Pain

Acute and Chronic Pain

Acute pain begins suddenly and usually feels sharp --- It is typically nociceptive in nature, such as a fracture, burn, acute illness, surgery or childbirth --- The pain can last just a few moments, or longer, and usually goes awat when the cause of the pain has resolved Acute pain can cause anxiety and physical symptoms, including sweating and tachycardia If acute pain goes untreated, it has been shown to increase the risk for the development of chronic pain Chronic pain has been described as pain that persistst beyond the normal healing time (or three months), but for some conditions ther is no acute injury IT can persist with a visible injury (such as crushed lumbar vertebrae, causing lowe back pain) or when no visible injury is present, such as OA or diabetic neuropathy OA is a common type of chronic pain caused by a break down in the cartilagae that pads the joint, which results in stiffness, pain and/or swlling Chronic pain is divided into cancer pain or chronic non-cancer pain, which have seperate treatment guidelines Poorly managed chronic pain is misreable and can cause depression and phhysical symptoms incudling muscle tension and fatigue

NSAID DIs

Additive bleeding risk with other agetns that can increase bleeding risk such as steroids Caution using aspirin with other ototoxic agents (E.g. AGs, IV loop diruectics Multiple NSAIDs should not be used together, except the addition of low dose adpirin for cardioprotection when idnicated If using ASPIRIN FOR CARDIOPROTETION NAD OBUPROFEN FOR PAIN, TAKE ASPIRIN ONE HOUR BEFORE OR 8 HOURS AFTER IBUPROFEN NSAIDS can increase the levels of LITHIUM nad methotrexate

Common Adjuvants for Pain Management

Adjuvants (e.g. muscle relaxants, antiepileptic drugs, antidepressants, topical anesthetics) are useful in pain management through theyy are not classified as analgesics They an be added to opiooid or non opoid analgesics (multimodal treatment) ADJUVANTS ARE COMMONLY USED IN PAIN asosciated with NEUROPATHY (from diabetes or spinal cord injury), POSTHERPETIC NEURALGIA (PHN), FIBROMYALGIA, OA and others AEDs (notably pregabalin and gabapentin) are useful for neuropathic pain TCAs and SNRIs block NE uptake, which has shwon to be beneficial in neuropathic pain SSRIs do not have this effect Muscle relaxants have various, porly understood MOA Some work predominately by CNS depression leading to relxation of skeletal musckles (e.g. carsioprodol, chlorzoxazone, metaxalone, methcarbamol), while others work by decreasing transmissio nof reflexes at the spinal level Inejctable adjuvants can be used in specific cases by pain specialists for example, CLONIIDNE injecetion can be added to opioids in intrathecal (EPIDRAL) pain ifusion pumps for patients with CANCER PAIN, when other agents are insufficient

Nno-Aspirin Boxed Warnings

All prescription, non-aspirin NSAIDs REQUIRE A MEDGUIDE due to these risks These warnings are NOT REPEATED in the drug tables - GI RISK: NSAIDS cna increase the risk of serious GI adverse events including BLEEDING AND ULCERATION Patients who are elderly, have a hidsotry of GI bleed, or are taking systemic steroids, SRIs or SNRIs are at greatest risk Aspirin and OTC NSAIDs do not carry a boxxed warning but still ave thew risk - CV RISK: NSAIDs can increase the risk of MI and STROKE Avoid use in patinets with CV diease or risk factors This warning includes all OTC non selective NSAIDS except aspirin -CORONARRY ARTERY BYPASS GRAFT (CABG) SURGERY: NSAID use is contraindicated after CABG surgery ANTIPLATELET THERAPY(COMMONLY ASPIRIN) IS RECOMMENDED after CABG surgery

NSAIDS AND THE DUCTUS ARTERIOSUS

BEFORE BIRTH, THE DUCTUS ARTERIOSUS (dA) CONNECTS THE PULMONARY ARTERY TO THE AORTA, ALLOWING OXYGENATED BLOOD TO FLOW TO THE BABY, BYPASSING THE IMMATURE LUNGS DO NOT USE NSIADS IN THE THIRD TRIMESTER OF PREGNANCY. NSAIDS CNA PREMATURELY CLOSE THE DA AFTER BIRTH, THE DA SHOULD CLOSE ON ITS OWN. IN SOME CASES, IT REMAINS PATENT (OPEN) AND NSAIDS CAN BE USED TO HELP IT CLOSE IV NSIADS (INDOMRTHACIN, IBUPROFEN) CAN BE USED WITH IN 14 DAYS OF BIRTH TO CLOSE A PTENT DUCTUS ARTERIOSUS (PDA)

Antispasmodics (Msucle relaxants) with analgesic effects. SUe caution with other CNS depressants (e.g. alcohol, benzos, and OPIOIDS): DUE TO THE ADDITIVE RISK OF CNS DEPRESION BACLOFEN (LIORESAL) DOSING 5-20mg TID-QID PRN Injection given via intrathecal pump for severe spasticity

BOXED WARNING Abrupt withdrawal of intrathecal baclofen has resulted in severe effects (high fever, lethargy, rebound/increase spasticity, muscle rigidity and rhabdomyolysis), leading to organ fialure and death SEs For ALL MSUCEL RELAXANTS: excessive SEDATION ,DIZZINESS, CONFUSION NOTES Do not overdose in elderly (e.g. start low, titrate carefully), watch or additive side effects

Hydrocodone ER (Zohydro, Hysingla ER, Vantrela ER CII ER caps: Zohydro ER tab: Hysingla ER, Vantrela ER DOSE Zohydro ((Caps) Start at 10mg Q12 H (opioid naive) Range 10-50mg Hysingla ER (tablet) Start at 20mg Q24 hours (opioid naiive) range 20-120mg

BOXED WARNING Initiation of CYP3A4 INHIBITORS (or stopping CYP3A4 inducers) can cause fatal over dose NOTEES SUbstrate of CYP3A4 (major) and CYP2D6 (minor) Preferably avoid use if breastfeeding Abuse deterrent formulations Hysingla: QT prolongation has occurred at doses > 160mg/day

FENTANYL (DURAGESIC, SUBLIMAZE) CII INJ, PATCH ACTIQ: ORAL TRANMUCOSAL LOZENGE ("LOLLIPOP," ON A STICK) Lazanda: Nasal spray Fentora: buccal tabs Abstral: table,t SL Subsys: spray , SL Onsolis: buccal film DOSE PATCH Apply 1 PATCH Q72H (CAN BE Q48H) Avialble in 12 (delivers 12.5 mcg/hr), 25,50, 75, and 100 mcg/hr patch strnegths LOZENGE ALwats start with 200mcg can titrate to 4 BTP episodes/day Only for cancer BTP

BOXED WARNING Potential for medication errors when converting between dosage forms, use with strong or moderate CYP3A4 INHIBITORS can result in increase effects and potentially fatal respiratory depression, avoid exposing transdermal fentanyl to external heat SEs Bradycardia, confusion, dizziness, diaphoresis, dehydration, dry mouth, NV, muscle rigidity, weakness, miosis, dyspnea NOTES Outpatinet use of fentanyl is for chronic pain managmenet only Fentaly is NOT USED IN OPOID NAIVE PATIENTS A patient who has been using MORPHINE 60MG/DAY or equivalent for at LEAST 7 DAYS CAN BE BCONVERTED TO A FNETANYL PATCH Actiq: cut off stick and flush unused/unneeded doses Short t1/2 when given IV (boluses given Q1-2H) Continuous infusion or PCA are most common Similar drugs (IV only) include alfentanil (Alfenta), REMIFENTANIL (Ultiva), sufentanil (Dsuvia) REMS program for transmucosal immediate release fentanyl requires documentation of patinet's opioid tolerance with each prescription FENTANYL PATCH ANALGESIC effect can be seen 8-16 hors after application Do not stop other analgesic immedialt (decrease dose 50% for the first 12 hours Do not apply> 1 patch at a time Some patche meed to be removed before MRI This is specific to eahc fomrulation and manufacturer DISPOSE OF PATCH IN TOILET

Common Opioids CODEINE (CII: ODEINE CIII: TABLET/CAPS COMBO PRODUCTS +ACETAMINOPHEN (TYL 2,3,4) CV: ORAL SOLUTION COMBINATION PRODUCTS (E.G. COUGH SYRUPS) Select combo products: +Chlorpheniarmine/PSe (Phenylhistine DH) +Promethazine +Promethazine/phenylephrine (Promtgazine VC/Codeine DOSE TYL3 1 tab (acetaimonphen 300mg _ codeine 30mg) Q4-6 hours as needed, range 15-20mg codeine

BOXED WARNING RESPIRATORY DEPRESSION AND DEATH have occured in CHILDREN following TONSILLECTOMY NAD/OR ADENOIDECTOMY found to have evvidence of being ULTRA RAPID METABOLIZERS OF CODEINE DUE TO CYP450 2D6 OLYMORPHISMS; deaths have also occurred in NURSING INFANTS after being exposed to high concentrations of morphine because the mothers were ultra rapid metabolizers; use with CYP3A4 inducers/inhibitors or CYP2D6 inhibitors should be carefully considered due to variable effectgs CIs Use in HICLDREN <12 YEARS OF AGE; USE IN CHILDREN<18 YEARS OF AGE FOLLOWING TONSILLECTOMY/ADENOIDECTOMY SURGERY WARNINGS Adolescents between 12-18 years who are obese or have sleep apnea or severe lung disease are at rincrease riks of breathing problems SEs Codeine has a high degree of GI side effects including CONSTIPATION NOTES Codeine ontaining cough and cold prepration are no longer indicated for patinets <18 years of age - do not use

HYDROMORHPNE (DILAUDID, Exalgo CII Exalgo: ER tab DOSE Initial(opioid naiive) ORAL: 2-4 MG Q4-6H PRN IV: 0.2-1MG Q-23H PRN

BOXED WARNING RIsk of MEDICATION ERROR WITH HIGH POTENC Y(HP) injection (use in OPIOID TOLERANT PATIENTS ONLY) NOTES POTENT; start low, convert carefully. HIGH RISK OF OVERDOSE Comonly used in PCAs and epudiurals Cna cause less nausea nad pruritus Dilaudid HP (0mg/mL) is a higher potenacny injection than Dilaudid (1mg/mL) Exalgo: abuse deterrent formulatiojn (crush and extraction resistant) CI in opioid naive patients. Two week washout required between Exalgo and MAO inhibitors

HYDROCODONE IR (combination products only) CII +ACEETAMINOPHEN (LORCET, LORTAB, NORCO, VICODIN, Verdrocet, Xodol) Select Combo Products: +chlorpheniramine (Tussionex Pennikinetic ER, TussiCaps) + chlorpheniramine/pse +pse +Homatroptin (Tussigon) +Ibuprofen (Vicoprofe, Ibudone) DOSE NORCO 2.5, 5, 7.5, 10mg Hydrocodone + 325mg ACETAMINOPHEN Usual starting dose: 5/325mg Q6H

BOXED WARNING Refer to APA drug table for boxed waring Initation of CYP3A4 INBITORS (OR stopping CYP3A4 inducers) cna cause fatal overdose WARNINGS Acetaminophen and opoids: respiratory and/or CNS depression, consitpation, hypotension, skin reactions (rare), caution in liver disease (avoid or limit alcohol intake and in CYP2D6 poor metabolizers SEs N/V, dizziness, lightheadedness, SEs related to APAP NOTES Hydrocodone containing coufh and cold preprationare no longer indicated in patients <18 years of age - do not use

OXYCODONE CII (as a subgke agent andin combination) IR: ROXICODONE, Oxyado, Roxyband CR: OXYCONTIN ER: Xtampza + ACETAMINOPHEN (ENDOCET, PERCOCET, Primlev, Xartemis XR) +Naltrexone (Troxyca ER DOSE IR: 5-20 mg Q4-6H CR 10-80 mg Q12H (60, 80mg only for opioid tolerant patients)

BOXED WARNINGS Initiation of CYP3A4 INHIBITORS (or stopping CYP3A4 inducers) can cause fatal overdose, caution with oxycodone oral soltuon and oral concentrate (confusion between mg and mL and different oconcentrations) NOTES Oxyado, Oxycontin, Targiniq ER, Troxyca ER, and Xtampza ER: abuse-deterrent formulaitons Xtampza ER capsules can be opened and contents administered with soft food or through a gastric tube Avoid high fat meals with higher doses (Except re-formulated OxyContin) If renally impaired, start at a lower dose, or avoid oxycodone, due to accumulation of parent drug and/or active metabolite

MORPHINE ER: MS CONTIN, KADIAN, Roxanol, MorphaBond, Arymo ER Injection: DURAMORPH, INFUMORPH, Astramorph CII IR (including solution): 10-30 mg Q4H PRN ER: 15, 30, 60, 100, 200 mg Q8-12 hours Morphabond BID Kadian Daily or BID IV: (opioid naive) 2.5-5mg Q3-4H PRN

BOXED WARNINGS Medicasiton errors with oral solution (note strenth), appropriate sstaff and equipment neded for intrathecal/epidural administration SEs N/V (may need anti emetics), dizziness, changes in mood, confusion, delirium; flushing pruritus, diaphroesis (may need antihistamine) NOTES DO not use MSO4 or MS abbreviations for morphine or magnesoim Do not crush or chew any ER prodcuts. Kadian can e opened and sprinkled on applesauce or soft food If renally impaired, start at a lower deose, or avoid morphine, due to accumulation of parent drug and/or active metabolite

ACETAMINOPHEN (TYLENOL, FEVERALL, OFIRMEV, most "Non-aspirin" pain releivers FEVERALL: Rectal suppository OFIRMEV: Injection + HYDROCODONE (LORCET, LORTAB, NORCO, VICODIN) +OXYCODONE (ENDOCET, PERCOCET, Primlev) +CODEINE (TYLENOL #2,3,4) +tramadol (Ultracet) +CAFFEINE (EXCEDRIN TENSION HA_ +ASPIRIN\/CAFFEINE (EXCEDRIN EXTRA STRENGTH, EXCEDRIN MIGRAINE, Goodys Powder CAFFEINE/PYRILAMINE (MIDOL) +butalbital/caffeine (Fioricet +/- codeine +diphenhydramine (Tylenol PM) And in multiple cough and cold products and OTC combos DOSE Adults MAXIMUM<4,000MG/DAY from all sources Maximum of 325mg per prescription dosing unit in combo products, per the FDA Dosing ranges and maximum doses depend on the formulation 325mg: Max 2 tabs Q4H/10 tabs per 24 hr (3,250mg) 500mg: max 2 ts Q6H/6 tabs per 24 hour (3,000mg) 650mg ER: max: 2 ts Q8H/6 tabs per 24 hour (3,900mg) IV max: 650mg Q4H or 1,000mg Q6H/4-6 injs per 24 hr (4,000mg) Rectal suppository 650mg: max: 1 PR Q4H/6 per 24 hours PEDIATRIC (<12 YEARS( 10-15MG/KG q4-6 HOURS MAX: 5 DOSES/DAY; 75 mg/kg/day Use weight and age based dosing table on label

BOXED WARNINGS SEVERE HEAPTOTOXICITY (can require liver transplant or result in death), associated with doses >4 GRAMS/DAY OR USE OF MULTIPLE APAP-CONTAINING PRODUCTS; risk of 10 fold dosing erros with injection SES Cases of SEVERE SKIN RASH (rare) including SJS, TEN, and AGEP; stop drug, seek immediate medical help Nephrotoxicity (rare, usually with chronic overdsose); generally safer than NSAIDs SAFETY AVOID THE APAP abbreviation PEDIATRIC ORAL SUSPENSION Use dosing syringe or cup provided with the medicine Infant and chidlrens suspesnsion concentraion is 160MG/5ML INJECTION COncentration is 10mg/mL (in 100mL vials); use caution with dosing Prescribe in mg, not mL (e.g. a 75mg dose is not 75mL, it is 7.5mL) All IV APAP doses should be prepared in the pharmacy

BUPRENOPRHINE CIII Injection, patch, buccal, film SL tab BELBUCA: buccal film BUTRANS: patch (only for mod-severe pain in patients who need ATC opioid) Buprenex: injection Probuphine: implant Kit Sublocade: once monthly injection + NALOXONE (SUBOXONE: SL film, ZUBSOLV: SL tabs, Bunavail: bucca film, Cassipa: SL film DOSING Butrans (opioid naive): 5mcg/hr patch once weekly Belbuca (opioid naive): 75mcg daily or Q12H Bunavail, suboxone, Zubsolvv: Used daily for addiction and used off label for pain PATCH APPLICATION Apply to upepr outer arm, upepr chest, side of chest, upper back CHANGE WEEKLY. Do not use same site for at least 3 weeks DISPOSAL: FOLD STICKY SIDES TOGETHER, FLUSH or put in disposal unit that comes with drug FILM APPLICATION Belbuca is a small film that has one white side and one yellow side The white side should be placed on fingertup and the film is inserted between gum nad cheek on the cheek The cheek must be wet from saliva or water and patient should be instructed not to eat or drink for 30 mins after placement of film

BOXED WARNINGS bELBUCA FILM, bUTRANS PATCH: RISK OF ADDICTION, ABUSE AND MISUE; RISK OF SERIOUS OR FATAL RESPIRATORY DEPRESISON; LIFE THGREATENING NEONATAL OPIOID WITHDRAWAL WITH PROLONGED USE DURING PREGNANCY, CCIDENTAL INGESTION (ESPCIALLY IN CHILDREN) CAN BE FATAL (none all caps) WARNINGS CNS depression, QT prolongation (do not exced one 20mcg/hr patch) SEs Sedation, dizziness, HA, confusion, mental and physical impairment diaphoresis, QT prolongation, resp depression (dose depentdent) Patch: nausea, HA, application site pruritus/rash, diziness, constipation, somnolence, vomiting, application site erythema, dry mouth NOTES Do not expose patch to heat TO RPESCRIBE FOR OPOID DEPENDENCE: prescetiber s NEED A Drug Addiction Treatment At (DATA 2000) WAIVER If they have it, the DEA will isue a unique identification number to the prescriber, which wWILL STARAT WITH X Sublocade: paitnets must hve been takign a stable dose of transmucosal buprenorphine for 7 days prior to initiation Cassipa avialbility is currentloy unknown

METHADONE (DOLOPHINE, Methadose, Methadone Intensol) CII Methadose - 40mg soluble table; for detox and maintanenace treatment in opioid addicted patients only DOSE Initial: 2.5-10mg Q8-12 H

BOXED WARNINGs Life threatening QT PROLONGATION and serious arrhythmias (E.g. Torsades de Pointes) have occured during treatment (most involve lare, multiple daily doses), should be prescribed by professionals who know requirements for safe use, intiation of CYP450 inhibitors (or stopping inducers) can cause fatal oversoe WARNINGS Combination with other serotonic drugs or MAO inhibtrs can increase the risk of serotonin syndrome. Methadone also blocks reuptake of NE NOTES Due to VARIABLE HALF LIFE, methadone is hard to dose safely Can DECREASE TESTOSTERONE AND CONTRIUTE TO SEXUAL DYSFUNCTION Mrthsadone is a MAJOR CYP3A4 SUBSTRATE; avoid use with inhibitors or lower methadone dose

SNRIs and TCAs Milnacipran (Savella, Savella Titration Pack DOSE: Day 1: 12.5mg daily Days 2-3: 12.5mg BID Days 4-7: 25mg BID, then 50mg BID Crcl<30ml/min: max dose is 25mg BID

BOXED WARNINGs Milnacipran is an SNRI Antidepressants increae the riks of suicidal thoughts and behavior in children, adolscenets, and young adults with depression and other psychiatric disorders (do not use in pedcatric patients) CIs Use with or within 2 weeks of MAO inhibitors, avoid with linezxolid ro IV methylene blue SEs Nausea, HA, constipation, dizziness, insomnia, hot flashes NOTES INdicated for fibromyalgia only (not approved for depression) Do not use with IV digoxin with milnacipran. Milnacipran can inrfeaser the toxic effect of digoxin including posstural hypotension and tachycardia (particularly IV digoxin) Increased bleeding risk with anticoagulants or antiplatelets

KETOROLAC (TORADOL, SPRIX ACULAR: OPTHALMIC DOSE ORAL: 10-20mg x 1, then 10mg Q4-6H PRN Max: 40mg/day IV: (_>50kg): 30 mg x 1 or 30mg Q6H (decreae dose if _>65 y/o) IM (_>50kg): 60mg x 1 or 30 mg Q6H (Decrease dose if _>65 y/o) NASAL SPRAY (Sprix) <65 yo and _>50kg: 1 spray in EACH nostril Q6-8H _>65 y/o or<50kg: 1 spray in ONE nostril Q6-8H

BOXED WARNINGs Oral ketorolac: for short term moderate to severe acute pain only as continuation of IV or IM ketorolac (MAX COMBINED DURATION IV/IM and PO/sanasal is 5 DAYS IN ADULTS); not for intrathecal or epidural use; avoid in patients with advanced renal disease or at risk for renal impairment due to volume depletion WARNINGs Increase bleeding, ACUTE RRENAL FIALURE, LIVER FIALUREM and anaphylactic shock NOTES usually used after surgery, never before

DICLOFENACE (VOLTAREN, Cambia, EnovaRx, Flector, Pennsaid, Xrylix, Zorvolex, Zipsor + misoprostol (Arthrotec) DOSE Oral Tabs: 50-75 mg BID-TID Voltaren (gel): 2-4g to affected joint QID Flector: 1 patch 180mg to most pain ful area BID Cambia: 1 packet (50mg) mixed in water for acute migraine ZIpsor: 25mg QID Zorvolex: 18mg or 35mg TID

BOXWED WARNING Arthrotec: AVOID IN WOMEN OF CHILDBEARING POTENTIAL unless woman is capable of complying with effective contraceptive measures NOTES Has some COX-2 slecctivity Oral diclofenac formulations are not bioequivalent even if mg strength is the same MISOPROSTOL i used to replace the gut protective PG to decrease GI risk; cna increase uterine contractions (which cna terminate pregnancy) and cuases cramping and diarrhea

Centrally Ating Analgesics

Both tramadol and tapentadol are MU OPIOID RECEPTOR AGONISTS AND INHIBITORS OF NOREPINEPHRINE REUPTAKE TRAMADOL ALSO inhibits reuptake of SEROTONIN Both tapentadol and tramadol have the SAME BOXED WARNINGS AS OPIOIDS (see OpioidsAnalgesics, Safety Concerns)

Opioid Abuse Agents

Buprenorphine is a PARTIAL MU OPIOID AGONIST It is an agonist at LOW DOSES and an ANTAGONIST AT HIGHER DOSES It is used in lower doses to treat pain, and higher doses to treat additcciton Naloxone is an opoid antagonist; it replaces the opioid on the mu receptor Given by itself , NALOXONE (INJECTION OR NASAL SPRAY) IS USED FOR OPIOID OVERDOSE BUPRENOPRHINE/NALOXONE combo products are used as LATERNATIVES TO METHADONE for opioid depndence (BUPRENORPHINE SUPPRESSES WITHDRAWAL SYMPTOMS, AND NALOXONE HELPS PREVENTS MISUSE Naltrexone is an opoid antaognist normally used to help treat alcohol nad opioid dependnece it is avialable as a daily oral fomrlation and a monthly IM injection (Vivitrol) Lofexidine (Lucemyra), a non-opioid, alpha 2 adrenergic agonist, was approved to treat withdrawal symptoms in patients who wish to abruptly stop use of opioids altogether While not a treatment for OUD, it is used as part of a long term treatment plan The non pharmacologic treatment reSET-O is a digital technology FDA cleared for OUD tretment Naloxone can be given if opioid oversdose is suspected due to resp symptoms and/or symptoms of CNS depression All aprpoved NALOXONE formulations cna be admnistered for prevention of pioid overdose death Mant states have made naloxone readily availble byt allowing first repsonders and laymen to obtain naloxone in case tyhy see someone overdosing

METHYLNALTREXONE (RELISTOR) DOSE OIC with chronic non cancer pain: 12 mg SC daily or 450 mg PO once daily OIC with advanced illness: weight based dose SC every other day CrCl<30 ml/min : Decrease dose

CI GI obstruction WARNINGS RIsk of GI PERFORATION (rare reports; monitor for severe ab symptoms), risk of opioid withdrawal (evaluate risk vs benefit nad monitor) use >4 months has not been studied, DC if opioid is DCed or if severe/persistent diarrhea SEs Ab pain, flaturlence, N/D NOTES Stay close to toilet after injecting DC all laxative prior to use Only for patients on opioids who have FAILED OTC LAXATIVES Do not use routinely; can often increase laxative to obtain effect

Tapentadol (Nucynta, Nucynta ER) CII DOSE IR: 50-100mg Q4-6H ER: 50-250mg BID CrCl<30mL/min: Use not recommended (not studied)

CI Use of MAOis together with or within 14 days WARNINGS Can increase SEIZURE RISK (avoid in patients with siezure history or seizure risk), risk of SEROTONIN SYNDROME when used with other serotonergic drugs SEs Dizziness, somnolence, nausea but lower severity of GI SEs than stronger opioids

TIZANIDINE (ZANAFLEX) DOSE 2-4 MG Q6-8H PRN (MAX 36MG/DAY)

CI Use with strong CYP1A2 inhibitors (e.g. fluvoxamine, ciprofloxacin) SEs HYPOTENSION, DRY MOUTH, WEAKNESS, QT prolongation NOTES CENTRALLY ACTING ALPHA 2 AGONIST

Naldemedince (Symproic) DOSE OIC with chronic non cancer pain: 0.2 mg daily

CI GI obstruction WARNINGs RIsk of GI PERFORATION (rare reports; monitor for severe ab symptoms), risk fo opioidf withdrawal (evalaute risk vs. benefitr and monitor SEs Ab pain, diarrhea, nausea

NALOXEGOL (Movatink) DOSE OIC with chornic non cancer pain: 25mf once daily in the morning on empty stomach CrCl <60 ml/min: 12.5 mg once daily

CIs Gi obstsruction, use wit strong CYP3A4 inhibitors WARNINGs RIsk of GI PERFORATION (rare reports; monitor for severe ab symptoms), risk of opioid withdrawal (evlauete risk vs. benefit and monitor SES Ab pain, diarrehea, HA, flatulence NOTES DC al llaxative prior to use; can reintroduce laxatives if suboptikmal response after 3 days Do not use wit strong CYP3A4 inhibitors. Avoid use or reduce dose to 12.5mg daily with moderate CYP3A4 inhibitors. Do not use with grapefruit juice

INCREASED COX 2 SELECTIVITY: LOWER RISK FOR G ICOMPLICATIONS (BUT STILL PRESENT), INCREASE RISK OF MI/STROKE (AVOID WITH CV RISK, AVOID INCREASING DOSES AND LOGNER DURATION IN PATIENTS AT RISK FOR CV DISEASE), SAME RISK FOR RENAL COMPLICATIONS CELECOXIB (CELEBREX) +amlodipine (Consensi) - for treatment of OA pain and HTN DOSE OA: 100mg BID or 200mg daily RA: 100-200mg BID Inidcaitons: OA, RA, juvenile RA, acutre pain, primairy dysmenorrhea, ankylosing spondylitis

CIs SULFONAMIDE ALLERGY NOTES HIGHEST COX2 SELECTIVITY Avoid in prgnancy; risj greatest at _>30 weeks gestation\ Severe skin reactions, including SJS/TEN

Exception: Fentanyl Patches

CONVERTIN TO A FENTANYL PATCH is most commonly done using a DOSING TALE PROVIDED in th e package insert (se table and example) If converting to fentanyl using the previous chart, remember that yo are finding the total daily dose in mg, and will then need to convert it to mcg (multiply by 1,000) and the ndivided by 24 to get the patch dose; the fentanyl patch is dosed in mcg Per hour (no oral dose conversion is listed on the conversio chart because fentnaly is not absorebed orally Some clinicians use this estimation (morphine 60mg TDD = 25mcg/hr fentanyl patch These methods can provide different answers: FOR THE EXAM FOLLOW THE SPECIFIC INSTRUCTIONS GIVEN WHERN CONVERTING TO OR FROM FENTANYL PATCHES

Steps To Convert

Calculate total 24 hr dose requirement of the currenet drug Use ratio conversion to calculate the dose of the new drug Refer t oCalc I chapter for a review of how to st up and perform ratio conversio ncalcs Calcualte 24 hr dose of new drug and reduce dose at elst 25% (IF THE PROBLEM ON THE EXAM DOES NOT SPECIFY TO REDUCE IT, JUST TO FIND THE EQUIVALENT DOSE, THEN DO NOT REDUCE IT Divide to attain approrpiate interval and dose for new drug Always have medication avialble for BTP while making changes. Guideline recommendaation for BTP dosing ranges from 5-17% of the total daily baseline opioid dose RATIO TABLE

APAP DIs

Can be used with warfarin, but if used chronically (doses >2g/day), APAP can increase the INR Avoid or limit use due to tothe risk of hepatotoxicty

Centrally Acting ANalgesic DIs

Caution with other agents that LOWER SEIURE THRESHOLD CAUTION WITH OTHER SEROTNGERGIC DRUGS AVOID tramadol wiuth CYP2D6 INHIBITORS Possibility of increased IN with warfarin; monitor

Opioid DIs

Caution with ue together with other CNS depressants: aditive somnolence, dizziness, confusion, increased risk of respiratory depression These include alcohol, hypnotics, BENZOS and muscle relaxants AVOID ALCOHOL WITH ALL OPIOIDS, especially ER formulations INCREASED RISK OF HYPOXEMIA with underlying resp disease (e.g. COPD) AND SLEEP APNEA iHYDROCODONE, FENTANYL, METHADONE, AND OXYCODONE are CYP3A4 SUBSTRARTES. Avoid use with CYP3A4 inhibitors

CHLORIDE CHANNEL ACTIVATOR

- APPROVED FOR OTHER INDICATIONS IN ADDITION TO OIC

SEs of AL NSAIDS

- NSAIDS can decrease renal clearance by reducing blood flow to the glomerulus; additional nephrotoxic agents or dehydration increases the risk All NSAIDs should be USED CAUTIOUSLY (OR AVOIDED) in RENAL FAILURE - NSAIDS can INCREASE BLOOD PRESSURE. Use cautiously in patients with controlled HNT, and AVOID IN patinets with UNCONTROLLED HTN - NSADS can cause PREMATURE CLOSURE OF THE DUCTUS ARTERIOSUS, which can lead to HF in the baby DO NOT USE NSAIDS i nthe THIRD TRIMESTER OF pregnancy (_>30 weeks) -All NSAIDs can cause nausea. Salicylates cause worse nausea compared to other NSAIDs Nausea can be minimized by TAKING WITH FOOD, switching to an enteric coated or buffered product or changing to a different NSAID

Safety Concerns

A RISK EVUALTION NAD MITIGATION STRATEGY (REMS) eixsts for ALL OPIOID MEDS Primary components of the REMS include prescriber education and counseling requirements OPioid medication have several boxed warnings Elderly, debilitated, cachectic patients and patients with chronic pulmonary disease (conditions associated with hypoxia) or head injury/increased intracranial presure should be monitored closely All are at increased risk of respirtoay depression In addition, opioids have a risk of hypotention

OPIOID BOXED WARINGS

ADDICTION, ABUSE AND MISSUE CAN LEAD T OOVERDOSE AND DEATH RESP DEPRESSION, WHICH CAN BE FATAL USE OF ANY OPIOID WITH BENZOS OR OTHER CNS DEPRESSANTS, INCLUDING ALCOHOL, CNA INCREASE THE RISK OF DEATH KADIAN, EMBEDA, ZOHYDRO, AND NYCNTA ER: DO NOT CONSUME ALCOHOL WITH THIS MEDICATION, CAN CAUSE POTNETIALLY FATAL OVERDOSE ACCODENTAL INGESTION/EXPOSURE OF EVEN ONE DOSE IN CHILDREN CAN BE FATAL. NEVER GIVE THIS MEDICATION TO ANYONE ELSE (INCLUDES PATCHES) CRUSHING, DISSOLVING OR CHEWING OF THE LONG ACTING PRODUCTS CAN CAUSE THE DELIVERY OF A POTENTIALL FATAL DOSE LIFE THREATENING NEONATAL OPIOID WITHDRAWAL WITH PROLONGED USE DURING PREGNANCY

OPIOID INDUCED CONSTIPATION (OIC0

ALL OPIOIDS CAUS CONSTIPATION, REFERRED TO AS OCI OPIOIDS REDUCE GI TRACT PERSTALSIS, MAKING IT DIFFICUTL TO PASS A BOWERL MOVEMENT UNLINKE CNS DEPRESION, OIC DOES NOT IMRPOVE OVER TIME WITHOUT REATMET, IT MUST VE ANTICIPATED AND TREATED WHEN OPIOIDS ARE DOSED AROUND THE CLOCK, SUCH AS WITH AN IR OPIOID, PROPHYLAXIS FOR CONSTIPATIONS IS REQURED STIMULANT LAXATIVES, INCLUDING SENNA, ARE THE TYPICAL FIRST LIEN LAXATIVE, WITH OR WITHOUT A STOOL SOFTENER. THE STIMLANT LAXATIVE BISACODYL COMES AS A TABLET (FOR PROPHYLAXIS) OR SUPPOSITRY (FOR TREATMENT) IF LAXXATIVES ARE NOT SUFFICIENT, SPECIFIC MEDICATIONS FOR OIC THAT COUTNERACT THE EFFECTS OF THE OPIOID RECEPTOR IN THE FUT (PAMORAS) CA BE USED LUBIPROSTONE WHICH IS USEDF FOR DIFFERENT TYPE OF CONSTIPATION COULD BE CONSIDERED FOLLOWING TRIAL OF LAXATIVES FOR PAMORAS

OPIOID INDUCED RESP DEPRESSION (OIRD) RISKS

AN OPOID PRESCRIPTION REQUIRES A RISK/BENEFIT ASSESSMENT NAD MONITORING A PRESCRIPTION FOR NALXOONE SHOUDL BE OFFERRED TO PATIENTS WITH ELEVATED RISK FACTORS FOR OIRD RISK FACTORS INCLUDE - HISTORY OF PREVIOUS OVERDOSE - SUBSSTANCE ABUSE - USING LARGE DOSES (_>50MORPHINE MILIGRAM EQUIVALENT DOSE) USING WITH BENZOS COMORBID ILLNESS SUCH AS RESPIRATORY AND PSYCHIATRIC DISEASE

Other less commonly used NSIDs include:

MEclofenamate Mefanamic acid (Ponstel) Ketoprofen Fenoprofen (Nalfon) Flurbiprofen (Ansaid) Oxaprozin (Daypro - caution similar to piroxicam - higher risk of SEs)

Non-opioid Analgesics

MILD PAIN (!-3) NON-OPIOID +/- ADJUVANT MODERATE (6-4) OPIOID FOR MILD-MODERATE PAIN +/- NON-OPIOID +/- ADJUVANT SEVERE PAIN (7-10) OPIOID FOR MODERATE-SEVERE PAIN +/- NON-OPIOID +/- ADJUVANT

Methadone Conversion: Not Straight FOrward; Shod be done by Pain Specialists

Morphine to methadone conversion ranges from 3:1 = 20:1; this is HIGHLY VARIABLE due to patient tolerarance and duration of therapy The HALF LIFE of methadone varies widely There are SEPARATE CONVERSIO CHARST FOR PAIN SPECIALISTS to estimate methadone dosing Shoudl be only done by specialistst with experience Merhadone is used for both the treatment of opioid addicitn and for chornic pain WHen used for chornic pai nsyndromes, it is administered 2-3 times per day after the proper dose is determined by titration It should be started at verly low doses of no more than 2.5mg PO BID or TID and escalated slowly

PAIN SCALE

NO HURT = 0 HURTS A LITTLE BIT = 2 HUTTS LITLE MORE =4 HURTS EVEN MORE = 6 HURTS WHOLE LOT = 8 HURTS WORST = 10

Oxymorphone (opana) CII DOSE IR (opioid naive) 5-10 mg Q-46 H PRN

NOTES Do not use with moderate to severe liver impairment Use lower doses in elderly, renal or mild liver impairment; there will be higher drug concentrations in these patients Take on EMPTY STOMACH

INDOMETHACIN (INDOCIN, Tivorbex DOSE IR: 25-50 mg BID-TID CR: 75mg daily-BID Tivorbex: 20mg TID or 40mg BID-TID

NOTES High risk for CNS SEs (avoid in psych conditions) The IR formulation is an older NSAID approved for gout Tivorbex is micronized for faster dissolution IV injection is indicated for closure of PDA in premature infants

Piroxicam (Feldene) DOSE 10-20mg daily

NOTES High risk for GI toxicity and severe ski nreactions, including SJS/TEN USed when other NSAIDs have failed; may need agent to protect gut (PPI, Misoprostol)

Non-Aspirin NSAIDs COX-1 and COX2 NON SELECTIVE NSAIDs: All agents have GI RISK, CV RISK and RISK in post operative CABG setting IBUPROFEN (aDVIL, CALDOLOR, MOTRIN. Neoprofen) DOSE ADULT OTC: 200-400 MG Q4-6H MAX 1.2 gm/day RX: 400-800mg Q6-8H Max: 3.2 gm/day PEDIATRIC 5-10MG/KG/DOSE Q6-8H (as an antipyretic) Max: 40mg/kg/day

NOTES Neoprofen inj is indicated for closure of PDA in premature infants OTC: limit self treatmet to _<10 days Severe skin reactions, including SJS/TEN

METHYLSALICYLATE topical OTCs (BENGAY, ICY HOT, SALON PAS Methylsalicylate plus other ingredients TROLAMINE (ASPERCREME)

NOTES OCcasionally, topicals have caused first to third degree burns, mostly in patientswith neurophatc damage: DC use and seek medical attention if signs of skin injury (pain, swlling or blisterintg) occur following aplication

Carbamazepine (Tegetrol Cabatrol) DOSE Initial: 100mg BID Max 1,200 mg/day

NOTES ONLY FDA APPROVED MEDICATION FOR THE TREATMENT OF TRIGEMINAL NEURALGIA See Seizures/Epilepsy Chapter

Antispasmodics (msucle relaxants) that exert their effects by sedation CARISOPRODOL (SOMA) CIV DOSE: 250-350mg QID PRN

NOTES POOR CYP2C19 METABOLIZERS wil have INCREASE CARIUSOPRODOL COCNETRATIONS (UP TO 4-FOLD_ rAPID cyp2c19 METBOLIZERS WIL LCONVERT TO THE ACTIVE METABOLITE MEPROBAMATE (INCREASE TOXICITY/SEDATION)

NAPROXEN (OTC: ALEVE, RX: Naprelan, Naprosn +sumatriptan (Treximet) + ESOMEPRAZOLE (VIMOVO) And in OTC combos witrh diphenhydramine and PSE DOSE Pain,Fever: 200mg (220mg naproxen Na) Q8-12 hours (1st dose can take 2 tabs) Max: 3 tabs in 24 hours RX Inflammatiom, mild-mod pain: 500mg Q12H (or 250mg Q6-8H) Max: 1,000mg/day (1,250mg day 1)

NOTES PRescribers and patients sometimes prefer naproxen since it can be doses BID Naproxen base 200mg = Naproxen Na 200mg PPI in Vimovo is used to prortect GI tract

AMITRYPTILINE DOE 10-50 MG QHS, sometimes higher Desipramine (Norpramin) DOSE IOnitial 25 mg daily Max 150 a day DULOETEING (CYMBALTA) 30-60mg/dat

NOTES See depressio nchapter Desipramine Tirate ever 3-7 days

Sulindac DOSE 150-200mg BID

NOTES Sometimes used with reduced renal functio, and in patients on lithium who requrie and NSAID

MELOXICAM (MOBIC, Vivlodex) DOSE Mobic: 7.-15 mg once daily Vivlodex: 5-10mg once daily Etodolac (Lodine) DOSE 300-500mg Q6-8H NABUMETONE (Relafen) DOSE 1,000-2,000mg daily (can be divided BID)

NOTES These agents have SOME COX 2 SELECTIVITY Vivlodex caps and other meloxicam formulations are not interchangeable

Treatment of Opioid Abuse NALOXONE (NARCAN, Evzio, SOS Nalxoione DOSING IV/IM/SC: 0.4-2mg Q2-3 min or IV infusio nat 0.4mg/hr IM: Give in thigh through clothing, hold for 5 seconds, then call 911 Nasal Spray: 1 spray (4mg) cna repeat REPEAT DOSING CAN VBE RQUIRED (opioid cna last longer than blocking agent)

NOTES Will cause ACUTE WITHDRAWAL (PAIN, anxiety, tachypnea) in patients who are physically dependent DUe to low bioavialbility, cna be given orally to prevent opioid induced constipation (off label)

OPIOIDS AND CHRONIC NON CANCER PAIN

OPIOIDS AR NOT FIRST LINE for chornic pain treatment and sohuld not be used routinely IN SOME CASES, THEY HAVE BENEFIT WHEN USED, FOLLOW SAFE USE RECOMMENDATIONS: - ESTABLISH MEASURE GOALS FOR PAIN AND FUNCTION. REACHING LOW PAIN RATHER THAN NO PAIN MAY E REASONABLE - IF USING OPIOIDS, START WITH IMMEDITE RELEASE. START LOW AND GO SLOW EVLAUATE RISK FACTORS FOR OPIOID REALTED HARM PHARMACSITS SHOULD CHECK THEIR STATES PRESCRIPTION DRG MONITORING PROGRAM (PDPM) DATABASE. LOOK FOR HIGH DOSAGES AND MULTIPLE PRESCRIBERS - USE URINE DRUG TESTING, AND WATCH FOR FALSE POSITIVE AND NEGATIVES - USE ADJUNCTIVE MEDS T OENABLE A LOWER OPIOID DOSE -AVOID BENZO AND OPIOIDS GIVEN TOGETHER, EXCEPT IN RARE CASES. THIS QUADRUPLES THE RISK OF OVERDOSE DEATH FOLOW UP, TAPER THE DOS,E CONSIDER DCING

Side Effects and Management

Opiod side effects, EXCEPT FOR CONSTIPATION IF a patient has a problem that persists or is bother some, such as pruritus, swithcing to another opioid is reasoable Hydroxyzine and diphenhydramine can be used for pruritus Postoperative nausea and votmint (PONV) ocurss in surgical patients due to primairly to the use of anesthesia and opiods PONV is treated in the hospital with a 5HT3 receptor antagonist, such as ondanstron, or phenothiazine, such a prochlorperazine AL LORAL OPIOIDS shoudl be TAEKN WITH FOOD TO LESSE NNAUSEA Sedative adn cogntoive effects occur when the opioid is started or the dose is increased and generally lsessen over time Pharmacists should advise patients not to drive or do anything potentially hazardous until they are accustomed to the edmication The use of other CNS depressants sohuld e mimized Alcohol should not be used with opioids

Opioid Analgesics

Opiods drugs interact in a variety of ways with the three primary types of opioid receptors: u (mu), k (kappa) and g (delta) Opioids are MU RECPTOR AGONISTS in the CNS, which primay produce PAIN RELIEF, but alos cause EUPHORIA and RESPIRATORY DEPRESSION These agents are primarily used to treat mderate to severe acute pain and chornic pain

Treatment of OIC

PERIPHERALLY ACTING MU OPIOID RECEPTOR ANTAGONISTS (PAMORAS) - BLOCK OPIOID RECEPTORS IN THGUT TO REDUCE CONSTIPATION WITHOUT AFFECTING ANALGESIA. PAMORAS ARE INDICATED FOR OIC AND ARE ONLY EFFECTIVE WHEN CONSTIPATION IS SECONDARY TO USE OF AN OPIOID

EXAMPLE

PG 806 WHenever possible, use an IR versio nof the long acting opiod for BTP Typically 10-15% of the total daily dose is administered Q1-2H for BTP (~5% administered Q4H in the elderly) EX: A rescue dose of 15mg IR morphine Q1-2 H could be used with morphine ER 60mg BID in te example and this would adhere to the hospice policy stated in the question Other agents commonly used for BTP include combo agents, such as hydrocodone/acetamophen IN an impatient setting, injectiosn can be given

Selecting an analgesic Regimen

Pain can be treated using a stepwise approach, where the choice of drug depends on the patinet's self-reported pain severity When initially using any class of analgesic (including opioids), start low and stop at the lowest dose that adequately reduces the pain Using medicines with multiple mechanisms of action (multimodal pain ocntol) often produces improved pain ocntrol via additive or synergistic effects Non-opioid analgesics (APA, NSAIDs) are most commonly used for mild pain but can be added to an opoid based regimen to reduce the total opioids dose required and provide better pain relief Opiods are, in general, strong analgesics, most appropriate for moderate to severe pain Adjuvants (e.g. antidepressants, antiepileptic drurgs (AEDs), msucel relaxants) should be considered for all severities of pain

Treatment Principles

Pain is subjective Primarily measured by the patinets own description, aliong with obserbvations Patients with chronic pain should be taught to monitor and document their pain by recording the pain level, the type or quality (using words such as burning, shooting, stabbing and aching) and the time of the day that the pain is better or worse Any thing that worsens or lessens the pain should be noted PAIN SCALES are useful to asses pain severity Pain is commonly rated using a numerical scale (0= no pain, 10 = worst pain) or with the visual analog scale for pediatric patinets HOspitals must inquire about, assess, treat and reassess pain in a timely maner using non-pharmacologic and/or pharmacologic treatments

Example of Conversio nto Fentanyl Patch using Conversio nTable

Pg 807

APAP

REDUCES PAIN AN DFEVER (IS AN ANTIPYRETIC) but does NOT provide an ANTI INFLAMMATORY effect The mechanism of action is not well defined but is thought to invovle INHIBITION OF PG SYNTHESIS in the central nervous system (CNS), resulting in reduced pain impulse generation

^Antispasmodic

Rarely used muscle relaxants include DANTROLENE (DANTRIUM USED FOR MALIGNANT HYPERTHERMIA, chlorzoxazone (Lorzone) and prhenadrine (Norflex)

OPIOID OVERDOSE MANAGEMENT

S/SX OF OVERDOSE EXTREME SLEEPINESS SLOW OR SHALLWO BREATHING FINGERNAILS OR LIPS TURNING BLUE OR UPURPLE EXTREMLEY SMAL LPINPOINT PUPULS SLOW HEARTBEAT AND OR BLOOD PRESSURE IF OVERDOSE IS SUSPECTED, CALL 911 AND GIVE NALOXONE IF INDIVUDUAL IS NOT BREATHING OR STRUGGLING TO BREATHE, LIFE SUPPORT MEASURES SHOULD BE PERFORMED IF THERE IS A QUESTION ABOUT WHETHER TO GIVE NALOXONE, GIVIE IT, BECUASE FATALITY COULD RESULT FROM NOT GIVINT IT OPIOID LASTS LONGER THAN NALOXONE SO MONITOR CLOSELY FOR RESP DEPRESSION NAD PROVIDE REPEAT DOSES AS NEEDED NALOXONE IS AVIALABLE IN THREE OPTIONS: - EVZIO (AUTO INJECTOR); EASY TO ADMINISTER WITH VISUAL AND VOICE INSTRUCTIONS, EACH AUTO INEJKCTOR PROVIDES 1 DOSE - NARCAN (NASAL SPRAY); ONSET OF ACITON IS SLOWER THAN INJECTION, A SINGLE USE NASAL SPRAY IS 4MG ADMINSTERTED IN 1 NOSTRIL, REPEAT DOSES IN ALTERNATIG NOSTRILS MAY BE NEEDED - NALOXONE (INJECTIO); GENERIC FOMRULATION PROVIDED IN MULTIPLE SIZE VIALS, SEPERATE SYRINGE WIL LBE NEEDED, MAY NEED TO REPAT DOSES EVERY 2-3 MINS UNTIL EMERGENCY MEDICAL ASSITSANCE ARRIVES

Lubriprostone (Amitiza) OIC: 24MCG BID

SEE constipation and Diarrhea chatper

CYCLOBENZARBRINE (AMRIX ER, FEXMID, FLEXERIL) DOSE IR: 5-10mg TID PRN ER: 15-30mg once daily

SEs DRY MOUTH NOTES Can have efficacy with fibromylagia SEROTONERGIC: do not combine with other serotonergic agents Can precipitate or exacerbate cardiac arrhythmias; caution in elderly or those with heart disease (similar to TCAs chemcially a tricyclic almost identical to amitriptyline)

Topical Adjuvants LIDOCAINE 5% PATCHES (LIDODERM) - RX LIDOCAINE VISOVOUS GEL- RX Lidocaine 1.8% patch (ZTlido Rx for PHN) Lidocaine 4% and lower (LidoPatch - OTC) DOSING Lidoderm: APPLY TO PAINFUL AREA 1-3 PATCHES/DAY AND WORN FOR UP TO 12 HRS A DAY APPROVED FOR PHN (SHINGLES) PAIN

SEs Minor topical burning pruritus, rash NTOES CAN CIT into smaller pieces (before removing backing) LIDODERM: DO NOT APPLY MORE THAN 3 PATCHES AT ONE TIME Caution with use dpathces; can harm children and pets; fold patch in half and discard safely Do not cover with heating pads/ electric blankets

CAPSAICIN 0.025% AND 0.075% (ZOSTRIX, ZOSTRIX HP) - OTC 8% patch (Qutenza) - Rx Apply to affcted area TID-QId

SEs Topical burning, which dissipates with continued use NOTES Qtenza is given in the healthcare providers office only 0 it causes topical burning and erquires pre treatment with lidocaine - applied for 1 hour and lasts for months - works in ~40% of patinets to reduce pain, indicated for PHN pain Decrease TRPV1-expressing nociceptive nerve endings (decrease substance P) Onset of pain releif takes 2-4 weeks of continuos application for OTC products and 1 week for Qutenza (Rx)

Alelrgy

Symptoms of an opioid allergy (rare, but dangerous if present) incldue difficulty breathing, severe drop in BP, serious rash, swelling of face, lips, tongue and larynx) in a TRUE OPIOID ALLERGY, use an agent in a DIFFERENT CHEMICAL CLASS Tramadol package labeluign warns of increased risk of reactions totramadol i nthose with previous anphylactic reactios to opioids Tapentadol does not have this warning in the US, though tramadol and tapentadol are structurally similar if allergic to tramadol, an allergy to tapentadol is likey and vise vesa

ACETAMINOPHEN OVERDOSE

THE ANTIDOTE FOR ACETAMINOPHEN OVERDOSAGE IS N-ACETYLCYSTEINE (NAC, MUCOMYST, CETYLEV, ACETADOTE) - RESTORES INTRACELLULAR GLUTATHIONE -AIVALBLE IN BOTH ORAL AND IV FORMULATIONS THE RUMACK-MATTHEW NOMOGRAM USES THE SERUM ACETAMINOPHEN LEVEL AND THE TIME SINCE INGESTION TO DETERMINE WHETHER HEAPTOTOXICTY IS LIKELY (AND THE NEED FOR NAC)

OPIOID ALLERGY

THE COMMON DRUGS IN THE SAME CHEMCIAL CLASS THAT CROSS REACT WITH EACH OTHER HAVE COD OR MORPH IN THE NAME BUPRENORPH INSTEAD OF MORPH CODEINE HYDROCODONE OXYCODONE MORPHINE HYDROMORPHI=ONE OXYMORPHONE BUPRENORPHINE HEROIN (DIACETYL-MORPHINE) WHAT TO DO IF A MORPHINE-TYPE ALLERGY IS REPORTED: IN PRACTICE MAKE SURE IT IS AN ACTUALY ALLERGY, AND NOT NAUSE OR ITHIGN IF IT SEEMDS TO BE ACCURATE, CHOSOE A DRUG IN A DIFFERENT CHECMIAL CLASS, SUCH AS MEHTHADONE OR FENTANYL MEPERIDINE IS ALSO IN A DIFFERENT CLASS, BUT NO LONGER RECOMMENDED AS AN ANALGESIC

Non-Steroidal Anti Inflammatory Drugs

The COX 1 and 2 enzymes catalyze the conversion of arachidonic acid to PGs and thromboxane A2 (TxA2) All NSAIDs decrease the formation of PGs whcih results in decreased inflammation, alleviation of pain and reduced fever NON SELECTIVE NSAIDS BLOCK the synthesis of BOTH COX ENZYMES COX 2 SELECTIVE NSAIDs BLOCK the synthesis of COX2 ONLY, which DECREASES GI RISK because COX 1 protects the gastric mucosa Blocking COX 1 decreases the formation of TxA2, which is required for both platelet actiation and aggregation ASPIRIN is an IRREVERSIBLE COX 1 INHBITOR and is an EEFFECTIVE ANTIPLATELET AGENT that provides CV beefit, often referred to as cardioprotection

Opioid Abuse

The US govt created five strats to prevent overdose deathL 1. Educate providers and general public about how to prevent and manage opioid overdose 2. Ensure access to treatment for patients addicted to opioids 3. Ensure ready access to naloxone 4. Encourage the public to cal l911 5. Encourage prescribers to sue state Prescrioption Drug Monitroing Programs (PDMPs) SOME OPIOID COMBO PRODUCTS such as SUBOXONE, Troxyca ER, or EMBEDA are fomrulated WITH AN ABUSE DETERRED medication such as NALOXONE OR NALTREXONE, hwile other su ch as OXYCONTIN, HYSINGLA ER OR Arymo ER are manufactured using SPECIFIC TECHNOLOGY designed to DETER CURSHING, DISSOLVING or other modiccations

Dosing Conversions

The correct dose is the lowest dose that provides effective pain relief If the medicine is effective but runs otu too fast, do not increase the dose This can cause resp depression Rather give the same dose more frequently If the md is not effective, consider increaseing the dose It is appropriate to consider switching to a different agent if 1. The dose has been increased or the interval shortened and the pain relief is not adequate The SEs are intolerable (patients react differently to different opioids) The drug is is unaffordable or not included on formulary Chanign formulations from IV to PO For opioids conversions (not methadone) you can use conversion (see table) When converting one opioid to another, rond down (do nto round up) and use breakthrogh doses for compensation A patient can respond better to one agent than anothe (likely due to to leess tolerance) and ROUNDING the dose DOWN WILL REDUCE THE RISK OF OVEDOSE

Pathophysiology

Two main categories of pain (nociceptive pain and pathophysiologic pain) based on the underlying cause of the pain NOCICEPTIVE PAIN occurs when sensory nerves (nociceptors) identify tissue damage. --- Injured tissue releases substances (such as PGs, substance P, histamine) which stimulate the nociceptors to send impulses to the brain that result in feeling pain Nociceptive pain results from injury to internal organs (visceral pain) or from an injury to the skin, muscles, bones, joints, or ligaments (somatic pain, which is commonly referred to as musculoskeletal pain) Pathophysilogic pain is different fro mnociceptirve pain as it does not result from tissue injury or damage, but from damage or malfunction of the nervous system This is commonly referered to as NEUROPATHIC PAIN Various pain syndromes are considered pathophysiologic pain, such as FIBROMYALGIA, DIABETIC NEUROPATHY, chronic headaches, drug-induced toxicities (E.g. Vinca alkaloids) and others

Buprenoprhine DIs

Use caution with CNS depresants Use cautiosly in patients taking other QT prolomging drgs or with aryhthmia risk

MEPEREDINE (DEMEROL) CII DOSING ORAL/IM: 50-150mg Q3-4H

WARNING RENAL IMPAIRMENT/ELDERLY AT RISK FOR CNS TOXICITY, avoid with or within 2 weeks of MAO inhibitor SEs Lightheadedness, dizziness, somnolence, N/V, sweating NOTES NO LONGER RECOMMENDED AS AN ANALGESIC (Especially in elderly and renally impaired) Avoid for chornic pain and even short term in elderly Acceptable for short term acute or single use (e.g. sutures in ER) and used off-label for post operative rigors (Shivering) SHORT DURATION of action (pain contrlled for ma x3 hrs) NORMEPERIDINE (METABOLITE) IS RENALLY CLEARED and can accumulate and cause CNS toxicity including SEIZURES In combination with other drugs, it is SEROTONERGIC and can increase risk of serotonin snydrome

Oral Adjuvants AEDs GAPENTIN (NEURONTIN, Fanatrex compounding kit Gralise - For PHN HORIZANT (ER) FOR PHN AND RESTLESS LEGS SYNDROME DOSE Initial: 300mg TID Max: 3,600 mg/day CrCl< 60ml/min: decrease dose and/or extend interval

WARNINGS Angioedema, anaphgylaxis, multiorgna hypersenstivity (DRESS) reactions, suicidal thoughts or behaior (all AEDs), increase seizure frequency if rapidly DCed in those with seizures, CNS effects SEs SOMNOLENCE, ATAXIA, PERIPHERAL EDEMA, WEIGHT GAIN, dizziness, diplopia, blurred vision NOTES Used most commonly off label for fibromyalgia, pain (neuorppathic), HA, drug abuse, alcohol withdrawal Take ER formulatio nwith food IR, ER and gabapentin enacarbil are not interchangeable

PREGABALIN (LYRICA) CV Initial: 75mg BID or 50mg TID Max 450 mg/day CrCl< 60mL/min: decrease dose and or extend interval

WARNINGS Angioedema, hypersenstivity reactions, risks of suicidal thougts or behavior (all AEDs), increase seizure frequency if rapidly DCed in those with seizures; can pause peripheral edema, dizziness and somnolence SES SOMNOLENCE, MILD EUPHORIA, peripheral edema, weight gain, ataxia, diplopia, blurred vision, dry motuh, dizziness NOTES APPROVED FOR use in FIBROMYLGIA, PHN AND NEUROPATHIC PAIN associated with diabetes and spinal cord injury

Lofexidine (Lucemra) DOSE Initial: 0.54mg QID in 5-6 hour intervals Max duration of treatment o14 days

WARNINGS Risk of hypotension, bradycardia and syncope, QT prplongation, increase CNS depression increase risk of opioid overdose after DCing, risk of DC smyptoms; must taper when DCing over 2 to 4 days SEs Orthostatic hypotension, dizziness and dry mouth NOTES Can reduce effucacy of oral naltrexone Paroxetine and other CYP2D6 inhibitors cna increase risk of orthostatic hypotension and braycardia, monitor closely

TRAMADOL (ULTRAM, ULTRAM ER, ConZip CIV +acetaminohen (Ultracet) DOSE IR: 50-100mg Q4-6H, max 400mg/day ER: 100mg once daily, max 300mg/day CrCl<30 mlmin: IR: decrease dose ER: do not use

WARNINGS SEIZURE RISK (avoid in patients with seizure history, head trauma), risk of SEROTONIN SYNDROME when used alone or with other serotonergic drugs or INHIBITORS OF CYP2D6 OR 3A4, CNS depression, respiratory depression (rarte), avoid in patients who are suicidal; misuse, abuse and diversion (similar to opioids); risk of serious breathing problems in adolescents age 12-18 years with obesity, sleep apne or lung disease; breastfeeding mothers should avoid due to increase risk of serious breathing problem in breastfed infants CI Use of tramadol in HICLDREN <12 YEARS OF AGE; USE IN CHILDREN < 18 YEARS OF age following tonsilletcomy/adenoictemoy surgery SEs Dizziness, nausea, constipation, loss of appetite, flushing, dry mouth, dyspepsia, pruritus, insomnia (some patinets find tramadol sedating but for most it is not), possible HA, ataxia Lower severity of GI side effects versus strong opioids NOTES Tramadol REQUIRES CONVERSION t oactive metabolite BY CYP2D6. Use with CYP2D6 INHIBITORS CNA HAVE VARIABLE EFFECTS due to mixed mechanism of actio of tramadol

Saliclate NSAIDs ASPIRIN/ACETYLSALICLYIC ACID (ASCRIPTIN, BUFFERIN, ECOTRIN ASCRIPTIN, BUFFERIN, ECOTRIN: EC/ BUFFERED Durlaza (Rx): ER caps Bayer "Advanced" Aspirin: dissolves slightly faster + APAP/CAFFEINE (EXCEDRIN, EXCEDRIN MIGRAINE, Goodys Powder) + antacid (Alka seltzer) +caffeine (BC powder, Stanback) +Calcium (Bayer Women's low dose) +Omeprazole (Yosprala) And in multiple OTC combos DOSING CARDIOPROTECTION DOSING: 81-162 MG ONCE DAILY Durlaza (Rx) 162.5mg once daily Analgeisc dosing: 325-650mg Q4-6H Goody's Powder: 520mg per packet BC: 845-1000mg per packet Standback: 845 mg per packet NON ACETYLATED SALICYLATES Salsalate DOSE Up to 3 g/day, divided BID-TID MAGNESIUM SALICYLATE (DOANS, DOANS ES DOSE 580MG ES TAB: 2 TABS Q6H MAX: 8 TABLETS/DAY Choline Magnesium Trisalicylate DOSE 1 gram BID-TID or 3 g QHS Diflunisal DOSE 500mg BID-TID. Max 1.5g daily Salicylate salts: No longer commonly used

WARNINGs Avoid with NSAID hypersensitivity (past reaction with trouble breathing), nasal polyps, asthma AVOID ASPIRIN in CHILDREN and TEENS with any VIRAL INFECTION due to potential risk of REYES SYNDROME (symptoms include somnolence, NV, lethargy, confusion) Other NSAIDs can be used in pediatrics Severe skin rash (rare) including SJS/TEN; stop drug, seek immediate medical help Increases the risk of bleeding Avoid in the third trimester of pregnancy due to fetal harm GI ulceration and bleeding can occur SEs DYSPEPSIA, HEARTBURN, BLEEDING, nausea, renal impairmenet, increase blood pressure, CNS effects (fatigue, confiusion, dizziness; caution in the elderly), photosensitivty, fluid retention/edema, hyperkalemia (in renal impairment or with potassium retaining agents), lburred vision NOTES TO decrease nausea, use EC or buffered product or take with food PPIs may be USED TO PROECT THE GUT with chronic NSAID use; CONSIDER THE RISKS FROM CHORNIC PPI USE (DECREASE BONE DENSITY, INCREASE INFECTION RISK) Do not use Durlaza or Yosprala when immediate effect is needed (e.g. myocardial infarction) Saliclyate OVERDOSE can cause TINNITUS METHYL SALICYLATE is a popular OTC topical found in BENGAY, ICY HOT, Flexal, Thera-Gesic, SALONPAS. See topical agents

mETAXOLONE (sKELAXIN) dose 800MG tid-qid prn

seS EPATOTOXIC

methocarbamol (robaxin, rOBAXIN-750) dose 1,500-2,000 MG qid prn

seS hYPOTENSION