10- Opioids Flashcards
codeine
Opioid agonist (morphine derivative)
- prodrug in which 10% of administered dose converted to morphine via demethylation by CYP2D6 to cause analgesia
- people who are rapid metabolizers via CYP2D6 can have inc. active drug levels (can have dangerous effects)
- less 1st pass metabolism when taken orally
- commonly mixed with acetaminophen (Tylenol #3)
fentanyl (Duragesic)
Opioid mu receptor agonist
- 50-100x more potent then morphine (100mcg fentanyl = 10mg morphine)
- onset 3-5 min, with variable T1/2 depending on length of administration
- 100% hepatic extraction (inactive metabolites)
- –clearance directly correlated to liver blood flow
- –decreased with P450 inhibitors (cimetidine, erythromycin)
heroin
Opioid agonist (morphine derivative)
- acetylated morphine
- 2-4x more potent then morphine with faster onset
hydrocodone (Vicodin)
Opioid agonist (morphine derivative)
- metabolized to hydromorphone by CYP2D
- commonly mixed with acetaminophen
hydromorphone (Dilaudid)
Opioid agonist (morphine derivative)
- about 5x more potent then morphine and more lipid soluble so faster onset
- onset in 5min; peak 10-20min
- can be given IV or PO
- 1-2mg IV Dilaudid = 10-20mg IV morphine
- glucuronide metabolism forms hydromorphone-6G (less efficacy then morphine-6G) and hydromorphone-3G (inactive metabolite)
meperidine (Demerol)
Opioid agonist
- 1/10th the potency of morphine but more lipid soluble so has faster onset
- less bradycardia and resp. dep. than with equianalgesic dose of morphine
- dysphoric and psychotomimetic effects- kappa receptor
- metabolized in the liver which produces an active metabolite normeperidine that has T1/2 of 14-21 hrs (can cause seizures and death)
- useful for post-op shivering
- inhibits serotonin reuptake and can cause Serotonin Syndrome in ppl taking MAOIs or SSRIs
morphine
- classic mu opioid receptor (mu 1 and 2) and influences motivational-effective aspect of pain
- only 23% non-ionized and able to cross BBB and also has low lipid solubility (1.4) so slow onset of action
- T1/2 of 2-3 hours and DOA of 4-6 hrs
- decreases ventilatory responses to inc. CO2 AND dec. O2
- metabolized (70%) in liver via glucuronidation
- liver disease has minimal effect on metabolism
- –reduced blood flow will slow metabolism
- metabolites excreted by the kidney
- –M-3-glucuronide 75-85% inactive metabolite
- –M-6-glucuronide 5-10% active metabolite (10x more potent then parent morphine)
- excretion of active metabolite can be impaired in renal disease leading to dangerous build-up
Alfentanil
μ receptor agonist
- roughly 10x more potent than MSO4 and 1/10th to 1/4th the potency of fenatnyl (1000mcg Alfent=100mcg Fent=10mg MSO4).
- Rapid onset of action (1-2”)
- Approximately 90% in the unionized form at physiological pH
- lower lipid solubility than fentanyl, so less accumulation in tissues.
- metabolized in liver, no active metabolites.
- Give in small increments to decrease onset of respiratory depression.
Remifentanil
μ receptor agonist
-“equipotent to Fentanyl”
-Very rapid onset (1”) and offset
-Offset not determined by length of infusion.
+metabolized by nonspecific esterases
-Not great for continued, ongoing pain post-op.
-Dose long acting narcotic and allow MEC to be reached before stopping Remi gtt to prevent hyperalgesia.
buprenorphine (Buprenex)
μ receptor Agonist-antagonist
- partial μ receptor agonist and K receptor agonist
- high affinity for μ (hard to reverse)
- good for opioid addiction at higher doses.
nalbuphine (Nubain)
μ receptor Agonist-antagonist
- K receptor agonist, partial μ receptor agonist, and μ receptor antagonist.
- good for acute moderate to severe pain (not for chronic pain).
- lower S/E profile.
- butorphanol is similar, but nubain is 10x more potent than butorphanol.
pentazocine (Talwin)
Opioid receptor Agonist-antagonist
- 2 isomers, but only + has affinity for K receptors.
- has ceiling effect.
tramadol
μ receptor partial agonist
- also inhibits MAO reuptake.
- metabolized by CYP2D6 to active metabolite
- combined with acetaminophen (Ultracet)
- for mild to moderate acute and chronic pain.
tapentadol
μ receptor partial agonist
- also inhibits MAO reuptake.
- less pharmacological variability than tramadol.
- greater μ receptor efficacy
- metabolized by CYP2C9, 2C19, and 2D6.
- for mild to moderate acute and chronic pain.
opioids
mu, kappa, delta receptor agonist
analgesic effects and other unwanted side effects
inhibit NT- block Ca2+ influx and increase K+ efflux
nocieptors
specialized nerve endings
gate control theory- input from afferent and nociceptors are gated in the spinal cord (T cell and substantia gelatinosa)
opioid intoxication
overdose
sedation, stupor, coma, death
-unresponsive, respiratory depression, pupil constriction
serotonin syndrome
Delirium
Fever
Convulsion
Meperidine inhibits the re-uptake of serotonin
dynorphins
endogenous opioid for the KAPPA receptor
endomorphins
endogenous opioid for the MU receptors
endorphins
endogenous opioid for the MU and DELTA receptor
enkephalins
endogenous opioid for the DELTA receptor
delta receptor
Location: BRAIN
Action: analgesia, antidepressant effects, CONVULSANT EFFECTS, physical dependence
kappa receptor
Location: brain, spinal cord, peripheral sensory neurons
Actions: analgesia, anticonvulsant effects, dissociative & delirium, diuresis, dysphoria, miosis, sedation, REDUCED SHIVERING
mu receptor
Location: brain, spinal cord, peripheral sensory neuron, intestinal tract
Actions: sedation, analgesia, physical dependence, respiratory depression, miosis, euphoria, reduced GI motility, vasodilation
motivational-affective
unpleasantness and bother to the patient (nauseating, sickening)
- opioids are most effective against this dimension of pain
sensory-discriminative
sensation, location, quality of pain
CYP2D6
metabolizes codeine to morphine
metabolizes oxycodone to oxymorphone
metabolizes tramadol and tapentadol
CYP3A
metabolize tramadol
morphine glucuronides
M3-glucuronides– 75-85% inactive metabolite, no analgesia, maybe hyper analgesic
M6-glucuronides– 5-10% ACTIVE metabolite, 10x more potent that parent morphine
(excreted by organic ion transporters in the kidney)
addiction
- primary, chronic, neurobiological disease with genetic, psychosocial and environmental factors influencing its development and manisfestations
- characterized by: impaired control over drug use/psychological dependence, compulsive use, continued use despite physiologic, psychosocial and/or econonmic harm, craving
- uncommon with appropriate medical treatment of acute pain
physical dependence
- withdrawl symptoms that are precipitated when an opioid agonist is stopped or an antagonist is given
- develops concurrently with tolerance
- common with prolonged use
psychological dependence
- impaired control over drug use
- taking it for the reinforcement
- related to the mesolimbic dopamine system
tolerance
decreased response to a drug with repeated use
develops to most opioids, but not to ocular/GI effects
withdrawl
s/sx: restlessness, insomina, perspiration, abdominal cramps, nausea, vomiting, diarrhea, tachycardia, tachypnea, HTN, hypotension, hot/cold flashes
-gradual reduction of the opioid dose may reduce or eliminate s/sx
side effects of opioids
bradycardia constipation dysphoria euphoria itching miosis othrostatic hypotension respiratory depression sedation stupor/coma vasodilation vomiting
Sufentanil
highly selective for μ receptors (synthetic derivative).
-Roughly 500-1000x more potent than eqivalent dosing of MSO4.
+5-10mcg Sufent=5-10mg MSO4.
-more lipid soluble than fentanyl, remifentail, and alfentanil.
+slower onset and offset than remifentanil and alfentanil.
+plan to discontinue infusion about an hour or so before conclusion of case to allow for offset.
-we do not have sufentanil on formulary at UIHC
oxycodone
- less first pass metabolism. CYP2D6 active metabolite oxymorphone
- sustained release when taken whole, bolus dose when crushed
methadone
- ultra long acting, half-life 15-60 hours
- useful for chronic pain management, addicted patients maintenance
naloxone
- competitive antagonist at mu, kappa, and delta receptors
- IV or IM effective in 1-2 minutes
- half-life 60 min (3hrs in infants), may need to redose for opioid reversal
- metabolized via glucuronidation
naltrexone
- oral opioid antagonist, much slower than naloxone, not for acute reversal
oxymorphone
- mu receptor and partial delta receptor agonist. 6-8 times more potent than morphine
- oral medication, NOT metabolized by CYP2D6
