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84 Cards in this Set
- Front
- Back
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Opioid Analgesic
-Defn? -AKA? -Why not used anymore? |
Defn
-Class of compounds that produce pain relief AKA -Narcotic analgesics -Narosis = stuporous/somnolent state and opioids provide pain relief w/o reduced consciousness -Narcotic has legal connotations that are not desirable |
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Opioid
-General term? |
Defn
-all agonists and antagonists that exert morphine-like activity -Can be naturally occuring or synthetic |
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Opiums different alkaloids
-4 |
Alkaloids
-Morphine -Codeine -Thebaine -Paraverine |
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Pain
-Defn |
Unpleasant sensory and emotional experience that alerts individuals to actual or potential tissue damage caused by exposure to noxious chemicals, mechanical or thermal stimuli or by the presence of a pathological process (inflammation)
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Pain
-2 important characteristics |
-Sensory process
-AND emotional response -Individual's response to noxious stimulation in greatly dependent upon prior experience and situational variables |
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Pain pathway
(6) |
-Activation of primary afferent neurons (nociceptors)
-Enter spinal cord where they synapse with spinothalamic neurons that form the ascending pain pathway -Interneurons present modulate spinothalamic neurons -Pain is sent to medulla, midbrain and thalamus -From thalamus --> relayed to cortical and limbic structures -Responsible for perception of pain and emotional responses to pain |
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Types of primary afferent neurons comprised of?
(2 types) |
Types
-A-delta fibers (sharp pain) -C fibers (dull pain) |
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3 receptor families
-Type of receptors? |
3 receptors
-MOR -DOR -KOR Type -G-protein linked receptors |
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Three main endogenous ligands
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-Endorphins
-Enkephalins -Dynorphins |
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Which receptor underlies analgesia?
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MOR
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Dynorphin is ligand for which receptor?
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KOR
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Enkephalin is ligand for which receptor?
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DOR
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Beta-endorphin is ligand for which receptor?
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MOR
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Opioids
-MOA |
-Couples cAMP signaling system thru inhibitory G proteins
-Reduction in cAMP --> reduction in phosphorylation state of protein substrates for cAMP-dependent protein kinase (PKA) -Reduce voltage-sensitive Ca2+ currents -Reduce NT release from presynaptic terminals -Also activates G(gamma-beta) subunit which activates outward K+ currents -Leads to hyper polarization of post-synaptic neurons, decreased excitability and inhibition of neuronal activity |
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Opioids
-Modulate multiple sites in pain pathway (5) |
-Reduction of effects of nociceptive afferents in dorsal horn (decrease release of glutamate and substance P)
-Increase inhibition by GABAergic afferent in dorsal horn (decreased GABA in RVM) -Inhibition of interneurons in dorsal horn -Modulation of forebrain sites (perception) -Modulation of nociceptive receptors in periphery |
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Phenanthrenes
-Drugs in this class? (8) |
-Morphine
-Heroin -Oxymorphone -Codeine -Oxycodone -Hydrocodone -Nalbuphine -Buprenorphine |
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Phenylpiperidines
-Drugs in this class? (5) |
-Fentanyl
-Sulfentanil -Remifentanil -Diphenoxylate -Meperidine |
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Phenylheptylamines
-Drugs in this class? (2) |
-Methadone
-Propoxyphene |
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Morphinans
-Drugs in this class? (2) |
-Levorphanol
-Butorphanol |
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Benzomorphans
-Drugs in this class? (1) |
Pentazocine
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"Others" class
-Drug in this class? (1) |
-Tramadol
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General classifications of opioid drugs?
(3) - |
Classification
-Full agonists -Mixed Agonist-Antagonists -Pure antagonists |
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Full agonists
-2 classifications -Characteristics of these classifications |
Strong
-Tolerated at doses sufficient to relieve severe pain -Strong tolerance and withdrawal typical Moderate -Can cause intolerable SEs when given at doses that alleviate severe pain -Given in submaximal doses + non-opioid analgesic to enhance effectiveness w/o the SEs |
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Pure antagonists
-Use |
Use
-NO analgesic effects -Used to counteract the adverse effects of opioid OD |
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Strong Agonists
-Drugs in this group? (7) |
-Morphine
-Heroin -Oxymorphone -Fentanyl -Sulfenanil -Methadone -Meperidine |
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Mild to moderate Agonists
-Drugs in this group? (4) |
-Codeine
-Hydrocodone -Oxycodone -Propoxyphene |
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Partial agonists/Mixed agonists-antagonists
-Drugs in this group? (4) |
-Buprenophine
-Nalbuphine -Butorphanol -Pentazocine |
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Antagonists
-Drugs in this group? (2) |
-Naloxone
-Naltrexone |
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Major Effects of Opioid Agonists
-CNS effects? (11) |
CNS
-Analgesia -Euphoria or dysphoria -Respiratory depression* -Inhibition of cough reflex -Miosis* (pupil constriction) -Sedation* -Physical dependence -Nausea (and vomiting)* -Truncal rigidity -Hyperthermia -Restlessness, hyperactivity, convulsions |
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Major Effects of Opioid Agonists
-Cardiovascular system (2) |
-No significant direct effects
-Decreased myocardial oxygen demand -Vasodilation and hypotension (orthostatic) |
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Major Effects of Opioid Agonists
-GI tract (4) |
-Constipation* (increase intestinal smooth muscle tone)
-Biliary colic -Contract smooth muscle and sphincter of Oddi -Reflux of biliary secretions -Elevated plasma amylase and lipase |
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Major Effects of Opioid Agonists
-Renal system (3) |
-Depressed renal function
-Antidiuretics -Increased sphincter tone may lead to urinary retention |
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Major Effects of Opioid Agonists
-Uterus (2) |
-Decreased uterine tone
-Prolonged labor |
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Major Effects of Opioid Agonists
-Pruritus (3) |
-Flushing* and warming of skin
-Itching* caused by peripheral histamine release -Sweating |
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Major Effects of Opioid Agonists
-Immune system (1) |
-Reduced immune function
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Major Effects of Opioid Agonists
-Endocrine system (2) |
-Inhibition of lutenizing hormone release
-Increase release of ADH and prolactin |
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Morphine
-MOA? -Kinetics? (4) -Administration? (3) |
MOA
-Prototypical MOR opioid analgesic -Most obtained from poppy Kinetics -Hyrophilic* -2 hr half life -Slower absorption and CNS entry -Sustained release available Administration -Oral (first pass metabolism, 25% bioavailability) -Less effective than parenteral but easier -Epidural route |
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Morphine
-Metabolism (2) -Effects? (3) |
Metabolism
-CYP450 (glucuronidation) -Morphine 3 and morphine-6-glucuronide (2x more potent)* Effects -Analgesia -Sedation -Euphoria (sometimes dysphoria) |
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Morphine
-Major SEs? (2) -Drug interactions (2) -Also useful for? (3) |
SEs
-Repsiratory depression --> arrest* -High potential for abuse Interactions -MAO inhibitors -Alcohol Uses -Myocardial Infarction pain (anxiolytic and sedating) -Epidural anesthesia (long lasting) -Cancer pain -Dyspnea w/ pulmonary edema (reduces anxiety due to SOB) |
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Fentanyl
-MOA -Kinetics? (2) -Administration (3) |
MOA
-Very potent MOR agonist (100X morphine) Kinetics -Lipophilic* -Faster absorption and CNS entry Administration -Parenteral (IV, epidural, intrathecal) -Oral mucosa (discontinued in US) -Transdermal patch |
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Fentanyl
-Uses? -SEs? (2) -Drug interactions? |
Use
-Anesthetic (with droperidol) --greater hemodynamic stability w/ no histamine release SEs -Less nausea -More muscle rigidity Interactions -Several -Aprepitant, antibiotics, diltiazem, verapamil, etc... |
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Fentanyl
-Derivatives? (2) -Uses of derivatives? |
Derivatives
-Sufentanil (more potent) -Alfentanil (less potent) Uses -Anesthetic adjuvants -Epidural analgesia |
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Methadone
-MOA? -Uses? (2) |
MOA
-Potent MOR agonist -Racemix mix also blocks NMDAR Uses -Treatment of opioid (heroin) addiction* -Sometimes for moderate to severe pain |
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Methadone
-Kinetics (4) -Caution? (1) |
Kinetics
-Orally as prescribed -> does NOT produce euphoria -Better oral availability than morphine -IV can produce euphoria -Long lasting/half life Caution -Risk of OD if pt uses heroin while taking methadone |
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Meperidine
-MOA -Differences from morphine? (4) |
MOA
-MOR agonist Comparison -Less potent and shorter acting -Does NOT prolong labor -Not antitussive -Less constipation |
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Meperidine
-Uses? -Not used for? (2) -Drug interactions? (1) |
Use
-Short-term treatment of acute pain syndromes Not used for -Chronic pain (toxic metabolite can accumulate) --dysphoria, irritability, tremors, myoclonus and seizures -MI pain --> anti-muscarinic activity leads to tachycardia Interaction -MAOIs (cerebral edema and 5HT syndrome) |
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Meperidine
-MOA -Differences from morphine? (4) |
MOA
-MOR agonist Comparison -Less potent and shorter acting -Does NOT prolong labor -Not antitussive -Less constipation |
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Meperidine
-Uses? -Not used for? (2) -Drug interactions? (1) |
Use
-Short-term treatment of acute pain syndromes Not used for -Chronic pain (toxic metabolite can accumulate) --dysphoria, irritability, tremors, myoclonus and seizures -MI pain --> anti-muscarinic activity leads to tachycardia Interaction -MAOIs (cerebral edema and 5HT syndrome) |
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Codeine
-MOA? -Uses? (3) -Kinetics? (1) |
MOA
-Moderate opioid agonists -Weak MOR agonist Use -Mild-moderate pain -Cough suppression -Useful antitussive Kinetics -Excellent oral bioavailability (less 1st pass metabolism) |
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Codeine
-Metabolism (2) -Genetics (1) -Commonly used with? |
Metabolism
-CYP450 system (can lead to interactions) -Metabolized to morphine Genetics -10% of population has polymorphism of CYP2D6 -Pts do NOT effectively convert codeine to morphine Used with -Acetaminophen or aspirin |
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Propoxyphene (Darvon)
-MOA? -Uses? (2) -Administration? (2) |
MOA
-Moderate opioid agonist -MOR agonist Use -Mild to moderate pain -Sometimes used b/c of overconern of abuse liability of codeine Administration -Orally less potent that codeine -IV or subQ (irritant) |
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Propoxyphene
-Commonly used with? (1) -SEs? (3) -Interactions? (2) |
Used with
-Aspirin SEs -Toxic psychosis -Pulmonary edema -Cardiotoxicity Interactions -Alcohol -Sedatives -Can be fatal |
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Propoxyphene
-Why has use been reduced? |
Reduced b/c
-Other meds are just as effective w/ less SEs -Risk of fatal OD --FDA now has stronger warnings |
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Oxycodene (OxyContin)
-MOA -Use (1) -Kinetics (1) |
MOA
-Moderate opioid agonist -MOR receptor agonist (fairly potent) Use -Mild to moderate pain Kinetics -Better oral bioavailability than morphine |
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Oxycodene
-Commonly used in combo with? -Metabolism (1) -Adverse effect (1) |
Used with
-Aspirin or acetaminophen -Synergistic pain relief (percodan or percocet) Metabolism -CYP2D6 (potential drug interactions) Adverse Effect -Widespread abuse of sustained release |
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Mixed opioid agonist-antiagonist
-2 types? -Effects? (6) |
Types
-Agonists at KOR and antagonist/partial agonists at MOR -Antagonist at KOR and partial agonist at MOR Effects -Precipates withdrawal in opioid dependent pts -Greater sedation -Psychotomimetic -Abuse liability |
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Pentazocine
-MOA? (2) -Uses? (2) -SEs? (8) |
MOA
-KOR agonist -Weak MOR antagonist/partial agonist Uses -Moderate pain -For pts NOT using other opioids SEs -Ceiling effects for analgesia -Respiratory depression -Sedation -Sweating, dizziness -Anxiety -Psychotomimetic effects -Increase HR/BP -Less nausea than morphine |
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Pentazocine
-Formulated with? -Adminstration (2) |
Formulated with
-Naloxone Administration -If injected, IV --> naloxone prevents euphoria -If taken orally --> naloxone metabolized before pentazocine reaches CNS |
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Buprenorphine
-MOA -Kinetics (4) |
MOA
-Mixed opioid agonist-antagonist -KOR antagonist -High affinity MOR partial agonist Kinetics -Slower onset and longer duration -Highly lipophilic -More potent analgesic than morphine -More resistant to naloxone reversal |
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Buprenorphine
-SEs? (3) -Uses? (2) |
SEs
-Greater sedation -Less respiratory depression -Mild morphine-like withdrawal syndrome Use -Antagonizes respiratory depression caused by fentanyl -Useful for treatment of addiction (low abuse liability but decreases cravings) |
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Butorphanol
-MOA? -Compared to pentazocine -Uses? (2) |
MOA
-Agonist at KOR Comparison -20X more potent as analgesic Use -Moderate to severe pain -Better suited for acute pain |
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Nalbuphine
-MOA (2) -Benefit? (1) -Compared to morphine |
MOA
-Mixed agonist/antagonist -Greater MOR antagonist activity Benefit -Fewer psychotomimetic effects than pentazocine Comparison -Equipotent to morphine (parenterally) |
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Opioid Antagonists
-MOA? -Uses? (3) |
MOA
-Higher affinity of MOR agonists but also bind to KOR, DOR Uses -Rapidly reverse effects of MOR agonists -Treatment of OD (higher doses needed for buprenorphine and pentazocine) -Useful as preventative to drug relapse |
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Opioid Antagonists
-SEs? (1) -Mixed with? (1) |
SEs
-Will precipitate withdrawal syndrome Mixed in -Formulations of some MOR agonists to minimize IV abuse |
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Naloxone
-MOA -Use (1) -Kinetics (3) |
MOA
-Opioid Antagonist Use -Reversal of opioid OD Kinetics -Poor oral availability -Rapid action (requires repeated dosing) -No effect on pts not on opioids |
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Naltrexone
-MOA -Use? (2) -Kinetics |
MOA
-Opioid antagonist Use -Treatment for opioid OD -Helpful in treatment of drug addition (alcohol and heroin-seeking) Kinetics -Longer duration of action -Greater bioavailability (given orally) -More potent than naloxone |
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General treatment strategy for pain
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Acute or chronic pain should be treated with the least potent analgesic that will control the pain
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Mild Pain treatment strategy
(1) |
Usually responsive to non-opioid analgesics
-NSAIDs |
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Moderate Pain treatment strategy
(2) |
-Codeine, oxycodone or hydrocodone
-In combo w/ aspirin or acetaminophen |
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Severe pain treatment strategy
(1) |
Strong opioid agonist
-Fentanyl and/or morphine |
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More effective dosing?
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Fixed interval dosing is more effective that dosing on demand
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Administration to achieve regional analgesia?
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Epidural injection
Less adverse effects |
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Additional use besides analgesia?
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-Premedicants due to sedative and anxiolytic properties
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Patient-controlled analgesia (PCA)
-Defn? |
Control of parenteral infusion
Better pain control with less use |
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Co-analgesics
-Defn? -Classes of drugs? (2) |
Defn
-Drugs that potientiate analgesic efficacy Classes -Anti-epileptic drugs (carbamazepine, gabapentin, phenytoin, valproate) -Tricyclic antidepressants |
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Tramadol
-MOA (2) -Benefits? (2) -Use (2) |
MOA
-Selective weak MOR agonist -Monoaminergic reuptake blockade Benefits -Lower affinity for opioid receptors than codeine -Less potential for abuse (still present though) -Less potential for respiratory depression Use -Very effective for moderate pain -Can be given w/ pure opioid agonist for severe pain |
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Tolerance develops to?
-Dose seen most with? -Tolerance weak for some SEs? (2) |
Develops to ALL
-Moderate and strong agonists -Requires escalating dosing -Occurs most readily when large doses at short intervals SEs? -Constipation -Miosis |
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Withdrawal
-Related to? -Actions taken? |
-Related to clearance of drug and duration of use
-Some cross tolerance -Seen less in mixed agonist-antagonists -Use decreasing dosage to minimize withdrawal -Tolerance disappears after withdrawal symptoms decrease -Craving may persist for months |
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Tolerance and withdrawal does not imply?
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-Addiction
-Treatment should NOT be withheld based on tolerance nor based on regulatory controls |
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OD of Opioid Analgesics
-Symptoms (3) -Treatment? (2) -Risks? (3) |
Symptoms
-Coma -Pinpoint pupils -Depressed repiration Treatment -Naloxone or naltrexone -Respiratory support Risks -Precipitate withdrawal symptoms -Return of pain -Overshoot/rebound sympathetic activation (careful titration of naloxone) |
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OD of Opioid Analgesics
-Risk of using antagonist with a short half life? |
-Patient may fall back into coma if antagonist not continued
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Contraindications of opioid anaglesics (6)
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Contraindications
-Full agonist + Partial agonist (withdrawal) -Head injuries (CO2 retention --> cerebral vasodilation and increased intracranial pressure) -Pregnancy (physical dependence in infant) -Impaired hepatic or renal function (accumulation of drug) -Impaired pulmonary function (depressant properties -> respiratory failure) -Endocrine disease (exaggerated response to opioids) |
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Opioid interactions with other drugs?
(3) |
Interactions
-MAOIs (hyperpyrexic coma, HT) -Antipyschotic tranquilizers (increased sedation, increased card effects) -Sedative-hypnotics (increase CNS depression) |
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Strategies to increase effectiveness of opioid treatments
(3) |
-Adjunct treatments (acetaminophen, aspirin, anti-epileptic drugs, TCAs, amphetamine)
-Opioid rotation since cross-tolerance incomplete -NMDA antagonists prevent tolerance |
