Week 2- OR Safety & Opioids Flashcards
The synthesis of heroin in 1874 was based on the empirical finding that boiling _________ caused the replacement of the two groups: __________ by __________
Morphine; -OH by -OCOH3
7 uses of opioids
- preoperative meds
- anesthesia
- Induction
- intraop pain control
- post op pain control
- spinal/epidural anesthesia
- OB
Normal fentanyl dose
50-100 mcg
Common opioid added to epidurals and spinal
Duramorph
Name the piperidines
-fentanyl
-sufentanil
-alfentanil
- remifentanil
Piperidine opioids are
Synthetic
Synthetic opioid commonly used for eye blocks due to its fast on/off onset/DOA
Alfentanil
What side effect may be seen after intraoperative morphine use in the postoperative area
Itching
Dilaudid:
Acts on _________ and is an __________
Comes in a ____________ vial
Typically it is ____________
Common name for Dilaudid is _________
Mu, agonist
10 mg/cc
Diluted
Hydromorphone hydrochloride
What type of agonist/antagonist is Ketamine and on what receptor does it act
NMDA receptor antagonist, also works on opioid receptors
Clinical effects of acting on mu-1
- supraspinal analgesia
- bradycardia
- Sedation
- pruritis
- N/V
Examples of mu-1 agonists
Morphine and meperidine
Clincal effects of acting on mu-2
- respiratory depression
- euphoria
- physical dependence
- pruritis
- constipation
Clincial effects of acting on the K (kappa) receptor
- Spinal analgesia
- respiratory depression
- sedation
- miosis
Clinical effects of acting on the delta receptor
- spinal analgesia
- respiratory depression
Example agonists of the mu-2 receptors
Morphine and meperidine
Example agonists of the kappa receptors
Fentanyl, morphine, and nalbuphine
Example agonists of delta receptors
Oxycodone, B-endorphine, Leu-enkaphalin
Are piperidines lipophilic or lipophobic
Lipophilic
Where are fentanyl, alfentanil, and sufentanil metabolized and what enzyme catalyzes these breakdowns
Liver; cytochrome P450 enzyme system
How much more potent is fentanyl than morphine
~ 100 x more potent
Why is fentanyl typically used in anesthesia
To decrease CV response to noxious stimuli from laryngoscopy, intubation, skin incisions, and surgical stress
Administering fentanyl can decrease inhalational anesthetic requirements by 50% by administered _________________ IV fentanyl
1.5-3 mcg/kg
The two most pain provoking things that occur in surgery
Intubation and skin incision
T or F: Fentanyl is considered an “additive drug”
T
Sufentanil is a ___________derivative of fentanyl and is _________ more potent than fentanyl
Thienyl; 10 X
What meds lipophilicity is 2x greater than fentanyl’s
Sufentanil
Is sufentanil metabolized to inactive or active compounds
Both
Where is sufentanil metabolized
Liver
Metabolizes remifentanil
Blood and tissue nonspecific esterases
What type of chemical side chain on remifentanil affects its metabolization
Methyl ester
CSHL of remifentanil
2 minutes
Most rapidly acting opioid available
Remifentanil
Clearance of remifentanil
3-5 L/min
Is remifentanil metabolized in liver? Why or why not
No. It’s clearance exceeds liver blood flow affirming its extrahepatic clearance
Why is remifentanil usually a continuous infusion
It’s plasma level decreases by 50% in ~ 40 seconds
Active metabolite of ________ can cause seizures
Meperidine
Does morphine cross BBB quickly or slowly? Why?
Slowly due to low lipophilicity
Goal for patient in preoperative timeframe
To RELAX then not to sedate them…. Yet
How long to the onset of action for dilaudid
10- 15 mins
Who tends to have higher effects from narcotics?
Neonates, elderly, patient with OSA
What causes an increase in biliary pressure
Contraction of the sphincter of Oddi as a result of opioid use
Can you reverse the contraction of of the sphincter of Oddi?
Yes with naloxone or glucagon
How do opioids cause N/V
- Stimulates the chemoreceptor trigger zone in the postrema of the brain stem.
- direct effects on the GI tract,
- increased sensitivity of the vestibular system
What can be given to descrease incidence of coughing during an EGD and why
Fentanyl … acts on medullary cough centers
What is wooden chest syndrome
After giving narcotics, you can’t ventilate
Risk factors for wooden (rigid) chest syndrome
- high cumulative doses
- extremes of age
- concamitant use of meds that modify dopamine levels
- rapid IV admin
- critical illness
- lipophilic opioids
The duration of effect of narcan is
15-45 minutes
Administration of narcan
40 mcg every 1-2 minutes until good RR/ventilation
How to dilute narcan
4 mg per vial, 1 vial diluted in 9 cc NS = 40 mcg/cc
Adverse effects of reversing the effects of narcotics with naloxone
- sudden pain
- pulm edema
- cardiac arrhthymias
- HTN
- Seizures
- cardiac arrest
What type of receptor family are opioids acting on
G-protein coupled receptor family
When opioid receptors are signaled, what happens to the channels
K+ and Ca2+ activation
In reference to the function of an opioid receptor, what is the cascade of the signaling pathway
- Inhibit adenyl cyclase & decrease cyclic AMP
- Activation of Ca2+ and K+ channels
- Activation of mitogen activated protein kinase/extra cellular signal/regulates kinase, protein kinase C, and P13 KK/Akt
What two things can antagonism of NMDA receptors lead to
-reduce opioid tolerance
- reduce opioid induced hyperalgesia and hypersensitivity (in chronic disease states)
What does NMDA stand for
N-methyl-D-Aspartate
Explain the receptors ketamine works on
NMDA antagonist causing anesthetic properties and analgesic effects due to MOR activation
What is nociception
Neural process of encoding and processing of noxious stimuli that can cause tissue damage
3 examples of analgesia driven by endogenous opioid system
- Stress induced
- Placebo induced
- Condition pain modulation (CPM)
What is conditioned pain modulation (CPM)
Pain from noxious stimuli applied to one part of body is decreased by application of second remote noxious stimuli
What causes CPM
Activation of descending inhibitory pathways by higher brain centers
Opioids are involved in peripheral analgesia in what ways
Act directly on sensory neurons (A and C fibers) to inhibit pain transmission
opioid receptors found in (name 2)
Neurons & immune cells (leukocytes)
OIH activation mechanisms (name 3)
- Central glutaminergic systems
- Central nitric oxide production
- Facilitation of descending pronociceptive systems
Postoperative patients who received _________ during surgery may have higher incidence of OIH. How can you prevent it
Remifentanil
- administer morphine (0.1-0.25 mg/kg) 45-60 minutes before surgery ends OR can add low dose ketamine (10-30 mg/hr)
Semisynthetic exogenous opioids
Dilaudid
Buprenorphine
Oxycodone
Codeine
Full opioid agonist of the MOR
Morphine, piperidines, and methadone
Opioids that are partial agonist
Buprenorphine
Opioid antagonists
Naloxone and naltrexone
Explain opioid metabolism that may occur in GI, brain, kidney
Extraction of parent drug/metabolites via kidney and/or biliary tract into the gut where some opioids reuptake the compound in the blood stream. Examples are morphine and buprenorphine
Enzyme metabolizing morphine in phase II reaction
UGT2B7
Active metabolite of morphine? What percentage is converted to active form? What should you be cautious of?
M6G
5-10%
Patient with decreased renal function
Transport protein that moves M3G and M6G to bloodstream? To bile ducts?
MRP3 bloodstream
MRP2 bile duct
Opioids that readily cross BBB
Pipieridines
The most important metabolic pathway of naloxone is via ________ and the metabolite is ________
Glucuronidation
Inactive naloxone-3-glucuronide
The opioid affect sites for analgesia, sedation, constipation, and respiratory depression
CNS- analgesia, sedation, respiratory depression
GI- constipation
Explain how opioids affect respiratory rate
Reduced TV due to decreases input to brain stem
If given slowly, respiratory neuron depression coincides with increased arterial CO2 accumulation which stiulates peripheral ad central chemoreceptors which offsets decrease in tidal volume and reduced RR
Opioids can increase collapsibility of upper airways d/t suppression of neurons in brain stem or from loss of muscle tone related to sedation
Naloxone onset
6.5 minutes
Special considerations when administering naloxone to reverse buprenorphine
Consider naloxone infusion d/t long actin buprenorphine and short acting naloxone
What area is triggered that could cause PONV following opioids
Chemoreceptor trigger zone (CTZ) which is near vagal nerve, and vestibular organs
Treatment for PONV from opioids
Dopamine antagonist (droperidol)
5HT-antagonist (Zofran)
Corticosteroids
What do opioids do to GI tract
- Inhibit intestinal and pancreatic secretion,
- increase bowel tone,
- decrease intestinal propulsive activity
How to treat opioid induced bladder dysfunction
Opioid antagonist
Remifentanil PCA for labor pain
- used when epidural contrainidcated
- bolus dose 30 mcg with a 3 minute lockout