Pain management w obj (2).pptx

Pain Management Jennifer Hofmann MS, PA-C Pharmacology Objectives Discuss the basic physiology of nociceptive pain. Assess physical pain and be familiar with methods of quantifying pain. Explain the goals of pain management List the primary classes of analgesics including acetaminophen, NSAIDs, op...

Pain Management Jennifer Hofmann MS, PA-C Pharmacology Objectives Discuss the basic physiology of nociceptive pain. Assess physical pain and be familiar with methods of quantifying pain. Explain the goals of pain management List the primary classes of analgesics including acetaminophen, NSAIDs, opioids and medications for neuropathic pain Objectives List the basic classifications of the opioids and provide examples from each class. Describe the different opioid receptors and their characteristic pharmacologic effects. Distinguish the most commonly used opioid analgesics and know their mechanism of action, therapeutic uses, and common adverse effects. Discuss the management of opioid adverse effects such as constipation. Objectives Examine tolerance, dependence and addiction in opioid users. Explain MAT is the use of medications to treat persons with opiate use disorder and the process for obtaining this training as a PA https://pcssnow.org/medications-for-opioid-use-disord er/waiver-training-for-pas/ Discuss the pharmacologic management of opioid use disorder including Subutex, suboxone and methadone Analyze the risks and benefits of combination opioids and NSAID/acetaminophen combination preparations. Pain- overview What is pain? Types of pain Nociceptive Neuropathic Acute pain Chronic pain Nociceptive Pain Somatic or visceral Acute, dull, sharp or aching Analgesics offer good response Painful stimuli at site of injury stimulate peripheral nociceptive receptors which release substances  afferent nerve fibers pick up message  spinal cord (dorsal horn)  cerebrum, thalamus other supraspinal structures in the brain where information is registered about nature of pain (PQRST) Modulation of pain via release of endogenous opiates such as enkephalins and endorphins and other substances Copyrights apply Topic: Neuropathic Pain Difficult to treat w/ poor response to analgesics Often chronic Nerve damage or persistent stimulation Examples Post stroke pain Post amputation pain (phantom limb) Spinal cord injury Post herpetic neuralgia Diabetic neuropathy Low back pain (some types) Acute and Chronic Pain Acute Chronic Depression HTN, tachycardia Insomnia Sweating Dependence and tolerance to pain meds Facial pain expressions Psych component is strong Organic cause Difficult to treat More responsive to meds Goal is pain relief and rehabilitation depending on cause Goal is cure of cause and relief of pain Overview:Pain Management Analgesics  most effective and least side effects Nonopioids such as acetaminophen, NSAIDS Acute mild to moderate pain Inflammatory pain (bone, joint, tissue)  NSAIDS Opioids  severe acute and chronic pain Effects mediated by opiate receptors (mu, delta and kappa) Most analgesic, euphoriant, respiratory depressant, and physical dependence results from actions at the mu receptors Drug name: Acetaminophen (Tylenol) Pharmacology: Metabolized in liver mostly by glucuronidation Small amounts N-hydroxylation to reactive metabolite which is conjugated by glutathione and may cause deplete hepatic glutathione and cause liver necrosis in high doses Actions: Analgesic and antipyretic Not anti-inflammatory Ceiling dose is 650-1000mg/dose for analgesia Maximum chronic daily dose is 4 grams Drug: Acetaminophen Adverse effects: Well-tolerated in therapeutic dosages Rash rarely Acute overdosage Hepatotoxicity may occur after single dose of 10-15g >150mg/kg in children Signs and symptoms Treatment Early diagnosis with gastric lavage, N-acetylcysteine (Mucomyst) po or IV to replace depleted glutathione ASAP Mucomyst is more effective if given within 10 hours after ingestion but can be given up to 36 hours post ingestion Class: Nonsteroidal AntiInflammatory Drugs (NSAIDs) Pharmacology Decrease prostaglandin synthesis by inhibiting COX enzymes (cyclooxygenase) More in NSAIDS lecture Actions Multiple types of pain Dental, dysmenorrhea, fever, post op ortho pain, joint pain Analgesic, antipyretic and anti-inflammatory Ceiling effect may occur Maximum effects are lower than opioids Can switch NSAID classes if response is inadequate NSAIDS Usual dose Drug Aspirin (ASA) 325-650mg poq4h Max dose 5400mg Namembutone (Relafen) 500-1000mg po 2000mg Choline Mg trisalicylate 750mg po BID-TID 3000mg Diflusinal (Dolobid) 250-500mg po q 8-12h 1500mg Etodolac(Lodine) 200-400mg po q 6-8hr 1200mg Ibuprofen (Motrin, Advil) 200-400mg po q6 h 3200mg Ketoprofen(Orudis ) 25-50mg po 6-8h 300mg Naproxen (Naprosyn) 250mg po q6-12 1250mg BID Naproxen sodium (Alleve, Anaprox) Diclofenac (Voltaren) NSAIDS 220mg-550mg po BID 1500mg 50mg po tid 150mg Ketorolac (Toradol) 10mg po q4-6h or Oral 40mg/day 60mg IM, or 30mg IV 120mg/day IM/IV single dose or q 6h prn Acetaminophen (Tylenol) 325-650mg po q4h Celecoxib (Celebrex)* 100-200mg BID (RA) 200mg/day OA Meloxicam (Mobic) 4000mg (4g) Class: NSAIDS Adverse effects Gastritis with N, dyspepsia, ulceration, GI bleed Blockade of platelet aggregation (bleeding) Hypersensitivity reactions Decreased GFR and renal blood flow in certain patients Some have more renal effects, some have more GI effects Pts with history of GI bleeds or serious risk factors and NSAIDS? Misoprostol COX 2 inhibitor Lowest dose NSAID with least GI toxicity plus PPI such as omeprazole NSAIDS- AE click image to return NSAIDS and Drug Interactions Anti-hypertensives – blunted antihypertensive efeffects with ACEI, diuretics, antihypertensives May potentiate anticoagulants effects Some decrease Lithium clearance NSAIDS are contraindicated in ASA allergic patients FDA Warning and NSAIDS Rx- NSAIDS FDA warning OTC Non-Selective NSAIDs A boxed warning regarding the potential serious adverse CV Similarlife-threatening warning in the Drug GI Facts events and the serious, and potentially adverse events associated with thelabels use for of OTC thisNSAIDS class of drugs. A contraindication for use in patients who have recently undergone coronary artery bypass surgery. A Medication Guide for patients regarding the potential for CV and GI adverse events associated with the use of this class of drugs . Opiates – Opioids Background Physiology: Endogenous Opioid Peptides Physiology Facts Three major precursor proteins make ENDOgenous beta- endorphins and enkephalins prepro-opiomelanocortin Preproenkephalin Preprodynorphin Physiology: Opioid Receptors General Opioid Receptor Characteristics: G protein coupled receptor family Mu1, Mu2 Delta1, Delta2 Kappa1, Kappa2 Receptor Type and effects Mu () :Analgesia, euphoria, respiratory depression, physiological dependence Most opioid analgesics: act at the mu receptor Delta (d) and Kappa (k): Spinal analgesia and other effects Opioid Analgesics Sir William Osler called morphine “God’s own medicine” Strongest analgesic Terminology: Opioids/ Opiates Any drug derived from or containing opium Opioid – Natural, synthetic, or semi-synthetic chemicals that interact with opioid receptors Opiates refer to natural opioids such as heroin, morphine and codeine. Agents that bind to opiate receptors Pure agonists Mild-moderate agonists Mixed antagonist-agonists Pure antagonists Morphine is the prototype opiate Topic: Opioid Analgesics MOA Opiate agonists exert analgesic and other effects via binding to mu opioid receptors Binding causes decreased release of neurotransmitters such as Ach, NE, Glutamate, substance P and serotonin from pain transmitting neurons AND Hyperpolarizes postsynaptic neuronal membranes to prevent response to painful neurotransmitters Mu receptors are found in spinal cord, thalamus, brainstem, descending pathways Tolerance to opioids develops Receptors are internalized Activation of adenylyl cyclase to counteract the decrease associated with opiates binding to receptors Copyrights apply Physiologic Effects of the Opiate/Opioids Agonists Analgesia Euphoria and tranquility Muscle rigidity Miosis Respiratory depression – monitor O2 saturation in pts receiving opiates (IV esp.) Dose limiting and cause of death in OD Cough suppressant N/V Activate brainstem chemoreceptor trigger Physiologic Effects of the Opiates/Opioids GI tract –slows, constipation is common and can be severe Urinary tract –retention Cardiovascular NO DIRECT effects but may see bradycardia Skin Tolerance and dependence Tolerance and dependence (withdrawal) are seen in all patients over time does not = addiction Addiction Overview of the Clinical Use of Opiates/ Opioids Analgesia Severe and constant pain Acute pulmonary edema MI Cough suppressant Codeine, hydrocodone and dextromethorphan OTC (free of analgesic and addictive properties) Diarrhea (Lomotil is diphenoxylate + anticholinergic, atropine) Imodium = generic loperamide which is OTC limited access to the brain) Precautions- OPIOIDS Previous addictions/ substance use d/o Drug seeking behavior (PMP) https:// www.health.ny.gov/professionals/narcotic/prescrip tion_monitoring/ Prudent prescribing Risk Evaluation and Mitigation Strategy (REMS) https://www.opioidanalgesicrems.com/home.html Tolerance Caution when switching between opioid classes Adjust dose when converting one opioid to another e.g. morphine to hydromorphone Dependence Withdrawal upon discontinuation Underlying Respiratory disease Renal and hepatic disease Caution with CNS depressants of all kinds Opioids – Topic: withdrawal Not deadly but awful Typically peak at 24 to 48 hours after onset may last days to weeks. flu-like illness Signs and symptoms include Anxiety and dysphoria, insomnia, pupillary dilation, piloerection, yawning, muscle aches lacrimation, rhinorrhea, nausea, fever, sweating, vomiting and diarrhea. Opioids - withdrawal Treatment of symptoms Variety of options for “cold turkey” symptom relief Treat dehydration and decrease external stimuli Clonidine decreases sympathetic outflow and may help with stimulatory symptoms. Anti-nausea/anti-vomiting medications may provide comfort and allow oral medication dosing. Bismuth subsalicylate or loperamide may help with diarrhea. Topic: Opioid Overdose Respiratory depression Miosis Hypotension Bradycardia Treatment Airway and ventilation as needed and cardiac monitoring Naloxone with repeated dosing OPIOIDS Opioid Class Name: Morphine Morphine: derived from opium from poppy plant Prototypical full mu agonist First line for treating moderate to severe nociceptive pain IV. IM, po and rectally Metabolized by the liver to active metabolite morphine 6-glucuronide Excreted in urine Pharmacokinetics vary depending on route of administration Newer oral morphine formulations allow for ATC dosing every 12-24 hrs MS Contin and Oramorph SR q 12 hr Kadian q 12-24 hrs Drug: Morphine sulfate -PK Route Po IV IM SC PR Epidural Intrathec al Onset 1hour 5min 10-30min 10-30min 20-60min 15-60min 15-60min Peak 1-2hr 20min 30-60min 50-90min 20-60min 15-60min 30-60min Duration 4-12h 4-5hr 4-5hrs 4-5hrs 4-5hrs 24hours 24hours Class: Opioids Morphine-like agents Other morphine-like agents include: Hydromorphone (Dilaudid) more potent than morphine Oxymorphone (Opana and Opana ER dosed q12hr) more potent Levorphanol- oral longer half life than morphine more potent also (po) Hydrocodone (in Vicodin, Lortab, Lorcet) Oxycodone- (Percocet) similar potency and excellent po for moderate to severe pain Oxycontin is controlled release oxycodone dosed q12 hr Codeine – weak – may not be effective in some patients with certain P450 polymorphisms Tylenol #3 and 4 has codeine and acetaminophen Class: Opioid Name: Meperidine Meperidine (Demerol) Shorter duration and less potent than morphine Metabolized in liver to normeperidine which can accumulate and cause neuro excitation and seizures (long half life) AE/ Drug interactions Dilated pupils unlike morphine and heroin Severe reactions with MAO inhibitors  delirium, hyperthermia, rigidity, convulsions and death (LIBBY ZION CASE) Class: Opioids Fentanyl and Similar Drugs Fentanyl and sufentanil- now that’s strong! Relief of severe cancer pain and as Adjunct to general anesthesia 100X more potent than morphine Also being used illicitly (misuse) Fentanyl is a Leading cause of OD deaths from opioids Sufentanil 1000X more potent (used in anesthesia) Peaks quicker than meperidine/morphine and recovery is quicker (30-60 minutes) Causes muscle rigidity more than morphine 50-100mcg IV slowly or IM for anesthesia Class: Opioids, Antidiarrheals Diphenoxylate (Lomitil) (Rx only) Antidiarrheal High doses can cause euphoria, physical dependence Given with atropine sulfate to reduce likelihood of abuse Loperamide (Imodium) OTC Antidiarrheal agent by slowing GI motility low solubility  low potential for abuse Class: Opioid Name: Methadone (Dolophine) Indications Oral efficacy, long-acting agents used mostly to maintain abstinence in heroin or opiate users (MMT clinics) OUD Reduces cravings and staves off withdrawal w/o causing high Also used in pain management Pharmacology: t1/2= 23hrs (LONG) Detoxification Maintenance Give doses that cause tolerance to heroin which may prevent drug-seeking behavior Doses of 60 to 100 mg, and sometimes more, are required for most patients Drug interactions and prolongs QT Type: Mixed agonists/antagonists and partial agonists Butorphanol (Stadol) Nasal, IM and IV formulations for acute pain Increases cardiac work so caution in CHF pts. Buprenorphine May reverse fentanyl induced anesthesia Used alone and in combination with naloxone for opiate dependence Buprenorphine alone or Suboxone sublingually as a single daily dose in the usual range of 12 to 16 mg per day. Drug Names: Subutex and Suboxone Topic: Opioid Use Disorders- OUD Subutex = buprenorphine ONLY (generics) is preferred for use during induction because it doesn’t contain naloxone. http://naabt.org/collateral/How_Bupe_Wor ks.pdf Suboxone = buprenorphine +naloxone preferred for long term maintenance treatment, which includes unsupervised administration. The naloxone component is added to deter patients from trying to inject the tablets. sublingual tablets or film under the tongue until they are dissolved. Recent issues with dental decay and cavities Topic: SUBOXONE for opioid use disorder– PAs/NPs On November 17, 2016, the Department of Health and Human Services (HHS) announced that NPs and PAs can immediately begin taking the 24 hours of required training to prescribe buprenorphine for opioid use disorder (OUD) NPs and PAs who complete the required training and seek to prescribe buprenorphine for up to 30 patients will be able to apply to do so beginning in early 2017. Once NPs and PAs receive their waiver, they can begin prescribing buprenorphine immediately. HHS is also announcing its intent to initiate rulemaking to allow NPs and PAs who have prescribed at the 30-patient limit for one year, to apply for a waiver to prescribe buprenorphine for up to 100 patients. https://pcssnow.org/education-training/mat-training/ Topic: Opioid Use Disorders- Other Meds Sublocade (SUB-loh-kayd) longacting buprenorphine product. Sublocade is a once-monthly subcutaneous injection Probuphine is an implant that lasts 6 months. Class: Opiate Antagonists Main therapeutic utility:Tx of overdosage with opioids Produce few effects unless opioid agonists are on board Drugs: Naloxone (Narcan) Known or suspected narcotic-induced respiratory depression, postop narcotic reversal IV, IM, SQ, ET prn (0.4mg-2mg) and SL with Suboxone Intranasal for community administration Naltrexone (ReVia) Orally active with longer duration of action for alcohol use disorder (once daily dosing) IM monthly injection for alcohol and opioid use d/o Opioids: Topic: Abuse Deterrent Formulations Designed to deter or dissuade chewing, snorting or parenteral abuse Role is still unclear and costly Formulated with physical or chemical barriers Abuse Deterrent Formulations Oxycodone (difficult to crush, tablet gels when dissolved can't inject) Hydrocodone Morphine Recap: Opioids AE Dose limiting and cause of OD or death = respiratory depression tx= naloxone Major AE with regular use: opioid induced constipation (OIC) Prevention and initial management w/ daily stool softener (e.g. Miralax (PEG) plus senna Intermittent rectal suppository or enema Refractory case can use peripherally acting mu-opioid receptor antagonists (PAMORAs) for refractory OIC subcutaneous methylnaltrexone once every Terminology Opioid tolerance occurs when a person using opioids begins to experience a reduced response to medication, requiring more opioids to experience the same effect. Opioid dependence occurs when the body adjusts its normal functioning around regular opioid use. Unpleasant physical symptoms occur when medication is stopped. Opioid addiction (Opioid use disorder (OUD)) occurs when attempts to cut down or control use are unsuccessful or when use results in social problems and a failure to fulfill obligations at work, school, and home. Opioid addiction often comes after the person has developed opioid tolerance and dependence, making it physically challenging to stop opioid use and increasing the risk of withdrawal. Topic: Miscellaneous Opioids for ANALGESIA Tramadol (Ultram and Ultracet w/ APAP) Codeine analog for moderate pain Other actions (NE and 5HT reuptake) Potent metabolite, duration of analgesia is 6 hours with peak in 2 hours Do not give with SSRIs Tapentadol (Nucynta) – like tramadol mu-opioid receptor (MOR) agonist and a norepinephrine reuptake inhibitor (NRI) Opioid Name: Dextromethorphan Dextromethorphan Use: Antitussive (cough suppressant) No analgesic or addictive properties at recommended dose and minimal side effects Over the counter 10-30mg three-six times a day for adults Overdosage and abuse issues (warning w/ labeling) NOTE: RX Hydrocodone and codeine are also used in cough suppressants Topic: Severe Breakthrough Pain in Patients with Cancer Fentanyl preps Transdermal patch (Duragesic) can provide pain support for 48-72 hours (use caution w/ patch) http://www.fda.gov/cder/drug/infopage/fentanyl/Dur agesicPPI.pdf Fentanyl losenge (Actiq) on a stick for breakthrough cancer and severe pain and Fentora buccal tablet Rapid acting for immediate breakthrough pain relief Onsolis – a buccal film Start with lowest dose and only for use in opioid tolerant pts High risk of resp depression Topic: Breakthrough Pain and ATC Dosing ATC= around the clock dosing for 24 hr pain control Breakthrough pain occurs during ATC dosing and must be treated with… End-of-dose pain can be managed by increasing the dose or decreasing the interval of the scheduled pain medicine Predictable incident pain can be managed with a short-acting opioid given 30 to 45 minutes prior to activity. Unpredictable or idiopathic pain requires an opiate with a fast onset. Breakthrough pain can have a neuropathic origin. Consider nonopioid analgesics (e.g., anticonvulsants). Topic: Conversion of OpioidsFYI When changing from one opioid to another or switching route of administration ? How do I switch from one opioid to another (dosing) FYI (see conversion tables) ALL conversions are based on potency ratio to morphine IV 10mg of morphine IV= 30mg morphine po so conversion factor is 3 Conversion factors provided by equianalgesia tables Example: Current opioid is morphine 50mg po TID Target is hydromorphone IV Total 24 hr dose is 150mg convert to morphine IV 150/3= 50mg IV morphine  50 (0.15), conversion factor for hydromorphone IV) = 7.5 HM IV /24 hours Opiates and Pregnancy, L/D Parenteral administration of opioids within 2-4 hours of DELIVERY may lead to transient respiratory depression in the neonate Epidural analgesia ? Effects on neonate depends on dose but generally very safe for neonate Good review slide Review slide BREAK Neuropathic Pain Abnormal processing by peripheral and CNS Nerve damage or persistent stimulation may cause pain circuits to rewire themselves causing spontaneous stimulation Burning, tingling, shock-like, shooting pains, hyperalgesia, allodynia Diabetes, cancer, metabolic disturbances Poor response to analgesics Meds for Neuropathic Pain Amitriptyline100-900mg Gabapentin 25mg-100mg po tid q hs Pregabalin 20mg Fluoxetine (Lyrica) po100 qd mg TID. Carbamazepine Sertraline 50-100mg 200mg po po qd bid Valproate po bid60 mg once or twice daily Duloxetine500mg (Cymbalta) Baclofen 5-15mg po bid-tid Topic: First line meds for Neuropathic Pain Duloxetine(Cymbalta) Antidepressants SNRI Tricyclic antidepressants (TCAs) e.g., amitriptyline (Elavil) Pregabalin (Lyrica) (AED) Topic Neuropathic Pain Second Tier Second tier guideline therapy includes: carbamazepine (Tegretol), AED gabapentin(Neurontin), AED lamotrigine (Lamictal), AED tramadol(Ultram) (opioid) Tapentadol (opioid) venlafaxine ER (Effexor XR) antidepressant