SM_236a, 240a: Pharmacology, Opioids, and Pain Concepts I and II Flashcards
Describe the opioid receptors
Opioid receptors
- Mu, kappa, delta
- One gene codes for each
- Subtypes come from splice variants
- All involved in brain, spinal, GI sites
The opioid receptors are _____, _____, and _____
The opioid receptors are mu, happa, and delta
Mu opioid receptor is responsible for ____, ____, ____, ____, ____, ____, and ____
Mu opioid receptor is responsible for analgesia, euphoria, dependence, respiratory depression, miosis, GI effects, and pruritis
(named after morphine)
Kappa opioid receptor is responsible for ____, ____, and ____
Kappa opioid receptor is responsible for mild analgesia, less respiratory depression, and pyschomimetic effects (unlike euphoria)
Delta opioid receptor function is ____
Delta opioid receptor function is unknown
Opioid receptors are found in the ____, ____, and ____
Opioid receptors are found in the brain, spinal cord, and gut
Describe the location of opioid receptors in the brain
- Amygdala - emotion
- Brainstem - ventilation
- Area postrema - vomiting
- Periaqueductal gray - inhibitory pathway
(gate control theory, periaqueductal gray inhibits pain transmission in dorsal horn via a relay in the rostral ventral medulla)
Opioid receptors work via ____, which ____, ____, ____, and ____
Opioid receptors work via G receptor proteins, which inhibit cellular adenylyl cyclase, increase K+ currents and decrease Ca2+ currents, cause hyperpolarization, and decrease nociceptive transmission
Opioids work on ____ and ____ receptors
Opioids work on presynaptic and postsynaptic receptors
Opioids activate the ____, triggering ____ and releasing ____
Opioids activate the periaqueductal gray, triggering the descending inhibitory pathways and releasing endorphins
(descending pathway modulates pain in transmission in the ascending pathway)
Opioids ____ the GABA neuron, which allows for ____ of the pain inhibitory neuron
Opioids inhibit the GABA neuron, which allows for activation of the pain inhibitory neuron
Opiate is a _____
Opiate is a drug derived from opium
Opioid is ____
Opioid is all drugs, both natural and synthetic, that bind to opioid receptor
Narcotic is ____, ____, and ____
Narcotic is any substance that induces sleep, acts on opioid receptors, and any illicit substance
Opioids that are agonists are _____ and include _____, _____, and _____
Opioids that are agonists are mu receptor agonists and include morphine, merepiridine, and hydromorphone
Opioids that are antagonists are _____ and include _____ and _____
Opioids that are antagonists are mu receptor antagonists and include naloxone and naltrexone
Opioids that are agonist/antagonists are _____ and include _____ and _____
Opioids that are agonist/antagonists are kappa agonists / mu antagonists and include butorphanol and nalbuphine
Opioids that are partial agonists are _____ and _____ and include _____
Opioids that are partial agonists are partial mu agonists with high affinity and meaningless kappa antagonists and include buprenoprhine
Describe opioids that are agonist/antagonists
Agonist/antagonist opioids
- Analgesia is kappa mediated
- Weak mu receptor antagonist
- Ceiling effect
- Less GI side effects
- Kappa: less respiratory depression / sedation / euphoria but makes person nuts
- Can trigger withdrawal so do not use in opioid tolerant patient
- Can reverse opioid side effects at low dose
Describe opioids that are partial agonists
Partial agonist opioids
- Only partial mu agonist
- Ceiling effect for agonism
- Binds mu with high affinity: higher than most opioids, prevents other opioids from binding, makes naloxone reversal difficult in overdose
- Current use: opioid maintenance, not so much for chronic pain
Partial agonist opioids are used for ____
Partial agonist opioids are used for opioid maintenance
Describe neurologic effects of opioids
Neurologic effects of opioids
- Analgesia: supraspinal and spinal cord level, not reliably associated with loss of consciousness, better for nociceptive pain (pain caused by stimulation of nociceptive receptors) than neuropathic pain (pain caused by damaged neural structures)
- Miosis (pinpoint pupil): seen with all opioid agonists
- No tolerance to this: useful in overdose diagnosis, even in tolerant addicts
____ is the major way that opioids kill
Respiratory depression is the major way that opioids kill
(hold if sedated)
Describe respiratory effects of opioids
Respiratory effects of opioids
- Therapeutic effects: prevent hyperventilation from pain and anxiety, opioids can be used for their antitussive actions, can help avoid increases in bronchomotor tone in asthma
- Adverse effect: respiratory depression is most serious, activation of mu opioid receptor in caidal medullary raphe region inhibits the ventilatory response to hypercapnia
Direct cardiac actions are _____ than for other inhalational or IV anesthetics
Direct cardiac actions are lower than for other inhalational or IV anesthetics
GI effects of opioids include ____ and ____
GI effects of opioids are slowed peristalsis and nausea/vomiting
- Slowed peristalsis: via enteric NS opioid receptors
- Nausea/vomiting: via chemoreceptor trigger zone
Tolerance to opioids does NOT include ____ and ____
Tolerance to opioids does NOT include miosis and constipation
(tolerant to euphoria, sedation, analgesia, N/V, respiratory depression)
Opioid withdrawal contains symptoms of ____
Opioid withdrawal contains symptoms of sympathetic overdrive
- Anxiety, insomnia, diaphoresis, yawning, rhinorrhea, lacrimation
- HTN, tachycardia
- Hyperventilation
- Mydriasis
- Also diarrhea and abdominal cramps
Opioid overdose symptoms include ____, ____, and ____
Opioid overdose symptoms include respiratory depression / arrest, sedation or unresponsiveness, and miosis
(ABCs - support ventilation, use naloxone as the antagonist)
List the agonist, antagonist, agonist/antagonist, and partial agonist opioids
Opioids
- Agonists: morphine, codeine, hydrocodone, oxycodone, merperidine, fentanyl, hydromorphone, methadone, tramadol
- Antagonists: naloxone, naltrexone
- Agonist/antagonist: nalbuphine
- Partial agonist: buprenorphine
Describe morphine
Morphine
- Hydrophilic: delayed transport across BBB so delayed onset of action
- Broken down into M3G and M6G - only M6G is active
- Duration of action is 4-5 hours (t1/2 = 2-3 hours)
- Causes histamine release: rash, hypotension
Describe oxycodone
Oxycodone
- Semisynthetic opioid closely related to morphine
- High bioavailability (60%) compared to morphine (33%)
- Analgesia is via parent compound but does metabolize into oxymorphone (often undetectable but 14x more potent)
- Immediate release and extended release formulation
Describe codeine
Codeine
- Prodrug (very low mu affinity)
- 10% metabolized to morpine - 7-10% of white population cannot
- Considered a weak opioid but can get nausea and constipation from parent drug at high doses
Describe hydrocodone
Hydrocodone
- Only sold as combo drug in US: Norco or vicodin (combined with acetaminophen)
- Breakdown into hydromorphone
- Unknown if analgesia is via parent drug or metabolite
Describe hydromorphone
Hydromorphone
- Analogue of morphine and similar in action (hydrophilic, duration of analgesia)
- Better side effect profile than morphine: pruritis, sedation, nausea, vomiting
- 5x more potent orally and 7x more potent parenterally
- Metabolized in liver to H3G: lacks analgesia, could potentiate side effects
Describe fentanyl
Fentanyl
- Highly lipophilic with high affinity for the mu receptor: fast onset IV, crosses skin and buccal tissue
- 75-125x more potent than morphine
- IV for OR anesthesia and ICU analgesia: fast onset, easy to titrate, short duration so good for outpatient surgeries
- Transdermal: slow onset because builds up subcutaneously, sustained release for chronic pain, more difficult to abuse, good for patients with GI issues, variable time achieving therapeutic levels with skin differences
Describe merperidine
Merperidine
- Lipophilic with rapid onset
- Weaker mu agonist as compared to morphine
- Potent inhibitor of serotonin reuptake
- Metabolite is normeperidine: long half life, CNS hyperactivity and seizures, cleared by kidneys, do NOT use in renal failure patients
Describe tramadol
Tramadol
- Oral analgesic
- Technically a prodrug: M1 metabolite is a mu agonist
- Works by two mechanisms: mu receptor agonist, blocks reuptake of 5-HT and NE
- Used for mild to moderate pain
Describe naloxone
Naloxone
- Opioid antagonist: IV only
- Short half life of 1 hour
- Duration of 15 min - 4 hours
- Reversal is short-lived
- Very poor bioavailability so combined in opioid pills to prevent IV abuse
- Competitive antagonist
Interpatient opioid receptor variability occurs with respect to ____, ____, and ____
Interpatient opioid receptor variability occurs with respect to receptor type, density, and location
Different opioids have ____ receptor affinities due to ____
Different opioids have different receptor affinities due to splice variants
(subtle differences between splice variant affinities)
Describe opioid receptor relevance
Opioid receptor relevance
- Interpersonal receptor density varaibility
- Different opioids have different receptor affinities
- Different opioids have different effects in different patients
- Titrate opioid to analgesic effect
- Change the opioid if side effects and not much analgesia
____ and ____ are problematic in patients with renal failure
Morphine and merperidine are problematic in patients with renal failure
- Morphine metabolites M3G and M6G cleared by kidney -> if not cleared can cause massive side effects
- Merperidine metabolite normoperidine is cleared by kidneys -> if not cleared can cause CNS hyperactivity and seizures
