Pain Lecture 2 PDF

Pharmacologic and Non Pharmacologic Therapy management of Pain Kannan O. Ahmed Assistant professor, uofg Faculty of pharmacy Clinical pharmacy and pharmacy practice department 2023 learning objectives ▪ To identify goals of th...

Pharmacologic and Non Pharmacologic Therapy management of Pain Kannan O. Ahmed Assistant professor, uofg Faculty of pharmacy Clinical pharmacy and pharmacy practice department 2023 learning objectives ▪ To identify goals of therapy. ▪ To recommend an appropriate choice of analgesic, dose, and monitoring plan for an individual patient. ▪ To identify the equianalgesic doses, and conversion of one opioid to another. Goals of therapy To prevent, reduce, and/or eliminate pain. To relive pain at the lowest effective analgesic dose. With chronic pain, this might not be possible, and goals might focus on improvement or maintenance of functional capacity and quality of life. General principles for pharmacotherapy ▪ Identify source of pain ▪ Assess level of pain using intensity scale ▪ Initial choice of analgesic based on: Severity & type of pain and patient’s factors. ▪ Use the least potent oral analgesic ▪ Give adequate doses and titrate the dose ▪ Taper & discontinue ineffective medications and try a different strategy ▪ Utilize combination therapy General approach to treatment ▪ For selection of pain treatment two common approaches are to be follow either based on severity of pain or mechanism responsible. ▪ It includes pharmacologic & non-pharmacological treatment. ▪ The most effective analgesics are expected to achieve 30- 50% improvement in chronic pain, i.e. 30% improvement is a good response for any analgesic. Pain algorithm of pharmacologic therapy Selection of agent based on severity of pain Selection of agent based on severity of pain WHO analgesic ladder Step 3: strong opioids +/- adjuvant analgesics Step 2: Non-opioid Severity of Pain analgesics + weak opioids +/- adjuvant analgesics Step 1: Non-opioid analgesics +/- adjuvant analgesics Non-pharmacologic therapy Non-Pharmacologic Therapy Psychological Physical Therapy interventions Acute pain Heat & Cold Imagery, distraction, Massage relaxation, hypnosis Therapeutic Exercise Chronic pain Transcutaneous Biofeedback, Electrical Nerve Psychotherapy, CBT Stimulation (TENS) Non-pharmacologic therapy ▪ Biofeedback ▪ Self-regulatory technique involves the use of a machine to allow monitoring and feedback control over a specific physiological responses exacerbating pain Non-pharmacologic therapy ▪ Cognitive- Behavioral Therapy CBT ✓Combines cognitive and behavioral therapies into a strategy for self- management of pain program includes: education, relaxation exercises, stress management, problem solving, goal setting. ✓ In cognitive therapy the therapist helps patient identify and correct distorted, maladaptive beliefs. ✓Behavioral therapy uses thought exercises or real experiences to facilitate symptom reduction and improve functioning Physical therapy Non-pharmacologic therapy ▪ Transcutaneous electrical nerve stimulation (TENS): ✓ is a therapy that uses low-voltage electrical current for pain relief. ✓The electricity from the electrodes stimulates the nerves in an affected area and sends signals to the brain that block or "scramble" normal pain signals. ✓Another theory is that the electrical stimulation of the nerves may help the body to produce natural painkillers called endorphins. Pharmacologic therapy  A- Non-Opioid Analgesics 1- Paracetamol (Acetaminophen) ✓Initial therapy (mild to moderate pain) & 1st line therapy (e.g. low back pain; osteoarthritis) ✓Usual dose ✓PO: 325 - 1000 mg q 4 - 6 hrs ✓IV: 650 mg q 4 hrs or 1000 mg q 6 hrs, or 15 mg/kg q 6 hrs if 1.3 g for > 1 week ▪ Monitor: liver function test (LFT) Non-Opioid Analgesics 2. Aspirin ✓ Is effective for mild to moderate pain but limited by risk of GIT irritation and bleeding. ✓ Irreversibly inhibit platelet COX-1 activity ✓ Aspirin (low dose) reduce risk of secondary thrombotic CV effects ✓ Chronic aspirin use increase risk of hemorrhagic stroke ✓ Hypersensitivity: with co-exsiting asthma or chronic urticaria; cross-sensitivity with NSAIDs in these patients. ✓ Low dose aspirin has no COX-2-inhibiting or prohypertensive effects. ✓ Monitor: minor and major bleeding. Non-Opioid Analgesics 3. Non-steroidal Anti-Inflammatory Drugs (NSAIDs) Preferred for mild to moderate inflammatory pain (e.g., osteoarthritis, menstrual cramps, postsurgical pain) ✓ Provide analgesia ≥ aspirin or acetaminophen + codeine ✓ There is a ceiling effect to analgesia (flat dose-response curve) ✓ At equipotent doses, efficacy of all NSAIDs are similar, but there is great intra patient variability in responses. ✓ If one agent failed (after an adequate trial), switch to another ✓ COX-2 inhibition anti-inflammatory effects ✓ COX-1 inhibition increased GI and renal toxicity NSAIDs ✓Difficult to identify the “safest” NSAIDs ✓NSAIDs have potentially important gastrointestinal, renal, and cardiovascular effects. ✓Other adverse effects: Hematologic, hepatic, pulmonary, anaphylaxis, CNS, Skin and malignancy. ▪ Gastrointestinal: ✓Peptic ulcer, bleeding ✓Watch for any sign of internal bleeding. ✓Avoid chronic use or, if necessary, add proton pump inhibitor (PPI). NSAIDs ▪ Renal adverse effects: ✓Acute renal failure, electrolyte & fluid abnormalities, worsening of hypertension, ✓Common in elderly, pre-existing renal disease, volume depletion or on diuretic therapy ✓Monitor: Renal function test (RFT) regularly. ▪ Hematologic: ✓Antiplatelet effects ✓Nonselective NSAIDs inhibit platelet COX-1 activity ✓Selective COX-2 inhibitors have no effect on platelet. ✓Monitor CBC. NSAIDs ▪ Cardiovascular adverse effects: ✓Increase BP. ✓Interfere with beneficial aspirin antiplatelet effect. ✓Blood pressure should be monitored regularly ✓ Increase risk of CV events; MI & stroke. ✓Naproxen the safest with respect to cardiac risk ✓Worsening of heart failure: avoid chronic NSAIDs Common NSAIDs drugs NSAID Usual dose PO (mg) Maximum daily dose (mg) Aspirin 325 to 650 q 4 to 6 hrs 4000 Ibuprofen 400 mg q 4 to 6 hrs 3200 acute, 2400 chronic Naproxen 250 q 8 hrs or 500 q 12 hrs 1250 acute, 1000 chronic (naproxen base) (naproxen base) 275 q 8 hrs or 550 q 12 hrs 1375 acute, 1100 chronic (naproxen sodium) (naproxen sodium) Diclofenac 50 q 8 hrs 150 Indomethacin 25 - q 8 to 12 hrs 150 Controlled release:75 q12 hrs Meloxicam 7.5 - 15 q 24 hrs 15 Piroxicam 10 - 20 q 24 hrs 20 Mefenamic acid 250 q 6 hrs 1000 Celecoxib 200 daily or 100 q 12 hrs 400  B- Opioid Analgesics ▪ The following aspects should taken into account when opioid analgesics are selected; ✓Opioid selection ✓Method of administration ✓Opioid dosing ✓Opioid conversion ✓Managing opioid side effects ✓Drug interaction ✓Non-opioid/opioid combinations ✓Chronic opioid therapy Opioid Selection ✓Selection of the agent and route depend on: Individual patient factors & drug characteristics. It selected based on pain severity: ✓Mild-moderate pain: Weak opioids (codeine, hydrocodone, oxycodone, meperidine) ✓Moderate-severe pain: Strong opioids (morphine, hydromorphone, oxymorphone, fentanyl, methadone) Opioid Selection ▪ Morphine (Standard opioid) ✓PO (immediate & sustained release), sublingual, IV, intrathecal/epidural, SC, rectal, PCA ▪ Oxycodone ✓PO formulation only (long- & short-acting, single drug) ▪ Fentanyl ✓IV, sublingual, intranasal & transdermal (patch) ✓Oral transmucosal & buccal tablet (breakthrough pain) Opioid Selection ✓Hydromorphone ✓Semi-synthetic, PO & IV (short- and long-acting) ✓Alternative to morphine with higher potency in patients with renal dysfunction ✓Oxymorphone ✓Semi-synthetic , immediate- & extended-release tablets ✓Should not be used in opiate-naïve patients Opioid Selection ▪ Tramadol ✓Has activity on opioid & monoaminergic (serotonin & noradrenaline) pathways in CNS (bimodal agent) ✓Moderate to moderately severe acute pain, & chronic pain (low back pain, neuropathic) ✓Dose: 50 - 100 mg PO q 6 hrs, maximum 400 mg/d ✓Advantages: Lower abuse liability & reduced respiratory depression ✓Disadvantages: Dizziness, sedation, dry mouth, constipation, seizures (rare, with overdose) Opioid administration ✓Opioids are administered by a variety of routes, including oral (tablet and liquid), sublingual, rectal, transdermal, transmucosal, IV, subcutaneous, and intraspinal. ✓The method of administration is based on patient needs (severity of pain) and characteristics (swallowing difficulty and preference). ✓IM not recommended because of pain at the injection site and wide fluctuations in drug absorption and peak plasma concentrations achieved. ✓Patient-controlled analgesia pump (PCA) ✓Delivers a self-administered dose via an infusion pump with a preprogrammed dose, minimum dosing interval, and maximum hourly dose. Use for Morphine, fentanyl & hydromorphone by IV route. Opioid dosing ▪ Starting dose ✓Severe pain in opiate-naïve: 5 -15 mg of morphine (or its equivalent) q 4 hrs ▪ Rescue doses ▪ used for breakthrough pain ▪ Breakthrough pain: ✓ it spontaneous, incident or end-of-dose failure ✓Use short-acting opioid ✓Doses equivalent to 10 - 20% of total daily dose & administered q 2 hrs if needed. Opioid dosing ▪ Maintenance dose ✓ Total daily dose = regular doses/d + rescue doses/d ▪ Dose titration ✓ Increase dose by 50-100% (severe) or 30-50% (moderate). ✓ Once pain relief is achieved, and if treatment is necessary for more than a few days, conversion to a controlled-release or long acting opioid should be made with an equal amount of agent. ✓ Some clinicians will reduce the total daily dose of the long-acting dosage form by 25% when initiating a sustained-release product to reduce the likelihood of oversedation. Opioid dosing ▪ Tolerance ✓Increase dose or opioid rotation (when doses > 1 g/d of morphine become ineffective) ▪ Tapering of opioids ✓Dose should be reduced by 15 - 20% each day to avoid withdrawal symptoms Opioid dosing ▪ Equianalgesic dosing of opioids ✓ Change dosage form of same opioid (e.g. IV to PO) ✓ Calculate current total daily dose & determine total of new dosage form using a ratio of equianalgesic doses. ✓ Opioid rotation: ✓ Is the switch from one opioid to another to achieve a better balance between analgesia and treatment-limiting adverse effects. This practice is often used when escalating doses (greater than 1 g morphine/day) become ineffective. ✓ In some settings, opioid rotation is used routinely to prevent the development of analgesic tolerance Opioid dosing ▪ Opioid conversion (changing analgesic or route) ✓After conversion, dose may be reduced by 25% when convert to sustained- release of same opioid to avoid initial sedation. ✓Dose reduction may not be needed if opioid switch is due to uncontrolled pain. Equianalgesic dosing of opioids Managing opioid side effects ▪ Common to all opioids: sedation, hallucinations, constipation, nausea & vomiting, dry mouth, urinary retention, myoclonus, respiratory depression ▪ Most frequent: sedation nausea, constipation ▪ Tolerance: ▪ Generally occur with in 3 - 7 days; except constipation ▪ Treatment strategies to handle tolerance: ✓Switch to a different opioid ✓Add medication to counteract undesired effect Managing opioid side effects ▪ Constipation: ▪ Prophylaxis (regularly) ▪ Stimulant laxatives (senna 1–2 tabs at bedtime or bisacodyl 5–10 mg daily) ▪ Add stool softener (docusate sodium) if not effective ▪ Add osmotic agent (polyethylene glycol powder) if not effective Managing opioid side effects ▪ Nausea & Vomiting ✓Prevention: Diphenhydramine, Ondansetron ✓Treatment: Prochlorperazine, Ondansetron ▪ Sedation ✓Improves with continued therapy but intractable at high doses. ✓If no tolerance & good pain control: Reduce dose by 25% or increase dose interval ✓If dose reduction compromises pain control: Stimulant e.g. dextroamphetamine, methylphenidate are used. Managing opioid side effects ▪ Respiratory depression ✓Opioid-naïve, precede by sedation, tolerance develop ✓Mild: Reduce dose by 25% ✓Moderate-severe: use naloxone. Start with low dose and titrate up to prevent profound withdrawal effects such as seizures, arrhythmias, severe pain ▪ Allergy ✓Pruritus / Urticaria /itching: use diphenhydramine ✓True allergy: rare, opioid rotation (different class) Managing opioid side effects ▪ Gastroparesis: Metoclopramide ▪ Urinary retention: common in elderly and with long acting formulations ▪ Vertigo: Meclizine ▪ Myoclonus: Clonazepam, reduce dose, opioid rotation ▪ CNS irritability: Discontinue opioid, benzodiazepine ▪ Dysphoria: Haloperidol or opioid rotation ▪ Cognitive impairment: Methylphenidate, opioid rotation Non-opioid/Opioid Combinations ✓Most common: aspirin, paracetamol or ibuprofen plus codeine, hydrocodone or oxycodone ✓Advantage: Enhanced analgesia & lower doses ✓Disadvantage: risk of overdose ✓In moderate pain (frequently used), severe pain (limited), chronic pain (not suitable) Chronic Opioid Therapy ✓Written agreements (contracts or informed consent) ✓Contract include: goals, how medications prescribed/ taken, follow-up and monitoring, potential for weaning and discontinuing therapy ✓Risk assessment of substance abuse, misuse, or addiction ✓Adverse effects on chronic use: ✓Hypogonadism ( drop of testosterone levels) ✓Osteoporosis (bone density testing) Terms related to Chronic Opioid Therapy Chronic Opioid Therapy ▪ Discontinuing chronic opioid therapy ✓When there are repeated aberrant drug-related behaviors, not reach therapeutic goals, or intolerable adverse effects ▪ Monitor withdrawal symptoms ✓Anxiety, tachycardia, sweating, other autonomic signs. ✓If occur use clonidine  C- Adjuvant analgesics ✓Antidepressants: Amitriptyline, duloxetine (neuropathic pain) ✓Anticonvulsants: Gabapentin, pregabalin, carbamazepine, (neuropathic pain) ✓Transdermal lidocaine: Localized neuropathic pain ✓Benzodiazepines: Diazepam, lorazepam & baclofen (muscle spasms) ✓Corticosteroids: Pain caused by nerve compression or inflammation, lymphedema, bone pain Outcome Evaluation ✓Routine pain assessment is essential for evaluating outcomes of therapy. ✓For example, pain goals for acute pain might include “pain scale less than 3.” ✓For Functional goals such as “be able to play a game with grandchildren,” or “be able to knit again” may be appropriate for chronic pain. ✓Assess patients periodically, depending on the method of analgesia and pain condition, for achievement of pain goals. ✓Evaluate the patient for the presence of adverse drug reactions, drug allergies, and drug interactions Reading activity ✓ Refernce Pharmacotherapy Principles & Practice 4th edition Thanks you