Week 2 Flashcards
opioid analgesics part 1
1
Q
What drug class(es) work on Transduction?
A
- NSAIDs
- Local Anesthetics
- Steroids
- Antihistamines
- Opioids
Apex Unit 5, Pharmacology 2 - Opioids & Non-Opioid Analgesics - 1. Pain Overview
2
Q
What drug class(es) works on Transmission?
A
- Local Anesthetics
Apex Unit 5, Pharmacology 2 - Opioids & Non-Opioid Analgesics - 1. Pain Overview
3
Q
What drug class(es) work on Modulation
A
- Neuraxial Opioids
- NMDA Antagonists
- a2 agonists
- Cholinesterase Inhibitors
- SSRIs
- SNRIs
NH lists NSAIDs, but the explanation is kind of roundabout/indirect
Apex Unit 5, Pharmacology 2 - Opioids & Non-Opioid Analgesics - 1. Pain Overview
4
Q
What drug class(es) work on Perception of pain?
A
- General Anesthetics
- a2 agonists
- Opioids
Apex Unit 5, Pharmacology 2 - Opioids & Non-Opioid Analgesics - 1. Pain Overview
5
Q
What endogenous ligands target the mu receptor?
A
- Endomorphin 1
- Endomorphin 2
- B-endorphin
- maybe enkephalins??
Nagelhout Ch. 11, pg 140, Table 11.2
6
Q
What endogenous ligands target the Delt receptor?
A
Enkephalins
- Enkephalins
- maybe B-endorphin??
Nagelhout Ch. 11, pg 140, Table 11.2
7
Q
What ligands target the kappa receptor ?
A
Dynorphins
- Dynorphin A
- Dynorphin B
- α-neoendorphin
Nagelhout Ch. 11, pg 140, Table 11.2
8
Q
What ligands target the nociceptin orphanin FQ peptide receptor (NOP)?
A
Nociceptin
- Nociceptin/orphanin FQ (N/OFQ)
Nagelhout Ch. 11, pg 140, Table 11.2
9
Q
What do opioids do to receptors on pre-synaptic neurons?
A
- They bind with G-Protein Coupled Receptors (GPCR)
- Which inhibits Adenylate cyclase
- Which inhibits conversion of ATP to cyclic adenosine monophosphate (cAMP)
- Closes Ca+2 gates channels
- Inhibits Neurotransmitter release (NE, Substance P, Acetylcholine, dopamine)
Apex Unit 5, Pharmacology 2 - Opioids & Non-Opioid Analgesics - 2. Opioid Receptors & Nagelhout Ch. 11, pg 141, Fig. 11.2
10
Q
What do opioids do to receptors on post-synaptic neurons?
A
- They bind with G-Protein Coupled Receptors (GPCR)
- Which inhibits Adenylate cyclase
- Which inhibits conversion of ATP to cyclic adenosine monophosphate (cAMP)
- Opens G protein coupled inwardly rectifying K+ (GIRK) channels
- Hyperpolarizes the post-synaptic neuron, preventing propagation of action potentials
Apex Unit 5, Pharmacology 2 - Opioids & Non-Opioid Analgesics - 2. Opioid Receptors & Nagelhout Ch. 11, pg 139
11
Q
What are the differences in analgesia between Mu, kappa, and delta receptors?
A
- All provide Supraspinal and Spinal Analgesia
- Delta modulates Mu activity
Nagelhout Ch. 11, pg 140, Table 11.1
Stoelting’s Ch. 7, pg. 219, Table 7.2
12
Q
What are the differences in CV effects between Mu, kappa, and Delta receptors?
A
Mu-1 = Brady
Nagelhout Ch. 11, pg 140, Table 11.1
Stoelting’s Ch. 7, pg. 219, Table 7.2
13
Q
What are the differences in respiratory effects between Mu, Kappa, and Delta receptors?
A
- Mu2 and Delta = depression
- Kappa= “possible depression”
same Kappa, same
Nagelhout Ch. 11, pg 140, Table 11.1
Stoelting’s Ch. 7, pg. 219, Table 7.2
14
Q
What are the differences in CNS effects between Mu, Kappa, and Delta receptors?
A
- Mu - Sedation, Euphoria, Prolactin Release, Hypothermia
- Kapa - Sedation, Dysphoria, Hallucinations, Delirium
- Delta - Nada
Nagelhout Ch. 11, pg 140, Table 11.1
Stoelting’s Ch. 7, pg. 219, Table 7.2
15
Q
What are the differences in pupillary effects between Mu, Kappa, and Delta receptors?
A
- Mu - Miosis
- Kappa - Miosis
- Delta - Nada
Nagelhout Ch. 11, pg 140, Table 11.1
Stoelting’s Ch. 7, pg. 219, Table 7.2
16
Q
What are the differences in GI effects between Mu, Kappa, Delta receptors?
A
- Mu- N/V, increased biliary pressure & decreased peristalsis, marked
- Kappa - Nope
- delta - minimal
Nagelhout Ch. 11, pg 140, Table 11.1
Stoelting’s Ch. 7, pg. 219, Table 7.2
17
Q
What are the differences in GU effects between Mu, Kappa, and Delta receptors?
A
- Mu - Urinary Retention
- Kappa - Diuresis (inhibits vasopressin)
- Delta - Urinary Retention
Nagelhout Ch. 11, pg 140, Table 11.1
Stoelting’s Ch. 7, pg. 219, Table 7.2
18
Q
Which opioid receptors induce pruritis?
A
- Mu & Kappa
Nagelhout Ch. 11, pg 140, Table 11.1
19
Q
Which opioid receptors have anti-shivering effects?
A
Kappa
Nagelhout Ch. 11, pg 140, Table 11.1
20
Q
What effects do Mu-1 and Mu-2 receptors share?
A
- Analgesia
- Bradycardia
Apex Unit 5, Pharmacology 2 - Opioids & Non-Opioid Analgesics - 2. Opioid Receptors
Stoelting’s Ch. 7, pg. 219, Table 7.2
21
Q
How do the effects of Mu-1 and Mu-2 receptors differ?
A
Mu-1 - Euphoria, Low Abuse Potential, Miosis, Hypothermia, Urinary Retention
Mu-2 - Respiratory Depression, Constipation, Physical Dependence (2 lungs, #2 = crap, PD = 2 words?)
Apex Unit 5, Pharmacology 2 - Opioids & Non-Opioid Analgesics - 2. Opioid Receptors
Stoelting’s Ch. 7, pg. 219, Table 7.2
22
Q
What’s Meperidine’s relative potency compared to Morphine?
A
0.1 or 1/10 the potency of Morphine
Stoelting’s Ch. 7, pg. 229
23
Q
What’s Fentanyl’s relative potency compared to Morphine?
A
- 75 - 125x
- APEX says 100x
Stoelting’s Ch. 7, pg. 231
24
Q
What is Sufentanil’s relative potency?
A
- 500 - 1000x Morphine
- Book says 5-10x fentanyl
Stoelting’s Ch. 7, pg. 235
25
What's Alfentanil's relative potency?
10x Morphine
* Book compares to Fentanyl, which is about 1/10 or 0.1
## Footnote
Stoelting’s Ch. 7, pg. 236
26
What's Remifentanil's relative potency?
100x Morphine
* Same as Fentanyl
## Footnote
Stoelting’s Ch. 7, pg. 237
27
What is Hydromorphone's relative potency?
5x Morphine
7x if you ask APEX
## Footnote
Stoelting’s Ch. 7, pg. 240
28
Morphine and Codeine are classified as what derivative?
* Phenanthrene
* Naturally occuring
## Footnote
Stoelting’s Ch. 7, pg. 217
29
Which drugs are Morphine derivatives
* Hydromorphone
* Heroin
* Naloxone & Naltrexone <-oxymorphone <-Hydromorphone
## Footnote
Stoelting’s Ch. 7, pg. 217, pg. 240
Nagelhout Ch. 11, pg. 148-149
30
Which drugs are Phenylpiperdine derivatives?
* Meperidine
* Fentanyl
* Sufentanil
* Remifentanil
* Alfentanil
## Footnote
Stoelting’s Ch. 7, pg. 217
31
Which opioid(s) are NOT biotransformed in the liver?
* Remifentanil- biotransformed by tissue & plasma esterases
## Footnote
Nagelhout Ch. 11, pg. 148
Stoelting's Ch. 7, pg. 238
32
Which opioids have active metabolites?
The M's
* Morphine (M6G)
* Meperidine (Normeperidine - neurotoxic)
* HydroMorphone (according to APEX -> H3G, not Nagelhout/Stoelting)
* & stupid Codeine (Technically becomes morphine)
## Footnote
Stoelting's Ch. 7, pg. 228, 229, 240
33
Supraspinal analgesia occurs through activation of opioid receptors in the ____________
* medulla
* midbrain
* "other areas"
## Footnote
Nagelhout, pg. 138
34
What are the 3 endogenous substances that are opiate receptor agonists?
* enkephalins
* endorphins
* dynorphins
## Footnote
Nagelhout, pg. 138
35
Which of the opioids are naturally occuring?
* Morphine
* Codeine
## Footnote
Nagelhout, pg. 139, Table 11.1
36
Name several semisynthetic opioid **agonists**
* oxycodone
* hydrocodone
* oxymorphone
* hydromorphone
## Footnote
Nagelhout, pg. 139, Table 11.1
37
What are the two semisynthetic opioid antagonists?
* naloxone
* naltrexone
## Footnote
Nagelhout, pg. 139, Table 11.1
38
Name several synthetic opioids
* All of the "ils/yls" - Fent, alfent, sufent, remi
* Meperidine
* Nalbuphine
* Methadone
## Footnote
Nagelhout, pg. 139, Table 11.1
39
What are the three classes of opiate receptors?
* mu, μ
* kappa, κ
* delta, δ
## Footnote
Nagelhout, pg. 139
40
Name the primary endogenous ligand for the opiate receptors:
* mu, μ -
* kappa, κ -
* delta, δ -
* mu, μ - endorphins & endomorphins
* kappa, κ - dynorphins
* delta, δ - enkephalins
## Footnote
Nagelhout, pg. 140
41
Opioid receptors are g protein-coupled receptors with the intracellular action of decreasing ___________ production, reducing the influx of __________ ions
* cAMP
* calcium
## Footnote
Nagelhout, pg. 139
42
Explain how activation of opioid receptors relates to intracellular potassium concentrations
* activation of opioid receptors leads to opening of G protein-coupled inwardly rectifying (GIRK) channels
* this allows efflux of potassium from the cell and hyperpolarization
* hyperpolarization prevents the propagation of action potentials
## Footnote
Nagelhout, pg. 139
43
Stimulation of the _________ receptor produces most of the classic clinical actions of the opioid agonists
* mu, μ
## Footnote
Nagelhout, pg. 139
44
The _________ receptor serves to modulate activity of the mu receptors
* delta, δ
## Footnote
Nagelhout, pg. 139
45
When small doses of opioids are used, the effects are usually terminated by _____________ rather than metabolism
* redistribution (from central to peripheral compartment
## Footnote
Nagelhout, pg. 140
46
The analgesic effects of opioids come from their ability to directily inhibit ascending transmission of nociceptive information and activate ________________ from the midbrain/rostral ventromedulla
* pain control pathways that descend
## Footnote
Nagelhout, pg. 142
47
Dysphoria appears more prominent with drugs that have strong ___________ receptor effects or when opioids are taken in the absence of ___________
* kappa, κ
* pain
## Footnote
Nagelhout, pg. 142
48
Opiates are not anesthetics, so _________ is a concern when even high doses are used
* awareness under anesthesia
## Footnote
Nagelhout, pg. 142
49
Acute and chronic tolerance can occur with opiates, and cross-tolerance among μ-agonists will occur. Usually a decrease in ____________ is noted first, followed eventually by __________
* duration
* decrease in effect
## Footnote
Nagelhout, pg. 142
50
All opiate agonists produce a dose-dependent depression of respirations via effects on ________ and ________ receptors in the brainstem respiratory centers
* mu, μ
* delta, δ
## Footnote
Nagelhout, pg. 142
51
What is the mechanism for opiate-induced respiratory depression?
* shift to the right in the CO2 response curve
* reduced responsiveness to increasing carbon dioxide levels - higher PCO2 required to maintain adequate respiration
## Footnote
Nagelhout, pg. 142
52
___________ is affected first, and a classic "narcotized" patient will take slow _______ breaths
* respiratory rate
* deep
| usually a decreased rate with increased tidal volume is observed - Dr. C
53
Pinpoint pupils, AKA _________, is a prominent action of opioids - minimal tolerance develops to this effect
* miosis
## Footnote
Nagelhout, pg. 142
54
# True or false:
The cough suppressant effect of opiates also causes a loss of protective glottal reflexes
* False - they are not effected
55
Because of their depressant effect on the cough center in the medulla, the clinical use of opiates can help patients better tolerate _____________ and ______________
* airway devices
* ventilators
## Footnote
Nagelhout, pg. 143
56
Opioids elicit nausea and vomiting by stimulating the __________ in the area postrema of the medulla - a ___________ component is also probable because the incidence is much higher in ambulatory patients
* chemoreceptor trigger zone
* vestibular
## Footnote
Nagelhout, pg. 143
57
When opiates are used as part of the anesthetic plan, there is a(n) ____________ incidence of postoperative nausea and vomiting
* increased
## Footnote
Nagelhout, pg. 143
58
Much of the hypotension produced by morphine, codeine, and meperidine is attributed to __________ release
* histamine
| hypotension minimal in healthy pts - especially when supine/normovolemic
## Footnote
Nagelhout, pg. 143
59
Histmaine release is absent in which opioids?
* fentanyl
* sufentanil
* alfentanil
* remifentanil
## Footnote
Nagelhout, pg. 143
60
Opioids decrease tone at the bladder detrusor muscle and constrict the ___________, producing an antidiuretic effect
* urinary sphincter
## Footnote
Nagelhout, pg. 143
61
Administration of opioids with which anesthetic gas may increase the frequency of muscluar rigidity?
* Nitrous oxide
## Footnote
Nagelhout, pg. 143
62
Activation of which opioid receptor results in diuresis? What is the mechanism?
* kappa, κ
* inhibition of vasopressin release
63
Muscular rigidity caused by large intravenous doses of opioids is easily reduced by the administration of ____________ or ______________
* NMBA
* naloxone
## Footnote
Nagelhout, pg. 144
64
# True or false:
Only histamine releasing opiates (morphine, codeine, meperidine) cause pruritus
* False - the mechanism for pruritus appears to be through central mu receptors and NOT local histamine release
## Footnote
Nagelhout, pg. 144
65
Pruritus is especially prominent in which route of opiate administration?
* neuraxial
## Footnote
Nagelhout, pg. 144
66
Which medication should be used as first-line treatment for opioid-induced pruritus?
* Nalbuphine - it is superior to placebo, diphenhydramine, naloxone or propofol
| agents like naloxone or naltrexone may also work but reverse analgesia
## Footnote
Nagelhout, pg. 144
67
The __________ opioid receptor is responsible for effects on GI function - name those effects
* Mu, μ
* decreased gastric motility → prolonged gastric emptying time
* decreased intestinal propulsive activity → constipation/postop ileus
* reduced secretory activity through GI system
## Footnote
Nagelhout, pg. 144
68
Opioids produce a dose-dependent ________ in biliary duct pressure and sphincter of Oddi tone
* increase
| questionable whether this has clinical relevance
## Footnote
Nagelhout, pg. 144
69
Opiates reduce the ________ to surgery by inhibiting release of ___________ from the pituitary
* stress response
* corticotropin
## Footnote
Nagelhout, pg. 144
70
What actions do opioids have on body temperature? How do they exert these actions?
* Slightly decreased body temperature
* Inhibit release of thyroid stimulating hormone → decreased basal metabolic rate
* Resetting of temperature set point in hypothalamus
## Footnote
Nagelhout, pg. 144
71
The analgesic response to neuraxial opioid administration is especially related to which opioid receptor subtype?
* kappa, κ
| located in the substantia gelatinosa
## Footnote
Nagelhout, pg. 144
72
Side effects with spinal administration of opioids are similar to systemic administration, except that ________ and __________ occur with much greater frequency
* urinary retention
* pruritus
## Footnote
Nagelhout, pg. 144
73
_________ is the most common serious complication associated with intrathecally and epidurally administered opioids
* Respiratory depression
## Footnote
Nagelhout, pg. 144
74
Why does neuraxial morphine cause both an early phase and late phase of respiratory depression?
* Rapid systemic absorption (similar to parenteral dosing)
* Rostral flow of CSF and delivery of morphine to the brainstem respiratory centers 8-12 hrs later
## Footnote
Nagelhout, pg. 144
75
Do hydrophilic or lipophilic opioids have a smaller area of distribution along the length of the spinal cord? Why?
* lipophilic
* they are rapidly absorbed into the spinal tissues before spreading
| lipophilic drugs also have a faster onset, but shorter duration
## Footnote
Nagelhout, pg. 145
76
Name several advantages of continuous opioid infusion when compared with intermittent bolus
## Footnote
Nagelhout, pg. 145
77
Why is sedation not a good indicator of appropriate analgesia with the administration of IV morphine?
* IV morphine causes sedation before it causes analgesia
## Footnote
Nagelhout, pg. 147
78
# True or false:
When administered intrathecally, morphine has the shortest duration of action of the specific opioids
79
Why is morphine contraindicated in a patient with renal failure?
* It has an active metabolite, M6G, which may cause a more prolonged effect
## Footnote
Nagelhout, pg. 147
80
_________ is a weak opioid with good antitussive activity - about 10% is metabolized to morphine
* Codeine
## Footnote
Nagelhout, pg. 147
81
________ is a drug derived from morphine with a similar pharmacokinetic profile, but is 5-7 times more potent
Hydromorphone
## Footnote
Nagelhout, pg. 147
82
Methadone is a synthetic opioid often indicated for ___________ because it produces less euphoria when compared to other common opioids
* opioid abstinence syndromes
* opioid use disorders
## Footnote
Nagelhout, pg. 147
83
_________ is a synthetic opioid agonist that is effective in reducing shivering - this appears to result from _________ receptor stimulation
* meperidine
* kappa
| BUT, it is technically classified as mu receptor agonist
## Footnote
Nagelhout, pg. 147
84
Meperidine is structurally similar to __________ and has similar antispasmodic effects
* atropine
## Footnote
Nagelhout, pg. 147
85
What are the major neurologic concerns with the active metabolite of meperidine (normeperidine)?
* Lowering of seizure threshold → seizures
* CNS excitability → tremors, muscle twitches
## Footnote
Nagelhout, pg. 147
86
___________ is the most widely used opioid analgesic in anesthesia
* Fentanyl
## Footnote
Nagelhout, pg. 147
87
The action of a single dose of fentanyl is terminated by _______________ and has a duration of approximately ___________
* redistribution (not metabolism/elimination)
* 20-40 minutes
## Footnote
Nagelhout, pg. 147
88
Fentanyl undergoes a significant first-pass uptake in the __________ with temporary accumlation before release
* lungs
89
Metabolism of ___________ by plasma and tissue esterases lends itself to ultrashort duration and titratability
* remifentanil
## Footnote
Nagelhout, pg. 148
90
Due to the high potential for respiratory depression, muscle rigidity, and bradycardia (per Dr. C), bolus dosing of __________ in the preoperative of postoperative period is not recommended
* remifentanil
## Footnote
Nagelhout, pg. 148
91
Why is remifentanil not administered epidurally or intrathecally?
* potential for neurotoxicity related to glycine use in powder preparations
## Footnote
Nagelhout, pg. 148
92
____________ is the most potent of the parenterally administered opioids
* Sufentanil
## Footnote
Nagelhout, pg. 148
93
Buprenorphine is a partial opioid agonist that, when used neuraxially, has a lower incidence of _________ and __________
* pruritis
* nausea
## Footnote
Dr. C, the man himself
94
Which drug has the ability to reverse opioid induced respiratory depression and pruritis while retaining analgesic properties?
* Nalbuphine
## Footnote
Nagelhout, pg. 148
95
Nalbuphine provides an agonist effect at the __________ receptors, and an antagonist effect at the __________ receptors, with an analgesic response equal to that of ___________
* kappa
* mu
* morphine
## Footnote
Nagelhout, pg. 148
96
_________ and _________ are pure opioid antagonsits
* Naloxone
* Naltrexone
## Footnote
Nagelhout, pg. 148-149
97
The following are drugs commonly used orally for treating acute pain:
_____________ is approximately twice as potent as oral morphine
____________ is similar in potency to oral morphine
* oxycodone
* hydrocodone
| morphine 10 mg = hydrocodone 5-10 mg
## Footnote
Stoeltings, pg. 240
98
When physical dependence is established, discontinuation of the opioid agonist produces a typical withdrawal abstinence syndrome - this usually requires _________ days with morphine but begins to occur within 48 hours of continuous medication usage
* 25 days
## Footnote
Stoeltings, pg. 225
99
While __________ has a more rapid onset than fentanyl, it has a much shorter duration of action, and its popularity in current practice is limited
* Alfentanil
