Opioid Analgesics Flashcards
1
Q
____ is known as the “fifth vital sign”
A
Pain
2
Q
Mu opioid receptors regulate…
A
-Analgesia
-Well-being
-Respiratory depression
-Physical dependence
3
Q
Mu-1 receptors are responsible for ___ and ___
A
Analgesia and euphoria
4
Q
Mu-2 receptors are responsible for ___ and ___ depression
A
Respiratory and cardiac
5
Q
Delta opioid receptors have a similar profile to mu receptors; they are primarily responsible for analgesia to ____ ____
A
Thermal pain
6
Q
Kappa opioid receptors are responsible for…
A
-Analgesia
-Sedation
-Anesthesia
-Miosis
7
Q
Sigma receptors are nonopioid receptors that mediate the ____ effects of opioids
A
Dysphoric
8
Q
Epsilon receptors have a high affinity for ____
A
Endorphins
9
Q
Interactions of drugs with opioid receptors can be ____
A
Selective
10
Q
Drugs can act as agonists, partial agonists, or antagonists ____ at each receptor
A
Independently
11
Q
Depending on the spectrum of interactions, there is a wide spectrum of ____ effects that may be seen with drugs
A
Pharmacological
12
Q
Opiate receptors outside of the CNS (like in the intestine and bladder) may mediate non-analgesic actions of the opiates like _____
A
Constipation
13
Q
What is a drug that treats opioid-induced constipation?
A
Naloxegol
14
Q
Immodium is designed to not get into the ____, but if it is abused, it will be able to
A
CNS
15
Q
With partial agonist antagonists, the receptors can’t become _____
A
Desensitized
16
Q
Opioid receptors are linked to ___ ___ and therefore are able to affect ion gating, intracellular Ca2+ disposition, and protein phosphorylation
A
G protein
17
Q
What are the two well-established direct actions that opioids have on neurons?
A
-Close voltage-gated calcium channels on presynaptic nerve terminals
-Opening potassium channels (hyperpolarize=inhibit) on postsynaptic neurons
18
Q
The net result of the cellular decrease in calcium is a decrease in the release of…
A
-Dopamine
-Serotonin
-Nociceptive peptides (substance P)
19
Q
The decrease in dopamine, serotonin, and nociceptive peptides results in a blockage of ____ transmission
A
Nociceptive
20
Q
Mu, kappa, and delta agonists reduce transmitter release from ____ terminals of nociceptive primary afferents
A
Presynaptic
21
Q
Mu agonists also ____ second-order pain transmission neurons by increasing potassium conductance, evoking and inhibitory postsynaptic potential
A
Hyperpolarize
22
Q
The net result of opioids on spinal sites is the blockage of ___ ___ to higher centers
A
Pain transmission
23
Q
Opioids are well absorbed from the ____ ____ and ____
A
GI tract and transcutaneously (skin)
24
Q
Drugs such as morphine that have a free ____ group in position 3 undergo first-pass effects (glucuronidation) and have reduced bioavailability
A
OH
25
Opioids distribute to all tissues depending on ____
Lipophilicity
26
Some opioids may sequester ___ and extend half-life relative of effect
Fat
27
____ and ____ pass readily into the blood-brain barrier
Heroin and codeine
28
____ is slow to pass through the blood-brain barrier
Morphine
29
____ and ____ can be redistributed into the brain
Fentanyl and methadone
30
Opioids readily cross the ____, so they should be used with caution during pregnancy and delivery
Placenta
31
The fetus is slow to _____ (similar to how an adult with reduced liver function)
Glucuronidate
32
The majority of opioid metabolites are ____
Inactive
33
What are three active metabolites of opioids?
-Morphine-6-glucuronide (analgesic)
-Normeperidine and norpropoxyphene (excitatory but not analgesic)
-6-beta-naltexol (less active than parent, but prolongs the effect)
34
Opioids are excreted through the ____ system
Renal
35
What effects might be seen from the interaction of sedative-hypnotics with opioids?
-Increased CNS depression, particularly respiratory depression
36
What effects might be seen from the interaction of antipsychotics with opioids?
-Increased sedation
-Variable effects on respiratory depression
-Accentuation on cardiovascular effects
37
What effects might be seen from the interaction of MAO inhibitors and opioids?
-Relative contraindication to all opioid analgesics because of the high incidence of hyperpyrexic coma
-Hypertension has also been reported
38
____ is the opioid prototype
Morphine
39
Minor alterations in the ____ of morphine lead to major changes in drug effects (morphine, codeine, oxycodone, and heroin are all basically the same molecule with very small differences)
Structure
40
The binding of opioids to the mu receptor causes...
-Analgesia
-Euphoria
-Respiratory depression
-Physical dependence of morphine
41
Most of the currently available opioid analgesics act primarily at the ____ receptor
Mu
42
Delta and kappa receptors can also contribute to _____
Analgesia
43
The primary clinical use of opioids is for ____
Analgesia
44
Opioids are most effective against constant, moderate-severe ____
Pain
45
Opioids suppress perception of pain by eliminating or altering the ____ aspects of pain and inducing euphoria
Emotional
46
Opioids may produce ____ and ____ when given in the absence of pain
Dysphoria and nausea
47
Codeine can be used for ____ ___, but the mechanism of action is not understood
Cough suppression
48
Opioids can also be used for the treatment of _____ as they increase the tone of the small and large intestine with decreased propulsive movement
Diarrhea
49
Opioids can also be used for ____ ____, as epidural or subarachnoid administration can produce regional analgesia with decreased side effects
Spinal analgesia
50
Opioid adverse effects include things like...
-Respiratory depression
-Miosis
-Nausea and vomiting
-Constipation
-Biliary colic
-Increased bladder and ureteral tone, urinary retention, exacerbation of ureteral colic caused by kidney stones
-Additive CNS depression
-Gynecomastia in men
-Itching sensation (often around the nose)
51
Respiratory depression from opioids is due to direct effects on the brain stem respiratory centers via the mu2 receptor at the level of the ____
Medulla
52
The respiratory depression is ____ with an opioid overdose
Fatal
53
Respiratory depression is the ___-___ side effect
Dose-limiting
54
____, or "pinpoint pupils" have little clinical significance, but are a good indicator of opiate abuse; no tolerance to this effect has been observed
Miosis
55
Opioids can also cause ____ and ____ due to stimulation of the chemoreceptor trigger zone in the brain stem
Nausea and vomiting
56
____ is a drug with no analgesic activity, but is a potent emetic agent
Apomorphine
57
Opioids can cause constipation by ____ sphincter tone and ____ gastric motility
Increasing; decreasing
58
Opioids mixed with sedatives/hypnotics, antidepressants, and antipsychotics can cause additive ____ ____
CNS depression
59
Stimulation of some opioid receptors in the hypothalamus causes the release of dopamine which cause ____ secretion, leading to gynecomastia in men
Prolactin
60
Opioids induce the release of ____, which leads to an itching sensation, often around the nose (this is often associated with the use and abuse of opioids)
Histamine
61
Symptoms of opioid dependence/withdrawal are related to the development of _____ followed by an abrupt withdrawal
Tolerance
62
Exaggerated rebound from the effects of opioids include...
-Chills
Hyperthermia
-Mydriasis
-Anxiety
63
Intensity of withdrawal depends on the ____, ____, and ____ of use
Drug, dose, duration
64
Opioids are classified by agonist/antagonist activity; the four classifications are:
-Strong/pure agonists
-Mild-moderate agonists
-Mixed agonist/antagonist or partial agonist
-Pure opioid antagonist
65
What are three examples of strong or pure agonists?
-Morphine
-Methadone
-Meperidine
66
_____ acts as a complete agonist primarily at mu, but also at delta and kappa receptors
Morphine
67
Morphine produces a typical "narcotic profile", which causes symptoms like...
-Analgesia
-Euphoria
-Sedation
-Respiratory depression and miosis
68
Long-acting preparations of morphine (MS Contin and Ora-Morph) are used for ____ ____
Cancer pain
69
The biggest problem with patient-controlled anesthesia is that people give themselves ____ drug because people fear they will become addicted
Less
70
Signs of morphine overdose:
-Respiratory depression
-Miosis
-Hypotension
-Coma
71
We can use IV ____ to reverse morphine toxicity
Naloxone
72
People who have overdosed on morphine may require multiple doses of naloxone due to the short ___-___ of naloxone
Half-life
73
____ is less potent than morphine with a more consistent oral absorption
Meperidine (Demerol)
74
Meperidine (Demerol) has a rapid onset and a shorter duration than morphine, therefore withdrawal symptoms appear ____
Faster
75
The primary metabolite of Meperidine (Demerol) is ____
Normeperidine
76
The active metabolite normeperidine may be responsible for...
-CN excitation
-Tremors
-Delirium
-Hallucinations
-Convulsions
77
Meperidine (Demerol) has significant ____ activity
Anticholinergic
78
The sign of Meperidine (Demerol) overdose is ____, not seizure
Sedation
79
Meperidine (Demerol) has ____ antitussive, GI, and GU tract side effects
Less
80
Related phenylpiperidines (loperamide in Imodium, diphenoxylate in Lomotil) poorly enter the CNS but produce peripheral opioid effects, and are therefore used as ____
Antidiarrheals
81
Methadone (Dolophine) is a synthetic mu opioid _____
Agonist
82
Methadone (Dolophine) is similar to morphine, but with a ____ duration of action and a longer, but less intense withdrawal syndrome
Longer
83
Methadone (Dolophine) is used primarily in ___ ___
Heroin detoxification
84
Methadone (Dolophine) has less ___-___ metabolism than morphine and a more predictable oral absorption
First-pass
85
An overdose of Methadone (Dolophine) is treated with ____
Naloxone
86
What are five fentanyl dosage forms?
-Transdermal- Duragesic
-SL-Tablet Abstral
-SL-spray Subsys
-Transmucosal lozenge-Actiq
-Buccal film; Onsolis
87
With transdermal fentanyl, the patch needs to be changed every ____ hours
72
88
An example of a buccal tab version of fentanyl is ____
Fentora
89
An example of a fentanyl nasal spray is ____
Lanzanda
90
Buccal tab and nasal spray fentanyl dose should be ___ mcg and should only be used for breakthrough pain in opioid-tolerant patients
100
91
The transmucosal lozenge and bucca film dose of fentanyl should be a ____ mcg dose and should only be used for breakthrough pain in opioid-tolerant patients
200
92
____ is a mu agonist that is half made up of the active ingredient and half of naloxone to prevent abuse/overdose
Buprenorphine
93
What are two examples of mild-moderate opioid agonists?
-Codeine
-Propoxyphene (Darvon)->recently withdrawn by FDA
94
Mild-moderate agonists (like codeine and propoxyphene (Darvon)) have ____ maximal effects than strong agonists
Lower
95
____ (methylmorphine) is a naturally occurring substance found in the poppy plant (0.5%) but is usually synthetically synthesized from morphine
Codeine
96
Codeine (Methylmorphine) is ____ potent than morphine, but more reliably absorbed
Less
97
Derivates of codeine have the same effects as both codeine and morphine; what are some examples of derivatives?
-Oxycodone (Roxycodone)
-Oxycodone/aspirin (Percodan)
-Oxycodone/acetaminophen (Percocet)
-Hydrocodone (Hycodan, Vicodin, Zohydro)
98
The FDA has reclassified all ___ products to Class II scheduled drugs
Hydrocodone
99
Propoxyphene (Darvon) is structurally related to ____, but much less potent as an analgesic
Methadone
100
Propoxyphene (Darvon) is used for ____ pain and is half as potent as codeine
Mild
101
Many safety issues and ____ ____ limit the use of propoxyphene (Dervon)
Drug interactions
102
____ and propoxyphene can cause death within 20 minutes to 1 hour
Alcohol
103
Propoxyphene (Darvon) is also ____ and can cause birth defects
Teratogenic
104
The FDA banned Propoxyphene in 2010 due to ____ risks (many people may still have leftover medication at home!)
Cardiac
105
_____ is a diacetyl derivative of morphine
Heroin
106
____ use of heroin is on the rise
Recreational
107
Heroid rapidly passed into the ____, contributing to its abuse liability
Brain
108
Injections of heroin under the skin leads to collapse of ____ (track marks)
Vessels
109
Use of heroin during pregnancy leads to ___ ___ ___ babies and babies who are born addicts
Low birth weight
110
Levo-alpha acetylmethadol (LAAM) was approved in 1993 for clinical management of ___ dependence in heroin addicts
Opioid
111
Levo-alpha acetylmethadol is well absorbed from the ____ ____
GI tract
112
The primary advantage of levo-alpha acetylmethadol over methadone is the long duration of action of ____ hours
72
113
Levo-alpha acetylmethadol is administered orally ___ times per week
3
114
A single dose of levo-alpha acetylmethadol can suppress opiate withdrawal symptoms for ___-___ days
2-3
115
____ opioid agonists are similar to strong or pure agonists such as morphine, but exhibit lower level of activity at the mu-opioid receptor
Partial
116
What are two examples of partial opioid agonists?
-Buprenorphine (Buprenex/Subutex)
-Tramadol (Ultram)
117
Buprenorphine (Subutex) is ___-___ times more potent of an analgesic than morphine for moderate to severe pain
25-50
118
Buprenorphine (Subutex) has more ____ than ____ activity
Agonist; antagonist
119
Buprenorphine (Subutex) causes long-lasting ___ and ___ ___
Sedation and respiratory depression
120
The respiratory depressant effects of Buprenorphine (Subutex) are not as easily reversed by ____
Naloxone
121
Buprenorphine (Subutex) is perceived as "morphine-like" yet it reduces craving for ___ and ____; it is a potential new therapy for addiction
Morphine and cocaine
122
Buprenorphine and naloxone combination is known as ____ (this makes the drug less likely to be abused/cause overdose)
Suboxone
123
_____ is a synthetic analgesic for moderate to severe pain
Tramadol (Ultram)
124
Tramadol (Ultram) binds to ____ receptors
Mu
125
Tramadol (Ultram) is only partially ____ by nalaxone
Antagonized
126
Tramadol (Ultram) is also a weak ___ ____ ___ ___; this might be an advantage because the stimulatory effects can prevent depressive symptoms
Serotonin and norepinephrine reuptake inhibitor (SNRI)
127
Tramadol (Ultram) has less _____ depression
Respiratory
128
What are symptoms of Tramadol (Ultram) toxicity?
-Constipation
-Dizziness
-Nausea
-Headache
-Itching
129
Tolerance, dependence, and abuse of Tramadol (Ultram) are ____ likely
Less
130
There has been a recent change to make Tramadol (Ultram) a schedule ____ drug
IV
131
Mixed agonists/antagonists are potent ____ for mild to moderate pain (agonist activity)
Analgesics
132
The analgesic effects of mixed agonists/antagonists are related primarily to ____ receptor agonist activity (sedating) and less ____ receptor activity (euphoria)
Kappa, mu
133
Mixed agonists/antagonists also have some ____ receptor agonist activity that causes dysphoria
Sigma
134
Mixed agonists/antagonists can displace ___ ___ from opioid binding sites, reducing their biological effect and precipitating withdrawal (antagonist activity)
Full agonists
135
The receptor mix of mixed agonist/antagonists results in drugs that exhibit a ceiling analgesic effect and a decreased liability for the development of ____
Dependence
136
What are some examples of mixed agonist/antagonists?
-Pentazocine (Talwin)
-Butorphanol (Stadol)
-Nalbuphine (Nubain)
-Dezocine (Dalgan)
137
Pentazocine (Talwin) is a potent analgesic with _____ activity used in opoiod-addicted patients
Antagonistic
138
IV abuse with Pentazocine (Talwin) is eliminated with Talwin-NX, which is a mix between ____ and _____
Pentazocine and nalaxone
139
With Talwin-NX, ___ and ____ are blocked by naloxone when given IV, but not orally
Analgesia and euphoria
140
The main side effect of Pentazocine (Talwin) is ____
Sedation
141
Other side effects of Pentazocine (Talwin) include...
-Sweating
-Dizziness
-Psychotomimetics (avoid use in patients with psychoses)
-Nightmares
-Headache
142
Butorphanol (Stadol) is pharmacologically similar to ____
Pentazocine (Talwin)
143
Butorphanol (Stadol) is a potent opioid analgesic for moderate to severe pain and is ____ times more potent than morphine as an analgesic
7
144
Butorphanol (Stadol) is generally given ____ because it has poor bioavailability
Parenterally
145
A ____ ____ dosage form of butorphanol (Stadol) is available for post-op pain and migraines
Nasal spray
146
The nasal spray Butorphanol (Stadol) has a low molecular weight and is ____ soluble
Lipid
147
What is the onset of action for Butorphanol (Stadol)?
15 minutes
148
Nasal spray Butorphanol (Stadol) is not scheduled as other ____ analgesics
Opioid
149
Nalbuphine (Nubain) has a similar structure to ___ and ____
Naloxone and oxymorphine
150
Nalbuphine (Nubain) is administered ____
Parenterally
151
Nalbuphine (Nubain) is _____ to morphine
Equipotent
152
Nalbuphine (Nubain) is indicated for moderate to severe pain, along with ___-___ or ____ analgesia
Post-surgical; obstetrical
153
Nalbuphine (Nubain) has similar effects as Pentazocine (Talwin), but far greater ____ than ____ activity
Antagonist; agonist
154
____ symptoms are likely from Nalbuphine (Nubain) in opioid-dependent patients
Withdrawal
155
High doses of Nalbuphine (Nubain) are perceived by addicts to be like ____
Barbituates
156
Dezocine (Dalgan) is a moderate ___ agonists, as well as a weak delta and kappa agonost
Mu
157
The Dexocine (Dalgan) agonist activity causes...
-Analgesia
-Respiratory depression
158
The antagonist activity is ____ potent than pentazocine
More
159
No abuse tendency is demonstrated with Dexocine (Dalgan); it is used for ____ pain patients and burn victims
Chronic
160
The main route of clearance of Dezocine (Dalgan) is the ____
Kidneys
161
What are three examples of pure opioid antagonists?
-Nalaxone (Narcan)
-Naltrexone (ReVia)
-Nalmefene (Revex)
162
Pure opioid antagonists act as pure ___ ____ at opiate receptors; they occupy opiate receptors without producing a pharmacological effect
Competitive antagonist
163
Pure opioid antagonists have minor structural differences from _____; they replace methyl groups of piperidine nitrogen with a long chain
Morphine
164
Pure opioid antagonists are used to treat ___ ___
Opiate overdose
165
Pure opioid antagonists precipitate ____ withdrawal symptoms in opioid-dependent patients
Rapid
166
Pure opioid antagonists precipitate ____ withdrawal symptoms in opioid-dependent patients
Rapid
167
Naloxone (Narcan) has a ____ onset of action when given intravenously
Rapid
168
The plasma half-life of Naloxone (Narcan) is...
1 hour
169
Naloxone (Narcan) is rapidly ____ and cleared by the kidney
Glucuronidated
170
We should administer Naloxone (Narcan) until the opioid has ___ the system
Cleared
171
Naloxone (Narcan) has been approved for use in neonates to reverse ___ ___ induced by maternal opioid use
Respiratory depression
172
____ is 3-5 times more potent than naloxone
Naltrexone (ReVia)
173
Naltrexone (ReVia) has a duration of action of ___-___ hours
24-72
174
Naltrexone (ReVia) is administered ____
Orally
175
Naltrexone (ReVia) produces an active metabolite, ___-___-___, which is also a pure opioid antagonist
6-beta-naltrexol
176
Naltrexone (ReVia) may be useful for treatment of ___ or ____ dependence
Opioid or alcohol
177
Does Naltrexone of Naloxone have more side effects?
Naltrexone
178
What are some side effects of Naltrexone (ReVia)?
-Headache
-Sleep disturbances
-Increased blood pressure
-Nausea
-Blurred vision
-Increased appetite
179
Nalmefene (Revex) is a long-acting, injectable opioid ____
Antagonist
180
The onset of action of Nalmefene (Revex) is ___ ___ after IV administration
2 minutes
181
Nalmefene (Revex) has slow hepatic metabolism and a half-life of ____ hours
11
182
Nalmedene (Revex) can be used for opioid overdose, but due to its long half-life, the duration of withdrawal symptoms is ____ compared to naloxone
Increased
183
What are two examples of opioid antitussives?
-Dextromethorphan
-Benzonatate (Tessalon)
184
Dextromethorphan has no ____ activity
CNS
185
Dextromethorphan acts at the cough center of the ____
Medulla
186
Dextromethorphan is half as potent as an antitussive as ____ (it can still produce high in large quantities)
Codeine
187
Benzonatate (Tessalon) is related to local anesthetic _____
Tetracaine
188
Benzonatate (tessalon) has no ____ activity
CNS
189
Benzonatate (Tessalon) anesthetizes ____ ____ in the lungs to reduce cough
Stretch receptors
190
Nucynta (Tapentadol) has a dual mechanism of action which are...
-Agonist mu-opioid
-Norepinephrine reuptake inhibitor
191
What is the indication of Nucynta (Tapentadol)?
-Moderate to severe pain in those 18 years old and up
192
Nucynta (Tapentadol) is ___% protein bound
20
193
___% of Nucynta (Tapentadol) is lost to first pass effect
10
194
What CYP450 enzymes metabolize Nucynta (Tapentadol)?
-2C9
-2C19
-2D6
195
If someone has major impairment of hepatic ____, they should not use Nucynta (Tapentadol)
Metabolism
196
Nucynta (Tapentadol) is ____ excreted
Renally
197
Nucynta (Tapentadol) has an affinity ____ times lower than morphine but a potency only ___-___ times lower than morphine
18; 2-3
198
Nucynta (Tapentadol) has no significant effects on ___ ___ or QT interval
Heart rate
199
What are some adverse effects of Nucynta (Tapentadol)?
-N/V/D
-Constipation
-Somnolence
-Pruritus
200
What are some precautions when taking Nucynta (Tapentadol)?
-Respiratory depression
-Serotonin syndrome
-Seizures
201
Nucynta (Tapentadol) is a schedule ____ drug
II
202
Taking Nucynta during pregnancy could cause the baby to be ___-___
Opioid dependent
203
Dosages of vicodin:
-Vicodin 5mg/300mg
-Vicodin ES 7.5mg/300mg
-Vicodin HP 10mg/300mg
204
All dosages of Vicodin are schedule ___ drugs, but FDA is recommending up scheduling because of abuse
III
205
Hysingla ER is ____ ____, and it is a Schedule II drug
Hydrocodone Bitartrate
206
Just like with Zorhydros ER, there are concerns with Hysingla ER for ____ potential
Abuse
207
Hysingla ER can cause life-threatening ___ ___
Respiratory depression
208
Hysingla ER can also cause neonatal opioid ___ ___
Withdrawal syndrome
209
Hysingla ER and Zorhydros ER are inhibitors and inducers of what CYP450 enzyme?
3A4
