Flashcards in Opioids Deck (47):
Which opioid is Fentanyl chemically related to?
Describe chemical component of opioids:
-neutral o rionized
high protein binding
largely ionized at physiologic pH
How would causing decreased protein binding and un=ionized forms of opioids effect their behavior?
- shorter latency to peak effect
MOA of opioids (general/basic)
Bind opioid receptor- G protein linked
downstream effects cause hyperpolarization of cell, and decreased neuronal excitability
mediators- K+ channel, AC, MAPK, Voltage gated Ca+ channels
Name the types of opioid receptors
(ORL1)- unclear clinical relevance
Major effect of opioids at
1. spinal cord
1. Spinal cord
a. inhibit release of substance P from primary sensory neurons in DH (mitigates painful sensation transfer to brain)
2. Brainstem- block nociceptive transmission from DH of SC via descending inhibitory signals
3. Forebrain- alter affective response to pain
General metabolism of opioids
Hepatic microsomal metabolism (conjugation)
Excreted by kidney
**not case with all**
Order the following opioids from QUICKEST peak effect to SLOWEST peak effect for a BOLUS
Alfentanil/Remifentanil --> Fentanyl -->Sufentanil -->Morphine
Order the following opioids from QUICKEST peak effect to SLOWEST peak effect for a INFUSION
Remifentanil -->Alfentanil --> Sufentanil -->Fentanyl/Morphine
Which opioids would be preferred in bolus form if you desire a brief duration with rapid dissipation?
Remifentanil or Alfentanil
Which opioid is best suited for a PCA? Why?
Fentanyl > Morphine
Peak effect as seen on front end kinetics shows that greatest effect of Fenatnyl occurs before "lock out period" ends for PCA...avoiding dose stacking and OD risk
What determines the latency to peak effect?
which factors effect this most?
speed that plasma and effect site come to equilibrium
i.e. Faster = Higher proportion of drug that is "diffusible", i.e. unbound and un-ionized.
Faster = higher lipid solubility
Clinical implication of stead-state concentration of opioid constant rate infusion? Exception to this?
- Latency to reach steady state effect
- demonstrates need for bolus prior to infusion to bridge to peak effect
Which drug is a good choice for total IV anesthesia for opioids?
Remifentanil- reaches a steady state quickly (drug will not be continuing to increase in concentration for hours despite continued or lowered infusion rate)
Define Context Sensitive Half Time (CSHT)
Time required to achieve a 50% decrease in concentration of drug after stopping continuious steady state infusion
How does decrease in opioid rate change over time re: infusion duration?
Longer duration = longer CSHT (Except Remifentanil)
Helps to determine which opioid is best based on case duration and length of time needed for drug
Major Mu opioids
Major opioid group with venitilatory depression
major opioid group with GI effects
mu and kappa
major opioid groups causing sedation
mu and kappa
Major side effects of opioids
1. Supraspinal/spinal analgesia
2. Miosis (small pupils)
3. cough suppression
4. vasodilation (hypotension)
6. ventilatory depression
7. increased biliary pressure
10. delayed gastric emptying
12. muscle rigidity
Which "type" of pain are mu opioids best at treating?
"second pain" - slow conducting unmyelinated C fiber pain
vs "first pain" via small myelinated A delta fibers or neuropathic pain
MOA of opioid induced vent depression
alter vent response to arterial CO2 in medulla (threshold for increase is paCO2 of 40 mmHg, linear increase there after, but slowed)
Both Vt and RR decrease --> progress linearly with increased conc until apnea
regulated via mu receptor
Factors increasing risk for opioid OD
1. large opioid dose
2. old age
3. use of other CNS depressants (benzos, etc)
4. renal insufficiency (for morphine)
5. natural sleep
CV effects of opioids (fentanyl, morphine)
Fentayl vs Morphine, greater CV effects?
Bradycardia (increased vagal nerve tone)
hypotension (vasodilation via brain effects, decrease pre and afterload)
Morphine > Fentanyl
Side effect that may make ventilation difficult with bolus doses of fentanyl?
muscle rigidity, causing vocal cord rigid/closure (hard to ventilate)
can be eliminated by NM blocking drugs
MOA of opioid induced nausea
chemoreceptors in area postrema on floor of 4th ventricle
worse with movement
Major pharmacokinetic interaction of opioids with other drugs
Opioids given with propofol infusion result in higher opioid concentrations
Major pharmacodynamic effect of opioids with other medications
synergy when combined with sedatives
moderate opioid levels dramatically reduce MAC of inhaled anesthetics (substantially, up to 75%).
Reduction is NOT complete...opioids are not a complete anesthetic
Which opioid is completely unaffected by the anhepatic phase of a liver transplant?
remifentanil- metabolism is completely unrelated to hepatic clearance
Pt population at increased risk of sedative effects of opioids?
pts with hepatic encephalopathy
Which opioids are affected by renal failure?
morphine - nearly half of the conjugation of morphine occurs in the kidney (in addition to excretion of m3g and m6g*active)
meperidine - active metabolites are excreted by kidneys. build up of normeperidine causes tremors, anxiety, frank seizures
Gender differences in opioid effects
Morphine - more potent in women, slower onset in women
Age differences in opioid effects
older = more potency of fentanyl cogeners
Decreased clearance and decreased distribution volume
RESULT: decreased dose requirements (50% reductions) for pts > 65yo
Obesity effects on opioids
Opioid requirements based on lean total body mass, not TBW
extremely obese people will not require doses suggested by their weight because lean body mass is smaller
What is the active component of codeine?
morphine is active compound of this prodrug
Side effects of morphine limiting its use intraoperatively? why?
Histamine release = hypotension (and itching)
Fentanyl routes of administration
Describe metabolism of alfentanil
liver via cyp3a4 (somewhat unrpredictable due to interindividual variation in this enzyme)
most potent opioid used in anesthesia practice
metabolism of remifentanyl
loses mu reactivity = short half life
speed and duration of action of remifentanyl
quick on and quick off (due to hydrolysis)
short CSHT (5 min)
- latency similar to alfentanil
- potency slightly less than fentanyl
Commonly used meds in total IV anesthesia
Remifentanil + Propofol
Questions to ask when choosing and opioid
1. how quick does it need to work?
2. how long will i need it to work?
3. How important is it that vent depression/sedation go away quickly?
4. will the opioid need to be titrated intraop (big changes in analgesia requirements)?
5. will there be a lot of pain post-op?
Your patient is getting a retrobulbar block and you need a brief pulse of opioid effect and then rapid recovery:
Your patient is getting a craniotomy, and neurosurgery wants to do a neuro exam on table immediately post-op (need good pain control, but awake/alert soon after procedure: