Opioids Flashcards
Which part of the pain pathway involves chemicals activating peripheral nerves and immune cells into an action potential?
Transduction
Which part of the pain pathway involves an electrical signal relayed through neurons in the afferent pathway along the spinothalamic tract?
Trasmission
Which part of the pain pathway involves the up and down regulation of pain signals?
Modulation
Which part of the pain pathway involves the processing of afferent pain signals in the cerebral cortex and limbic system?
Perception
What kind of pain is transmitted by A delta fibers?
fast, sharp pain that is well localized
What kind of pain is transmitted by C fibers?
slow, dull pain that is poorly localized
What are the two excitatory neurotransmitters that are important in the dorsal horn?
Glutamate & Substance P
How does inflammation contribute to pain?
-reduced threshold to pain stimulus
-increased response to pain stimulus
What drugs target transduction?
NSAIDs
Local anesthetics
Steroids
Antihistamines
Opioids
Where are the first, second, and third-order neurons located?
1st: periphery to dorsal horn
2nd: dorsal horn to thalamus
3rd: thalamus to cerebral cortex
What drugs target transmission?
local anesthetics
Where is the most important site of modulation?
substantia gelatinosa in the dorsal horn
Where does the descending inhibitory pathway begin?
the periaqueductal gray and the rostroventral medulla
How is pain inhibited?
-spinal neurons release GABA and glycine
-descending pathway releases NE, serotonin, and endorphins
How is pain augmented?
-central sensitization
-wind-up
What drugs target modulation?
neuraxial opioids
NMDA antagonists
alpha-2 agonists
AchE inhibitors
SSRIs
SNRIs
What drugs target perception?
general anesthetics
opioids
alpha-2 agonists
What is the mechanism of action of an opioid receptor?
-opioid binds to receptor
-G protein is activated
-adenylate cyclase is inhibited
-less cAMP is produced
-Ca+ conductance is decreased
-K+ conductance is increased
What is the precursor of Endorphins?
pre-proopiomelanocortin
What is the precursor of Enkephalins?
pre-enkephalin
What is the precursor of Dynorphins?
pre-dynorphin
What is the endogenous ligand for the mu receptor?
Endorphin
What is the endogenous ligand for the delta receptor?
Enkephalin
What is the endogenous ligand for the kappa receptor?
Dynorphin
Which receptor subtype causes bradycardia?
mu
Which receptor subtype has no CNS effects?
delta
Which receptor subtype does not cause miosis?
delta
Which receptor subtype causes N/V, increased biliary pressure, and decreased peristalsis?
mu
Which receptor subtype does not cause pruritis?
kappa
Which receptor subtype has an anti-shivering effect?
kappa
What are the gender differences in women noticed with administration of morphine?
-greater analgesic potency
-slower onset of action
-longer duration of action
-lower postoperative opioid consumption
Which drugs are naturally occurring phenanthrene derivatives?
morphine
codeine
thebaine
Which drugs are semisynthetic morphine derivatives?
hydromorphone
heroin
naloxone
naltrexone
Which drugs are semisynthetic thebaine derivatives?
oxycodone
Which drugs are synthetic piperidines?
meperidine
Which drugs are synthetic phenylpiperidines?
fentanyl
sufentanil
remifentanil
alfentanil
Which drugs are synthetic diphenylpropylamines?
Methadone
What is the order of relative potency of opioids with equianalgesic IV dose?
Meperidine (0.1-100 mg)
Morphine (1-10 mg)
Hydromorphone (7-1.4 mg)
Alfentanil (10-1000 mcg)
Remifentanil (100-100 mcg)
Fentanyl (100-100 mcg)
Sufentanil (1000-10 mcg)
What is the term for when a person taking a drug will go through withdrawal upon discontinuation of that drug?
dependence
What is the term for when a patient requires higher doses of a drug to achieve a given effect?
tolerance
What is the term for when tolerance to one drug produces tolerance to another drug that has similar functions or effects?
cross-tolerance
What is the term for when a person cannot stop using a drug despite the negative consequences from using that drug?
addiction
What are the signs and symptoms of opioid withdrawal?
early: diaphoresis, insomnia, restlessness
late: abdominal cramping, N/V
Which of these has the longest duration of withdrawal?
-methadone
-morphine
-fentanyl
methadone (6-7 weeks)
morphine (7-10 days)
fentanyl (4-5 days)
Which opioids have active metabolites?
morphine (M6G)
meperidine (normeperidine)
Which opioids should be avoided in dialysis patients?
morphine and meperidine due to their active metabolites being excreted in the urine
What are the side effects of Normeperidine?
reduced seizure threshold and increased CNS excitability
What is Remifentanil dosage based on?
lean body weight
*metabolized in the plasma
Which opioid should be avoided in patients taking MAO inhibitors?
Meperidine
*risk of serotonin syndrome
What are the s/sx of serotonin syndrome?
hyperthermia
mental status changes
hyperreflexia
seizures
death
What are examples of MAO inhibitors?
phenelzine, isocarboxazid, and tranylcypromine
What are the anticholinergic effects of Meperidine?
tachycardia, mydriasis, dry mouth
Which opioids have an antishivering effect?
Meperidine & Butorphanol
*kappa stimulation
Which opioids cause histamine release?
Meperidine
Morphine
Codeine
How is Alfentanil cleared?
Liver P450 enyzmes (3A4)
*low hepatic extraction ratio
What is the most common use for Alfentanil?
blunting the hemodynamic response to short, intense periods of stimulation
*tracheal intubation
What does the administration of Alfentanil and Erythromycin cause?
prolonged respiratory depression
*erythromycin inhibits metabolism of Alfentanil
What receptor does Remifentanil target?
mu
What is the maintenance infusion dose of Remifentanil?
0.1-1 mcg/kg/min
How does the context-sensitive half-time change for Remifentanil?
no change, stays around 4 minutes regardless of infusion duration
What is a major side effect of Remifentanil and how can it be prevented?
-acute opioid-induced hyperalgesia
-ketamine or magnesium sulfate
Which opioid should not be administered in the epidural or intrathecal space?
Remifentanil
*solution contains glycine which is an inhibitory neurotransmitter
What is methadone useful for treating?
-chronic treatment of opioid abuse
-chronic pain syndromes
-cancer pain
What is the mechanism of action of methadone?
-mu receptor agonist
-NMDA receptor antagonist
-inhibits reuptake of monoamines in the synaptic cleft
What is the duration of action of Methadone?
3-6 hours
How is Methadone cleared?
liver P450 enzymes
What is a critical side effect of Methadone?
QT prolongation
What is the dose for Oliceridine?
load: 1-2 mg IV
repeat: 1-3 mg IV
cumulative: <27 mg
What are considerations to take into account for Oliceridine?
-QT prolongation
-risk of hypotension with GA
-risk of seizures with hx
-risk of serotonin syndrome
Which medications are more likely to result in skeletal muscle rigidity?
Sufentanil
Fentanyl
Remifentanil
Alfentanil
What is the best treatment for skeletal muscle rigidity?
paralysis and intubation
Which opioid is difficult to reverse by Naloxone?
Buprenorphine
*high affinity for mu receptor
Which opioid is good for patients with a history of heart disease?
Nalbuphine
Which opioid has the side effect of reflexive coughing?
Fentanyl
Which opioid is used to treat itching caused by other opioids?
Nalbuphine & Naloxone (neuraxial opioids)
What is Naltrexone commonly used for?
ETOH withdrawal
recovering opioid abusers
How long does it take to develop physical dependence of opioids?
about 25 days
What is the dose of Naloxone?
1-4 mcg/kg
What is the duration of action of Naloxone?
30-45 minutes
What are critical side effects of Naloxone administration?
SNS activation: neurogenic pulmonary edema, tachycardia, cardiac dysrhythmias, sudden death
What is the duration of action of Nalmefene?
10 hours
What is the duration of action of Naltrexone?
24 hours
What is a benefit to using Sufentanil?
longer period of analgesia with less respiratory depression
What is a major side effect of Sufentanil?
significant bradycardia which leads to a decreased CO and BP
