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1. 701 Exam 4 Opioids

Terms in this set (118)

what are opiates made from/have in them?
opium
what are two examples of an opiate?
codeine
morphine
How do opioids compare to opiates>
they are "opiate-like" but not made from opium, they have the same effects but not the same chemical structure
what are two examples of opioids?
methadone
demerol
what effect do opioids have on volatile anesthetics?
reduce the MAC
explain the hemodynamic stability of opioids with and without anesthetics
hemodynamically stable when used alone but can cause changes in CO, CV and BP when used with anesthetics
are opioids natural?
no they are semi-synthetic. Made in a lab but is derived using part of natural alkaloids such as morphine
are opiates natural?
yes- from natural alkaloids and derived from opium poppy
what are the neurologic effects of opioids?
-decrease pain perception w/o amnesia
-large doses will lead to unconsciousness with no reliable amnesia
-reduction in CBF, cerebral oxygen consumption and ICP with minimal effect on the the EEG pattern
what kind of effect do opiods have with other CNS depressants? what about with inhaled/IV anesthetics
-CNS depressants: synergistic
-inhaled and IV anesthetics: additive
what effect do opioids have no the respiratory system?
the apneic threshold increases and hypoxic drive decreases
what are the various clinical uses of opioids?
Primary: analgesia
Secondary: sedation
Anesthesia (@ high doses, but more often used as an adjunct)
others: cough suppression (codeine), anti-diarrheal (lamotrigine)
what is the definition of analgesia?
pain relief w/o LOC and total loss of feeling or movement
what is the definition of anesthesia?
loss of physical sensation with or w/o the LOC
What are pharmacodynamics of opioids dependent on?
-the receptor they bind
-the binding affinity
-if activation occurs
What is the mechanism of action of opioids?
opioid receptor agonist
opioid recepors couple with G-proteins and inhibit adenyl cyclase which will:
-inhibit voltage-gated Ca2+ channels
-activates and opens K channels
-increased intracellular K will decrease neurotransmission
what are the opioid receptors?
Mu, Kappa, Delta
what are the physiologic opioid effects?
-pain relief
-cough suppression
-decreased gut motility
-respiratory depression
-pupillary constriction
-itching
-dependence
what are the psychological opioid effects?
-drowsiness/sedation
-mental confusion
-loss of memory
-lethargy
-euphoria
-mood swings
-depression
-withdrawal
-dependence
what are the functions and effects or the Mu1 receptors
-euphoria
-supraspinal analgesia
-confusion
-dizziness
-nausea
-low addiction potential
what are the functions and effects of the MU2 receptor?
respiratory depression
cardiovascular and GI effects
miosis
urinary retention
what are the functions and effects of the Kappa receptor?
-inhibit neurotransmission via type-N Ca channels
-dysphoria and diuresis
-spinal analgesia
-psychomimetic effects
-feedback inhibition of endorphin system
what are the functions and effects of the delta receptor?
-modulate Mu receptor activity
-receptor for endogenous opioids (endorphins)
-responsible for opioid tolerance
-spinal analgesia
-cardiovascular depression
-decreased brain and myocardial oxygen demand
what are each of the opioid receptors antagonized by?
naloxone
Where are opioid receptors located?
CNS, neuroendocrine, immune cells, GI tract, and the biliary system
what are the endogenous opioids and what receptor do they bind to?
enkephalins: mu and delta
dynorphins: kappa
beta-endorphins: mu and delta
If a receptor is supraspinal, where is it typically located?
periaqueductal gray matter
If a receptor is spinal, where is it typically located?
substania gelatinosa
how do opioids work in the spinal cord?
they inhibit the release of substance P from primary sensory neurons in the dorsal horn. which attenuates the transmission of painful stimuli from peripheral nerves to the cerebral cortex.
how to opioids work in the brain stem?
opioids act at the descending inhibitory pathways to attenuate painful stimuli
mechanisms of absorption of opioids
oral, IV, oral transmucosal, IM and transdermal
what three mechanism of absorption are rapid?
IV, oral transmucosal and IM
what is the peak time for IM opioids?
20-60 minutes
why do we use fentanyl as a transdermal patch?
low molecular weight and high solubility
onset and duration of action for an opioid will depend on...
ionization and lipid solubility
what will the onset and duration be for an nonionized and lipophilic opioid? why?
fast onset, short duration
easily crosses the BBB but then leaves the CNS following its concentration gradient
where do opioids commonly redistribute to?
skeletal muscle or fat
what happens when you give high doses of lipid soluble opioids in regard to distribution?
they will saturate the inactive tissues and thus accumulate in the plasma resulting in a longer DOA
what are the faster acting iv opioids? what are their peak effect times?
remifentanil, alfentanil, fentanyl, sufentanil
remi and alfent: 1.5
fentanyl: 3-5 minutes
sufent: >5 minutes
what IV opioids are not as fast acting/slower. peak. times?
dilaudid and morphine
at what frequency will providers order fentanyl? morphine/dilaudid?
fentanyl: q5 minutes
morphine and dilaudid: q 10-30
how are opioids metabolized?
liver - CYP3A4
how are opioids excreted?
the kidneys
why should be careful when administering opioids in patients with renal failure?
many opioids have active metabolites
what is special about remifentanil metabolism?
they are not metabolized by the liver. there are plasma esterases that that hydrolyze in the blood and tissues
in what situations would remifentanil be a good option? why?
-short painful procedures
-as an infusion for longer sedation procedures and GA
has a very short context-sensitive half time and the effects will terminate shortly after the infusion is stopped. always 3-5 minutes
what is special about fentanyl's metabolism?
also has extrahepatic metabolism in the lungs
what is the role of the first pass effect?
to convert drugs to less lipophilic molecules that are more easy to excrete
what is the context-sensitive half time?
Time necessary for plasma concentration of a drug to decrease 50% after discontinuation of a continuous infusion.
what is unique about fentanyl's context sensitive half time?
once you run a fentanyl infusion longer than 60-120 minutes, the half time becomes significantly longer because fentanyl starts to accumulate in the fat. at the same time fentanyl has a very predictable curve for "return to breathing" making it useful for infusion
what are two most opioids that have active metabolites? what are those metabolites?
morphine: morphine-3-glucuronide and morphine-6-glucuronide
meperidine: normeperidine
what is the concern with morphine-6-glucuronide?
potent analgesic properties and has a longer half life than the original compound
what is the concern with normeperidine?
potential for accumulation in chronic renal failure patients that will lead to CNS excitatory effects:
-anxiety
-tremors
-possibly seizures in large dosages
what opioids are safe with chronic renal failure patients?
fentanyl, alfentanyl, remifentanyl
what are common s/e of opioids?
-sedation
-resp depression
-chest wall rigidity
-bradycardia
-hypotension
-pruritus
-n/v
-ileus
-urinary retention
-miosis
what opioid does not have a side effect of bradycardia?
meperidine, this medication has atropine like effects and leads to increased HR and dry mouth
what opioid most commonly has a histamine release? what does this cause?
morphine
results in pruritis, vasodilation and hypotension
-according to outline bronchospasm
what opioids most commonly cause chest wall rigidity?
fentanyl and sufenta
why do most opioids cause bradycardia?
vagal nucleus stimulation
what are the immune effects of opioids?
-depress cellular immunity by inhibiting IL-2 transcription
-impair wound healing
-may contribute to cancer recurrence
what can opioids administration with MAOis lead to?
serotonin syndrom
what are most cases of serotonin toxicity provoked by?
-therapeutic doses of tow or more serotonergic drugs
what are common serotonergic drugs?
antidepressants-MAOI, TCA, SSRI, SNRI
antipsychotics
opioid analgesic-fentanyl, tramadol, meperidine, methadone and sometimes morphine
what other serious syndromes can serotonin syndrome mimic?
MH
sepsis
thyroid storm
neuroleptic malignant syndrome
What are the S/S of serotonin syndrome?
Hot, shakes, delirious, dead
-Hot: Fever, sweating
-Shakes: chills, myoclonus
-Delirious: agitation, confusion
-Dead: respiratory depression, coma and death
Another way to remember the s/s of SS is the triad of changes. what is the triad?
-NM hyperactivity
-ANS hyperactivity
-Changes in mental status
what is the most common reversal agent for opioid intoxication and how does it work?
naloxone; it competitively binds to the mu receptor to reverse the opioid intoxication. the sympathetic release of epi in the plasma from large doses of narcan will also antagonize the mu-opioid receptors in the adrenal medulla
how do we dilute naloxone?
-common concentration is 0.4 mg in 1 mL
-we dilute with 9 mL of saline to get a concentration of 0.04 mg/mL
how much naloxone should be enough for anesthesia purposes to get respiratory function? what about in an emergency?
-0.04-0.12 mg (1-3 mL diluted)
-0.4-2mg (1-5 mL undiluted)
what s/e do large naloxone doses have other than opioid reversal?
catecholamine-mediated response:
-HTN, tachycardia and diaphoresis
-fluid shift from sympathetic outflow will lead to increase blood volume in the pulmonary system and cause PHTN which can lead to pulm edema
-N/V
what is the DOA and half life of naloxone?
half life is 1 hour and DOA is 30-60 minutes
equianalgesic chart for fentanyl, hydromorphone, morphine, meperidine
fentanyl: 100 mcg
hydromorphone: 1.5 mg
morphine: 10 mg
meperidine: 75 mg
what is the prototype opioid agonist?
morphine
what kind of pain is morphine more effective for?
continuous, dull pain
what is morphine's onset, peak, DOA and starting dose and a common bolus dose?
onset: 5-15 minutes
peak: 20-30 minutes
DOA: 2-4 hours
starting dose: 0.1-0.2 mg/kg
bolus dose: 1-5 mg
what are the effects of opioids on the carbon dioxide response curve and what do that does this mean? what about hypoxic drive?
opioids shift the curve down and to the right meaning for a given carbon dioxide level, the alveolar ventilation will be reduced and an increase in arterial carbon dioxide will not stimulate ventilation as you would expect.
-impairs hypoxic drive
the depression of ventilation from opioids will manifest as....
decreased RR and increase Vt
what are the uses for meperidine?
local anesthetics and to treat shivering
what structure is meperidine similar to?
atropine so will have anticholinergic propoerties
what kind of medications would you want to avoid in meperidine?
MAOIs (marplan and nardil)
what kind of patient would you want to avoid meperidine administration?
renal failure or renal insufficiency. Accumulation of the metabolite normeperidine can cause seizure activity
what effect of merperidine is similar to morphine?
histamine release and will cause euphoric effects with less respiratory depression
what is a typical dose for merperidine?
12.5-50 mg IV/IM
what medication is often given with IM Meperidine?
hydroxyzine (vistaril)- antihistamine
what dose is is IM meperidine given for outpatient surgeries? what does it do?
50 mg IM
sedation, pain and reduces PONV
How does hydromorphone compare to morphine?
similar pharmacokinetic profile but is more potent
Does dilaudid have an active metabolite?
no
dilaudid: onset, peak and DOA
onset: 15-30 minutes
peak: 30-90
duration: 4-5 hours
what is a common dosage of dilaudid to give in the perioperative period?
0.2-0.4 mg IV
chronic opioid users: 0.5-1 mg IV
is there a histamine release with dilaudid?
no
how does fentanyl work?
stimulates the mu receptor
how would you intervene if a patient had chest wall rigidity from fentanyl?
NMB or opioid antagonist
what is the onset, peak and DOA of fentanyl?
onset: 2-5 minutes
peak: 20-30 minutes
DOA: 30-60 minutes
how much time after administration of high dose fentanyl poses the greatest risk for respiratory depression?
5-15 minutes
what is the induction dose for fentanyl? what does it aid in during induction?
1-2 mcg/kg
prevents SNS activity during laryngoscopy
what is the bolus dose for fentanyl?
25-100 mcg
what is vital for the termination of action of fentanyl?
hepatic blood flow
what kind of metabolite is fentanyl converted into?
inactive
what is the context sensitive half life?
very long
If a procedure requires a patient to not move and NMB cannot be used, what opioid infusion is useful?
remifentanil
How is remifentanil metabolized?
rapidly by plasma esterases
what is common side effect of remifentanil?
bradycardia
what are negative s/e of long, high dose infusions of remifent?
opioid induced hyperanalgesia
what can happen if you suddenly stop a remifent drip?
acute opioid tolerance
what is a typical dose of remifentanil?
25-100 mcg IV bolus
0.05-0.15 mcg/kg/min IV infusion
what phase of care should you avoid remifent bolusing? why?
pre and post op.
potential for resp depression and muscle rigidity
most common dilution for remifent infusion? (according to the transcript)
50 mcg/mL
you can add 1 mg to 20 mL or 2 mg to 40 mL
how do we commonly administer sufentanil?
infusion
great for intraop pain control
if you use sufentanil, when should you turn off the infusion?
30 minutes prior to the end of surgery
which opioid is the most potent opioid commercially available for human use?
sufentanil
dosing of sufentanil
infusion: 0.2-1 mcg/kg/hr
IV: 5-15 mcg
at what infusion does is the context sensitive half time very reliable for sufentanil?
0.2-0.4 mcg/kg/hr
how to dilute sufentanil
vial is 250 mcg/5 mL
you want to dilute down to 10 mcg/mL:
-1 mL of sufent with 4 mL of NS will given you 50mcg/5 mL=10mcg/mL
-4 mL of sufent with 16 mL of NS in a 20 mL syringe will give you 200 mcg/20 mL=10mcg/mL
how is alfentanil commonly adminstered?
as a bolus for short periods of intense pain (ENT, Eye blocks, CABG induction)
Why is alfentanil metabolized so quickly?
nonionized and Short Vd (cross BBB rapidly)
alfentanil has a higher incidence of what?
chest wall rigidity and respiratory depression
what is the dosage for alfentanil?
150-300 mcg IV
when does alfent reach its peak effect?
90 seconds
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