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Acute Pain Pharmacotherapy Daniel Wermeling, Pharm.D. Professor 225 COP Pharmacists Patient Care Process Acute Pain Characteristics Indication or symptom of tissue damage and the underlying cause of the pain should be identified and treated. Examples of Acute Pain – – – Cholecystitis, 3rd molar impaction where pain is a symptom of a medical problem Post-surgical pain Trauma What are the signs and symptoms of acute pain? Typical Observations and Information to Collect For the Event – – – – – – Nature of Injury & Examination Affective Distress Vital Signs Guarding at Site PQRST Demographics Additional Information – – – – – – Medications Pain meds in past Medical history Mental illness Substance use Allergy Additional Factors to Consider Use of other CNS depressants can be additive or multipliers – common postgeneral anesthesia Concurrent medical problems, like COPD Obesity – obstructive airway the patient can not protect & Sleep apnea syndrome Mental Illness These may all be relevant to some patients creating a riskier situation. Patients with Other Chronic Problems Examine drug profile Examine reasons for PK differences, disease, renal, hepatic, age, etc. Respiratory disorders Psychiatric disorders Neuromuscular disorders Assessment Does the clinical picture make sense? Are there risk factors that affect Plan? Understand patient concerns and goals Plan and Implement Plan in context of clinical setting such as ER, PORR, Outpatient discharge, etc. Individualized plan considering relevant data and consider cost-effectiveness Set goals of therapy and options Educate patient on choices made Make sure patient understands when to come back for additional care Monitoring and Evaluation In the setting context, is the plan working and are goals being met? Re-assess and document findings. What were the outcomes? – Is pain level clinically acceptable? Are there adverse effects that are troublesome? In collaboration, modify Plan if goals not met Try again and re-assess Pharmacologic Treatment Options Follow Algorithm in DiPiro Assess pain severity and follow options for pain severity – – – Mild – APAP/NSAIDs, ATC and BTP, Adjuvants Moderate – Above in combination with Opioids Severe – Opioids, ATC plus BTP, Dose Finding Is relief adequate? Side Effect Issues? Monitor and Reassess Mild Pain & Non-opioid Analgesics Share many properties in relieving pain and are pharmacologically similar Differences are based on cost, pharmacokinetic profile, side effects, onset, duration, etc. Inadequate pain relief with one agent still warrants trying other agent Examples – ASA, APAP, NSAIDS Give around the clock initially, not PRN Rx dosing higher than OTC label dosing Have a ceiling effect, dose increases = side effects with no more efficacy Characteristics to Consider in Choosing Agents GI Irritation – ASA high, COX-2 lower intensity CNS effects – most are low Hepatic toxicity – ASA and APAP have greatest dose dependent risks – Be careful with fixed combinations Renal Toxicity – ASA, NSAIDS Platelet inhibition with NSAIDs Consider the common risks as applied to your patient Additional Features to Consider Depending on clinical situation Tmax - Analgesic onset Elimination half-life Analgesic duration Injectable – acetaminophen IV, ketorolac IM & ibuprofen IV Ketorolac nasal spray Cost – COX-2 drugs expensive Moderate Pain Therapy First Line Add moderate potency opioid to drugs in the mild treatment category Synergy by acting through different mechanisms Give round the clock, PRN for breakthrough pain Examples – Tylenol with Codeine – Oxycodone or Hydrocodone with APAP or ibuprofen – Meperidine no longer recommended Second line therapies – Tramadol/Tapentadol – weak opiate and NE/SE reuptake inhibitor – Mixed agonist/antagonist opioids – pentazocine, butorphanol, etc. Second Line Therapy Cautions Understand mechanisms and examine concurrent medications Can antagonize or exacerbate other therapy Tramadol/Tapentadol with antidepressant and opioids – Serotonin syndrome Mixed agonist-antagonists with opioids – Potential antagonism of agonists Severe Pain Management Use of Potent Opioids Potent mu receptor agonists Examples – – – – – Morphine – prototypical Hydromorphone Oxymorphone Fentanyl Methadone Differences in chemistry, PK, dosing, potency, metabolite formation, active vs inactive metabolites acute vs. chronic effects, etc. Opioids—Drug Selection Choice of agent based on pain intensity, pharmacologic factors, coexisting condition, economic factors Available forms: Tablet, liquid, sublingual, rectal, transdermal, transmucosal, nasal, parenteral, intra-spinal Select the form most convenient and comfortable for the patient Oral ER/LA products not for Acute Pain Opioids—Dosing Wide variation in effects in different patients Dosage must be individualized “Opioid-naïve” patients should usually start with lower doses because of higher susceptibility to adverse effects Opioids—Titration Depending on the clinical setting repeated dose adjustments may be necessary Titrate upward until patients achieve relief or experience intolerable adverse effects Rate of titration depends on pain severity, comorbid conditions and pain relief goals Tolerance: With existing tolerance due to chronic opioid use may require increased dose or trial of another agent Opioids—Dose Schedule In the setting: – – – – Should be designed to optimize analgesia and patient convenience Persistent pain: Around-the-clock dosing Intermittent pain: Short-acting opioids Break-through: Rescue doses of short-acting agent for breakthrough pain Opioids—Conversion Switching is done due to lack of efficacy, poor tolerance, change in patient metabolic capacity status, or formulary and reimbursement issues Requires careful calculation of daily intake and use of equi-analgesic dosage table Be careful when changing routes of administration, PO to IV and IV to PO, etc. Use caution when calculating dose of new agent; some recommend starting at 75% dosage conversion and provide BTP doses – Incomplete cross tolerance See DiPrio for equi-analgesic dose comparisons Minimizing Adverse Effects Titrate gradually Determine cause of symptoms Change dosing route or regimen Switch to another opioid Add an adjuvant and reduce dosage Eliminate other nonessential agents Assume that constipation will occur and provide preemptive treatment – Stimulant and stool softener Drowsiness A dose and concentration related side effect Tolerance develops over a few days Care in driving, but once stable, can drive fine. Care again when dose is changed. Monitor closely after surgery – additive effects of medication and leading toward respiratory depression. Highest risk in first 24 hours post-operatively. Why? Lower dose or change drugs if persistent Hospital Monitoring Vital signs (BP,HR, RR) and the Ramsey Scale 1 Anxious agitated restless 2 Cooperative, oriented and tranquil 3 Responds to vocal commands 4 Asleep, responds to voice or shaking 5 Asleep does not respond except pain 6 Unarousable Respiratory Depression Respiratory depression is an extension of the CNS depressant effects of opioids Dose-dependent continuum of drowsiness to lethargy to non-responsiveness, to decreased rate of breathing and/or decreased tidal volume or depth of breathing Patient retains CO2, oxygen saturation drops Respiratory failure and arrest are the final stages CNS and Respiratory Depression Monitoring in Hospital or PORR/ER Uncomplicated patients need vital signs, pain score and Ramsey score Observe rate and depth of breathing Observe skin color Higher risk patients – Pulse oximeter monitor – Records pulse and oxygen saturation of hemoglobin in the blood Alarms when abnormal parameters observed A monitored bed in step-down unit or ICU Respiratory Depression Treatment Actions follow the degree of depression Respiratory rate 10-12 – – Reduce dose of opioid medication Monitor more frequently Rate of 4-10 – – – – Add supplemental oxygen Stimulation – physical and verbal Low-dose naloxone 40 mcg doses until respiratory rate increases and patient is more responsive (Why this way?) Temporarily stop opioid and then adjust down Respiratory Failure - Apnea Full emergency measures ABC – airway, breathing, circulation Intubation, assisted ventilation, CPR Naloxone 400 mcg IV bolus and repeat to effect Other supportive measures Stop opioid; Patient will need pain medicine at some point after recovery Common Acute Pain Syndromes and Their Management Acute Low Back and Neck Pain Low Back Pain Epidemiology/Etiology Second to the common cold the most common affliction of mankind 80% of the world’s population has an episode 20% of the US population has an episode each year 90% of LBP is of mechanical origin (muscle strain, facet arthritis, stenosis) Neck Pain Epidemiology/Etiology Neck occurs about a quarter as often as low back pain Frequency of events affecting the world’s population is unknown 10 - 15% of the US population has an episode each year 90% of neck pain is of mechanical origin (muscle strain, whiplash, facet arthritis) AHCPR Treatment Recommendations Acetaminophen and NSAIDs (ibuprofen, naproxen, ASA) are effective for pain relief Spinal manipulation (chiropractors, osteopaths, physical therapists) are helpful at pain onset; reevaluation is required if pain continues for 4 weeks Low-stress exercises (walking, swimming, biking) should start 2 weeks after onset of mild to moderate pain Conditioning exercises for trunk muscles should start after the first 2 weeks of symptoms Clinical Use of Analgesics in Acute Use/Surgical Situations Goals of pain assessment & treatment in regard to procedures – – – – Decrease incidence and severity of patients’ post surgery or trauma pain Educate patients about their role to communicate unrelieved pain Enhance patient comfort & satisfaction Reduce postoperative complications and in some cases length of hospital stay Pre-surgical Plans Include a Pain History Significant prior experiences with pain Previous methods for pain control and their outcome Patient attitudes toward certain meds Substance abuse Fears – overmedication, side effects, “addiction” Coping styles in dealing with stress & how patient describes and shows pain Family expectations about the experience Pre-emptive or Preventative Analgesia Prevention is always better than treatment whenever possible. Patient outcomes are routinely better Examples – – – Give analgesic prior to painful stimulus Pre-procedure medications, local anesthesia, general anesthesia Site Specific Pain Management Dental Surgery Prophylaxis is good – NSAIDS Simple extractions – minor pain, local anesthesia and then APAP or NSAIDS Wisdom teeth extraction, bony impactions and periodontal procedures – moderate pain – – Long acting local “Moderate” pain analgesics like Tylenol#3, etc. Neurosurgery Craniotomy Need to monitor patients for abnormal neurological signs CNS active drugs for edema and seizures used Relative contraindication to use opioids This procedures produces mild to moderate pain and should respond to NSAIDS Balance of bleeding disorder, antipyretic vs CNS depressant Abdominal and Thoracic Surgery Invasive procedures inducing severe pain Aggressive treatment required Combinations are useful – – Epidural/regional anesthetic blockade Epidural or IV opioids and IV PCA Use around the clock Patient outcomes much better if pain control is successful Musculoskeletal Surgery Joint replacement (hip, knee, etc.) & spine procedures tend to have moderate to severe pain These patients may also be chronic pain patients and using analgesics pre-op There may be tolerance to opioids Muscle spasms are common and muscle relaxants needed Caution: additive CNS depressant effects Epidural and IV medications early on & convert to orals Epidurals can reduce additive CNS effects from other medicaions by using local delivery Trauma and Burns Minor fracture, long bones – oral or parenteral and convert to oral Severe injuries and pain Concurrent CV instability Titrate small IV doses of morphine to treat pain and prevent CV instability Severe pain is recurrent due to future manipulations and procedures during days of recovery Tolerance develops Use short-acting benzodiazepines as adjuncts if fear and anxiety are problematic, but must monitor closely for CNS and respiratory depression How to Handle Patients with Current History of Licit or Illicit Opioid Use Mehta, Anesthesia, 2006 Audience Participation Minicases Face-lift operation Total hip replacement 2nd degree sunburn Wisdom teeth extraction (all four) Three fingers crushed in stamp press Sickle-cell crisis in IV drug abuser