Pharmacotherapy of Pain

Pharmacotherapy of Pain

1. PHARMACOTHERAPY OF PAIN Presenter – Dr. Sneha Dange , Jr2 Dept. of Pharmacology, GMCH, Nagpur One of the greatest service a doctor can do his patients is to acquire skill in the management of pain - John Milton

2. OVERVIEW 16-Jul-21 Pharmacotherapy of Pain 2

3. Introduction : Pain - An unpleasant sensory & emotional experience associated with actual & potential tissue damage It is universally understood as a signal of disease & is the most common symptom that brings a patient to a physician’s attention It often becomes worse during the night when the distractions of daytime are absent The intensity of pain suffered differs with the personality, intelligence and culture of the individual 16-Jul-21 Pharmacotherapy of Pain 3

4. Two components of pain 16-Jul-21 Pharmacotherapy of Pain 4 Affective component : Which is the psychological response towards the pain conveyed from CNS to dorsal horn by descending pathways Nociceptive component : Disabling, unpleasant sensation evoked by noxious stimuli and conveyed to CNS by ascending pathways physiology of pain :

5. Ascending pain pathway : Transmits pain impulses from the dorsal horn of the spinal cord to medulla, midbrain, thalamus, limbic structure and the cortex Pain activates terminals of primary afferent neuron (PAN) fibres ( A δ & C) & synapse onto spinothalamic tract (STT) neurons A δ fibres (fast conducting) project to somatosensory cortex (SSC) & alerts the person about presence & location of intense, sharp somatic (integumentary) pain 16-Jul-21 Pharmacotherapy of Pain 5 Physiology of pain contd …

6. Ascending Pain Pathway Contd … Person uses withdrawal reflexes to avoid noxious stimuli The C fibres (slow conducting) projects to limbic structure and mediate the motivational affective (mood) response towards dull aching visceral pain or burning neuropathic pain The function of this is to enable the person to bear the pain, experience the discomfort and modify his emotional reaction to the pain 16-Jul-21 Pharmacotherapy of Pain 6 Physiology of pain contd …

7. DESCENDING PAIN PATHWAY : It exerts inhibitory effect on dorsal horn transmission This tract from periaqueductal grey ( PAG) matter activate rostroventral medulla (RVM) & nucleus raphe magnus (NRM) 5-HT, enkephalin are released at substatia gelatinosa of dorsal horn to inhibit ascending pain transmission 16-Jul-21 Pharmacotherapy of Pain 7 Physiology of pain contd …

8. Gate Control theory : 16-Jul-21 Pharmacotherapy of Pain 8 Physiology of pain contd … Proposed by melzak & Wall(1965) explain mechanism – why painful sensation is reduced by activating nonpainful sensation Touch sensation inhibit transmission of pain signals from dorsal horn of spinal cord (Gate) substantia gelatinosa of spinal cord Used in acupuncture, rubbing counter irritantat painful site Wind up phenomenon – Repeated firing increases synaptic potential amplitude & results in activity dependent facilitation of transmission NMDA, substance P, Nitric oxide causes facilitation by tissue damage results in hyperalgesia

9. Modulators Of Pain : 16-Jul-21 Pharmacotherapy of Pain 9 Physiology of pain contd … Peripheral modulators & neuromodulators - Capsaicin →acts on TRPV1 → Depolarisation It is obtained from bell peppers & irritates skin on applying used in patients with incontinence of bladder (spinal injury & stroke) TRPV1- (Polymodal receptor potential vanilloid receptor-1) Polymodal, closely related to nociceptive neurons Activated by a range of stimuli (heat, protons, lipids & changes in osmolarity or pressure) Cannabinoids are endogenous ligands for vanilloid receptors

10. 16-Jul-21 Pharmacotherapy of Pain 10 Physiology of pain contd … Kinins - Bradykinins & kallidin produced during tissue injury Potent pain producing substance, releases prostaglandins Prostaglandins - Enhances 5HT & bradykinins Sensitizes nerve terminal by inhibiting K+ channels Other peripheral mediators - ATP, Protons, 5HT, Histamine, K+ ions, Substance P, Glutamate, GABA, Noradrenaline, Adenosine Modulators Of Pain contd …

11. Types of pain : Chronic Pain : Persists beyond 3 months or persists > 1 month beyond resolution of underlying injury 16-Jul-21 Pharmacotherapy of Pain 11 Acute Pain : Produced by underlying injury to body & activation of nociceptive transducers at site of local tissue damage

12. CLASSIFICATION OF PAIN : 16-Jul-21 Pharmacotherapy of Pain 12 Somatic Visceral Superficial Vascular Referred Neuropathic Phantom Cancer Psychogenic Central Major types of pain

13. Pharmacotherapy : Attempt should always be made to asses pain, to find out the cause & if possible treat it If the cause not treatable immediate relief of pain obtained by modifying the mechanism e.g. use of nitrates in angina pectoris Some conditions are so painful that rapid & effective analgesia is essential 16-Jul-21 Pharmacotherapy of Pain 13 Pharmacotherapy Physiotherapy Cognitive Behavioral Therapy The management of pain is multidisciplinary

14. 16-Jul-21 Pharmacotherapy of Pain 14 Assessment of Pain : Pharmacotherapy Contd.. Helps in identifying the patients at risk of developing pain & intensity of Pain is measured using different types of rating scales

15. 16-Jul-21 Pharmacotherapy of Pain 15 Analgesic - A drug that selectively relieves pain by acting in the CNS or on peripheral pain mechanisms, without significantly altering consciousness Pharmacotherapy Contd..

16. 16-Jul-21 Pharmacotherapy of Pain 16 1. Mild Acetaminophen NSAIDs ± Adjuvants Spasmolytic 2. Moderate Weak opioids ± non- opioids ± Adjuvants Codeine Oxycodone Tramadol 3. Severe Potent opioids ± non- opioids ± Adjuvants Morphine Oxycodone Hydromorphone Methadone Fentanyl WHO 3- Step Ladder Using this ladder individual treatment is devised for each patient by starting bottom of the ladder & progressing upwards & move down the ladder as soon as pain is relieved

17. 1- Non-opioid analgesics : (NSAIDs) 16-Jul-21 Pharmacotherapy of Pain 17 Pharmacotherapy Contd.. First line drug effective for mild pain, more commonly employed & many are over-the-counter drugs Have analgesic, antipyretic activity & anti-inflammatory at higher doses They act primarily on peripheral pain mechanisms (inhibit formation of Prostaglandins) , but also act on CNS to raise pain threshold Can be given orally, intramuscularly or by topical application In contrast to morphine, NSAIDs do not depress CNS or tolerance or physical dependence or have no abuse liability

18. 16-Jul-21 Pharmacotherapy of Pain 18 NSAIDS : ( Non-steroidal Anti Inflammatory Drugs ) NSAIDS acts here Pharmacotherapy Contd.. Tissue injury causes local release various mediators including prostaglandins (PGs) Causes hyperalgesia by sensitizing nerve endings NSAIDs prevents these actions by stopping synthesis of PGs

19. Non-opioid Analgesics : 16-Jul-21 Pharmacotherapy of Pain 19 Pharmacotherapy Contd.. They are absorbed well from the gastrointestinal tract With chronic use, gastric irritation is a common side effect of aspirin and NSAIDs leading to erosion, ulceration & perforation NSAIDs should cautiously used in O lder age and with history of gastrointestinal disease Patients with chronic diuretic use or acute hypovolemia as they are nephrotoxic I ncreases blood pressure in some individuals & are hepatotoxic at higher doses

20. 16-Jul-21 20 Non-opioid Analgesics : Pharmacotherapy Contd.. Drug Dose Analgesic property Antipyretic property Anti-inflammatory property Remarks Aspirin 75-150 mg/day 300-600mg/6hrly 3-6gm/day ++ ++ ++ - irreversibly acetylates platelet COX & causes bleeding - First drug in acute rheumatic fever/disease Post MI back pain, menstrual pain, headaches, toothache, muscle pain Ibuprofen 400-600mg TDS ++ ++ ++ Weak anti-inflammatory effect Better tolerated alternative to aspirin , patent ductus arteriosus Piroxicam 20 mg daily ++ ++ +++ Potent anti-inflammatory effect Osteoarthritis, rheumatoid arthritis Ketorolac 10-20mg oral 15-30 mg im /iv 6hourly +++ + + Moderate-severe acute pain Injectable used for postoperatively, renal colic, migraine, bony metastasis & topical for ocular conditions

21. 16-Jul-21 21 Pharmacotherapy Contd.. Indomethacin 25mg BD/TDS ++ +++ +++ Reserved drug for - Ankylosing spondylitis, arthropathies, psoriatic arthritis, acute gout, rheumatoid arthritis not responding to other NSAIDs & malignancy associated fever Diclofenac 50-75mg BD/TDS ++ ++ ++ back pain, menstrual pain, headaches, postoperatively, renal colic , Osteoarthritis, ankylosing spondylitis, rheumatoid arthritis Paracetamol 650mg every 4hourly (4gm/24hr) ++ +++ + -Less gastric irritation and does not interfere with platelet function - Used in allergic to aspirin, peptic ulcers - First choice for osteoarthritis & fever, back pain, menstrual pain, mild headaches, can be used in all age groups Selective COX-2 inhibitors 100-200mg BD (celecoxib) +++ ++ +++ -Has a significant benefit in acute postoperative pain & used in patients at high risk of peptic ulcer/perforation. -Should be avoided in cardiac patients & elderly

22. 16-Jul-21 Pharmacotherapy of Pain 22 Pharmacotherapy Contd.. Agonists Agonist – Antagonist Partial Agonist Moderate Pain – Codeine Oxycodone Dihydrocodeine Dextropropoxyphene Tramadol Pentazocine Butorphanol Nalbuphine Meptazinol Buprenorphine Strong Pain (short half life)- Morphine Oxycodone Oxymorphone Pethidine Pentazocine Diamorphine Fentanyl Strong Pain (long half life)- Methadone Levorphanol 2 – OPIOID ANALGESICS : Classification -

23. Opioid analgesics : Morphine and other opioids exert their actions by interacting with specific receptors present on neurons in the CNS and in peripheral tissues Receptors are μ, K, δ A ll 3 receptors are GPCRs located mostly o n prejunctional neurons They generally causes neuronal inhibition by decreasing release of the junctional transmitter ( eg. GABA, glutamate) 16-Jul-21 Pharmacotherapy of Pain 23 Pharmacotherapy Contd..

24. 16-Jul-21 Pharmacotherapy of Pain 24 Opioid Analgesics Contd.. Opioid receptor activation ↓ intracellular cAMP Opening of K+ channels (µ, δ ) or closing voltage gated N type Ca2+ channels ( κ ) Neuronal hyperpolarization ↓ intracellular Ca2+ ↓neurotransmitter release

25. O pioids suppress both perception of pain and its emotional component (suffering, distress, anxiety, fear) 16-Jul-21 Pharmacotherapy of Pain 25 Opioid Analgesics Contd.. Pharmacotherapy Contd.. Natural ligands β endorphin Dynorphins Enkephalins

26. Endorphins: Derived from POMC (Pro-opiomelanocortin ) Primarily μ agonist and also has δ action (µ > δ >> κ) Enkephalins : Derive from Proenkephalin, Met-ENK and leu-ENK Met-ENK - Primarily μ and δ agonist and leu-ENK – δ agonist (δ ≥ μ >> κ) Dynorphins: Derive from Prodynorphin: DYN-A and DYN-B Potent κ agonist and also have μ and δ action 16-Jul-21 Pharmacotherapy of Pain 26 Endogenous Opioid Peptides : N ormally modulates pain perception, mood, motor behaviour , emesis, pituitary hormone release and g.i.t. motility, etc.

27. More effective for d ull, poorly localized visceral pain than somatic also for nociceptive pain than neuretic pain The associated reactions to intense pain (apprehension, fear, autonomic effects) are also dampened At spinal site - acts at dorsal horn cells to inhibit release of excitatory transmitters (e.g. glutamate, substance P) At supraspinal sites in medulla, limbic and cortical areas alter processing and interpretation of pain impulses augments the inhibitory impulses through descending pathways to the spinal cord 16-Jul-21 Pharmacotherapy of Pain 27 Opioid Analgesics Contd.. Pharmacotherapy Contd..

28. D egree of analgesia increasing with the dose Higher & repeated doses – respiratory depression, sedation, vomiting, dysphoria, tolerance & dependence Infused intrathecally or epidurally- side effects reduced & used extensively during labor, delivery, postoperative pain relief & cancer-related pain I ntranasally (butorphanol), rectal(morphine), transdermal (fentanyl and buprenorphine), or through the oral mucosa (fentanyl) 16-Jul-21 Pharmacotherapy of Pain 28 Opioid Analgesics Contd.. Pharmacotherapy Contd..

29. 16-Jul-21 Pharmacotherapy of Pain 29 Opioid Analgesics Contd.. Opioid Analgesics Contd.. Drug Dose Use Remark Oral IV/IM Morphine Hydromorphone Oxycodone Hydrocodone 30mg/3-4hr 6mg/3-4hr 20mg/3-4hr 30mg/3-4hr 10mg/3-4hr 1.5mg/3-4hr NA Potent μ agonists • Strong analgesic in moderate-to-severe pain • useful adjunct in pulmonary edema & general anesthesia ↓ GI motility • Hydrocodone, oxycodone, & fentanyl are more potent than morphine Fentanyl Transdermal (25 μg/h) Transdermal fentanyl - cancer/terminal illness pain More potent μ agonist, Rapid onset, short duration of action Meperidine (pethidine) 300mg/2-3hr 100mg/2-3hr • Not for extended use due to accumulation of seizure inducing metabolite • μ agonist • Rapid onset, intermediate duration of action

30. 16-Jul-21 Pharmacotherapy of Pain 30 Opioid Analgesics Contd.. Opioid Analgesics Contd.. Drug Dose Use Remark Oral IV/IM Methadone 10mg/ 6-8hr 10mg/6-8hr • Used in maintenance/rehab programs Analgesic use same as morphine Potent μ agonist than morphin • Rapid onset, long duration of action Codeine 130mg/ 4hr 75mg/4hrly • Useful antitussive effects (10-30mg) • Useful for mild-to-moderate pain Weak prodrug for morphine levorphenol 4mg/6-8hr 2mg/6-8hr Same use of morphine Rapid onset, modest duration More potent than morphine Buprenorphine Butorphenol Transdermal patch- cancer pain For mild – moderate pain μ- Agonist k-antagonist μ- Antagonist k-agonist Tramadol 100mg 100mg • mild-to-moderate short-lasting pain due to diagnostic procedures, injury, surgery • As an adjunct to other opioids for chronic pain • Potential for seizures • Serotonin syndrome risk • Weak μ agonist and a 5HT/NE uptake inhibitor Tapendalol 50-100mg QID Alternative t o tramadol for acute & chronic pain o f moderate severity.

31. 16-Jul-21 Pharmacotherapy of Pain 31 Opioid Analgesics Contd.. Pharmacotherapy Contd.. A transitory increase in pain that occurs on a background of controlled persistent pain B reakthrough dose is calculated by taking 10% of the total daily dose of the scheduled opioid Eg. , patient receiving controlled release (CR) Oxycodone 40mg every 12 hour then breakthrough dose calculated as follows: Breakthrough Pain 40mg X 2doses = 80mg/day 80mg ÷ 10 mg =8mg (approximately 10mg IR oxycodone as needed)

32. 16-Jul-21 Pharmacotherapy of Pain 32 Opioid Analgesics Contd.. Pharmacotherapy Contd.. Add up the dose of breakthrough opioid & total daily dose of the regular administered opioid in previous 24 hours which gives the total dose in 24 hour That total dose divided into the number of intervals, will be the new regular dose Eg. , if the regular morphine is 50mg/4 hourly (300mg/day) the breakthrough dose=30mg IR morphine & 5 breakthrough doses were taken, Titration of Opioids 5 X 30mg = 150mg ( breakthrough medication) + 300mg/day of regular opioid = 450mg used over the last 24 hours Divided into 6 doses, the new regular opioid dose is 75mg/4 hours (450÷6) The new breakthrough dose will be 45 mg

33. 16-Jul-21 Pharmacotherapy of Pain 33 Opioid Analgesics Contd.. Pharmacotherapy Contd.. Guidelines for Selecting and Monitoring Patients Receiving Chronic Opioid Therapy (COT) for the Treatment of Chronic, Noncancer Pain Clinicians should outweigh expected benefits upon risks C linicians should establish treatment goals and should consider how opioid therapy will be discontinued if the risk is more than benefit Should prescribe immediate-release opioids instead of extended-release/ long-acting (ER/LA) opioids S hould prescribe the lowest effective dosage of 50 morphine milligram equivalents (MME)/day , and should avoid dose ≥90 MME/day E valuate w ithin 1 to 4 weeks of starting opioid & every 3 months or more in continued opioid therapy

34. 16-Jul-21 Pharmacotherapy of Pain 34 Opioid Analgesics Contd.. Pharmacotherapy Contd.. C onsider use of naloxone in risk for opioid overdose, substance use disorder, higher dosages (≥50 MME/day), or concurrent benzodiazepine use Clinicians should review PDMP ( prescription drug monitoring program) data when starting opioid therapy for chronic pain C onsider urine drug testing at least annually to assess for prescribed medications A void prescribing opioids and benzodiazepines concurrently S hould offer or arrange evidence-based treatment for patients with opioid use disorder Guidelines :

35. 16-Jul-21 Pharmacotherapy of Pain 35 Opioid Analgesics Contd.. Pharmacotherapy Contd.. Transdermal Fentanyl Patches : Available in dosage of 25, 50 & 100 mcg Usually applied below collar bone Dose increased at 2-3 days intervals Provides fairly steady plasma levels Simple to use, relief for 72 hours Least side effects, but costly Sublingual Fentanyl - 10 -50 mcg/30-25 minutes effective within 15 mins & last for 45 mins maximum dose of 300 – 400 mcg/hour

36. P atient-controlled analgesia (PCA) a microprocessor-controlled infusion device that delivers a baseline continuous dose of an opioid drug as well as preprogrammed additional doses whenever the patient pushes a button PCA device delivers small, repeated doses to maintain pain relief Can then titrate the dose to the optimal level To prevent overdosing, PCA devices are programmed with a lockout period after each demand dose & a limit on the total dose delivered per hour 16-Jul-21 Pharmacotherapy of Pain 36 Opioid Analgesics Contd.. Pharmacotherapy Contd..

37. U sed most extensively for the management of postoperative pain Used for short-term home care of patients with intractable pain of metastatic cancer S hould not be used for hospitalized patient with any persistent severe pain I n severe pain, the pain must first be brought under control with a loading dose before transitioning to the PCA device 16-Jul-21 Pharmacotherapy of Pain 37 Opioid Analgesics Contd.. Pharmacotherapy Contd..

38. 16-Jul-21 Pharmacotherapy of Pain 38 P atient-controlled analgesia (PCA) Device

39. 3 - Adjuvant analgesic : 16-Jul-21 Pharmacotherapy of Pain 39 Pharmacotherapy Contd.. Which enhance analgesic efficacy, treat symptoms which ↑ pain, provide independent analgesic activity for specific pain Specially useful in pain insensitive to opioids or in neuropathic pain Also useful in counteracting side effects of opioid like nausea, vomiting, itching, dyspepsia, constipation They are not analgesics but relieve pain by acting on excitatory (e.g., substance P, and glutamate), inhibitory neurotransmitters (e.g., GABA), or on neurotransmitters that modulate pain experience (e.g., serotonin, norepinephrine)

40. Adjuvant Analgesic : 16-Jul-21 Pharmacotherapy of Pain 40 Pharmacotherapy Contd.. Muscle Relaxants – Skeletal muscle relaxants are used to ‘relax muscles,’ relieve stiffness, and decrease pain and discomfort caused by strains, sprains, or other injury to muscles or joints baclofen, carisoprodol, cyclobenzaprine, diazepam, methocarbamol, orphenadine , metaxalone, and tizanidine It is used for acute low back pain, acute musculoskeletal neck pain, and chronic tension headache

41. 16-Jul-21 Pharmacotherapy of Pain 41 Adjuvant Analgesic : NMDA Receptor Antagonists- Ketamine - Used to treat cancer and non-cancer pain, chronic neuropathic pain Benzodiazepines - Diazepam and midazolam (high level of anxiety and insomnia), reduces muscle spasms Spasmolytics - Visceral cancer pain due to distention of hollow organs Steroids - Acute nerve compression, Visceral distension, Increased intracranial tension, Soft tissue infiltration Dexamethasone 8 – 16 mg OD, (IV / PO) Prednisolone 15 to 30 mg OD, PO Antiarrhythmics – mexiletine for neuropathic pain Adjuvant Analgesic :

42. 16-Jul-21 Pharmacotherapy of Pain 42 Adjuvant Analgesic : Lidocaine – Systemic administration produce sodium channel blockade & analgesia N europathic pain and phantom limb pain Calcitonin – Bone pain refractory to NSAIDs and steroids Acute pain caused by osteoporotic vertebral compression fractures Bisphosphonates – Etidronate sodium, Sodium didronate , Pamidronate, Ibandronate and Zoledronate Bone pain associated with metastasis - Breast/ Multiple myeloma/ Paget’s disease Adjuvant Analgesic :

43. 16-Jul-21 Pharmacotherapy of Pain 43 Pharmacotherapy Contd.. Defined by International Association for Study of Pain (IASP) as pain caused by a lesion or disease of somatosensory nervous system Such pains are severe & are resistant to standard treatments for pain Has an unusual burning, tingling or electric shock-like quality & occur spontaneously without any stimulus or triggered by very light touch Hyperpathia - & allodynia - are characteristic of neuropathic pain Etiology – damaged primary afferents become highly sensitive to mechanical stimulation & to norepinephrine increased density of sodium channels in the damaged nerve fiber Neuropathic Pain :

44. Tricyclic Antidepressants (TCAs) D esipramine and nortriptyline - Inhibit norepinephrine transporter & serotonin transporter used for any neuropathic pain Sedation, anticholinergic effects, orthostatic hypertension, weight gain - side effects Cautiously used in patients of cardiovascular disease, elderly patients & in patients with suicide tendency Serotonin & norepinephrine reuptake inhibitors (SNRIs) Venlafaxine, Duloxetine also inhibit the uptake of both norepinephrine and serotonin Does not interact with cholinergic, adrenergic or histaminic receptors Used in the elderly or in patients whose daily activities require high-level mental activity 16-Jul-21 Pharmacotherapy of Pain 44 Pharmacotherapy Contd.. Neuropathic Pain contd …

45. 16-Jul-21 Pharmacotherapy of Pain 45 Pharmacotherapy Contd.. Calcium channel α 2- δ ligands Binds to α 2- δ subunit of voltage gated calcium channels, decreasing the release of glutamate Gabapentin or Pregabalin FDA approved for post-herpetic neuralgia Topical Lidocaine Block the nerve conduction by decreasing the entry of sodium ions 5% Lidocaine for Localized peripheral neuropathy , maximum of 3 patches daily for of 12 hour, duration – 2 weeks Anti-epileptics Carbamazepine ( Trigeminal neuralgia ), lamotrigine, oxcarbazepine, Topiramate They reduce neuronal excitability by means of frequency-dependent blockade of Na+ channels Neuropathic Pain contd …

46. 16-Jul-21 Pharmacotherapy of Pain 46 FDA-Approved Treatments for Neuropathic Pain

47. Mild-to-moderate pain with little inflammation - paracetamol or low-dose ibuprofen Postoperative , renal colic, acute gout, acute back pain, dental pain, fractures and other grievous trauma – parenteral Ketorolac, diclofenac and parecoxib Acute headaches due to common cold, influenza or other fevers - paracetamol or aspirin In severe pain - morphine is more efficacious than NSAIDs & t he optimum dose for each patient is determined by titration Severe pain of sudden onset, such as in visceral pain (acute MI, fractures and pneumothorax) - opioids should be administered 16-Jul-21 Pharmacotherapy of Pain 47 Conclusion : Treatment in Acute Pain -

48. In inflammatory conditions such as RA and gout, the NSAID relieve pain without affecting the basic disorder Exacerbation of rheumatoid arthritis, ankylosing spondylitis, gout, rheumatic fever - naproxen, piroxicam, indomethacin, high dose aspirin In advanced osteoarthritis when paracetamol fails to work - smaller doses of ibuprofen are needed to control pain Mild backache of spinal osteoporosis may be relieved by oral calcium, vitamin D, bisphosphonates, Unremitting osteoporosis respond to calcitonin Severe pain of ankylosing spondylitis needs treatment with indomethacin/diclofenac 16-Jul-21 Pharmacotherapy of Pain 48 Treatment in Chronic Pain – (Non-malignant) Conclusion contd …

49. In chronic cancer pain analgesics are used in a step ladder fashion, starting with NSAID then changing to weak and finally strong opioids Ibuprofen and other NSAID can be useful in relieving pain of bony metastases & mechanical compression of tissues other than nerves Glucocorticoids are prescribed in the palliative treatment of cancer pain In severe cancer pain, morphine is used by round the clock at commonly used dose of 5-30 mg every 4 hours Extended release oral preparations, fentanyl transdermal patch, Patient-controlled analgesia 16-Jul-21 Pharmacotherapy of Pain 49 Treatment in Chronic Pain - (Malignant) Conclusion contd …

50. References : Goodman & Gilman’s The Pharmacological Basis of Therapeutics; 13th edition Basic & Clinical Pharmacology – Katzung ; 14th edition Harrison’s Principles of Internal Medicine, 21th edition https://www.practicalpainmanagement.com/treatments/pharmacological/adjuvant-analgesia-management-chronic-pain , Volume 6, Issue #3 16-Jul-21 Pharmacotherapy of Pain 50

51. 16-Jul-21 Pharmacotherapy of Pain 51 All the kingdom, the throne and the crown is in vain Without freedom from pain Thank you