnalgMorphPal 89 lCarePharmacolTheEIS2023Nov Medication Management Deprescribing: to improving care and minimizing unecessary polyfarmacy Reduce the burden to pts due to. ADR of drug (s). DDI. Inappropriate medications Reduce medication burden, decreased mortality, shorter hospitalization, and improvementsFKUKWMS7.5 in pts01overall health 02 AnalgMorphPal lCarePharmacolTheEIS2023Nov 90 Medication Management Drug candidates for deprescribing :. WO. an indication. High risk and benefit ratio. Drug initiated to control ADR associated w. another drug. Preventive drug whose benefit is unlikely to be realizedgiven pts’s life FKUKWMS7.5 01 02 AnalgMorphPal lCarePharmacolTheEIS2023Nov 91  Special challenges for pharmacotherapy recognizing the end is near is important : Dysphagia of liquids, pulselessness on the radial, respiration w. movement, decreased urine out put, Cheyne-Stokes breathing, death rattle, periods of apnea,peripheral cyanosis. Attention to symptoms arise or worsen ; delirium, dyspnea, fatique, pain, cough, death rattle, myoclonus, fever, and emergency such as catastrophic hemorrhage FKUKWMS7.5 01 02 AnalgMorphPal 92 lCarePharmacolTheEIS2023Nov  Medication management at this point :. Elimination of medications unlikely benefit. Switching to non oral ROA. Opioids,. Lorazepam,. Dexamethasone,. Haloperidol. Intensol formulation → 1ml instilled in the buccal cavity. Discussed w. the family member and caregivers FKUKWMS7.5 01 02 AnalgMorphPal 93 lCarePharmacolTheEIS2023Nov Non-drug treatment 01  Education: basic knowledge about pain (diagnosis, treatment, complications, and prognosis), other available treatment options, and information about over-the- counter medications and self-help strategies.  Exercise: tailored for individual patient needs and lifestyle; moderate-intensity exercise, 30 min or more 3-4 times a week and continued indefinitely.  Physical modalities (heat, cold, and massage) Cold for acute injuries in first 48 hours, to decrease bleeding or hematoma formation, edema, and chronic back pain. Heat works well for relief of muscle aches and abdominal cramping. FKUKWMS7.5 01 02 AnalgMorphPal 94 lCarePharmacolTheEIS2023Nov Non-drug treatment 02 Physical or occupational therapy; should be conducted by a trained therapist Chiropractic: Effective for acute back pain. Potential spinal cord or nerve root impingement should be ruled out before any spinal manipulation Acupuncture: Performed by qualified acupuncturist. Effects may be short lived and require repetitive treatments FKUKWMS7.5 01 02 AnalgMorphPal 95 lCarePharmacolTheEIS2023Nov Non-drug treatments 03  Relaxation: repetitive focus on sound, sensation, muscle tension, inattention towards intrusive thoughts. Requires individual acceptance and substantial training.. Meditation: Guided or self-directed technique for calming the mind, allows thoughts, emotions and sensations to travel through conscious awareness without judgment. Progressive muscle relaxation: Individual tensing and relaxing of certain muscle groups.  Hypnosis: effective analgesic, state of inner absorption and focused attention. Reduces pain by distraction, altered pain perception, increased pain threshold. Norelli L J et.al., : Behavioral approaches to pain management in the elderly, 24(2), Clinics in Geriatric Medicine, 2008. FKUKWMS7.5 01 02 AnalgMorphPal 96 lCarePharmacolTheEIS2023Nov Non-drug treatment 04  Cognitive-behavioral therapy: Pain is influenced by cognition, affect and behavior. Conducted by a trained therapist, focuses on changing individual cognitive activity to modify associated behavior, thoughts, and emotions. 10-12 weekly individual or group sessions Participants have to be cognitively intact  Operant behavior therapy: Use of negative and positive consequences to modify the behaviors.  Mind-body conditioning practices: Yoga, tai chi, qigong. Norelli L J, et.al.,: Behavioral approaches to pain management in the elderly, 24(2), Clinics in Geriatric Medicine, 2008. FKUKWMS7.5 01 02 AnalgMorphPal 97 lCarePharmacolTheEIS2023Nov Consequences of untreated pain  Impaired function: Pain can lead to decreased activity and ambulation leading to de- conditioning, gait disturbances and injuries from falls.  Sleep deprivation: decrease pain thresholds, limit the amount of daytime energy, increased risk of depression and mood disturbances.  Increases financial and care giving burdens placed on families and friends by increased utilization of health care services.  Diminished quality of life by isolating individuals from important social stimulation, amplifying the functional and emotional losses already experienced from undertreated pain. Jakobsson, U. et.al., Old people in pain: A comparative FKUKWMS7.5 01study. Journal of Pain and Symptom Management, 26, 625- 02 AnalgMorphPal 98 636,2003. lCarePharmacolTheEIS2023Nov Weiner, D.K., et.al., Pain in nursing home residents; management strategies. Drugs and Aging, 18(1), 13-19,2001. Cancer Pain Initial tx. based on the severity. Mild pain (eg. pain rated ≤ 4) non-opioid or a combination of non opioid and an opioid analgesic. Moderate to severe pain → usually requires an opioid analgesic. Neuropathic pain tx. → anticonvulsant or antidepressant medication. Nerve blocks and invasive surgical procedures → option for pain control that is refractory to conventional medication management FKUKWMS7.5 01 02 AnalgMorphPal 99 lCarePharmacolTheEIS2023Nov Cancer Pain The analgesic ladder progresses in a stepwise manner. Acetaminophen. NSAIDs and. Adjuvant medication (eg. coanalgesics such as anticonvulsants and antidepressants for neuropathic pain ) as initial tx.. If pain intensity >4 of 10 but not severe, weak opioid analgesics may be added to the pain regimen.. Severe pain → strong opioids such as morphine, hydroxymorphone, fentanyl, oxycodone are recommended FKUKWMS7.5 01 02 AnalgMorphPal 100 lCarePharmacolTheEIS2023Nov Cancer Pain Hydromorphone → good choice for iv. Opioid tx.. Does not have active metabolite (could accumulate w. renal insufficiency) Fentanyl (transdermal patch) → excellent for out pt. (provide continuous release of opioid and convenient to use). Intended for opioid tolerant pt. w. stable chronic pain Kadian (ER morphine capsule) can be admin. Via gastric feeding tube because the capsule is opened and contentsflush through the gastric feeding tube w. water Limitation → pt. manipulation of the gastric feeding tube w. self-admin. and potential for morphine SEs secondary to metabolite accumulation if renal insufficiency persists FKUKWMS7.5 01 02 AnalgMorphPal lCarePharmacolTheEIS2023Nov 101 Cancer Pain Opioid tx. for breakthrough pain → spontaneous pain (frequently idiopathic, occurring w. no known stimulus) a) Incident pain (secondary to a stimulus that the pt. may or may not be able to control) → can be reduced by take a dose of short-acting opioid 30 minutes before activity Or b) End-of-dose failure (pain at the end of the dosing interval of the long-acting opioid) Spontaneous breakthrough pain → tx. a short-acting opioid as soon as the pain is experienced Pt. on long-acting opioid, end-of- dose failure, → supplementary doses of a short-acting opioid doses eq. to 5% to 15% to the total daily dose to be taken every 2Hs as needed. FKUKWMS7.5 01 02 AnalgMorphPal 102 lCarePharmacolTheEIS2023Nov Cancer Pain Short-acting opioid/acetaminophen → have a maximal dose to prevent liver toxicity w. acetaminophen → creating a ceiling limit on the analgesic efficacy Plain short-acting opioids (eg. morphine, oxycodone, hydromorphone) → should be used for pt. requiring La-Do for breakthrough pain Fentanyl admin. by oral transmucosal (Actiq) or buccal (Fentora) routes → approved for breakthrough pain management in cancer pt. FKUKWMS7.5 01 02 AnalgMorphPal 103 lCarePharmacolTheEIS2023Nov Methadone Opioid agonist w. analgesic activity at mu and delta Rs. Long HL 15- 60Hs; DOA 6-12Hs Good option for neuropathic pain → 5-HT and NE reuptake inhibition and antagonist effects at the NMDA –Rs The single methadone conversion factor for acute pain and does not account for chronic use Rotation to methadone → if pt. has inadequate respons w. to other opioids or experiences intolerable SE such delirium, myoclonus, or nausea FKUKWMS7.5 01 02 AnalgMorphPal 104 lCarePharmacolTheEIS2023Nov Methadone Toxicity. Risk of fatal respiratory depression. QT interval prolongation > 500 milliseconds reducing or discontinuing methadone. CIE → sign and symptoms of methadone toxicity shallow breathing, slowed respiration followed by periods of not breathing, slurred speech or difficulty talking FKUKWMS7.5 01 02 AnalgMorphPal lCarePharmacolTheEIS2023Nov 105 Pharmacological Treatments for Opioid-Related SEs Side Effect Treatment.Constipation. Stool softener, laxative, methylnaltrexone, oral naloxone. Sedation. Methylphenidate, modafinil. Pruritus. Diphenhydramine, hydroxyzine. Nausea. Prochlorperazine, haloperidol, metoclopramide, ondansetron, antihistamine.Dysphoria. Haloperidol, opioid rotation. Cognitive impairment. Methylphenidate, modafinil, opioid rotation. Myoclonus FKUKWMS7.5. 01 Clonazepam, 02 AnalgMorphPal dose reduction, 106 opioid rotation lCarePharmacolTheEIS2023Nov Thank You FKUKWMS7.5 01 02 AnalgMorphPal 107 lCarePharmacolTheEIS2023Nov