Opioid Agonist & Antagonist Flashcards
1
Q
A synthetic analog of codeine
A
Tramadol (Ultram)
2
Q
This prodrug is helpful with pain management in patients unable to take NSAIDs
A
Tramadol (Ultram)
3
Q
Tramadol MOA
A
Weak mu agonist from inhibition of NE and serotonin and presynaptic stimulation of 5-HTP release.
4
Q
How does Naloxone effect Tramadol SE?
A
analgesia partially intact
respiratory depression reversed
5
Q
Toxicity seen in Tramadol overdose is related to what?
A
amine uptake inhibition
6
Q
Tramadol is a racemic mixture, what are the effects of the + and - enantiomers?
A
+ binds to mu and decreases serotonin while the - inhibits NE uptake and stimulates alpha 2 receptors
7
Q
Tramadol(Ultram) half-life:
A
5-6h
8
Q
Significant CNS SE of Tramadol
A
Seizures
9
Q
Tramadol toxicity symptoms include:
A
hypotension, bradycardia, seizures, coma, rhabdomyolysis
10
Q
Disadvantages of Tramadol:
A
Interaction with Warfarin, occurrence of serotonin syndrome, and increased risk of seizures in epileptic/high-risk patients.
11
Q
Tramadol (Ultram) causes what significant GI side effects?
A
High incidence of N/V
12
Q
Why is PO use of meperidine limited?
A
Significant first-pass effect
13
Q
Meperidine interacts with which class of drugs, and how do the SE present?
A
MAOIs; respiratory depression, excitation, and delirium
14
Q
How does Meperidine toxicity present, and what is the cause?
A
Active metabolite Normeperidine leads to CNS excitation and seizures.
15
Q
Use of Meperidine (Demerol) in anesthesia:
A
postop shivering
16
Q
The potency of meperidine to morphine:
A
Meperidine has 1/10 the potency of morphine.
17
Q
What SE occur if Meperidine is given in high enough doses?
A
negative inotropic and histamine release
18
Q
What are these symptoms reflective of? Autonomic instability with hypertension, tachycardia, diaphoresis, hyperthermia, behavioral changes including confusion and agitation, and neuromuscular changes manifesting as hyperreflexia
A
Serotonin Syndrome
19
Q
Severe Serotonin Syndrome symptoms include:
A
Coma, seizures, coagulopathy, and metabolic acidosis
20
Q
Which medications place patients at increased risk of Serotonin Syndrome?
A
Those on medication including MAOIs, Fluoxetine, and other antidepressants.
21
Q
Meperidine receptor activity:
A
Mu & Kappa agonist
22
Q
Fentanyl receptor activity:
A
Mu antagonist
23
Q
Fentanyl v. morphine potency:
A
Fentanyl 100x more potent than morphine.
24
Q
After high doses of fentanyl, dopaminergic stimulation in the corpus striatum may lead to what SE?
A
Muscle rigidity
25
This accounts for the rapid onset and duration of fentanyl:
high lipid solubility
26
Fentanyl peak effect:
3-5m
27
Fentanyl Vd
4L/kg
28
What happens when fentanyl doses exceed 20mcg/kg?
Redistribution is insufficient to drop plasma levels as fentanyl sequesters itself in the lungs.
29
Fentanyl induction dose:
1-2mcg/kg
30
Fentanyl metabolism:
Lungs (75%) & Liver (phase 1)
31
Which opioid requires reduced doses of benzos, propofol, or IA with induction:
Fentanyl (Sublimaze)
32
Pros of sole fentanyl use in anesthesia
lacks cardiac depressant and histamine effects, and also suppresses stress
33
Cons to sole fentanyl use in anesthesia:
fails to blunt SNS, awareness, ventilatory depression
34
Compare the potency of sufentanil to both fentanyl and morphine:
Sufentanil is 1000x more potent than morphine and 100x more potent than fentanyl.
35
Sufentanil has greater affinity for opioid receptors and a shorter EHL than fentanyl, why?
Twice as lipophilic as fentanyl
36
Sufentanil induction & infusion doses:
IVP: 0.1-0.2mcg/kg
Infusion: 0.1-0.2mcg/kg/hr
37
Alfentanil potency v fentanyl; alfentanil v. morphine:
Alfentanil is 1/3 potency of fentanyl, alfentanil is 20x more potent than morphine
38
Compare lipid solubility of alfentanil and fentanyl:
Alfentanil is less lipid soluble than fentanyl
39
Why did alfentanil lose popularity?
Unpredictable responses to medication administration, and the development of remifentanil.
40
What drug has been shown to prolong the metabolism of alfentanil (Alfenta) leading to prolonged respiratory depression and sedation?
Erythromycin
41
Drug 100x more potent than morphine, and equipotent to fentanyl:
Remifentanil
42
Metabolism of Remifentanil:
Non-specific plasma and tissue esterases
43
How does the Vd of remifentanil compare to the other opioids?
smallest Vd
44
Remifentanil CSHT:
<5 minutes
45
Remifentanil has the potential to cause glycine neurotoxicity, how does this impact administration?
No epidural/intrathecal administration
46
What plan should be in place for patients on remifentanil in the OR once they head to the PACU.
The administration of a longer-acting opioid.
47
This drug is an NMDA antagonist used in heroin addiction, it is a racemic mixture with a long half-life and has the potential to prolong QT intervals:
Methadone (methadose, dolophine)
48
Opioid usually combined with Tylenol:
Hydrocodone
49
This oral opioid is 10x more potent than morphine, has rapid onset, but poses high risk of N/V:
Oxymorphone (Opana)
50
This prodrug is metabolized into morphine. It is used as a cough suppressant, and has minimal sedation, but can lead to N/V, constipation, and dizziness:
Codeine
51
Patients lacking CYP2D6 or taking Quinidine will have difficulty metabolizing this drug into it's active form:
Codeine
52
Rapid metabolizers of codeine experience:
Toxicity
53
Pure opioid competitive antagonist:
Naloxone (narcan)
54
Naloxone dose:
0.4-0.8mg IV
onset 1-2m
duration 1-4h
55
Naloxone SE:
Pain
Pulmonary edema
sudden death
56
This peripheral opioid mu antagonist maintains analgesia while also treating delayed gastric emptying and N//V.
Methylnaltrexone (Relistor)
57
Mu selective oral peripheral antagonist that depends on gut flora for metabolism, is approved for ileus and constipation treatment, but could lead to unwanted CV effects:
Alvimopan (Entereg)
58
Peripherally acting mu-opioid antagonist with high abuse potential, used for constipation:
Naloxegol (Movantik)
59
This oral opioid antagonist with high oral efficacy, used in the treatment of opioid dependence and ETOH withdrawal; however, active metabolite can lead to prolonged elimination:
Naltrexone (Vivitrol)
60
All opioid agonist-antagonists have a ceiling on their clinical effects, what does this mean?
Increased doses will not increase respiratory depression or analgesic effects further.
61
What effects seen with opioid agonist-antagonist differ from pure agonists?
Dysphoria, competitive antagonism at mu receptors, and agonize kappa receptors.
62
This agonist-antagonist reverses narcotic-induced postop ventilatory depression, maintains analgesia, and relieves itching.
Nalbuphine-Nubain
63
NSAIDs act as:
analgesic, antipyretic, and anti-inflammatory
64
Acetaminophen acts as:
analgesic, antipyretic
minimal anti-inflammatory
65
NSAIDs: Inhibition of ______ leads to platelet aggregation.
COX-1
66
NSAID use is avoided in what patients:
GI ulcers/bleeds, H. Pylori, caution in colorectal surgery
67
act additively with antiplatelet agents resulting in increased bleeding risk:
NSAIDs (non-specific)
68
What unwanted side-effect results from giving NSAIDs along with phenytoin, valproic acid, or digoxin?
increased plasma concentrations and toxicity: dig, valproic acid, phenytoin
69
Which drug, when given with aspirin, decrease plasma salicylate concentrations?
corticosteroids
70
This drug causes irreversible inhibition of COX enzymes
Aspirin
71
What drug levels are associated with mild, moderate, and severe ASA toxicity?
mild: 300-600mg/L
moderate: 600-800mg/L
severe: >800mg/L
72
ASA toxicity symptoms:
nausea, vomiting, abd pain, tinnitus, hearing impairment, CNS depression
73
ASA toxicity symptoms with higher doses:
metabolic acidosis, renal failure, agitation, confusion, hyperventilation with respiratory alkalosis
74
Acidemia has what effect on ASA absorption?
more readily crosses the BBB
75
ASA toxicity treatment
Hydration, activated charcoal (in 1hr), alkalinization of urine.
Severe cases require HD.
76
NSAID: potent analgesic, moderate anti-inflammatory
Ketorolac (Toradol)
77
Ketorolac dose:
30-60mg IV
78
Ketorolac is contraindicated in what patients?
renal impairment, ASTHMA, bleeding disorders, ASA sensitivity, nasal polyps, lactating mothers
79
Dexamethasone (Decadron) has what SE that is useful in anesthesia
antiemetic
80
NSAID contraindicated in perioperative CABG patients:
Ibuprofen (Caldolor)
81
What effect do NSAIDs have on the CV system?
It may increase the risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. The risk may increase with the duration of use.
82
Caldolor (Ibuprofen) is contraindicated in:
asthma, pregnancy, periop during a CABG.
83
Common SE with Gabapentin:
dizziness, somnolence
84
Which drug binds to auxiliary subunits 1 and 2 Ca2+ channels , reduce calcium currents. It Halts new synapses decreases sympathetic tone.
Gabapentin
85
Approved for postherpetic neuralgia and partial seizures
Gabapentin
86
common adverse reactions in patients treated with______were nausea, vomiting, headache, and insomnia in adult patients and nausea, vomiting, constipation, pruritus, agitation, and atelectasis in pediatric patients
Ofirmev
87
Ofirmev is approved for patients. of what age?
2 and older
88
Max single dose v. max daily for Ofirmev:
Single max: 1000mg
Daily max: 4000mg
89
Magnesium MOA
regulation of calcium influx into cells and antagonism of NMDA receptors in the CNS, this blocks painful stimuli allowing narcotics to work better.
90
Ketamine MOA
NMDA non-compitative antagonism
91
Why would one give glucagon during a Lap choly procedure?
Opens biliary duct
92
Respiratory depression is expected during a spinal except under what circumstances?
The patient is sitting when the spinal was given (lowest risk).
93
receptor responsible for neuraxial effects of opioids
Mu 2
94
Why is Toradol (Ketorolac) not given to asthma patients?
Bronchospasm
95
Nubain classification
Agonist antagonist
96
What is the result of the active metabolite morphine-6-glucuronide?
analgesia and respiratory depression via mu 2 receptor
97
Increased lipid solubility translates to:
rapid drug onset
98
decreased RR is due to what receptor?
mu 2
99
Pure opioid antagonist
Narcan (Naloxone)
100
Difficulty with ventilation after giving sufentanil is due to what?
chest wall rigidity
101
side effects of neuraxial epidurals:
respiratory depression, itching, N/V, urine retention, sedation, CNS excitation, herpes virus reactivation
102
How is remifentanil metabolized?
nonspecific esterases
103
Where is substance P found?
Substantial gelatin
104
Why would a shivering patient not receive demerol?
They are on MAOI/psych meds
105
why is fentanyl eliminated more quickly than morphine?
more lipid soluble, and a larger Vd
106
Morphine onset
15-30m
107
Morphine half time
1.7-3.3h
108
Effect of morphine on the immune system?
histamine release
109
Meperidine effects what receptors?
Mu and kappa
110
Meperidine effect on pupils:
mydriasis
111
Why would we use nubain?
relieve itching while maintaining analgesia.
112
Toradol is contraindicated in:
asthma
113
Which opioid requires a drip to maintain therapeutic range?
remifentanil
114
Effects of opioids on GI
spasm of biliary smooth muscle, decreased LES, increased pyloric tone and sphincter of oddi tone
115
Effects of opioids on respiratory:
Increased RR, decreased TV, chest wall rigidity
116
Where do opioid agonists work? (locations, not receptor)
pre & post synaptic, spinal cord, peripherals
117
presynaptic release of _____ stops substance P.
glutamate
118
A decrease in what cation results in diminished action potential and signaling. (decreased pain)
Calcium
119
This opioid agonist may cause an increase in HR and negative inotropy due to histamine release:
Meperidine (Demerol)
120
Methadone receptors
mu, delta agonist, NMDA antagonist
121
Can lead to QT prolongation and torsades:
Methadone
122
Least lipophilic opioid agonist, causes extreme itching, and can lead to urine retention
Morphine
123
Remifentanil CSHL and wake up time?
cshl is <5 min, wake up in 20m
124
Naloxone (Narcan) SE:
Increased RR, NV, sphincter spasm, decreased sedation, itching, pulm. edema, pain, sudden death
125
How long should one wait between doses of Naloxone?
3-5m
126
Agonist-antagonist MOA
Compete with opioids for mu receptors
127
Butorphanol (stadol) receptors
Kappa agonist, mu antagonist
128
Buprenorphine (Subutex) receptor
weak mu agonist, weak kappa antagonist
129
Buprenorphine (Subutex) should be stopped 2-4 wks before surgery; why?
not fully reversible with Narcan
130
How long are platelets inhibited after the use of NSAIDs?
7 days
131
This drug's antipyretic effect may mask post-op fever:
Ofirmev (acetaminophen)
132
How often is Ofirmev given to maintain SS?
Q6H
133
Avoid use of this NSAID with epileptic/ those at risk for seizures:
Tramadol (Ultram)
134
Alkaloid extract most widely used to relieve pain:
Morphine
135
Opioids bind to ________ that are associated with mu receptors.
G-proteins
136
Endogenous opioids are released by ______.
interneurons
137
What two mechanisms occuring at the mu opioid receptor result in the decreased transmission of pain?
Inhibition of presynaptic glutamate release
Increased potassium conductase across the post-synaptic membrane.
138
How does dosing for chronic and acute alcohol use differ?
acute intox= decreased dose
chronic intox= increased dose
(phase 1 enzyme induction-Py1)
139
Drug withdrawal symptoms:
diaphoresis, lacrimation, coryza, insomnia, restlessness
140
Severe withdrawal symptoms peaking in 72 hours & diminish progressively over 7-10 days:
abd cramps, N/V, diarrhea
141
Opioids metabolized by phase I:
Fentanyl, alfentanil, sufentanil, methadone
142
Opioids metabolized by phase 2:
Hydromorphone, Meperidine, Morphine
143
Receptor related to euphoria
mu1
144
receptor related to drug dependence and depressed RR
Mu2
145
receptor related to constipation:
mu2
146
receptor related to hallucinations
Kappa
147
endogenous ligand for delta receptors:
enkephalins
148
This drug is used to suppress cough. Does not produce analgesia or depress ventilation:
Codeine
149
These drugs are associated with reflex coughing:
fentanyl, sufentanil, alfentanil
150
How is the CO2/hypoxia response curve affected by opioids?
decreased response, shifts right
151
What CV SE can express in patients with increased SNS activity?
hypotension (worse)
152
These two drugs have the most histamine release:
morphine and meperidine
153
Codeine 60mg is equivalent to what dose of ASA?
650mg
154
Codeine 120mg IM is equivalent to how much morphine?
10mg
155
Heroine (diacetylmorphine) v. morphine potency:
Heroine is 2.5x more potent than morphine
156
This drug is five times more potent than morphine leading to increased sedative effects.
Hydromorphone (Dilaudid)
157
Can cause serotonin syndrome
Tramadol, meperidine
158
Alfentanil pKa
6.5
159
Narcan preperation
0.4mg/cc, dilute with 10cc to make 0.04mg/cc
