Opioids Flashcards
How do you treat opioid-induced biliary spasms?
Naloxone or glucagon to relax
the sphincter muscle
Which opioid should not be used in patients taking MAOI?
Meperidine (demerol) because it can lead to serotonin syndrome
If the potency of morphine is 1, what are the relative potencies of meperidine, codeine, methadone, butorphanol, hydromorphone, nalbuphine, alfentanil, fentanyl, and sufentanil?
Most —> least potent:
sufentanyl
Fentanyl
Alfentanil
Hydromorphone
Morphine - codeine
meperidine
Are opioids lipid soluble or water soluble?
high lipid soluble
rapidly cross BBB
Which opioids are strong? medium?
The lipid solubility of opioids affects their…
onset and duration
T/F
the lungs can serve as a reservoir of opioid drug molecules
true
Opioids are classified on the basis of…
their synthesis
chemical structure
potency
receptor binding
effect at the opioid receptors
Natural opioid
morphine
Semisynthetic opioid
hydromorphone
Synthetic opioid
fentanyl
alfentanil
sufentanil
remifentanil
meperidine
piperidines
Drugs with high ___ solubility cross the BBB.
lipid
Properties affecting the passage of the drug into the brain across the blood-brain barrier
o Molecule size
o pKa : affects the degree of ionization of the molecule and depends on the plasma pH
o Protein binding: to albumin and a 1-acid glycoprotein
o Lipid solubility
The piperidines are (natural/semi-synth/synthetic).
synthetic
The piperidines
- Lipophilic opioids that rapidly cross the BBB
*shared backbone - Fentanyl
- Sufentanil
- Alfentanil
- Remifentanil
Fentanyl
o x100 more potent than morphine
o Decrease CV responses to noxious stimulation from laryngoscopy, intubation, skin incision and surgical stress
o Lasts abt 10-20 min (dose dependent)
Sufentanil
o a thienyl derivate of fentanyl and about 10-times more potent than fentanyl
o 1000x potent > morphine
o its lipophilicity is two times greater than that of fentanyl
o long acting
Remifentanil
o Is not metabolized in the liver and is 100 to 200x more potent than morphine
o methyl ester side chain that is metabolized by blood (within the erythrocyte) and tissue nonspecific esterase’s
o Rapid action & clearance (context sensitive half-life of 2-3 minutes)
o Extrahepatic clearance
o Usually infusion; decreases by 50% in as little as 40 seconds
o MAC (minimim alveo. [ ]) is reduced w a remifentanil infusion
o Very fast wake up!
Which piperidine is not metabolized in the liver?
Remifentanil
T/F
Ketamine is a non-opioid that works on opioid receptors.
True
it works at NMDA (antagonist) & opioid receptors
Requirements for inhalational anesthetics and propofol are reduced by about 50% when administering ___ IV fentanyl
1.5 to 3 μg/kg
decreases cardiovascular responses to noxious stimulation
Fentanyl
thienyl derivate of fentanyl
Sufentanil
Longer duration
good for longer cases
bonds stronger than fentanyl
Sufentanil
Benefits of using opioids
less volatile anesthetic
faster wake up
Clearance of remifentanil is ____ L/min. Liver blood flow is ___ L/min. This affirms its ____ clearance.
3-5 L/min
2-3 L/min
extrahepatic
Remifentanil plasma levels decrease by 50% in…
40 seconds
give as infusion
MAC (minimum alveolar concentration) is reduced with ____ infusion.
remifentanil
Opioid-induced hyperalgesia (OIH)
-paradoxical opioid effect
-pain sensitivity increases during/after escalating opioid treatment
-postop if using remifentanil infusion
-treated/prevented: low dose of ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist
Treatment of Opioid-induced hyperalgesia (OIH)
Antagonism of the NMDA receptor
(low dose Ketamine)
various mechanisms for OIH
-activation of the central glutaminergic system
-central nitric oxide production
-facilitation of descending pronociceptive systems.
Most piperidines are metabolized by…
CYP 450 enzyme system
most rapidly acting opioid currently available
remifentanil
T/F
Piperidine can anesthetize patients.
False
no amnesia
need other drugs
contains a methyl ester side chain that is metabolized by blood & tissue nonspecific esterases
Remifentanil
not metabolized in liver
ReMi —> Methyl ester chain
T/F
Emergence from remifentanil is longer than other opiods.
False
fast wake up
“Rapid remi”
Heroin
AKA diamorphine
-boiling morphine with specific acids
-two −OH groups —> −OCOH3 = heroin
Hydromorphone preparation
2mg/1 ml vials
mix with 9 cc of NS in a 10 cc syringe
(.2 mg/cc titrated to effect)
Hydromorphone is mostly used in which settings?
intraop
PACU
More frequently associated with nausea/vomiting
hydromorphone
Which opioid has low lipophilicity?
morphine
Morphine
- Natural
- Low lipophilicity (crosses the BBB slowly)
- Rapid metabolism in the liver
- Excreted via the kidney (renal dysfunction=accumulation)
- Most often given in the PACU rather intraoperatively
⭐️
How do opioids cause bradycardia?
-affect central and peripheral cardiac sites
Central:
-activate vagal nuclei
-depress brainstem vasomotor centers
Peripheral: (supraclinical doses)
-direct myocardial depression
-arterial and venous dilatation
-Morphine additional effects; release of histamine; mild at clinical doses; orthostatic hypotension, mild bradycardia, reduction of systemic & pulmonary resistance
Opioid associated with histamine release
morphine (mild histamine release)
additional effects:
orthostatic hypotension
mild bradycardia
reduction of systemic & pulmonary resistance
Meperidine in cardiac patients may cause
tachycardia
Opioids can contract the sphincter of Oddi which causes…
-increases biliary pressure
can be reversed with either naloxone or
glucagon
N/V from opioids is caused by…
-stimulates the CTZ-chemoreceptor trigger zone in the
postrema of the brainstem
-increased sensitivity of the vestibular apparatus
-direct effects on the GI tract
-PONV history
Opioids during gallbladder surgery
not ideal
Contraction of the sphincter of Oddi (increases biliary
pressure)
wont see contrast in choliangiogram
Opioids in sleep apnea pts
decrease central hypoxic drive to breathe & CO2 sensitivity
short acting, minimum dose
avoid
Wooden Chest Syndrome
all opioids; esp fentanyl
concomitant use of dopamine altering meds
rapid IV administration
rigid chest
CANNOT VENTILATE
reverse Rx (full dose Narcan) or paralyze
Naloxone
Narcan
reverse opioid toxicity
short acting 15-45 mins
displaces opioid from Mu receptors
Naloxone duration of action
15-45 mins
often given as drip
Naloxone dosing
Titrate (40 mcg at a time every 1-2 minutes until good
respirations/ventilation)
0.4 mg per vial, 1 vial Narcan diluted n 9 cc NS = 40
mcg/cc
(1 mg=1000mcg)
Naloxone displaces opioids from ___ receptors. It can do this because…
Mu
stronger affinity for receptor than opioids
knocks opioid off receptor
Side effects of Naloxone (reversing narcotics)
Pulmonary edema
Cardiac arrhythmias
Hypertension
Seizures
Cardiac Arrest
Sudden pain
Why notify PACU if you give Narcan?
risk of being reintubated in PACU
“re-narcotization” is high with opioids with a longer plasma half-life because the rate of decay in the plasma of naloxone is short
Which opioids are metabolized by the liver?
Fentanyl, alfentanil, and sufentanil
High volume of distribution in lipophilic opioids with
low protein-binding affinity
fentanyl
Moderate potency opioids
morphine
hydromorphone
Low volume of distribution due to high clearance and/or high protein binding
Remifentanil
Morphine is excreted via ____. Careful consideration in ____ patients.
kidneys
renal dysfxn (accumulation)
How is morphine metabolized?
rapid
UGT2B7
liver
Within minutes after admin, hydrophilic metabolites are present in plasma.
60% converts to morphine-3-glucuronide (MG3)
5-10% to morphine-6-glucuronide (M6G)(active).
Slow limited crossover to BBB
How remifentanil metabolized?
1/2 life?
rapidly metabolized by non-specific blood and tissue esterases. Half life is about 3-10 mins
Peak analgesic effects for IV doses?
1-2 H
Morphine is an agonist for which class of opioid receptors?
Full MOR agonist
What are the most prominent CNS effects of opioids?
Analgesia
sedation
respiratory depression
hypotension
bradycardia
What is the proposed site of action of neuraxial opioids?
The exact site of action of subarachnoid and epidural anesthesia remains unknown
How do opioids affect the CO2 response curve?
Decrease in slope and shift to
the right
Which morphine metabolite is active?
morphine -6-glucuronide
How do opioids affect cerebral blood flow?
Reduce CBF, usually proportional to
the decrease in CMRO2. (brain blood flow is based on metabolic needs)
What are the mechanisms of opioid-induced hypotension?
Depression of vasomotor centers in the brainstem, causing vasodilation
Which opioid is cardiac depressant and increases heart rate?
Meperidine
What are the effects of opioids on cerebral metabolic rate?
Decreased cerebral metabolic rate, reducing the brains consumption of oxygen.
Which opioid is effective in treating shivering?
Meperidine (Demerol)
Do opioids cross the placenta?
Yes; drugs with low molecular weight diffuse
freely
(Drugs that do not cross Heparin, Insulin, Glycopyrrolate, NDNMB, Succinylcholine)
How do opioids affect the respiratory pattern?
Opioids decrease respiratory rate, and decrease tidal volume
What is the mechanism of opioid-induced bradycardia?
Activation of the vagal nuclei in the brain stem
The receptors where opioids demonstrate effects?
Opioid receptors on neuronal tissues (central and peripheral)
𝛍-opioid receptor (MOR) [mu-1 and mu-2]
𝛅-opioid receptor (DOR)
𝛋-opioid receptor (KOR)
Weak opioids
codeine
tramadol
intermediate strength opioids
morphine, methadone, oxycodone, and buprenorphine
For anesthesia and pain relief, the ___ opioid receptor is most important.
MOR
(μ-opioid receptor )
context-sensitive half-time (CSt½)
time needed for drug plasma concentration to decrease by 50% from a steady-state concentration
For most opioids, context-sensitive half-time (CSt½) is dependent on ____ except for the drug ____.
duration of infusion
remifentanil is independent of infusion duration due to its rapid elimination from plasma
delay between the administration of an opioid and its effect
blood–effect site equilibration half-life, or t½ke0
When should morphine be given when used for post-op pain relief?
give initial bolus dose at least 60 minutes before the end of surgery
t½ke0 (delay between the administration of an opioid and its effect) of morphine is about 90 minutes
How can we lower the probability of apnea when giving opioids?
careful, slow, infusion of opioids allows the gradual accumulation of arterial CO2, which serves as a respiratory stimulant at the chemoreceptors
What kind of drug is nalaxone
opioid antagonist
required dose of naloxone
depends on pharmacokinetic/dynamic properties & dose of the opioid that needs reversal
