SM 236/240: Pharmacology Flashcards
1
Q
What is pain?
A
Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage
2
Q
What are the most common drugs involved in prescription overdose?
A
Prescription opioids, including: Oxycodone, Methadone, and Hydrocodone
3
Q
What race is most impacted by opioid overdose death?
A
Caucasians
4
Q
What are pain systems?
A
Peripheral neurons with nociceptors or central neuronal relay pathways
5
Q
What are nociceptors?
A
Peripheral pain sensors
6
Q
How do pain systems alter pain perception?
A
Pain systems impose excitatory or inhibitory influences on nociceptive information throughout many levels of the neuraxis
7
Q
Where can nociception occur?
A
Skin, Muscle, Joints, Viscera, Dura
8
Q
What are the two types of pain fibers?
A
A-delta and C fibers
9
Q
How do A-delta and C pain fibers compare?
A
A-delta is fast, C is slow
10
Q
How do fibers explain “double pain”?
A
After a traumatic injury, A-delta fibers produce initial sharp pain while C pain fibers produce later dull, throbbing pain
11
Q
What molecules initiate pain?
A
Central: Glutamate and Substance P
Peripheral: Bradykinin
Both: Prostaglandins
12
Q
What are the central pain initiators?
A
Glutamate and Substance P
13
Q
What are the peripheral pain initiators?
A
Bradykinin
14
Q
What molecules can initiate pain both centrally and peripherally?
A
Prostaglandins
15
Q
What are the pain inhibitor molecules?
A
Serotonin, Norepi, Endorphins, Enkephalisn, Dynorphin
16
Q
Describe the general pain pathway:
A
Pain is detected by the Nociceptor
Pain travels up sensory axon through the Dorsal Horn of a Spinal Cord neuron via Substance P/Glutamate
Pain signal is amplified
17
Q
What is the anterolateral pathway?
A
The pathway that conveys pain and temperature, as well as crude touch
18
Q
What is the posterior column pathway?
A
The pathway that covneys proprioception, vibration, and fine touch
19
Q
Where does the anterolateral pathway cross over in the spinal cord?
A
At the level a signal, such as pain, is received
20
Q
Where does the posterior column pathway cross over in the spinal cord?
A
At the Medulla Oblongata, a higher level than where the pain is received,
21
Q
Which pathway does pain use?
A
The Anterolateral Pathway
22
Q
What is gate control theory?
A
Idea that you can “shake off” pain with non-painful stimuli distracting you from painful stimuli
23
Q
What is the Periaqueductal gray?
A
An area that inhibits pain transmission in the dorsal horn via relay to the rostral ventral medulla
24
Q
What are the “ascending” and “descending” pain pathway sand how do they relate to Opioids?
A
Pain is detected and travels to brain via Ascending pathways
Pain is inhibited by central neurons using Descending pathways
Opioids inhibit Ascending pathways and activate Descending pathways to inhibit pain
25
How do Opioids activate the Descending pain inhibition pathway?
Double negative: normally, GABA neurons inhibit the pain-inhibiting neurons of the Descending pathway
Opioids inhibit GABA neurons to disinhibit pain inhibition, potentiating the Descending pathway
26
What are the Opioid receptors and how many genes code for them?
3 receptor: Mu, Kappa, and Delta
All coded for by the same gene with varied splicing
27
How does the same gene give rise to Mu, Kappa, and Delta Opioid receptors?
Subtypes come from splice variants
28
Describe the Mu Opioid receptor?
Mu for Morphine
Causes Analgesia/Euphoria, Dependence, Respiratory Depression and Miosis
29
Describe the Kappa Opioid receptor?
Mild analgesia, less respiratory depression than Mu , and psychomimetic effects
30
How do the Mu and Kappa Opioid receptors compare?
Mu causes stronger analgesia and respiratory depression than Kappa
Kappa also has psychomimetic effects
31
Describe the Delta Opioid receptor?
Function unknown
32
Where are Opioid receptors expressed?
Brain, spinal cord, gut
33
Where are Opiod receptors located in the brain and with what function?
Thalamus = detect pains sensation
Amygdala = emotional aspect of pain
Area Postrema = nausea from pain
Brainstem Ventilation Nuclei = assist breathing
Periaqueductal Gray = Inhibit pain transmission
Substantia Gelatinosa = nociceptor connecting to SC
34
Which area of the brain is responsible for detecting pain sensations?
The Thalamus
35
Which area of the brain encodes the emotional aspect of pain?
Amygdala
36
Which area of the pain is responsible for the nausea caused by Opioids?
Area Postrema
37
Which part of the brain is responsible for respiratory depression caused by Opioids?
Brainstem Ventilation Nuclei
38
What is the term for where a nociceptor axon first interfaces with the spinal cord?
Substantia Gelatinosa
39
What type of protein are Opioid receptors?
GPCR's
40
Describe the signalling changes caused by Opioid binding to Opioid receptors?
Inhibit cAMP
Increase K efflux and decease Ca influx = hyperpolarize
Decrease nociceptive transmission
41
What effect do Opioids have on motor and touch fibers?
They don't
42
Why are Opioids able to disinhibit pain inhibitory neurons?
GABAnergic interneurons that inhibit pain inhibitory neurons have Opioid receptors, which can bind Opiods and inhibit the interneuron, potentiating the Pain inhibitory neuron
43
What is an Opiate?
A drug derived from Opium
44
What is an Opioid?
All drugs, natural and synthetic, that bind to Opioid receptors
45
What is a Narcotic?
Any substance that induces sleep, actors on opioid receptors, or any illicit substance
46
What are the 3 broad ways to categorize Opioids?
Naturally occurring
Semisynthetic
Synthetic
47
What are examples of naturally occurring Opioids?
Morphine and Codeine
48
What are examples of semisynthetic Opioids?
Heroin
49
What are examples of synthetic Opioids?
Methadone and Fentanyl
50
What are the weak Opioids?
Codeine and Hydrocodone
51
What are the strong Opioids?
Everything other than Codeine and Hydrocodone
52
What are Opioid Agonists?
Mu receptor agonists:
Morphine and Hydromorphone
53
What are Opioid Antagonists?
Mu receptor antagonists:
Naloxone, Naltrexone
54
What are Opioid Agonist/Antagonists?
Medications that activate Kappa and inhibit Mu, to provide some pain relief and minimize side effects
Ex: Butorphanol
55
What are Opioid Partial Agonists?
Buprenomorphine, causes high affinity partial Mu agonism
56
Which Opioid receptor mediates Analgesia in an Agonist/Antagonist medication?
Analgesia and Kappa mediated
57
Which Opioid receptor is inhibited in an Agonist/Antagonist medication?
Mu is weakly antagonized
58
What are the pros and cons of Agonist/Antagonist Opioids?
Less GI side effects and respiratory depression due to weak Mu inhibition, but have a ceiling effect and can trigger withdrawal
59
When should an Agonist/Antagonist Opioid never be used?
Never use them on an Opioid tolerant patient because they can trigger withdrawal and psychosis
60
Describe how the binding of Buprenomorphine leads it's effects?
Buprenomorphine is a high affinity partial Mu agonist
Has a ceiling on agonism and binds with such high affinity that other Opioids and even Naloxone cannot bind
Makes reversal following OD difficullt
61
What is the current use of Buprenomorphine?
Opioid maintenance
62
How does lipophilicity relate to Opioid use?
Lipophilicity sets the efficacy with which an Opioid crosses the BBB
High Lipophilicity = fast onset and short duration
Low Lipophilicity = slow onset and long duration
63
What are the high lipohilicity Opioids?
Fentanyl, Meperidine
64
What are the low lipophilicity Opioids?
Morphine, Hydromorphone
65
What are the neurologic effects of Opioids?
Analgesia
66
What is Analgesia?
Pain relief at the supra spinal and spinal cord level not reliably associated with a loss of consciousness
67
Does Analgesia cause a loss of consciousness?
Nope
68
Is Analgesia better at controlling Nociceptive Pain or Neuropathic Pain?
Nociceptive Pain
69
How do Nociceptive and Neuropathic Pain compare?
Nociceptive Pain is due to pain caused by nociceptor stimulation
Neuropathic pain is pain caused by damaged neural structures
Analgesics work better on Nociceptive pain
70
What is Miosis?
Pinpoint pupils associated with Opioid agonist OD
71
Which Opioid agonists cause Mioisis?
All of them
72
How long does it take to build up tolerance against Mioisis?
There is no tolerance, even in addicts, making it useful for diagnosis of Opioid OD
73
What is the major cause of Opioid mortality and how can it be avoided?
Opioid induced respiratory depression is a major cause of death
Best way to avoid this is to hold the Opioid if a patient is sedated
74
What receptor mediates Opioid respiratory mortality?
Mu receptors bind Opioids and cause respiratory depression leading to death
75
What effect do Opioids have on the respiratory system other than respiratory depression?
Opioids inhibit the ventilatory response to hypercapnia, preventing tachypnea and causes respiratory depression
76
Why are Opioids used for anxiety?
Anxiety causes hyperventilation while Opioids slow the respiratory drive
77
Can Opioids be used in patients with Cardiac problems?
For the most part, yes, since Opioid don't have much of an effect on the heart
78
What are the GI effects of Opioids?
Opioids can slow peristalsis due to enteric Opioid receptors, and lead to Nausea or vomiting
79
What Opioid effects can tolerance develop toward?
Tolerance can emerge to: Euphoria, sedation, analgesia, respiratory depression and Nausea/vomiting
80
What Opioid effects can tolerance not develop toward?
Tolerance never emerges to Miosis or Constipation
81
How do Tolerance and Dependence vary?
A patient is dependent when the body is physically dependent on a drug for normal function
Tolerance refers to acclimatization of the body toward the drug's effects
82
What are the symptoms of Opioid withdrawal?
Sympathettic overdrive:
Anxiety, Insomnia, HTN, Tachycardia, and Hyperventilation
83
Can you die from Withdrawal?
Nope, but it feels miserable
84
What are the signs of Opioid Overdose?
Respiratory depression/arrest, Sedation/Unresponsive, Miosis/pinpoint pupils
85
What should be done if you suspect an Opioid OD?
Supportive ventilation + Naloxone
86
Describe the hydrophilicity/phobicity, duration, and MoA of Morphine?
```
Hydrophilic = delayed transport across BBB = delayed onset
Duration = 4-5 hours
MoA = histamine release (risk of hypotension)
```
87
Describe the metabolism of Morphine?
Morphine is converted into Morphine-3-Glucoronide and Morphine-6-Glucororide in the Liver for excretion in the Kidney
88
Why shouldn't you give someone with renal failure Morphine?
Morphine is gloconidated and excreted in the Kidneys, and renal failure impairs excretion
89
What is the significance of the metabolites of Morphine?
Morphine is glucoronidated into M3G and M6G
M6G is a minor metabolite and 10-100x more potent than Morphine and is believed to cause the Analgesic effects
M3G can cause myoclonus/twitches and seizures
90
Describe the PK/PD of Oxycodone?
High bioavailability compared to Morphine
| Analgesia via Oxycodone itself, but can be metabolized in small amounts into the more potent Oxymorphone
91
What is Oxymorphone?
A metabolite of Oxycodone that is a rare byproduct but much more potent
92
What is Codeine?
A prodrug with low Mu affinity, and 10% is metabolized to Morphine that in some patients cannot be metabolized
93
How is Hydrocodone administered in the US?
Always combined with Acetamniophen
Both prodrug and metabolites are potentially efficacious
94
How does Hydromorphone compare to Morphine?
Both are Hydrophilic with similar duration of Analgesia
Hydromorphine has a better side effect profile and is more potent
95
How is Hydromorphone metabolized?
Hydromorphone is metabolzied in the Liver to H3G, which lacks analgesic effects
96
Describe the binding of Fentanyl?
Fentanyl is highly lipophilic with high affinity for the Mu receptor with a fast onset and short duration
97
Which is more potent, Fentanyl or Morphine?
Fentanyl is 100x more potent than Morphine
98
When is Fentanyl used and why?
Because it has a fast onset and short duration, it is used in the OR and ICU for analgesia via IV
99
Why is Fentanyl given transdermally?
The transdermal patch causes a SubQ deposit of Fentanyl for slow sustained release, prolonging it's otherwise shortlived effects and duration
Also helps prevent abuse
100
Can you give Transdermal Fentanyl to patients with GI issues?
Yes, this is ideal because it doesn't need to be absorbed by GI
101
What is Merperidine?
A lipophilic drug with very rapid onset, albeit less potent than Morphine at binding Mu
102
How does Merperidine work outside of Mu agonismW?
Serotonin Reuptake Inhibitor
103
What is the metabolite of Merperidine?
Normeperidine, which has a long half-life as it is not cleared by the kidneys and can cause CNS hyperactivity
104
Why should you not give Merperidine to patients with renal failure?
Merperidine is metabolized into Normeperidine, which is not cleared by the Kidneys effectively, and can therefore reach very toxic conc. that leads to seizures
105
What is Tramadol?
A prodrug that has Mu receptor agonism as well as blocking the reuptake of Serotonin and Norepi, to treat mild/moderate pain
106
What is Naloxone?
An Opioid competitive antagonist with a short duration that temporarily reverses the effects of Opioid pills
107
How must Naloxone administered?
Only via IV
108
How do the density of Opioid receptors vary within patients?
Every patient has a different distribution of Opioid receptors throughout their body
109
Why do different Opioids have varying effects on patients?
Not only do patients have a different distribution of Opioids in each patient, but they also have different affinities for an Opioid ligand based on their subtype and splice variation, leading to different effects in different patients
110
What should you do if an Opioid has harsh side effects and poor analgesia?
Switch Opioids, just don't go too high
