Opioids Flashcards
1
Q
What are the 4 steps of the pain pathway?
A
Transduction
Transmission
Modulation
Perception
2
Q
What is transduction?
A
Converts a noxious stimulus into an action potential through the release of various chemicals
3
Q
What is transmission?
A
The pain signal is relayed through three neurons along the spinothalamic tract (afferent)
4
Q
What is modulation? Where is the most important site?
A
-Pain is inhibited or augmented as it advances towards the cerebral cortex
-Substantia gelatonisa in the dorsal horn (rexed lamina 2 and 3)
5
Q
What is Perception?
A
Processing of afferent pain signals in the cerebral cortex and limbic system. How we “feel”
6
Q
What are nociceptors?
A
Free nerve endings that respond to pain
7
Q
What are the specialized nociceptors?
A
Merkel’s disks
Ruffini endings
Meissner’s corpuscles
Pacinian Corpuscles
8
Q
What drugs target transduction?
A
NSAIDS
Local’s
Steroids
Antihistamines
Opioids
9
Q
How does inflammation contribute to transduction?
A
Allodynia - Reduced threshold to pain
Hyperalgesia - Increased response to pain
10
Q
What drugs target transmission?
A
Local’s (blocking the nerve)
11
Q
Where is the first order neuron? Where is the cell body?
A
Periphery to dorsal horn
Cell body in the dorsal root ganglion
12
Q
Where is the second order neuron? Where is the cell body?
A
Dorsal horn to thalamus
Cell body in the dorsal horn
13
Q
Where is the third order neuron? Where is the cell body?
A
Thalamus to cerebral cortex
Cell body in the thalamus)
14
Q
How is pain inhibited during modulation?
A
Spinal neurons release GABA and Glycine
The descending pathway releases NE, serotonin, and endorphins
15
Q
How is pain augmented during modulation?
A
- Central sensitization
- Wind-up
16
Q
What drugs target modulation?
A
Neuraxial opioids
NMDA antagonists
SSRI
SNRI
AchE inhibitors
Alpha 2 agonists
17
Q
What drugs target perception?
A
General anesthetics
Opioids
Alpha 2 agonists
18
Q
What type of receptor is the opioid?
A
G linked protein
19
Q
What are the steps of an opioid binding to the receptor ?
A
- Opioid binds to the receptor
- G protein is activated
- Adenylate cyclase is inhibited
- Decreased cAMP
- Ca is decreased
- K is increased
20
Q
What are the 4 types of opioid receptors?
A
Mu
Kappa
Delta
ORL-1
21
Q
What opioid receptor produces the most classic signs of opioid administration?
A
Mu
22
Q
Where are they located?
A
Brain - Periaqueductal gray, locus coeruleus, rostral ventral medulla
Spinal Cord - Primary afferent neurons in the dorsal horn
Peripheral - sensory neurons and immune cells
23
Q
What are the precursors to endogenous opioids?
A
Pre-proopiomelanocortin - endorphins (Mu)
Pre-enkephalin - Enkephalins (Delta)
Pre- dynorphin - Dynorphins (Kappa)
24
Q
Which opioid receptor produces bradycardia?
A
Mu
25
Which opioid receptor produces diuresis?
Kappa
26
Which opioid receptor does not produce respiratory depression?
Kappa
27
Which opioid receptor produces GI symptoms?
Mu
28
Which opioid receptor does not produce pruritis?
Kappa
29
Which opioid receptor produces antishivering?
Kappa
30
Which opioid receptor does not produce CNS effects?
Delta
31
Which opioid receptor does not produce miosis (pupil constriction?
Delta
32
How does gender play a difference in PK/PD among opioids?
Women have a;
Greater analgesic potency
Slower onset of action
Longer duration of action
Lower postoperative opioid consumption
33
How do opioids affect ventilation ?
Shifts response curve to the right and reduces the response to CO
Decreased RR
Increased VT
34
How do opioids affect pupils?
Constriction through stimulation of PNS ciliary ganglion and CN3
35
How do opioids affect N/V?
Increases in the chemoreceptor zone (Medulla)
Possible vestibular apparatus
36
How do opioids affect SSEP?
Minimal effect
37
How do opioids affect Cardio ?
Bradycardia
Hypotension ONLY through histamine release
Baroreceptor not affected
38
How do opioids affect GI?
Contraction of sphincter of Oddi -Increases biliary pressure
Decreased motility
39
How do opioids affect GU?
Urinary retention
Histamine release, suppression of immune function and natural killer T cells
Resets hypothalamic temp set point which decreases core body temp
40
What are the naturally occurring opioids?
Phenanthrene derivatives
Morphine
Codeine which is the precursor to morphine
41
What are the semisynthetic opioids?
Hydromorphone, heroin, naloxone, naltrexone
Thebaine derivative - Oxycodone
42
What are the synthetic opioids?
Piperidines - Meperidine
Phenylpiperidines - Fentanyl, remi, su, al
Diphenylpropylamines - Methadone
43
What is the standard potency all opioids follow?
10mg IV morphine
44
Opioid chart
45
What are tolerance and dependence most likely related to?
Receptor desensitization and increased synthesis of cAMP
Not due to enzyme induction
46
Tolerance develops to all side effects accept...?
Miosis and constipation
47
What are the early sign of withdrawal? Late signs?
Early - Sweating, insomnia, restlessness
Late - cramping, N/V
48
Timing of withdrawal for fentanyl, morphine, methadone? Chart?
49
What opioid is not metabolized by the liver?
Remi
50
What opioids have active metabolites?
Morphine
Meperidine
Hydromorphone
51
What is the metabolite of morphine? What can it cause?
M6G - does not cross BBB
Dialysis patients are unable to secrete M6G
Do not give morphine to renal failure patients AND can cause toxicity with chronic use even with normal renal function
52
What cautions should be taken with meperidine?
Reduces seizure threshold
Careful with renal failure and elderly
Don't use with PCA pump
Histamine release
Antishivering effects
Weak serotonin reuptake inhibitor - careful with MAOI
Anticholinergic effects
53
What class is meperidine? What opioid receptor does it stimulate
Synthetic phenylpiperidine
Mu and Kappa
54
What is the half life of meperidine ?
15 hours but can take 35 hours.
55
What is the pKa of Alfentanil ? special characteristics?
-Weak base - 6.5 pKa
-Fastest onset of action
-90% is non ionied
-Low Vd - since it doesn't distribute, more goes to the brain
-High protein binding
56
Metabolism of Alfentanil?
CYP3A4
Low extraction ratio - erythromycin inhibits the metabolism
No active metabolite so renal function does not matter
57
Special characteristics of Remifentanil ?
Similar potency to fentanyl
Context sensitive half time is about 4 minutes
Calculated on LEAN body weight, does not distribute to fat
Small Vd due to fast clearance of Esterases
Causes opioid induced hyperalgesia
Can cause muscle weakness due to being mixed with glycine
58
Does a pseudocholinesterase deficiency affect the metabolism of remifentanil?
No
59
How is methadone prepared? When is it used?
As a racemic mixture
Used for chronic pain, opioid abuse, and cancer pain
60
How does methadone decrease pain? Three ways
1. Mu agonist
2. NMDA antagonist
3. Inhibits reuptake of MAO's
61
How is methadone metabolized? Active metabolite?
Oral - Bioavailability 80%
Duration of action is 3-6 hours
Chronic use prolongs duration of action
No active metabolite
62
How does methadone prolong QT?
Inhibits the delayed rectifier K channel
63
Facts about Oliceridine
Brand new selective Mu receptor
Do not exceed 27mg
Increases all symptoms - seizure risk, QT prolongation, hypotension, significant respiratory depression, GI obstruction
64
How do opioids affect skeletal muscle? Which ones?
Rapid IV infusion causes chest wall rigidity and issues with the larynx
-More common with potent compounds such as sufentanil, remi, fentanyl, and alfentanil
Likely from the Mu receptor
Best treatment is to paralyze and intubate
Naloxone does work
65
What complications develop from a stiff chest?
-Increased pressure, CVP, RAP, PVR
-Increased O2 consumption
Hypoxia, Hypercapnia
Decreased SvO2, FRC, MV, FRC
66
Special characteristics of partial opioid agonists?
-Produce analgesia with reduced symptoms
-Lower risk of dependence
-Have a ceiling effect and reduces the efficacy of previous opioids
-Can cause acute opioid withdrawal
67
Special characteristics of Buprenorphine?
Partial Mu agonist
Greater analgesia than morphine
Not reversed by naloxone
Long duration and available in transdermal route
68
Special characteristics of Nalbuphine?
Kappa agonist + Mu antagonist
Similar analgesia to morphine
Reversed by Naloxone
Useful in heart disease because does not cause many cardiovascular effects
69
Special considerations for butorphanol?
Kappa agonist + Mu antagonist
Greater analgesia than morphine
Reversed by naloxone
Useful for postop shivering
Transdermal route
70
How does Naloxone work?
Antagonizes all opioid receptors but has the greatest affinity at the Mu receptor
71
Key facts about Naloxone
1-4mcg/kg
Duration 30 minutes
Liver metabolism with significant first pass
ACTIVATES THE SNS
Can cross the placenta and can cause acute opioid withdrawal in the fetus
Anti pruritis
72
Key facts about Methylnaltrexone?
Does not cross the BBB so does NOT reverse respiratory depression
Useful in bowel dysfunction
73
Key facts about Nalmefene?
Similar to Narcan however much longer duration of action, 10 hours
74
Key facts about Naltrexone?
Can be given orally and does not undergo first pass metabolism
Can give extended release
Good for abusers
75
What is the gold standard for postoperative opioid delivery?
PCA due to increased patient satisfaction and better pain control
Incidence of respiratory depression is NOT increased
76
Key facts about PCA pumps
-Demand should provide pain relief without toxicity
-Lockout interval is based on the time it takes to reach an effective plasma concentration
-Basal rate is used for chronic pain, not postoperative
-Use scheduled NSAIDS
-END TIDAL is the best monitor
-Morphine is not used due to the M6G metabolite
-Can use in pregnancy
77
What is the most important site of pain modulation?
Dorsal horn of the spinal cord - Rexed lamina 2 and 3
78
What is the process of transduction?
Injured tissues release various chemicals that release proinflammatory compounds
Peripheral nerves transduce this chemical soup into an action potential
79
What type of nerves transmit pain?
A - delta fibers (fast sharp pain, well localized)
C - fibers (slow, dull pain)
80
What is the role of inflammation in pain transduction?
-Reduces the threshold to a pain stimulus (allodynia)
-Increases the response to a pain stimulus (hyperalgesia)
81
What is the process of pain transmission?
Pain signal is sent through the afferent pain pathway along the spinothalamic tract
82
What are the three neurons in the pain transmission pathway?
First - periphery to dorsal horn in the dorsal root ganglion
Second - dorsal horn to the thalamus, cell body in the dorsal horn
Third - thalamus to cerebral cortex, cell body in the thalamus
83
Where is the most important site of pain modulation?
Substantia gelatinosa in the dorsal horn (rexed lamina 2 + 3)
84
Where is the descending inhibitory pain pathway begin and end?
being sin the periaqueductal gray and medulla. Projects to the substantia gelatinosa
85
When does pain inhibition occur?
-Spinal neurons release GABA and Glycine
-Descending pathway release NE, Serotonin and endorphins
86
How is pain augmented?
Wind up and central sensitization
87
Where does the perception of pain occur?
Afferent pain signals in the cerebral cortex and limbic system
88
What is unique to Kappa?
Anti shivering
Diuresis
Dysphoria
Delirium and Hallucinations
89
How do opioids affect myocardial function?
-Doesn't unless combined with N20
90
How can opioids affect ICP?
May increase due to an increase in CO2
91
How do opioids affect the pupil?
Edinger Westphal nucleus stimulation
Increases PNS stimulation of ciliary ganglion and oculomotor nerve CN3)
Pupil constriction
92
How do opioids affect the bladder?
Causes detrusor relaxation and urinary sphincter constriction
93
How does methadone reduce pain?
Mu receptor agonist
NMDA antagonist
Inhibits MAO
94
Opioid with the greatest Vd? Least?
Greatest - Fentanyl
Least - Remi
95
Which opioid is the most likely to prolong QT?
Methadone
96
Which opioid receptor can causes skeletal muscle rigidity ?
Mu
97
What are characteristics of opioid agonists - antagonists ?
Produce pain relief with reduced risk of respiratory depression
Have a ceiling effect
Reduce the efficacy of previous opioids
Can cause acute opioid withdrawal
Can cause dysphoric reactions
Low risk of dependence
98
What are some side effects of naloxone?
SNS activation - PULMONARY edema
N/V
Crosses BBB - fetal opioid withdrawal
99
Which opioid antagonist does not cross the BBB and does not reverse respiratory depression?
Methylnaltrexone
100
Which opioid antagonist is the longest acting ? What's it used for?
Naltrexone - does not undergo first pass metabolism
-Alcohol withdrawal/ opioid abusers
101
What are two important excitatory neurotransmitters in the dorsal horn?
Glutamate and substance P
102
What nerve bypasses the spinal cord?
Trigeminal nerve
103
What two medications help prevent hyperalgesia related to D/C of remi?
Ketamine and magnesium
