opioid pharmacology

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Terminology Opioids : refers broadly to all compounds that work at the opioid receptors Narcotics : derived from the Greek word for stupor. Once used to describe medications for sleep Then used for opioids Now a legal term for drugs that are abused

Opioid Receptors:

Opioid Receptors Receptors are located on the brain, spinal cord, gut, peripheral nerves, and peripheral tissues Mu (mu 1 and mu 2 ) Mediates the analgesic effects and most of the side effects of MSO4 Miosis, bradycardia, respiratory depression, constipation, histamine release Strong naloxone sensitivity Kappa (K 1 and K 2 and K 3 ) Sedation Intermediate naloxone sensitivity Sigma Mydriasis, delirium, dysphoria ? No naloxone sensitivity

Opioid Receptors:

Opioid Receptors RECEPTOR PROPOSED LOCATION PROPOSED EVENTS Mu 1 Supraspinal, peripheral analgesia, spinal cord, substantia gelatinosa, periductal gray, locus ceruleus Analgesia Mu 2 Spinal trigeminal nucleus, limbic area, reticular activating system, medullar raphe nucleui Sedation, pruritis, prolactin release, vomiting, urinary retention, respiratory depression, euphoria, miosis, dependence, anorexia, decrease GI motility, histamine release Kappa K 1 spinal cord K 2 poorly defined K 3 supraspinal Spinal analgesia, dyspnea, resp depression, miosis, sedation, diuresis (lower ADH release), dependence, endocrine events Delta D 1 spinal, supraspinal D 2 frontal cortex, limbic area, olfactory tubercle, spinal Sigma Psychomimetic effects, dysphoria

Opioid Receptors:

Opioid Receptors


Endorphins Identification of opioid receptors lead to the discovery of “endogenous morphines”  endorphin (31 amino acids)- receptor  endorphin (17 amino acids)- receptor Leu-enkaphalin (5 amino acids)- receptor Met-enkephalin (5 amino acids)- receptor Dynorphin (17 amino acids)- receptor Methorphamide (7 amino acids)-  receptor

Opioid Receptors:

Opioid Receptors Presynaptic (75%)

Opioid Receptors:

Opioid Receptors Postsynaptic (25%)

Receptor Affinity:

Receptor Affinity

Classification of Opioids:

Classification of Opioids Full Agonists - bind opioid receptors MSO4, oxycodone Partial Agonists- bind opioid receptors at a lower level Buprenorphine, etorphine Mixed agonist/antagonists - agonist effect at one receptor and antagonist effect at another receptor Nalbuphine, butorphanol Agonist at the kappa receptor Antagonist at the mu receptor Antagonists - bind to opioid receptors but have no activity naloxone, naltrexone

Odd Case - Tramadol:

Odd Case - Tramadol Works partially at the mu receptor M1 metabolite Works partially at the norepinephrine receptors Additional unknown activity Where does it fit?

Opioid Therapy: Routes of Administration:

Opioid Therapy: Routes of Administration Oral and transdermal—preferred Oral transmucosal—available for fentanyl and used for breakthrough pain Rectal route—limited use Parenteral—SQ and IV preferred and feasible for long-term therapy Intraspinal—intrathecal over epidural generally preferred for long-term use

Chemical Classes of Opioids:

Chemical Classes of Opioids Phenanthrenes Benzomorphans Phenylpiperidines Diphenylheptanes

Chemical Classes of Opioids:

Chemical Classes of Opioids Phenanthrenes Prototype of opioid Not tolerated by some because of 6-OH group Causes nausea and hallucinations * indicates lack of 6-OH (may decrease nausea sensitivity)

Chemical Classes of Opioids:

Chemical Classes of Opioids If a patient can not tolerate a dehydroxylated phenanthrene, don’t give a hydroxylated phenanthrene Example: patients who can not tolerate oxycodone (dehydroxylated) because of nausea, would be expected to have worse nausea with morphine (hydroxylated)

Opioid Metabolism:

Opioid Metabolism Codeine Metabolized to MSO4 via CY2D6 and G6PD Not effective in people lacking 2D6 27% of Caucasians Not effective with 2D6 inhibitors Haloperidol, paroxetine, fluoxetine “Queen mother of emesis” Small doses stimulate CTZ before analgesia Ceiling effect Dihydrocodeine Very similar to codeine

Metabolism of Codeine and Morphine:

Metabolism of Codeine and Morphine

Morphine Metabolism:

Morphine Metabolism Morphine Metabolized to M3G and M6G (normorpine) Accumulates in renal failure and hepatic failure M6G has potential nocioceptive activity Significant polymorphism Potent histamine release


Morphine At a dose of 10mg per 70 kg body weight, gives relief in 70% of patients Available in short and long acting formulations

Metabolism of Hydrocodone:

Metabolism of Hydrocodone Hydrocodone metabolized to hydromorphone (Dilaudid) via CY450 2D6 No wonder hydrocodone is so popular. However, if there is CY2D6 inhibition… We have all heard patients say “nothing works for me except Dilaudid” - Maybe they are right. Highly addictive, the most commonly abused opioid FDA is considering changing hydrocodone to schedule 2

Metabolism of Oxycodone:

Metabolism of Oxycodone Metabolized to oxymorphone via CY450 2D6 ? How much of the analgesia from oxycodone is from oxymorphone Anecdotal reports of decreased efficacy with 2D6 inhibitors

Chemical Classes of Opioids:

Chemical Classes of Opioids Benzomorphans Pentazocine Agonist/antagonist High incidence of dysphoria Poor choice for chronic pain

Chemical Classes of Opioids:

Chemical Classes of Opioids Diphenylheptanes Propoxyphene Available with or without APAP High incidence of liver toxicity Probably not a good long term medication, high incidence of sedation Methadone Long acting NMDA receptor inhibitor Neuropathic pain Cheap

NMDA Receptor:

NMDA Receptor Site of opioid tolerance NMDA antagonists reduce the incidence of tolerance to morphine Dexamathorphan Methadone Ketamine

Chemical Classes of Opioids:

Chemical Classes of Opioids Phenylpiperidines Fentanyl Of all the opioids, has the least histamine mu-activity Least allergenic Meperidine Only has a 2-3 hour duration Metabolized to normeperidine Renally excreted Causes seizures, myoclonus Not reversible by naloxone

Opioid Therapy: Side Effects:

Opioid Therapy: Side Effects Common Constipation Somnolence, mental clouding Less common Nausea – Sweating Myoclonus – Amenorrhea Itching – Sexual dysfunction Urinary retention – Headache

DEA Classification:

DEA Classification Schedule 1 - no legitimate medical use Heroin Schedule 2 (CII) - high risk of abuse Written Rx only, no refills Oxycodone, morphine Schedule 3 (CIII) - intermediate risk of abuse Telephone, up to 6 refills Hydrocodone, codeine Schedule 4 (CIV) - lower risk of abuse Fioricet, Soma

Unscheduled and C IV Opioids:

Unscheduled and C IV Opioids Medication drug APAP Ultram 50 none Ultracet 37.5 325 Fioricet 50 325 Fiorinal 50 none (ASA) Talwin(NX) 50 none Talacen 25 650

C III Opioids:

C III Opioids Medication drug APAP Fioricet #3 50 325 Tylenol #3 30 300 Darvocet-100 100 650


Hydrocodone Medication drug APAP Lortab 7.5 7.5 500 Lorcet Plus 7.5 650 Vicoden ES 7.5 750 Zydone 10 400 Norco 10 325


Vicoden ES = 750mg/tablet Sig: one to two q 4 to 6 hours 2 tablets q 4 hours = 9000mg/day 1 tablet q 6 hours = 3000mg/day Acetaminophen

C II Opioids - Short Acting:

C II Opioids - Short Acting Medication drug APAP Percocet 5 5 325 Tylox 5 500 Percocet 7.5 7.5 500 Percocet 10 10 650/325

CII Opioids - Long Acting:

CII Opioids - Long Acting Sustained release morphine MSContin Kadian Oramorph Avinza Methadone Sustained release oxycodone OxyContin Transdermal fentanyl Duragesic Levorphanol

Opioid dosing:

Opioid dosing Rapid titration but start low (you can always add more) Lowest dose that gives analgesia Balance analgesia with onset of side effects Usually most effective when give round-the -clock Long acting rather than short acting Avoids peaks and valleys

Serum Levels:

Serum Levels

Opioid Therapy: Prescribing Principles:

Opioid Therapy: Prescribing Principles Prescribing principles Drug selection Dosing to optimize effects Treating side effects Managing the poorly responsive patient

Opioid Therapy: Drug Selection:

Opioid Therapy: Drug Selection Immediate-release preparations Used mainly For acute pain For dose finding during initial treatment of chronic pain For “rescue” dosing Can be used for long-term management in select patients

Opioid Therapy: Drug Selection:

Opioid Therapy: Drug Selection Extended-release preparations Preferred because of improved treatment adherence and the likelihood of reduced risk in those with addictive disease Morphine, oxycodone, fentanyl, buprenorphine, methadone Adjust dose q 2–3 d

Opioid Selection: Poor Choices for Chronic Pain :

Opioid Selection: Poor Choices for Chronic Pain Meperidine Poor absorption and toxic metabolite Propoxyphene Poor efficacy and toxic metabolite Mixed agonist-antagonists (pentazocine, butorphanol, nalbuphine, dezocine) Compete with agonists  withdrawal Analgesic ceiling effect Produce psychotomimetic effects


OxyContin® Advantages Well tolerated Easy to convert oxycodone to long acting form Minimal drug interactions Disadvantages Cost Recent stigma Ease of abuse


Methadone Prescribed every 24 hours for prophylaxis of withdrawal Prescribed every 4-6 hours for pain Biphasic pattern of elimination Lower affinity for  receptor compared to morphine Effect is longer than the effect of naloxone Structurally unrelated to other opioids Useful in patients with “morphine allergy”


Methadone Advantages Low cost, asy to titrate Absence of active metabolite NMDA antagonist Disadvantages Stigma, multiple pills/multiple drug interactions Peripheral edema, potential for arrhythmias (prolonged QT), excreted renally (decrease dose 50% in CRI) Poorly tolerated initially Unpredictability of blood levels and wide variation in response; difficulty calculating equipotent dose Fishman SM et al. Pain Medicine 2002;3(40:339-348


Methadone Butalbital (Fiorinal/Esgic/Phrenalin) induce metabolism, decreasing blood levels Cimetidine (Tagament) inhibit metabolism, increasing blood levels CY3A4 inhibitors like Cipro will increase blood levels Synergistic with benzodiazapams (increased sedation) Do not use with MAO inhibitors like Strattera


Urban myth - “I have to have a special license to prescribe methadone”. Not True Special license for heroin “maintenance” or “addiction” No special license for pain treatment Prescription must read “for pain” Methadone


2002 Interim Report of Drugs (Florida) 254 deaths related to methadone 31% increase compared to the last 6 months of 2001 The single largest increase in any category 133 cases were overdoses 110 involved the use of another drug as well meprobamate (Soma) Methadone


Levorphanol Mu agonist, K 3 agonist T 1/2  12 to 16 hours Given subq Less constipation than morphine Accumulates after 2-3 days Avoid in renal compromise (creatinine clearance < 500 cc/min)


Hydromorphone A hydrogenated ketone of morphine Can be administered orally, rectally, parenterally, and intrathecally High lipid solubility, can be given parenterally in high concentrations Particularly useful in opioid tolerant patients who require unusually high doses of analgesics Long acting formulation pending

Transdermal Fentanyl:

Transdermal Fentanyl

Transdermal Fentanyl:

Transdermal Fentanyl

Metabolism of Fentanyl:

Metabolism of Fentanyl No active metabolites, low histamine release Fentanyl is metabolized in the liver by CY3A4 to inactive metabolite 3A4 inhibitors (macrolid antibiotics, antifungals, and protease inhibitors) may lead to increased blood levels No CY2D6 interaction No first pass effect

Transdermal Fentanyl:

Transdermal Fentanyl

Duragesic® Patch Conversion:

Duragesic® Patch Conversion Start with 25µg if current regime is: Codeine 30 mg tablets 6 per day Hydrocodone 5mg 6 tablets per day Oxycodone 5mg 4 tablets per day OxyContin® 10 mg BID MSContin® 15 mg BID Divide current 24 hrs morphine dose by 2 e.g. 10 mg morphine QID = 40 mg/2= 20 Therefore start with 25µg

Sustained Release Formulations Pending:

Sustained Release Formulations Pending Oxymorphone Mu 1 selective Active metabolites via 2D6 Hydromorphone A hydrogenated ketone of morphine Can be administered orally, rectally, parenterally, and intrathecally High lipid solubility, can be given parenterally in high concentrations Particularly useful in opioid tolerant patients who require unusually high doses of analgesics

Equianalgesic Dosing:

Equianalgesic Dosing Drug Oral Dose IV Dose Duration morphine 30 mg 10 mg 3-4 hrs hydromorphone 4-8 mg 1.5 mg 3-4 hrs methadone 10-20 mg 6-12 hrs codeine 300 mg 150 mg 3-4 hrs oxycodone 20-30 mg 3-4 hrs hydrocodone 30 mg 3-4 hrs meperidine 300 mg 100 mg 2-3 hrs All doses are approximate, and vary between authors. Do Not Use

Dose Related Opioid Side Effects:

CNS Analgesia, chemical dependency Sedation/drowsiness Dizziness, mental clouding, depression, mood changes Nausea, emesis (CTZ) Antitussive (medullary cough center) Disorientation, delirium, hallucinations, agitation, restlessness, nervousness, seizures Dose Related Opioid Side Effects

Dose Related Opioid Side Effects:

Cardiovascular effects Bradycardia (morphine, fentanyl) Tachycardia (meperidine) Cholinergic effects Histamine release (fentanyl is the least) Dermatologic effects Diaphoresis, flushing, pruritis, urticaria Genitourinary effects Urinary retention, oliguria, vasopressin release Dose Related Opioid Side Effects

Dose Related Opioid Side Effects:

Dose Related Opioid Side Effects Respiratory effects CO2 tension response at the brainstem is decreased (decreased minute ventilation, rate, tidal volume) Neuromuscular effects Tremors (meperidine) Rigidity (fentanyl) Endocrine effects Increased prolactin and growth hormone Decreased LH, testosterone, 17-ketosteroids, thyrotropin release Gonadotropin suppression (impotence), decreased libido

Dose Related Opioid Side Effects:

Dose Related Opioid Side Effects Gastrointestinal effects Xerostomia, decreased motility, increased sphinchter tone Nausea, emesis (CTZ), orthostatic hypotension Increased vestibular sensitivity

Anticipate and Manage Side Effects:

Anticipate and Manage Side Effects Constipation (opioid-induced bowel dysfunction) No tolerance to this side effect therefore need to treat throughout opioid use Senokot, Ducolax, lactulose, Miralax, Colase Avoid bulk laxatives Consider metaclopromide or Arthrotec® (mistoprostal causes diarrhea) Oral naloxone has been described New agents such as methylnaltrexone and alvimopan (0.5 to 1mg) are insoluble and therefore effect is limited to gut

Anticipate and Manage Side Effects:

Anticipate and Manage Side Effects Nausea and emesis Promethizine, compazine Oral and rectal Metaclopromide Subligual droperidol Itching Not an allergic reaction Reverses with low dose naloxone IV Antihistamines Reassure

Anticipate and Manage Side Effects:

Anticipate and Manage Side Effects Sedation Tolerance usually develops rapidly Consider smaller am/larger hs dosing Consider stimulants Ritalin© Provigil®

Anticipate and Manage Side Effects:

Anticipate and Manage Side Effects Respiratory Depression Clinically significant respiratory depression is rare when patients are in severe pain Sedation precedes respiratory depression Respiratory rate alone is not an indication of respiratory function Use naloxone sparingly Respiratory depression reverses before analgesia Limit to doses of 100µg at a time One amp (0.4mg) in 4cc NS, inject 1cc at a time “You can always give more”

Respiratory Depression:

Respiratory Depression

Rescue Dose for Breakthrough Pain:

Rescue Dose for Breakthrough Pain Anticipate unexpected increases in pain that was previously well controlled Should be a short acting (not long acting) medication Prn rather than regularly Should be less than 10% total dose If more than 3 doses per day, consider increasing the baseline medication

Opioid- Induced Androgen Deficiency:

Opioid- Induced Androgen Deficiency Low serum levels of testosterone and: Decreased libido Erectile dysfunction Fatigue Depressed mood Hot flashes 70% of men on long term opioids have have subnormal testosterone levels Daniel 2002

Opioid Responsiveness:

Opioid Responsiveness Opioid dose titration over time is critical to successful opioid therapy Goal: Increase dose until pain relief is adequate or intolerable and unmanageable side effects occur No maximal or “correct” dose Responsiveness of an individual patient to a specific drug cannot be determined unless dose was increased to treatment-limiting toxicity

Poor Opioid Responsiveness:

Poor Opioid Responsiveness If dose escalation  adverse effects Better side-effect management Pharmacologic strategy to lower opioid requirement Spinal route of administration Add nonopioid or adjuvant analgesic “Opioid rotation” Nonpharmacologic strategy to lower opioid requirement

Opioid Rotation:

Opioid Rotation Based on large intra-individual variation in response to different opioids Reduce equianalgesic dose by 25%–50% with provisos: Reduce less if pain severe Reduce more if medically frail Reduce less if same drug by different route Reduce fentanyl less Reduce methadone more: 75%–90%

Opioid Therapy and Chemical Dependency:

Opioid Therapy and Chemical Dependency Physical dependence Tolerance Addiction Pseudoaddiction

Opioid Therapy and Chemical Dependency :

Opioid Therapy and Chemical Dependency Physical dependence Abstinence syndrome induced by administration of an antagonist or by dose reduction Assumed to exist after dosing for a few days but actually highly variable Usually unimportant if abstinence avoided Does not independently cause addiction

Opioid Therapy and Chemical Dependency :

Opioid Therapy and Chemical Dependency Tolerance Diminished drug effect from drug exposure Tolerance to side effects is desirable Tolerance to analgesia is seldom a problem in the clinical setting Tolerance rarely “drives” dose escalation Tolerance does not cause addiction

Opioid Therapy and Chemical Dependency :

Opioid Therapy and Chemical Dependency Addiction Disease with pharmacologic, genetic, and psychosocial elements Fundamental features Loss of control Compulsive use Use despite harm Diagnosed by observation of aberrant drug-related behavior

Opioid Therapy and Chemical Dependency :

Opioid Therapy and Chemical Dependency Pseudoaddiction Aberrant drug-related behaviors driven by desperation over uncontrolled pain Reduced by improved pain control Complexities How aberrant can behavior be before it is inconsistent with pseudoaddiction? Can addiction and pseudoaddiction coexist?

Opioid Therapy and Chemical Dependency :

Opioid Therapy and Chemical Dependency Risk of addiction: Evolving view Acute pain: Very unlikely Cancer pain: Very unlikely Chronic noncancer pain: Surveys of patients without abuse or psychopathology show rare addiction Surveys that include patients with abuse or psychopathology show mixed results

Comprehensive Review of Opioid Therapy for Chronic Pain:

Comprehensive Review of Opioid Therapy for Chronic Pain “Satisfactory analgesia” can be achieved using stable doses <195 mg/d MSO4 or equivalent Tolerance and opioid-induced pain sensativity Prescribing recommendations Decision phase (comprehensive diagnostic assessment) Dose -adjustment phase (may last up to 8 weeks) Stable phase Opioid rotation Ballantyne JC and Mao JM. N Engl J Med 2003;349:1943-1953

DAWN Data:


Opioid Therapy: Monitoring Outcomes:

Opioid Therapy: Monitoring Outcomes Critical outcomes Pain relief Side effects Function—physical and psychosocial Drug-related behaviors

Monitoring Drug-Related Behaviors :

Monitoring Drug-Related Behaviors Probably more predictive of addiction Selling prescription drugs Forging prescriptions Stealing or “borrowing” drugs from another person Injecting oral formulation Obtaining prescription drugs from nonmedical source “Losing” prescriptions repeatedly Probably less predictive of addiction Aggressive complaining Drug hoarding when symptoms are milder Requesting specific drugs Acquiring drugs from other medical sources Unsanctioned dose escalation once or twice

Monitoring Drug-Related Behaviors (cont.):

Monitoring Drug-Related Behaviors (cont.) Probably more predictive of addiction Concurrent abuse of related illicit drugs Multiple dose escalations despite warnings Repeated episodes of gross impairment or dishevelment Probably less predictive of addiction Unapproved use of the drug to treat another symptom Reporting of psychic effects not intended by the clinician Occasional impairment

Monitoring Aberrant Drug-Related Behaviors: 2-Step Approach:

Monitoring Aberrant Drug-Related Behaviors: 2-Step Approach Step 1: Are there aberrant drug-related behaviors? Step 2: If yes, are these behaviors best explained by the existence of an addiction disorder?

Opioid Therapy and Chemical Dependency:

Opioid Therapy and Chemical Dependency Addressing aberrant drug-related behavior Proactive and reactive strategies Management principles Know laws and regulations Communicate Structure therapy to match perceived risk Assess behaviors comprehensively Relate to addiction-medicine community Possess a range of strategies to respond to aberrant behaviors

Opioid Therapy and Chemical Dependency:

Opioid Therapy and Chemical Dependency Addressing aberrant drug-related behavior Strategies to respond to aberrant behaviors Frequent visits and small quantities Long-acting drugs with no rescue doses Use of one pharmacy, pill bottles, no replacements or early scripts Use of urine screens Coordination with sponsor, program, addiction medicine specialist, psychotherapist, others

Urine Drug Testing (UDT):

Urine Drug Testing (UDT) Oxycodone and methadone do not appear on standard UDTs Gas chromatography-mas spectrometry Codeine will appear as morphine Heroin will appear as morphine Von Seggern RL et al. Headache 2004;44:4-47

State Specific Documentation Requirements:

State Specific Documentation Requirements Arizona requires physicians to keep records such that they provide “sufficient information to allow another physician to assume care”. Colorado suggests physicians use a written contract. Mississippi requires physicians to keep patient records that include the presence of one or more recognized medical indications for the use of controlled substances. Pennsylvania requires physicians to have a specific statement regarding patient symptoms, the diagnosis and the specific directions given for controlled substances Jennifer Bolen, The Legal Side of Pain

Opioid Therapy: Conclusions:

Opioid Therapy: Conclusions An approach with extraordinary promise and substantial risks An approach with clear obligations on the part of prescribers Assessment and reassessment Skillful drug administration Knowledge of addiction-medicine principles Documentation and communication



PowerPoint Presentation:

A patient complains of inadequate analgesia and increases his use of his medication. This behavior may represent: Addiction Pseudoaddiction Tolerance All of the above Answer: D If the patient increases the medication despite the knowledge that he will be discharged, this may be addiction. If he increases the medication because of inadequate dosing, that may be pseudoaddiction. If he increases the medication because it is no longer effective, that may be tolerance .

PowerPoint Presentation:

Demerol (meperidine) should not be used for chronic pain because: A. it is addictive B. it is ineffective C. the metabolite causes seizures D. all of the above All opioids can potentially be abused. Meperidine may be useful for acute pain. The metabolite normeperidine can cause seizures and can accumulate with chronic dosing, especially in renal failure. Answer: C.

PowerPoint Presentation:

Strategies to reduce aberrant drug behaviors include: 1. Random urine drug screens 2. Narcotic contracts 3. No early refills 4. Opioid rotation Random drug screens, narcotic contracts, and aggressive refill policies have been felt to help control aberrant drug behaviors. Opioid rotation tries to address the issue of drug tolerance. Answer: A

PowerPoint Presentation:

30mg of MSO4 orally is equivalent to: 1. 30mg MSO4 IV 2. 20mg of oral oxycodone 3. 30mg hydromorphone IV 4. 20mg methadone Answer: C Although equipotent charts may vary, in general, 30mg of oral MSO4 is equivalent to 10mg MSO4 IV, 20mg of oral oxycodone, 1.5mg of IV hydromorphone, or 20mg of methadone.

PowerPoint Presentation:

Receptors involved in opioid activity include: Mu Sigma Kappa Gamma Answer: A Mu, sigma, and kappa are opioid receptors. Gamma is not.

PowerPoint Presentation:

The most appropriate type of opioid for chronic pain might be an: Agonist Agonist/antagonist Antagonist Antihistamine Answer: A Mixed agonists/antagonists are poor choices for chronic pain treatment. Antagonists counteract the effect of opioids. Antihistamines are not opioids.

PowerPoint Presentation:

Patients usually develop tolerance to all opioid effects EXCEPT: Sedation Pruritis Constipation Pain relief Answer: C Sedation and pruritis (due to direct histamine release) abate over time. Although tolerance to pain relief can occur, with long acting narcotics (especially methadone) it is less likely. Constipation, however, should be expected to be a problem for the entire length of treatment.

PowerPoint Presentation:

Once an opioid treatment is selected, titration upwards should continue until: a ceiling is reached. addiction occurs tolerance occurs a balance between analgesia and side effects is reached. Answer: D There is no ceiling for opioids (other than the limitations of agonist/antagonists or APAP). The goal is to prevent addiction. Tolerance is less likely with long acting opioids. The goal is a balance between pain relief and intolerable side effects.

PowerPoint Presentation:

Examples of the phenanthrene class of opioid include all except: Morphine Fentanyl Codeine Meperidine Answer: B Morphine and codeine are phenanthrenes. Fentanyl and meperidine are phenylpiperidines.

PowerPoint Presentation:

If a patient is unable to tolerate oxycodone because of nausea, the least likely opioid to be tolerated would be: Fentanyl Propoxyphene Morphine Methadone Answer: C Morphine is in the same class of opioids (phenanthrenes) as oxycodone, but morphine has a 6-OH group (associated with more nausea). Fentanyl, propoxyphene, and methadone are completely different classes of opioids.

PowerPoint Presentation:


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