Preeyaphan Arunakul MD FRCAT Department of Anesthesia Faculty of Medicine, Thammasat University Definition
“An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.”
Classification of pain by time
• Acute pain - Pain less than 12 weeks • Chronic pain - Pain longer than 12 weeks Nociceptive Nonnociceptive Somatic Visceral Neuropathic Psychogenic
sharp, dull Poorly localized, Burning, electrical -Rarely pure aching deep squeezing, (lancinating), -No nociceptive or crampy numbing, neuropathic mechanism allodynia, can be identified -Myofascial hyperalgesia -With sufficient -Metastatic -Small bowel psychogenic symptoms bone pain obstruction -Postsurgical -Carcinomatosis -Trigeminal neuralgia -Arthritis peritonii -Postherpetic neuralgia -Painful peripheral neuropathy NSAIDs -CRPS I,II Opioids TCA/SSRI -Phantom limb pain Muscle relaxants Gabapentin Aniline deriv. Opioids Anticonvulsants Antidepressants Multimodalities Interventions Antidepressants Psychological therapy Psychotherapy Interventions Multimodalities Acute Postoperative Pain ผู้ป่วยมีอาการปวดเฉียบพลัน “5th Vital sign”
มีสาเหตุที่ท าให้เกิดอาการปวด รักษาสาเหตุ
ประเมินระดับความปวด ไม่ต้องการ อาการปวดต้องการการรักษาหรือไม่ ประเมินซ ้าและบันทึก ต้องการ (PS ≥ 4 หรือปวดปานกลางขึ้นไป) เครื่องมือที่ใช้ประเมินความปวด รักษาโดยใช้ยา - VAS/VRS/NRS รักษาโดยไม่ใช้ยา - FACE/FLACCs รักษาแบบผสมผสาน - CHEOPS
ไม่ได้ผล การรักษาได้ผลดีหรือไม่ ปรึกษาผู้เชี่ยวชาญ ได้ผลดี เกิด เกิดภาวะแทรกซ้อนจากการรักษาหรือไม่ รักษาภาวะแทรกซ้อน ไม่เกิด ประเมินซ ้าและบันทึก Postoperative pain
• Acute pain • Choices: - iv bolus/iv PCA/oral opioids - neuraxial opioids (spinal & epidural) - peripheral nerve blocks with LAs - NSAIDs and other medications • Effects of pain on systems CNS & Neuroendocrine
1. Secretes enkephalins, endorphins 2. Reflex escape response “Fight or Flight” - stimulated sympathetic nervous system - increased E and NE - inhibit peristalsis and secretion of digestive enzymes 3. Increasing CRH, ACTH, Cortisol from hypothalamus 4. Increasing glucagon and reduce insulin level CNS & Neuroendocrine
5. Increasing E & NE from adrenal medulla 6. Decreasing ADH = Na & water retention 7. Increasing renin & AT II secretion from adrenal gland 8. Increasing protein breakdown = reduce wound healing
9. Increasing IL-1 level = increase inflammatory effect Cardiovascular system
Increasing sympathetic activity Hypertension increase myocardial
Tachycardia O2 consumption
Myocardial ischemia GI and Immune system
• Depress immune system • Impaired GI function - delayed gastric emptying - reduce bowel motility, potential paralytic ileus - nausea & vomiting (also from CTZ) Respiratory system
Limiting movement of thoracic & abdominal muscles
Respiratory dysfunction Retained sputum and secretion (reluctant to cough) Reduction in vital capacity
Hypoxia
Cardiac complication, disorientation, confusion, and delayed wound healing KUB system
Increasing CAs, aldosterone, ADH, cortisol, AT-II, and PGs
(regulate urinary output, fluid & electrolyte balance, blood volume, and BP)
Na & water retention Increase K+ excretion
Fluid overload Increase cardiac workload
Hypertension Musculoskeletal system
Reflex muscle spasm, impaired muscle function Muscle fatigue
Immobility
Venous stasis Increase coagulability
Increase risk of developing DVT Psychological & Cognitive function
Acute stress-induced hormonal changes
1. Anxiety interrupt sleep pattern (insomnia) Depression interfere daily activity
2. Distressing cognitive impairment - disorientation - mental confusion - reduce ability to concentrate 3. Poorly-controlled acute pain --> chronic pain Neuropathic pain Definition
• “Pain caused by a lesion or disease of the somato- sensory nervous system”
• Clinical description
(not a diagnosis) ; requires demonstrable lesion or disease that satisfies established neurological diagnostic criteria
• Central and peripheral neuropathic pain Management
• Pharmacotherapy • Physical and Psychotherapy • Interventions • Surgery • Lifestyle modifications • Alternatives • Neurostimulation (SCS) Pharmacotherapy
• Gabapentin/Pregabalin (Neurontin®/Lyrica®)
• Carbamazepine/Oxcarbazepine (Tegretol®/Trileptal®)
• Duloxetine/Venlafaxine (Cymbalta®/Effexor®)
• Tramadol (for acute exacerbation only) Cancer pain Medications
• Opioids • Gabapentin and pregabalin • NSAIDs (for bone metastasis) • Antidepressants/antianxiety Nociceptive Neuropathic Cancer- Tumor- Visceral pain ยา pain cancer pain induced induced MBO* bone pain headache ดีมากสาหรับอาการ Opioids ดีมาก ปานกลาง ดีมาก ดี ปวดตลอดเวลา NSAIDs ดีมาก ไม่ดี ดีมาก ดี ไม่แนะนา Antidepressants น้อย ดีมาก ปานกลาง ไม่แนะนา ไม่แนะนา TCAsและSNRIs ดีสาหรับ visceral Gabapentinoids น้อย ดีมาก ดี ไม่แนะนา hyperalgesia ดีสาหรับ paroxysmal น้อย ยกเว้นใช้เป็นยา Carbamazepine ไม่ดี น้อย ไม่ดี sharp shooting pain กนั ชกั
Bisphosphonates ไม่ดี ไม่ดี ดีเมื่อให้ระยะยาว ไม่ดี ไม่ดี ดีมากสาหรับ ดีสาหรับ liver capsule Corticosteroids ไม่แนะนา nerve/cord ปานกลาง ดีมาก distension compression
Strong opioids
• Morphine (Morphine, MST, Kapanol) • Meperidine (Pethidine) • Fentanyl (Fentanyl, Duragesic, Durogesic) • Methadone • Oxycodone Visceral Pain Visceral pain Clinical features :
• Diffuse localization, deep, squeezing, crampy
• Unreliable association with pathology
• Referred sensation to cutaneous structures
• Cutaneous or deep tissue hyperalgesia
• Strong autonomic and emotional response may be evoked with minimal sensation
Referred pain
• Pain referred from a deep somatic or visceral structure to a distant region within the same segment
• With/without hyperalgesia and hyperesthesia, deep tenderness, muscle spasm, and autonomic disturbances.
• No changes in reflexes, no weakness or atrophy
• Segments involved are identified (all somatic and visceral structures innervated are carefully examined for a pathologic process)
• Ex: Shoulder pain in subphrenic abscess Visceral pain etiologies
• Inflammation (acute and chronic), including inflammation caused by mechanical irritants (kidney stone)
• Infection
• Disruption of normal mechanical process (GI dysmotility)
• Neoplasms (benign or malignant)
• Alterations in nerves carrying sensations from the viscera
• Ischemia Medications & Interventions
• Opioid for cancer in origin • Antidepressants • Gabapentin/pregabalin • Sympathetic plexus block/neurolysis Musculoskeletal pain
Pharmacotherapy
. NSAIDs
. Muscle relaxants Medications Oral medications - Acetaminophen (paracetamol) - NSAIDs - opioids = tramadol, codeine - tramadol + paracetamol (Ultracet®) - antidepressants/anticonvulsants IV medications - Opioids = morphine, pethidine, tramadol, fentanyl - NSAIDs = Parecoxib (Dynastat®), Ketorolac WHO step ladder
modified by TASP Patient-controlled analgesia (PCA) Patient-controlled epidural analgesia (PCEA)
1. Improved pain control 2. Receive immediate delivery of pain med. 3. Patient control 4. Frequent but smaller dose, less side effects PCA variables
• Bolus dose or PCA dose or demand dose (self-administered intermittently) • Lock out interval (time between dose) • Loading dose • Background infusion • Dose limit in 1 or 4 hour Using PCA
- Patient education
- Monitor O2 saturation (in high risk patient) 1. Pain scores at rest/movement
2. Side effects Sedation, N/V, pruritus, respiratory depression, urinary retention
3. Total amount of opioids delivered Neuraxial Opioids Spinal/epidural morphine - duration 18-24 hours/it depends - no sedatives or sleeping pills (except for order from anesthesiologist) - side effects : respiratory depression nausea and vomiting pruritus urinary retention Local anesthetic for epidural
. 0.0625% - 0.15% Bupivacaine/Levobupivacaine
. 1-2% Lidocaine with or without adrenaline Opioids
• Morphine 1-5 mg bolus or epidural infusion at
0.005-0.02 mg/ml
• Fentanyl 1-2 mcg/ml epidural infusion Peripheral nerve blocks
- Local anesthetics only - Single shot or catheter - US-guided and/or peripheral nerve stimulator - 18-24 hours - Side effects : motor weakness catheter migration Acetaminophen Acetaminophen (paracetamol)
• tablet 500 mg 1 tab oral prn/every 4-6 hrs
• tablet 650 mg 1 tab oral prn/every 8 hrs • FDA Liver warning: Severe liver damage may occur if you take
- more than 4,000 mg of acetaminophen in 24 hours - with other drugs containing acetaminophen
- 3 or more alcoholic drinks everyday while using this product • FDA reminds health care professionals to stop dispensing prescription combination drug products with more than 325 mg of acetaminophen (4/28/2014) • Acetaminophen in both OTC and prescription products and the risk of attention deficit hyperactivity disorder (ADHD) in children born to women who took this medicine at any time during pregnancy.
Liew Z, Ritz B, Rebordosa C, Lee PC, Olsen J. Acetaminophen use during pregnancy, behavioral problems, and hyperkinetic disorders. JAMA Pediatr 2014;168:313-20. NSAIDs
Role of NSAIDs
• Acute postoperative pain
• Chronic musculoskeletal pain
• Cancer-induced bone pain Evidence-based practice • Prevent and treat postoperative pain in ambulatory surgery • Decrease: opioid consumption early return of bowel function early recovery of physical activity increase patient satisfaction • No difference if given before or after surgery Maximum Drug mg Frequency dose/day Parecoxib (dynastat®) 40 IV q 12 h 80 Ketorolac 15, 30 IV q 8 h 90 Ibuprofen 200,400,600 q 4-6 h 2400 25,50 q 8 h Diclofenac 150 SR75,100 q 12-24 h Indomethacin 25 q 8-12 h 200 Naproxen 250 q 12 h 1000 Piroxicam 10,20 q 24 h 20 Meloxicam 7.5 q 12-24 h 15 Celecoxib 200,400 q 12 or 24 h 400 q 24 h Etoricoxib 30,60,90,120 120 120 mg < 8 days Compounds appearing above the line are COX-1-selective, those below the line COX-2-selective.
Warner TD, Mitchell JA. FASEB J 2004; 18: 790-804
FDA Black box warnings GI toxicity
“NSAIDs cause an increased risk of serious gastrointestinal adverse events including inflammation, bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at anytime during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events.” Relative Risk in developing NSAIDs-induced Gastropathy
• History of complicated ulcer 13.5
• Multiple NSAIDs (including ASA) 9.0
• High dose of NSAIDs 7.0
• Use of anticoagulant 6.4
• Age > 70 5.6
• Use of corticosteroids 2.2
Tannenbaum, et al. J Rheum 2006 NSAID-induced small bowel injury • Rebamipide (Mucosta®) • Gastroprotective effect by modulate gene expression of protein -increases growth factors thus accelerates healing -reduces inflammatory cytokines -acts as free radical scavengers -increases PGs production • Peak serum concentration at 2.4 hrs • Distribute mostly to GI mucosa • Does not require CYP450, less drug interaction
J Gastroenterl 2009; 44:879-88 Role of COX-2 inhibitors
• Developed to reduce GI complications • CLASS trial1 - Symptomatic ulcer and ulcer complications 2.1% in Celecoxib group 3.5% in conventional NSAIDs group (p=0.02) - Presence of aspirin negated GI benefit - After 1 year, no difference in GI events2
1.Silverstein FE, et al. JAMA 2000; 284: 1247-55 2. Wright JM, et al. JAMA 2001; 286:2398-400 What if patients also taking aspirin
• Risk of GI complications ASA + coxib = nonselective NSAID alone • Risk of hospitalization for adverse GI event ASA + coxib = 0.86 (hazard ratio) ASA + NSAIDs = 1.61 (hazard ratio) FDA Black box warning Cardiovascular risk
“NSAIDs and COX-2 inhibitors may cause an increase risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.” 1.01
1.63
2.13
2.01
0.97
Healthy Individuals Cox proportional hazard ratios for the composite end point of death and myocardial infarction associated with exposure to NSAIDs in a study population of 1,028,437 individuals characterized by no prior concomitant pharmacotherapy and no comorbidity.
Fosbol. Clinical Pharm Ther 2009; 85(2):190-7 AVG GI risk High GI risk NSAID alone NSAID + PPI/Misoprostol/Rebamipide or AVG Coxib + CV risk PPI/Misoprostol/Rebamipide Naproxen (if no ASA) Avoid NSAIDs if possible High CV risk Naproxen + Naproxen + PPI/Misoprostol PPI/Misoprostol/Rebamipide (if ASA) (regardless of ASA use)
Chan Am J Gastroenterol 2008; 103: 2908-2918 What’s happening to kidney? Serious side effects
• Myocardial ischemia/infarction • Hypertension, stroke • Heart failure (fluid retention) • Renal insufficiency • Bleeding & ulcers • Life-threatening skin & allergic reactions • Liver failure • Induce asthmatic attacks in asthmatic patients Contraindications for NSAIDs
• Cardiovascular thromboembolic events
• CrCl < 30 ml/min
• Active GI bleeding
• Thrombocytopenia from chemotherapy
• Active liver disease (enzymes rising > 3 times)
• Allergic to Sulfonamides
• Pseudo-allergic reactions from NSAIDs Prolonged use of NSAIDs
• Baseline • 2 weeks after starting - Serum Cr - Serum Cr - Hepatic function - K+ • Periodically - K+ - Serum Cr - CBC - K+ - BP, pulse, BW - BP, pulse, BW - Hepatic function Other drug interactions
• Celecoxib metabolized by CYP2D6, 2C9 - Celecoxib + warfarin = increase INR - Conventional NSAIDs + warfarin/clopidogrel = increase risk of bleeding • SSRIs itself increase risk of GI complications - SSRI + NSAIDs even more risk Do NSAIDs interact with aspirin??
8 hrs Ibuprofen Aspirin 30 mins
• Other NSAIDs (naproxen) also have been considered to attenuate the effect of aspirin. Risk Reduction
• Avoid NSAIDs in pts with existing renal dysfunction,
CHF, resistant hypertension
• Monitor BP and serum Cr in high risk patients
Elderly, cirrhosis, HT, DM, hypovolemia
“Lowest effective dose with shortest duration” Muscle relaxants
Eperisone (Myonal)
Tolperisone (Biocalm, Mydocalm)
Orphenadrine (Pormus)
Baclofen
Tizanidine (Sirdalud, Zanaflex, Tizan)
Cyclobenzaprine (Flexeril)
Benzodiazepines (Diazepam) Contraindications: Myasthenia gravis Eperisone (Myonal)
• Centrally-acting skeletal muscle relaxant used to improve myotonic symptoms
• Should be taken with food. Take after meals
• Weakness, dizziness, insomnia, drowsiness, hepatic and renal dysfunction
• Avoid concomitant use with Tolperisone
• Muscle spasm
• Adult: 50 mg 3 times/day Tolperisone (Biocalm)
• Centrally-acting muscle relaxant
• Adult: PO 50-150 mg 3 times/day with food
• Well absorbed from GI tract.
• Bioavailability: 20%
• Extensively metabolized by liver and kidney
• Excreted mainly via urine as metabolites
• Side effects: muscular weakness, headache, hypotension, N/V, sedation, drowsiness, ataxia, dizziness, confusion
• Concomittant use with levodopa in Parkinson pts may result in confusion, agitation, hallucinations Pormus • Orphenadrine 35 mg + Paracetamol 500 mg • Dosage: PO BID, Duration: 4-6 h • Indications: Adjunctive treatment for acute, painful musculoskeletal conditions. • Contraindications: Glaucoma, pyloric/duodenal obstruction, PU, prostatic hypertrophy, obstruction of bladder neck, and esophageal achalasia. Norgesic
Orphenadrine 35 mg + Paracetamol 450 mg Multilayer: Orphenadrine 25 mg + Aspirin 385 mg + caffeine 30 mg Orphenadrine citrate
• Derivative of diphenhydramine, acts on brainstem • Pharmacology:, antihistamine and anticholinergic • Onset 1 hr, duration 4-6 hrs • Maximum 100 mg divided into BID
• Pharmacokinetics: good GI absorption, T max is 2 hrs • Side effects: tachycardia, lightheaded, N/V, dry mouth • Caution in renal and liver impairment Baclofen
• GABA derivative binds to GABAB, antispastic
• Inhibits Glu and SP release at both monosynaptic and polysynaptic reflexes at spinal level
• Onset 3-4 days, variable duration
• 5 mg PO TID (40-80 mg/day)
• Side effects: drowsiness, slurred speech, hypotension, constipation, urinary retention, short-term memory loss Tizanidine (Sirdalud, Tizan)
• α2-adrenergic receptor agonist • Decrease spinal excitatory amino acid release
• FDA-approved for mx of increased muscle tone
• Onset 2 wks, 2-8 mg PO TID-QID
• Clearance is reduced >50% in pt with CrCl<25 mL/min
• Side effects: bradycardia, dose-related hypotension, dizziness, lightheadedness but rarely syncope Diazepam
• GABA agonist • Onset 30 min, variable duration • 2-10 mg PO TID • Side effects: Sedation, fatigue, hypotension, ataxia, respiratory depression • Must be slowly tapered after long-term use to avoid withdrawal symptoms Opioids Opioid Pharmacodynamics
. Alters perception of pain . Mesolimbic dopamine system = reinforcing and rewarding properties (euphoria) . Modulates nociceptive pathways, enhancing effects of endogenous opioids How does opioid inhibit pain transmission??
Opioids
Opioid receptors (mu, kappa, delta)
Inhibits voltage-gated Ca2+ channels Opens K+ channels causing hyperpolarization
Decreases synaptic transmission of pain signals in the spinal cord dorsal horn Weak opioids “Never combined with Strong Opioids” Tramadol
Dosage: 0.5-1 mg/kg iv (prn) q 4-6 H
50-100 mg oral (prn) q 4-6 H
max 400 mg/day
Forms : - Tramol 1-2 caps oral (prn) q 6 H
- Ultracet 1-2 caps oral (prn) q 6-24 H (37.5 mg of Tramadol + 325 mg of paracetamol) Side effects: dizziness, N/V, constipation Cautions: Epilepsy, Serotonin syndrome (SSRI/SNRI), liver or renal insufficiency Serotonin syndrome
- mental status change - autonomic instability (labile BP, tachycardia, dizziness, diaphoresis, flushing, hyperthermia) - neuromuscular changes (tremor, rigidity, myoclonus, hyperreflexia, incoordination) - seizure, use BZD - GI symptoms (N/V/D) Rx: Cyproheptadine in severe case Codeine • Tylenol with codeine (TWC) • Codeine 15-60 mg + Tylenol 300 mg
• Q 4-6 H, max 240-360 mg of codeine/day
• metabolized by CYP2D6 to morphine (10%) • extra careful in ultra-rapid or rapid metabolizer • Analgesic effect is reduced when combined with CYP2D6 inhibitor (fluoxetine, paroxetine) • Side effects: drowsiness, N/V, constipation (>mo) • Renal excretion Strong opioids
• Morphine (Morphine, MST, Kapanol) • Meperidine (Pethidine) • Fentanyl (Fentanyl, Duragesic®) • Methadone • Oxycodone
* Commonly used in acute pain Intravenous dosage
Morphine
• binds to mu receptor
• Hepatic metabolism to M3G, M6G (active metabolite)
• consider other opioids in stage 4-5 CKD, dialysis pt
• respiratory depression in high risk pts :
1. respiratory problems (+ benzodiazepine) 2. severe cardiovascular problems
3. renal dysfunction Meperidine (pethidine)
• binds to mu and kappa receptor • Short term use only!!!! ( < 72 hrs) • prolonged use may lead to addiction and seizure (toxic metabolites = Normeperidine) • Delirium, myoclonus • Reversal with naloxone can exacerbate convulsant effect of normeperidine Fentanyl
• potent mu agonist • immediate onset, duration 30-60 min • can also be used in epidural/spinal analgesia Central effects of opioids
- Analgesia - Mood effect - Sedation - N/V - Respiratory depression - CNS excitation - Pupil constriction - Tolerance - Antitussive effect - Dependence - Hypothalamic effects - Addiction Peripheral Effects of Opioids
• Constipation • Itching/pruritus How to deal with complications from opioids? Constipation Colon contains large population of mu opioid receptor
Inhibit peristalsis
Rx : Drink lots of water Exercise Stimulating laxatives/stool softener Senokot 1-4 tabs oral hs MOM 15-30 ml oral hs Itching Release of histamine from mast cells
Rx : Antihistamines CPM 10 mg iv Ondansetron 0.1 mg/kg IV prn q 6 h Opioid Rotation Nausea and vomiting
- stimulate CTZ in area postrema of medulla
- alter vestibular sensitivity
Rx - 5HT3 antagonist : Ondansetron
- Gastric prokinetic : Metoclopramide Respiratory depression - acts on brainstem and “dose-related” - depress all phases of respiratory activity (Rate, MV, TV) - high risk pt: - impaired respiratory function - opioid-naïve pt - OSA Rx - Naloxone (mu antagonist) (0.1 mg/ml iv titration) titrated carefully (excessive saliva, bronchial spasm) (in meperidine overdose : seizures) Is your patient overdosed?
3 Pathognomonic signs : 1. Miosis (pinpoint pupil) 2. Respiratory depression (RR≤10/min) 3. Loss of consciousness (sedation score ≥ 2) Rx 1. Intubation 2. respiratory support 3. iv Naloxone Opioids in Chronic pain Chronic pain divided into 2 groups 1. Chronic non-cancer pain 1.1 Chronic neuropathic pain antidepressant/anticonvulsant gabapentin/pregabalin 1.2 Chronic musculoskeletal pain
muscle relaxant, α2-agonist NSAIDs interventions 2. Cancer pain – depend on causes of pain Opioid for chronic non-cancer pain Evidence of opioid efficacy
* A limitation of these trials was that the duration of opioid therapy was a maximum of 3 months. Evidence of opioid efficacy • Nociceptive pain of musculoskeletal origin Only small-moderate benefits in improving function and relieving pain • Neuropathic pain Only small-moderate benefits • Migraine, tension headache, functional GI problems Not indicated • Widespread soft tissue pain Only small benefit with weak opioid Opioids for Cancer Pain MST
• MST 10, 30, 60 mg tablets oral q 8 or 12 h (not TID/BID)
• peak onset 2-4 h, duration 8-12 h • no crushing/chewing
• IV 24-hr dose x 3 = oral maintenance dose per day
• then divide maintenance dose into q 8 or 12 h Kapanol
• Sustained-release capsule of morphine sulfate
• 20, 50, 100 mg capsules with pellets
• peak onset 2-4 h, duration 24 h
• pellets can be dispersed in water, juice, yogurt, custard, ice cream, and drink within 30 min without crushing or chewing on pellets Morphine for breakthrough pain
Syrup 10 mg/5 ml • peak onset 30 min, duration 3-4 h • always use exact measurement (syringe) Immediate release tablet 10 mg
• Onset 15-30 min, duration 4-6 h (t1/2 2-4 h) Fentanyl transdermal patch
• Release 12, 25, 50 microgram/hour topical patch
• Onset 8 h, duration 72 h • NOT used in acute pain/ opioid-naive patient • chest, back, flank, upper arm (no shaving) • Need subcutaneous fat for absorption • No sauna, hot bath, tanning, electric heating pad, or exercise that may increase body temperature
• caution in MRI Methadone
• tablet 5, 10 mg or syrup 1, 5 mg/ml
• binds to mu receptor, NMDA receptor antagonist, inhibits serotonin reuptake transporter
• Not recommended as 1st line medication
• oral bioavailability 36-100%, half-life 8-59 h
• peak plasma concentration at 1-7.5 h
• Not dialyzed, inactive metabolites Oxycodone
• moderate-severe pain if morphine is not tolerable
• Morphine : Oxycodone = 2:1
• binds to mu and kappa receptor
• controlled release (Oxycontin)
• metabolized by CYP3A4/CYP2D6 to
• noroxycodone : weak analgesic
• oxymorphone : strong analgesic (14 times potency)
Key principles of care
• pain reduction • adverse effects • daily activities and participation (such as ability to work and drive)
• mood (depression and/or anxiety) • quality of sleep • overall improvement as reported by the person Take home message Pain
? Type or characters of pain ? Causes ? Medications (benefits vs risks) ? Patients’ conditions
Start a possibly effective smallest dose of appropriate drugs If not sure, consult!!
Dose titration/adjustment according to pain score and side effects