Exam 1 Flashcards
1
Q
What is pain?
A
An unpleasant sensory and emotional experience that has actual or potential tissue damage. The emotional response to pain is very important.
2
Q
Nociceptors
A
Free nerve endings of primary afferent A and C fibers. Detect noxious stimuli.
3
Q
Nociception
A
The process by which information about tissue damage is conveyed to the CNS. Transient process that should be relieved in the absence of painful stimuli.
4
Q
5 steps in nociception
A
- ) Transduction and inflammation
- ) conduction
- ) transmission
- ) modulation
- ) perception
5
Q
Transduction
A
An injury stimulates the peripheral ends of our nociceptors. This stimulus is translated (transduced) from a physical signal into an electrical action potential.
6
Q
Inflammation
A
Trauma causes damaged cells to release inflammatory substances. Different cell types release different substances. Substances can directly stimulate an action potential while others increase the sensitivity of nociception.
7
Q
Which inflammatory substances increase the sensitivity of nociception?
A
Prostaglandins
Leukotrienes
Substance P
8
Q
Conduction
A
Once pain signals have been transduced, those electrical action potentials are conducted along the nerve fibers.
9
Q
What are the 2 types of pain fibers?
A
A-delta
C fibers
10
Q
A-Beta fibers
A
Touch receptor,
synapses in the dorsal horn and onto inhibitory interneurons.
Largest in diameter and the most myelinated.
11
Q
A-Delta fibers
A
Transmits fast, sharp pain. Prickling, cold, heat. Easily located.
Medium size in diameter, myelinated
12
Q
C fibers
A
Most common throughout the body. Slowly transmits pressure, aching, burning pain.
Dull pain, temp, itch
Unmyelinated, small diameter
13
Q
Transmission
A
When one nerve ends and connects (synapses) with the beginning of another nerve.
First order neuron to second order neuron.
The electrical signals transmits across the synaptic cleft via neurotransmitters.
14
Q
What neurotransmitters help the electrical impulse transmit across the synaptic cleft?
A
Glutamate, substance P, NE, dopamine, serotonin
15
Q
Where does transmission occur?
A
Transmission occurs in the spinothalamic tract/ ascending pathway.
- )First order neuron meets second order neuron at the Dorsal horn of spinal cord.
- ) Second order neuron travels up and meets a third order neuron in the thalamus and the top of the brain stem.
- ) The third order neuron then finally synapses in the cerebral cortex (somatosensory cortex).
16
Q
Anterolateral System
A
Made up of 3 main tracts:
- ) Spinothalamic tract
- ) Spinomesencephalic tract
- ) Spinoreticular tract
17
Q
Modulation
A
Modulation is the reduction of pain intensity using an anti-nociception system in our bodies. Endogenous opioids and other anti-nociceptive neurotransmitters act on nerve junctions to modulate pain transmission.
18
Q
Where does modulation occur?
A
In various places- periphery, spinal cord, and within supraspinal structures
19
Q
Spinomesencephalic tract
A
Modulates pain,
Innervates the descending tract from the PAG
20
Q
Which neurotransmitters modulate pain?
A
Opioids (enkephalins), NE, serotonin, GABA
21
Q
Perception
A
Pain is processed in the brain as the signals reach the cerebral cortex via the thalamus.
The thalamus acts as a “relay station” within the brain.
22
Q
T/F: Our pain processing system can become sensitized over time
A
True
23
Q
Peripheral sensitization
A
Injury in the periphery leads to the release of inflammatory mediators. These lead to vasodilation and local swelling (increases blood flow). Leads to inflammation as a guard against infection and protected the area/promote healing.
24
Q
Allodynia
A
Normally innocuous stimuli now cause a pain resposne
25
Hyperalgesia
Painful stimuli may illicit a pain response that is more significant than what would normally be felt.
26
Central sensitization
At the synaptic junction in the dorsal horn, glutamate is released to stimulate the second order neuron. In central sensitization, the neuron is constantly stimulated. The consistent stimulation of the AMPA receptor changes the resting membrane potential and displaces magnesium ions. Glutamate then binds the NMDA receptor which leads to a hyperresponsiveness and increases the threshold of opioid receptors.
27
When does central sensitization occur?
Can be due to peripheral sensitization or can result from damage to a c-fiber
28
What causes allodynia and hyperalgesia?
Peripheral or central sensitization
29
Secondary hyperalgesia
Hyperalgesia that occurs in locations other than the area of injury.
30
When does central sensitization heal?
When the injury heals. Goal of process is for human to protect the injury.
31
T/F: Central sensitization occurs on the post-synaptic neuron in the dorsal horn
T
32
Acute pain
Suden onset
Warning to tissue injury, disease, procedure
May see increased HR and BP
Pain subsides when stimulus does
33
Chronic pain
Pain which exists past the normal healing time,
Pain without an identifiable etiology
May be nociceptive, result from nerve damage, or be both
34
Nociceptive pain
Temporary, localized pain resulting from the direct activation of nociceptors by noxious stimuli. Pain is then classified by where the nociceptors are located.
35
Neuropathic pain
Pain is caused by damage to the nervous system rather than tissue damage.
36
Somatic pain
Pain involving skin, bones, joints, or soft tissue.
Pain is well localized, patients can typically point to the sight of pain.
Sharp, aching, throbbing pain
37
Visceral pain
Arises from the stimulation of afferent nerves located on soft tissue or viscera. Commonly cardiac, lung, GI tract pain.
Mostly due to c-fibers
Pain is poorly localized and not well described.
38
What causes neuropathic pain?
Typically caused by injured C-fibers that cause pain signals to continuously or intermittently fire without direct nociception
39
Opioids receptor locations and effect
Dorsal horn- inhibit the transmission of nociceptive input
PAG- activate descending inhibitory pathways limiting pain transmission
Limbic system- modify the emotional repsonse to pain (euphoria), addiction
Brain stem-inhibits the respiratory systems response to CO2 levels in the blood
Receptors in the periphery-activates opioid receptors in the gut, decreasing peristalsis
40
Tolerance
The body will adapt to the presence of exogenous opioids by down regulating opioid receptors at the neuronal junction (synapse). This leads to a decrease in effect over time.
41
Cross Tolerance
Tolerance to one drug may produce tolerance to other drugs within the same class. The development of cross tolerance is incomplete in opioids, meaning if a patient is tolerant to an opioid they will not have the same level of tolerance to another opioid.
42
Ceiling effect
Some drugs will not exert more beneficial effects after achieving a specific blood concentration. Opioids do not have a ceiling effect. No max dose and increased doses will have increasing effects
43
Dependence and withdrawal
The body will begin to rely on the presence of exogenous opioids. The drug becomes required for the individual to function normally. Removal of opioid will cause withdrawal symptoms
44
Addiction
The use of the drug is beginning to impact normal functioning. Repeated use in hazardous situations, use despite negative personal consequences, unsuccessful attempts to curb use.
45
Opioid induced hyperalgesia
With chronic use, opioids may induce hyperalgesia and worsen pain as doses increase. This is complex and rare.
46
When do we use opioids for pain?
Severe pain
Acute- surgery, trauma
Breakthrough pain prn
cancer pain
chronic noncancer pain (usually try to avoid)
Opioids are only effective in nociceptive pain
47
Why are opioids not effective in neuropathic pain?
Due to the near constant signals of damaged c fibers, neuropathic pain opens up the NMDA receptor. Opioids do not act on the NMDA receptor.
48
How do you classify opioids?
Impact on opioid receptors (mu, kappa, delta)
DOA
Where they came from
49
Full mu agonists- opioids
```
Morphine sulfate
Oxycodone
Hydrocodone
Hydromorphone
Codeine
Meperidine
Fentanyl
Oxymorphone
Methadone
```
50
Partial agonist and/or mixed agonist/antagonist- opioids
Buprenorphine, butorphanol, nalbuphine
51
Dual mechanism opioids
Tramadol
| Tapentadol
52
Which opioids are naturally short acting but have long acting oral forms available?
```
Morphine
Oxycodone
Hydrocodone
Hydromorphone
Buprenorphine
Tramadol
```
53
Which opioids are naturally short acting and do not have long acting forms available?
Codeine
Meperidine
Fentanyl
54
Which opioids are naturally long acting
Oxymorphone
| Methadone
55
Short acting formations onset and dosing
Onset: 10-30 min
Dosing: Q 4-6 H
56
Long acting forms onset and dosing
Onset: 30-60 min
| Dosing- QD or BID
57
Morphine
```
The gold standard opioid
Available in PO, SL, IV, SQ, Epidural
IR lasts 3-6 H
Long acting lasts 12-24 h
Various long acting forms available
Causes significant histamine release, leading to rash, itching, and potentially hypotension
Doesnt cross the BBB as quickly as others, slower IV onset
May accumulate in renal or liver failure
```
58
Hydromorphone
Alternative option to morphine.
Available in variety of routes (PO, iV, SQ, epidural)
IR lasts 4-6 H
LA lasts 24 H
Significantly less bioavailability with PO dosing vs IV dosing.
Around 5 times more potent than morphine.
Better tolerated than morphine with less histamine release.
59
Oxycodone
Well tolerated but may have a higher euphoric effect than other opioids.
PO have IR, LA and combo pills
No IV
Greater potency than morphine (5mg oxy= 7.5mg morphine)
60
Hydrocodone
Similar potency to morphine
Only PO, but has IR and LA forms
IR forms only available as combo med
LA forms can be Q12 or Q24 H
61
Why might we use ER/LA opioid forms?
Low peaks- less euphoria
Higher troughs- more consistent pain control
Less frequent dosing, potentially better adherence
62
Issues with long acting opioids
Indicated for chronic pain. Should not be used for prn use
May lead to more tolerance, dependence, and withdrawal
Only effective if used appropriately. A lot of misuse.
63
Codeine
Has a low affinity for the opioid receptor and considered a "weak" opioid.
Much of its activity comes from its active metabolite (morphine). About 10% of patients cant metabolize.
Most common opioid for cough.
64
Meperidine
Different class of opioid than morphine, alternative if there is an allergy.
Only used for acute pain (PO and IV)
Not commonly used
Can cause CNS toxicity and accumulate in renal failure
Risk of Neuroleptic Malignant Syndrome if given with MAO-Is
65
Fentanyl
Same chemical class as meperidine, good option for allergies.
100 x more potent than IV morphine.
10mg morphine= 0.1mg Fentanyl= 100mcg
Fentanyl is dosed in micrograms
Short IV half life (1-2 hours). No active metabolite.
Commonly used for analgesia/sedation in ICU and during procedures
Not available PO
66
Transmucosal Immediate Release Fentanyl
Lozenges, SL tablet, buccal tablet, nasal spray, buccal soluble film, SL spray
All products dosed differently
Only PRN for breakthrough pain in the chronic setting, typically only for cancer patients.
67
REMS program
All transmucosal IR fentanyl products approved under a shared REMS program.
Requirement for REMS program:
Prescriber must enroll
Pharmacies must be certified
Patient must sign a patient-prescriber agreement
68
Transdermal fentanyl
Absorbs the the skin to form a subq depot. Takes 6-12 hours to reach the blood. Blood levels continue to rise for 24 hours.
69
How often do you change fentanyl patches?
Apply to a new sight every 24 hours. Do not titrate the patch dose for 72 hours.
70
Can you use fentanyl patches in opioid naive patients?
No
| Patients must have taken >60 MME's for >1 week.
71
Temperature effect on fentanyl patches
Increasing temperature will increase absorption
72
Disposal of fentanyl patches
Sticky sides together then flush
73
Oxymorphone
Technically LA but the duration of action is only 6 hours. IR form has a slower onset than other IR medications.
Expensive and rarely used.
74
Methadone
Full mu agonist and NMDA antagonist
LA, accumulates with repeated dosing.
Only use in chronic pain
Takes about 3-5 days to achieve SS
75
Which opioid is most effective in neuropathic pain?
Methadone
76
Methadone dosing
Start with small doses (2.5mg-10mg) Q 8-12h
Do NOT adjust sooner than Q 3 days
Breakthrough pain relief should rely on other opioids
Potency charts are not accurate to methadone, dose conversion must be done carefully based on MMEs
77
Methadone warning
Can cause life threatening QTc prolongation
78
Buprenorphine MOA
Partial mu agonist with high binding affinity.
79
Buprenorphine uses
OUD >2mg
| Acute pain 0.2mg
80
Butorphanol
Partial mu antagonist
Full Kappa agonist
Used to reduce post operative shivering
81
Nalbuphine
```
Mixed antagonist (mu) and kappa agonist
Commonly used for analgesia during labor and delivery.
```
82
Tramadol
Weak mu agonist
| Inhibits the reuptake of NE and serotonin
83
Tramadol warnings
Can reduce seizure threshold
| High doses can cause serotonin syndrome
84
Tapentadol
Weak my opioid receptor agonist. Inhibits reuptake of NE.
| Same warnings as tramadol
85
Opioid AE
```
Itching
Respiratory distress
Constipation
Sedation
Nausea
```
86
Pruritis with opioids
All opioids induce histamine release which leads to itching. Most common with morphine.
Least common with methadone and fentanyl.
87
Constipation with opioids
Tolerance does not develop.
Need a stimulant laxative- senna
Can use local opioid antagonists- naloxegol and methylnaltrexone but use is limited due to cost.
88
Nausea with opioids
Primarily mediated via dopaminergic pathways (some serotonin involvement as well)
Also caused by reduced gastric motilty.
Treat with prochlorperazine and metoclopramide.
Tolerance develops quickly.
89
Sedation with opioids
Occurs most commonly as initiation and after dose increases.
Use the Ramsay Sedation Scale to assess (1-6)
A score of 5 or 6 suggests we should reduce or hold the dose.
90
Respiratory depression with opioids
Tolerance develops over time
Greatest risk when starting therapy, raising dose, or changing agents
Sedation almost always proceeds respiratory distress. Administer an opioid antagonist (naloxone) if sedated and respiratory rate <8
91
Naloxone
Opioid antagonist
Used for acute reversal of opioid toxicity
Short duration of action. Need continuous drip in hospital
92
Naltrexone
Opioid antagonist
Slower onset of action
Not for acute OD
93
Suboxone
Buprenorphine/naloxone
Naloxone has extremely poor oral bioavailability and is not effective when suboxone is used appropriately.
It is in the drug to prevent tampering.
94
Acetaminophen MOA
Not fully known, thought to inhibit central cox enzymes.
| Lacks anti-inflammatory activity
95
Acetaminophen max dose
4g
96
Acetaminophen caution
Hepatotoxicity. make sure to account for all products containing tylenol
97
COX-2 selective NSAIDs
Celecoxib
98
Semi-selective NSAIDs
```
Diclofenac
Etodolac
Indomethacin
Meloxicam
Nabumetone
```
99
Nonselective NSAIDs
Ibuprofen
Naproxen
Ketorolac
Aspirin
100
NSAIDs MOA
Inhibits COX1 and 2
| Decreases prostaglandin production
101
NSAID AE
Gastrointestinal
Renal
CV
102
Which NSAID is safest for GI issues?
Celexocib followed by Ibu
103
Which NSAID has the highest rate if GI ulceration and bleeding?
Ketorolac
104
Renal Effects of NSAIDs
Can cause AKI and worsen CKD
No recommendations for one NSAID vs another
Avoid NSAIDS in CrCl <30
NSAIDs constrict blood from into the glomerulus via the afferent arteriole
105
NSAID CV effects
Increase BP, fluid retention, edema
106
Which NSAID has the highest chance of causing CV events?
Systemic diclofenac and celexocib
107
Which NSAID has the best CV safety profile?
Naproxen
108
Dosing of aspirin and other NSAIDs?
Give the non-aspirin NSAID 30 minutes before or 8 hours after aspirin
109
NSAIDs in pediatrics
Ibuprofen if >6 months, naproxen >12 years
Acetaminophen DOC if <6 months
Do not use aspirin
110
Topical NSAIDs
Little systemic abs and therefore a favorable safety profile.
Very effective for localized pain (osteoarthritis of hand)
Can be considered in patients who otherwise wouldnt be an NSAID candidate.
Diclofenac
111
Topical anesthetics- Lidocaine
MOA- blocks Na channels within nerves to prevent depolarization. Preventing both the initiation and conduction of nerve impulses.
Used for neuropathic pain
112
Capsaicin
Induces burning via the release of substance P. After repeated use (2-4 weeks) substance P is depleted and blocked from reaccumulating.
Used for neuropathic pain primarily.
113
Counter irritants
Methyl-salicylate and menthol
These products irritate the skin (typically via hot or cold) and induce a non-nociceptive signal that will override the nociceptive signal at the spinal cord.
114
Spasticity
An increase in contraction/muscle stiffness and tone (hypertonicity) due to underlying damage to the brain or spinal cord.
This increase in tone/contraction mat lead to involuntary muscle movements (spasms)
115
Antispastics
Improve (reduce) muscle hypertonicity and reduce involuntary spasms.
Baclofen, dantrolene
116
Spasm
A sudden stiffening of a muscle which may cause a limb to kick out or jerk towards your body.
117
Antispasmotics
Decrease muscle spasms by altering CNS conduction and transmission.
Benzodiazepines- inhibit transmission on the postsynaptic GABA neurons
Non-benzos- act at the brain stem and spinal cord.
118
Antispasmotic agents
```
Carisoprodol
Cyclobenzaprine
Metaxalone
Methocarbamol
Orphenadrine
```
119
Antispastic agents
Baclofen
| Dantrolene
120
Combo antispasmodic/ antispastic agents
Diazepam
| Tizanidine
121
Antispasmodic key points
Recommended as adjunct to rest and PT for short term use (<2-3weeks)
All cause sedation
Caution in elderly
122
What is the preferred antispasmodic?
Cyclobenzaprine
123
Cyclobenzaprine
Related to TCAs
Antispasmodic
Anticholinergic AE
124
Carisoprodol
Antispasmodic
| High abuse potential
125
Orphenadrine
Antispasmodic
| Anticholinergic AE
126
Tizanidine
Alpha 2 adrenergic agonist
-Antispasmodic and antispastic
Can cause orthostatic HTN and rebound HTN
127
Components of a pain assessment
Build rapport
Subjective assessment of pain
Objective assessment of pain
128
Unidimensional assessment of pain
Subjective
| Pain scales
129
Multidimensional assessment of pain
Subjective
Evaluates pain in several domains
PQRSTU method
130
PQRSTU method
P (palliative/provocative)- what makes it better/worse?
Q (quality)- what does the pain feel like?
R (region/radiating)- Where do you feel the pain? Does it move?
S (severity)- How would you rate your pain 1-10? Give directionality.
T (timing/treatment)- when did the pain first start? Is it constant or intermittent? How long does it last? Have you tried anything/ did it work?
U (you)- how is th epain impacting you physically, mentally, spiritually?
131
Common PQRSTU findings with somatic pain
P- may be provoked by movement
Q- The pain is sharp or dull, achy. The pain is familiar.
R- well localized, doesnt move
S- varies
T- may have a specific start time (injury), may have been present for years and recently worsened.
132
Common examples of somatic pain
Joint pain
Bone fractures
skin cuts, scrapes, burns
Muscle pains
133
Typical analgesic approach of somatic pain
Typically APAP and NSAIDs
Duloxetine if it becomes chronic.
Opioids effective but only if severe
Nonpharm (PT, RICE) crucial
134
Common PQRSTU findings for visceral pain
```
P- may be provoked by organ functions
Q- Deep, squeezing, crampy, pressure. Often accompanied by N/V/sweating
R- poorly localized, may be referred
S- varies
T- may come about out of nowhere
```
135
Common examples of visceral pain
Cancer pain
Appendicitis
Pancreatitis
Bowel obstruction
136
Typical treatment approach of Visceral pain
Treat the underlying cause
Opioids may be required, especially in cancer pain
Non pharm varies greatly between conditions. Cancer- massage, behavioral therapy, etc.
137
Common PQRSTU findings with neuropathic pain
P- May be provoked by normally non-painful stimuli and come out of nowhere.
Q- Unfamiliar. Burning, electrical
R- Often radiates
S- varies
T- May have paroxysms of pain (shooting electrical pain)
138
Common examples of neuropathic pain
Sciatica, diabetic neuropathy, posttherpetic neuralgia
139
Typical treatment approach for neuropathic pain
Antidepressants, anticonvulsants, anesthetics (centrally acting agents)
Limited role of opioids
Non-pharm- crucial
Behavioral therapy, PT, acupuncture, spinal stimulation, nerve block
140
Steps in chronic pain management
1. ) Build rapport
2. ) Perform a multidimensional pain assessment
3. ) Establish the goals of tx and ensure pt buy-in
4. ) Tailor therapy to the pain type present, the location, and the patient characteristics
141
Treatment outcomes and goals of pain therapy
Three A's of pain assessment
Analgesic efficacy- severity of pain
Ability to function- work, sleep, socialize, activities of daily living
AE- GI bleed, liver toxicity, sedation/OD, addiciton
142
Chronic cancer related pain
Often visceral
Can be neuropathic or somatic
Mild pain- non-opioid +nonpharm
Mild-moderate pain- Opioid (tramadol) +/- non-opioid + nonpharm
Severe pain- opioid +/- non-opioid + nonpharm
143
Opioid use in cancer pain
Start low and titrate up to the desired effect. Titrate with IR, then convert to LA.
Use LA and use IR 10-15% TDD for breakthrough pain
Opioid rotation- switching opioids if one doesnt work
144
Chronic noncancer pain nonpharm
PT
Psychological therapy
Integrative health (hypnosis, massage, acupuncture, etc.)
145
Neuropathic pain 1st line treatment
Antidepressants- TCA's or SNRIs
Calcium channel ligands- gabapentin, pregabalin
Topical lidocaine
146
When do you favor use of SNRIs?
Depression, anxiety
147
When do you avoid use of SNRIs?
Restless leg syndrome, sexual dysfunction
148
When do you favor use of TCAs?
Depression, anxiety, insomnia, para/dysthesias
149
When do you avoid use of TCA's?
Cardiac disease, sexual dysfunction, urinary retention, suicidal ideations
elderly, seizure history, glaucoma, orthostasis
150
When do you favor use of calcium channel ligands?
Restless leg syndrome
Tremor
Insomnia
Lancinating pain
151
When do you avoid use of calcium channel ligands?
Substance use disorder, edema
152
TCA moa
Inhibit the reuptake of both NE and serotonin.
153
TCA dosing
Analgesia typically achieved at much lower doses than used in depression. Start low and titrate up.
Inexpensive
QD dosing
154
TCA agents
Tertiary amines- amitriptyline, imapramine, doxepin
| Secondary amines- nortriptyline, desipramine
155
TCA AE
Anticholinergic
Tertiary amines have more ae
Nortriptyline has best AE profile. If patient has insomnia use amitriptyline
156
TCA DDI
MAOIs, SSRIs, anticholinergic agents, antiarrhythmics, clonidine, lithium, tramadol, agents that prolong QTc
157
SNRIs agents
Duloxetine, venlafaxine
158
SNRIs AE
Insomnia
Duloxetine- dose related N
Venlafaxine- increased diastolic BP, sexual dysfunction
159
1st line SNRI
Duloxetine
160
Calcium channel ligands MOA
Modulates the alpha-2-delta protein subunit of the voltage-gated calcium channel blocker. The binding of gabapentin/pregabalin to this presynaptic protein inhibits calcium influx into the neuron and thereby decreases the release of glutamate into the synapse
161
Calcium channel ligands DDI
Few, may potentiate opioids, alcohol, benzodiazepines, increase risk of resp depression
162
Calcium channel ligands AE
Sedation, edema
| Lower doses in elderly and in renal insufficiency
163
Calcium channel ligand agents
Gabapentin
| Pregabalin
164
Topical lidocaine
Patch to be placed at the site of pain unless it is radiating pain, then place patch on the side of the spine at the vertebrae
165
Additional neuropathic agents (2nd line)
```
Dual mech opioids- tramadol, tapentadol
Capsaicin
Topical clonidine
Other antidepressants and anticonvulsants
Ketamine, dextromethorphan, memantine
```
166
When should be consider that central sensitization is a factor?
When NSAID therapy has failed in nociceptive pain.
167
How do you treat central sensitization?
The same way you treat neuropathic pain
168
Opioids in chronic non cancer pain
Rarely used
| If used, use IR formulations. Do not use ER/LA unless absolutely needed.
169
Clinical features of fibromyalgia
Widespread pain, cognitive and memory impairment, tenderness, sleep disturbances, fatigue/stiffness
170
Fibromyalgia ACR diagnostic criteria
Widespread pain index (WPI) >7 and symptom severity scale score >5
OR
Symptom severity score >5 or WPI a3-6 and SS >9
Symptoms have been present for at least 3 months with no known cause
171
Non pharm therapy for fibromyalgia
Education, aerobic exercise, cognitive-behavioral therapy
172
Fibromyalgia therapy
Pregabalin, duloxetine, milnacipron
| 2nd line- tramadol, cyclobenzaprine, amitriptyline
173
Goals of acute pain therapy
1. ) Patient comfort
2. ) Promotion of healing/recovery
3. ) Prevention of chronic pain
If acute pain is inadequately controlled, it can lead to chronic pain
174
Consequences of inadequately controlled pain
Patient suffering
Physiological- increased stress hormones, cortisol, glucose, increased risk of diabetes
Psychological- increased risk of anxiety and depression
Functional
175
How do we achieve acute pain goals?
Individualized approach to managing pain
| Look at severity of pain, etiology of pain, PMH, current treatment settings
176
How do you design therapy for acute pain?
Design to take advantage of synergistic effects of multimodal therapy.
Non-pharm + Non-opioid + opioid
177
Opioids for acute pain
Opioids should be used prn for acute pain. Only use after non-opioid therapies are maximized and continue non-opioid therapies while taking opioids.
Initiate the lowest effective dose of opioid
178
Opioids for acute pain parenteral agents
Morphine, Hydromorphone, fentanyl
179
Opioids for acute pain oral agents
Morphine, hydromorphone, oxycodone, hydrocodone, tramadol
180
Opioid administration in acute pain
Oral opioids are preferred over IV opioids.
| If a pt needs IV opioids, as needed is preferred over continuous infusions. PCA is preferred.
181
Patient controlled analgesia (PCA)
Pt can press a button to receive small doses of their IV opioid.
Loading dose- given up front to reach baseline analgesia
Bolus dose- amount of drug the pt self-administers
Lockout interval- minimal time required in between bolus doses
182
What is the purpose of the lockout interval on PCA?
Allows the drug time to take effect and the patient time to assess the impact before requesting another dose.
Prevents OD
183
Advantages of PCA
Better titration analgesia
Better pain control
Less sedation
Patient has some control and better satisfaction
184
Safety concerns of PCA
Operator errors- programming, inappropriate dose, wrong analgesic
Patient errors- triggering by proxy, unable to trigger (physical or mental)
Equipment errors-false triggering, hardware/software failure
185
Therapeutic window of pain control
Spot in covering pain and staying within analgesic window.
| Less CNS AE with oral opioids
186
Plasma concentrations with PCA?
Plasma concentrations stay within the comfort range.
| Avoid sedation/ CNS effects and pain
187
PCA patient selection
Mentally alert and understands the instructions
Physically capable of operating the device
Pain problem for which PCA represents that most appropriate analgesic treatment
Has active IV access
188
Converting PCA to oral medications
Switch as soon as a patient can tolerate.
1. ) Determine the TDD
2. ) Covert TDD into total daily oral morphine equivalents. Covert to other opioid if needed.
3. ) Reduce for cross tolerance if needed
189
Ketamine MOA and uses
NMDA receptor antagonist (blocks glutamate)
Used as an anesthetic
Impacts pain, hyperalgesia, central sensitivity
IV only and nasal for refractory depression
190
Ketamine AE
Produces a dissociative effect
191
Lidocaine IV
Sodium channel blocker. Blocks the transmission of nerve impulses by decreasing the permeability to sodium ions.
192
Sodium channel blockers
Block the transmission of nerve impulses by decreasing the permeability to sodium ions. Pain is not the only sense that is impacted- temp, touch, muscle tone
Most common- lidocaine, ropivacaine, bupivacaine
193
Regional anesthesia peripheral nerve blocks
Injection near a cluster of nerves.
Commonly used for surgery/trauma on the arms and hands, the legs and feet, groin, or face
Admin-
Single dose with short acting lidocaine, single dose with long acting bupivacaine, continuous infusion
194
Regional anesthesia neuraxial nerve blocks
Injection in or around the spine. Commonly used for surgery/trauma in a general region of the body such as the abdomen/hips
Admin- single dose or continual infusion to the epidural space (given outside the dura mater)
Given to intrathecal space (inside the dura mater)
195
Common epidural agents
Opioids:
Hydrophilic- morphine, hydromorphone
Lipophilic- fentanyl, sufentanyl
Local anesthetics- bupivacaine, ropivacaine
196
Long acting vs short acting epidural agents
Hydrophilic substances have a longer onset of action and duration of action
Lipophilic substances have a short onset of action and DOA
197
Does the location of epidurals matter?
Yes
Intrathecal- inside dura mater
Epidural- directly next to dura mater
Doses vary (tiny small doses in intrathecal) and you could easily harm a patient.
198
Non pharm options for acute pain
Physical therapy
Distraction (guided imagery)
TENS application (music therapy, massage, hypnosis, biofeedback)
Effective sleep is super important
199
When do you decrease non-opioids in acute pain?
Only when patients are already off opioids and returning to baseline
200
Approach to perioperative pain
1. ) Pre-operative
2. ) Intra-operative
3. ) Post- operative
201
Goals of perioperative pain
1. ) improve comfort
2. ) Promote healing
3. ) Prevent chronic pain
4. ) minimize AE
202
Pre-operative phase
Preemptive analgesia- providing analgesia prior to pain to prevent sensitization to the pain signals.
Reduce peripheral sensitization- 1 dose celecoxib if not contraindicated
Reduce central sensitization- one dose gabapentin, pregabalin 1-2 hours prior if not contraindicated
203
Intra-operative phase
Anesthesia. Goal is to prevent painful sensation during the operation and prevent conscious awareness of the procedure
Agents- continuous infusion opioids, NMDA antagonists (ketamine), sodium channel blockers, sevoflurane, isoflurane, desflurane
204
Post-operative phase
Goals: improve patient comfort, promote healing, prevent chronic pain, minimize AR
Use multimodal therapy
205
DSM-5 definition of a substance use disorder
Control- need more doses, unsuccessful quitting attempts, cravings, large time seeking
Social- work, school, home issues, giving up on other activities
Risky use- use despite harm, use in hazardous situations
Pharmacological- tolerance and withdrawal
206
Intoxication
Reversible substance induced- maladaptive behavioral or psychological changes after recent ingestion of substance
NOT due to a medical or psychiatric illness
Does not always co-occur with a SUD
207
DSM-5 classes of drugs
Alcohol, caffeine, cannabis, hallucinogens, inhalants, other, tobacco, stimulants, sedative/hypnotics, opioids
208
Health consequences of alcohol use
CV- high BP, heart disease, stroke
Malignancies- breast, mouth, throat, liver, colon
Mood and cognition- Depression, anxiety, dementia
Social consequences- unemployment, lost productivity, interpersonal conflict
209
Alcohol effects on glutamate
Alcohol inhibits glutamate receptor function.
| This causes muscular relaxation, clumsiness, slurred speech, staggering, memory disruption, blackouts
210
Alcohol effects on GABA
Alcohol reduces GABA receptor functions
| This causes calm, anxiety-reduction, sleep
211
Alcohol effects on dopamine
Alcohol raises dopamine levels causing excitement and stimulation
212
Alcohol effects on endorphins
Alcohol raises endorphin levels
| This kills pain and leads to an endorphin high
213
Binge and excessive drinking in women
Binge is 4 or more drinks in 1 sitting.
| Heavy drinking is 8 or more drinks in 1 week
214
Binge and excessive drinking in men
Binge is 5 or more drinks in 1 sitting.
| Heavy drinking is 15 or more drinks in 1 week.
215
CAGE
```
Substance abuse screening tool
Self administered/interviewed 1 minute assessment.
Cut down
Annoyed
Guilty
Eye-opener
```
216
AUDIT-C
Substance abuse screening tool
Self administered 1 min assessment
How often, how much, binge frequency
217
Baseline assessment in patients with AUD
```
Vitals
EKG
LFTs
Toxicology: Blood alcohol level, co-exposure to other substances
Infectious disease screening
Pregnancy tests
H/O alcohol withdrawal seizures
Social history
```
218
Tx of acute alcohol intoxication
Supportive care- IV hydration, education
| Banana bag- 100mg thiamine, 1mg folic acid, 1-2 grams magnesium, multivitamin
219
Wernicke-Korsakoff "Wet brain"
Due to thiamine deficiency
Wernickes- ataxia, confusion, ophthalmoplegia (oculomotor dysfunction), may progress ot coma/death
Korsacoff syndrome- chronic amnesia, lack of insight, apathy. Consequence of wernickes
220
Alcohol withdrawal symptoms
Early: 6-12 h after last drink. Mostly autonomic (increased HR/BP)
Middle: 12-24 hrs after last drink. Tremors and autonomic symptoms, audio/visual hallucinations, anxiety
Late- onset 48-72 hours after last drink. Delirium Tremens (DTs)
221
AUD severe/complicated withdrawal risk factors
```
H/O alcohol withdrawal delirium or seizures
Multiple prior withdrawal episodes
Traumatic brain injury
Age >65
Long duration of heavy use
Autonomic hyperactivity on presentation
Dependence on CNS depressants
```
222
CIWA-Ar
Withdrawal assessment
| Complicated if >19
223
Levels of care for alcohol withdrawal
Level 1- mild. Daily monitoring for up to 5 days
Level 2- outpatients who become agitated, oversedated, other conditions worsen, unstable vitals
Inpatient- CIWA >19
224
Inpatient monitoring for alcohol withdrawal
Moderate to severe- monitor 1-4 hours for 24 hours or until CIWA-Ar <10 for 24 hours
Mild- every 4-8 hours for up to 36 hours
225
Treatment for alcohol withdrawal- Benzos
Benzodiazepines are DOC
Symptom triggered dosing based on CIWA-Ar score is preferred.
Longer acting for pts with rebounding symptoms (diazepam, chlordiazepoxide)
Shorter acting for liver disease, elderly, or overly sedated (lorazepam, oxazepam)
226
Alcohol withdrawal other medications
Gabapentin
| Carbamazepine
227
Alcohol vs Benzodiazepines
Benzos have reversal agent (Flumazenil)
| No maintenance treatment for benzos other than recovery programs
228
Benzodiazepine tapers
Must taper off of benzos
Withdrawal symptoms can be persistent and unpleasant, lasting weeks-months ("protracted withdrawal")
When a benzo is used regularly for 8 or more weeks, a taper should be used
10-25% every two to four weeks may be reasonable (can take 6+ months)
Recommend psychotherapy for anxiety/withdrawal
229
Maintenance therapy for AUD
Decrease total drinking days and heavy days
Decrease number of drinks/day
Decrease any harm
230
APA guideline recommendations for mod-severe AUD
1st line- Naltrexone or acamprosate if the goal is to reduce/abstain
2nd line-Disulfiram only if goal is to abstain, Topiramate or gabapentin
Avoid antidepressants, benzos, etc. for maintenance
231
Acamprosate
333mg-666mg TID. Used infrequently because of TID dosing.
AE- diarrhea, suicidality
Avoid use in CrCl <30
Safe in hepatic impairment
232
Disulfiram
250-500mg QD
AE- dysgeysia (taste changes), HA, hepatotoxicity, sexual dysfunction
Must be abstinent 12+ hours and 14 days after d/c
Hidden alcohols- mouthwash, hand sanitizer, etc.
Avoid use of metronidazole
233
Naltrexone for AUD
Can be orally QD or monthly injection
Causes hepatotoxicity
Do not use in patients that take opioids for pain. Can precipitate opioid withdrawal, only use if opioid free for 7 days.
234
Topiramate
Alternative option for AUD
Causes cognitive dulling, kidney stones, appetite suppression
Slow titration improved tolerability
Monitor renal function
235
Gabapentin for AUD
Alternative option for AUD
HA, sleep disturbances, suicidality
Dose adjustment required for renal impairment
Risk of misuse
236
S/S of an opioid intoxication
```
Drowsiness
Slurred speech
Constricted pupils
Impaired attention
Shallow breaths
Bradycardia
OD-death
```
237
S/S of opioid withdrawal
```
Nausea
Diarrhea
Coughing
Lacrimation, rhinorrhea
Chills, diaphoresis
Yawning
Piloerection
Drug craving
```
238
Assessing opioid withdrawal scales
COWS
SOWS
WAT-1
Finnegan neonatal abstinence scoring system
239
COWS vs SOWS scales
COWS- clinician rated
SOWS- patient rated
Follows opioid withdrawal
240
WAT-1
Clinician scale used for iatrogenic withdrawal in pediatrics (ex.- due to receiving opioids for trauma inpatient).
Higher scores= more withdrawal
241
Someone comes in with opioid withdrawal, what do we look at?
```
Vital signs
EKG
LFTs
Toxicology: Urine drug, consider serum tox
Infectious disease screening
Pregnancy test
Social history
```
242
Opioid withdrawal timeline
Symptoms begin 6-12 hours after short-acting opioid and 30 hours after long-acting opioids
Symptoms peak at 72 hours
243
OUD treatment process
Withdrawal
Induction (medication)
Maintenance
244
Which drugs are used to treat OUD detoxification?
Clonidine and lofexidine can both be given for symptom support. They do not treat withdrawal.
Buprenorphine and methadone treat detoxidication and withdrawal
245
OUD maintenance treatment
Naltrexone- only use if patient is not on opioids
Buprenorphine
Methadone
246
Acute opioid withdrawal treatment approach
Medically-assisted opioid withdrawal (detoxification)
Methadone and buprenorphine can be used. Both 1st line.
Buprenorphine is more flexible and safer.
a-2 agonists are considered second line and can reduce symptoms of withdrawal.
247
What is "induction?"
Initiating a partial/full opioid agonist, usually during the withdrawal phase.
Need to have confirmation of recent opioid use or forced abstinence.
Initiate therapy when withdrawal symptoms appear (COWS 6-10)
Monitor closely
Agents- Methadone and buprenorphine
248
General evaluation for medications for opioid use disorder (MOUD)
Medical conditions- STIs, hepatitis, HIV, trauma, pregnancy
Co-occuring psychiatric illness
Other substance abuse
249
Treatment initiation for OUD
Withdrawal management- buprenorphine, methadone for treatment
lofexidine, clonidine for symptoms only (if needed)
MOUD- buprenorphine, methadone, LAI naltrexone
Psychosocial is important
250
Clonidine
Hypotension may occur
2nd line for withdrawal management in OUD
a-2 agonist
251
Lofexidine
a-2 agonist
2nd line for withdrawal management in OUD
Hypotension, bradycardia, etc.
252
Buprenorphine for OUD
Opioid dependence
2-16mg QD daily (max 32mg)
Boxed warnings- REMS program
ADR- CV and resp depression, HA, N/V
253
Methadone for OUD
20-120 mg QD
Boxed warnings- death, QTc prolongation
ADRs- resp depression, hypotension.
254
Boxed warning on Naltrexone
Hepatocellular injury
| REMS- LAI risk of injection site reactions
255
OUD in pregnancy
Opioid agonist therapy recommended as early as possible
Should receive methadone or buprenorphine .
Avoid opioid antagonist therapy (naltrexone)
256
Neonatal abstinence syndrome (NAS)
Nonpharm- breastfeeding, swaddling, rooming-in, mother education
1st line- morphine, methadone
257
OUD in children
Screening for SUD should start at age 11
1st line- psychosocial interventions
Ages 16 and over- buprenorphine, naltrexone
Methadone requires parental consent if <18.
258
OUD in patients with pain
Consider non-opioids, behavioral therapies, and physical therapy
With pain and OUD, treat both concurrently. Consider prn buprenorphine if used as MOUD
Consider short acting full agonists if methadone used as MOUD
259
OUD in jails
Ensure narcan kits are available in correctional facilities
Care should be patient specific.
Buprenorphine most common
260
Stimulant intoxication S/S
Increased attention and wakefulness, decreased appetite, euphoria, increased respiration, rapid HR, hyperthermia
261
Stimulant withdrawal
```
Hunger/thirst
Difficulty concentrating
Terrible depression/suicidality
Anxiety
Fatigue
Sleep disturbances
```
262
Tx for stimulant use disorders
No medicagtions
| behavioral therapy, 12 step programs, support groups
263
Management of acute stimulant intoxication
Vital signs
Hydration- decreases risk of rhabdo
Benzos- decreases anxiety, agitation, seizures
Prolonged psychosis- add anti psychotic if it doesnt clear
264
Brain anatomy and addiction
3 brain processes involved in addiction
1- Basal ganglia- involved in reward and motivated behaviour. Releases dopamine.
2- Extended amygdala- involved in memory, emotion, stress
3- prefrontal cortex- involved in executive function/decision making
265
3 stages of addiction
1. ) Binge/ intoxication- basal ganglia, euphoria
2. ) Withdrawal- extended amygdala
3. ) Preoccupation/Anticipation- prefrontal cortex
266
Binge/intoxication stage in addiction
Drugs with high addictive potential release dopamine in the reward pathway (N/ accumbens and dorsal striatum in basal ganglia)
This causes reward, motivated behavior, and habit circuitry
Changes in the dopamine system over time promotes substance taking habits
267
Withdrawal/ negative stage in addiction
Diminished activation of reward circuit. Decrease in dopamine receptors and activity in amygdala
Activation of stress systems
Drive to reduce negative affect reinforces drug seeking behavior. Ppl take drugs to feel normal
268
Preoccupation/Anticipation stage in addiction
Highlighted by craving
Dysfunction of prefrontal cortex. Hypofrontality.
Increased "GO" system. Enhanced activation of dopamine reward system.
Diminished "STOP" system- increased impulsivity
269
Hypofrontality
Addiction begins with the genes and the rewards system
Addiction ends with disorder of choice- loss of insight and impaired decision making.
Ramped up reward system and deficient cortical glutamate system (cognitive system)
270
Pharmacology of alcohol
```
Activates GABA/Benzo receptor complex.
Inhibits glutamate receptor function
Releases dopamine
Releases endogenous opioids
(activates inhibitory system, inhibits excitatory systems)
```
271
Alcohol effects on glutamate
Receptor antagonism and reduces release
Hyper-excitability and up-regulation of receptors.
Behavioral- memory loss, rebound hyper-excitability, brain damage
272
Alcohol effects on GABA
Enhances GABA induced Cl influx to hyperpolarize
| Behavioral- sedative effects, anxiety, tolerance and signs of hyper-excitability during withdrawal
273
Alcohol effects on dopamine
Increases transmission acutely,
| Behavioral- reinforcement, withdrawal
274
Alcohol effects on opioids
Increases endogenous opioids acutely
Behavioral- reinforcement (euphoria)
dysphoria
275
Metabolism of alcohol
2 step process
Alcohol get metabolized into acetaldehyde by alcohol dehydrogenase.
Then gets further metabolized into acidic acid by acetaldehyde dehydrogenase
276
Toxicity of alcohol
Brain
Liver
Digestive system: gastritis
Fetal alcohol syndrome
277
Kratom
Plant from southeast asia.
Analgesic without much resp. depression
Activates mu opioid receptors, adrenergic mechanism and has serotonergic activity
Withdrawal and high are minimal, but can still OD
278
Sympathomimetic drugs of abuse
Mimic stimulation of nervous system
Mephedrone, methamphetamine, methcathinone, MDMA, amphetamine
Release dopamine in reward pathways and NE(increases HR)
279
Bath salts
Cathinone analogues
| Sympathomimetic stimulant
280
Methamphetamine dependence
S/S- decreased appetite, dilated pupils, tooth decay, picking hair or skin, excessive sweating, disregard for physical appearance
No effective pharmacotherapy for meth addiction
281
MOA of cocaine and amphetamine
Both increase synaptic dopamine in reward pathway
282
Desired/adverse psychoactive effects in sympathomimetic drugs (ritalin)
```
Increased concentration
Increased sexual performance
Increased sociability
Increased energy
Euphoria
Mild empathogenic effects
AE: excited delirium
```
283
Marijuana
Cognitive effects: impaired memory, distorted thinking
Psychomotor- performance deficits
Physiological- increased HR and hunger
We have endogenous cannabinoid in body (anandamide)
284
Cannabinoids
Marinol and nabilone (synthetic THC)- treatment of AIDS wasting and cancer chemotherapy
Epidiolex (cannabadiol based)- seizure disorders
Sativex (THC and CBD)- approved in Europe for MS
285
Synthetic cannabinoids
K2, spice
500x more potent than THC
AE- seizures, agitation, anxiety, confusion, hallucinations, paranoia
286
Psilocybin
Tested in end of life anxiety, treatment resistant depression, addiction
287
Psychedelics
Indole type (LSD) and phenylethylamine type (mescaline)
Both activate 5-HT2A receptors leading to increased glutamate release in frontal cortex.
5-HT2A is responsible for active coping, cognitive flexibility, creative thinking
288
Psychoplastogens
Psychedelics and Ketamine
Neuroplasticity inducing drugs
Both drugs increase glutamate release leading to increased brain growth factors and new synapses.
289
MDMA (ecstasy)
Releases serotonin and to a lesser extent dopamine
effects- hug drug, increased awareness of emotions and communication, entactogen (feeling within)
FDA breakthrough status for treatment of PTSD
290
What is inflammation?
Complex biological response of bodys tissues to harmful stimuli.
It is an innate, nonspecific response.
It is protective
291
5 stages of inflammation
```
Rubor (redness)
Calor (heat)
Tumor (swelling)
Dolor (pain)
Functio Laesa (loss of function)
```
292
Immune systems
Innate immune system and adaptive immune system
| Both immune systems work together
293
Innate immune system
Nonspecific responses involving the activation of Toll- like receptors.
Utilizes neutrophils, macrophages, and NK cells.
Generates a lot of inflammation.
Due to local injury
294
Adaptive immune system
Includes antibody- and cell- mediated immunity.
| Involves B and T cells
295
B cell activation
Activation of B cell receptor (BCR) orchestrates different signaling events.
Acts to change cytoskeletal arrangement and transcription within the cell. Notably within the p38 MAPK and NF-kB signaling.
296
Antibody production
Activated B cells turn into plasma cells that make large quantities of antibodies. Expand ER to increase protein synthesis capacity.
297
Inflammatory mediators of the immune system
Prostaglandins, Leukotrienes, histamine, bradykinin
298
Cytokines of the immune system
Interleukins, Tumor necrosis factor, chemokines
299
Eicosanoids
Leukotrienes and prostaglandins.
| Have a role in the inflammatory system, CV system, and reproductive system
300
Production of eicosanoids
Revolve around arachidonic acid, which is required ot generate a lot of mediators
301
Which COX enzyme is inducible?
COX 2
302
What is the main activity of COX enzymes?
Primarily vasodilation
303
Arachidonic acid and platelet aggregation
Aspirin works by shutting down COX mediated platelet aggregation.
304
Cytokines
small protein signaling molecules.
Provide for intercellular communication
IL-1. IL-2, IFN, and TNF-a
305
Interleukin-1 signaling
Involved in inflammation, cartilage breakdown, bone reabsorption.
Increases the expression of other cytokines.
Large family
306
Tumor necrosis factor-alpha signaling
Secreted by macrophages.
Activates phosphorylation cascades involving p38 MAPK and ultimately alters gene expression.
Bone changes= IL-8
Cartilage degradation- IL-6 signaling downstream of TNF-a
307
Interleukin-6 Signaling
Activates JAK/STAT signaling, specifically STAT3
| Results in a variety of cellular processes being altered.
308
Which anti-inflammatory meds can be used for RA?
Mild- APAP, NSAIDs
Moderate- DMARDs
Severe- steroids, anti-proliferative drugs
309
Anti-histamines
Histamine is produced by basophils and mast cells
Local regulation on inflammation
4 isomers of histamine receptors
310
Hydroxychloroquine
Can be utilized for inflammatory disorders.
Works through TLR9 blockade.
Rapid abs, slow distribution.
1/2 life of 30-60 days
311
COX-1 expression. tissue localization, role
Expression- constitutive
Tissue localization- Ubiquitous
Role- Housekeeping and maintenance roles
312
COX-2 expression, tissue localization, role
Expression- inducible by inflammation stimuli
Tissue localization- inflammatory and neoplastic sites
Role- pro-inflammation and mitogenic functions
313
Aspirin MOA
Nonselective, irreversible COX inhibitor
314
This cytokine is an orchestrator of inflammatory processes relevant to several disease states
IL-1, IL-6, TNF-a
315
Opiates
Drugs derived from opium or having morphine like profile.
| Morphine and codeine are the only true opiates
316
Endogenous opioid peptides
Families of peptides
| Endorphins, enkephalins, and dynorphin
317
What is beta-endorphin derived from?
Proopiomelancortin (POMC)
318
What is dynorphin derived from?
Prodynorphin
319
What is enkephalin derived from?
Proenkephalin
320
Which endogenous opioids are analgesic?
Endorphin and Enkephalin
321
Which endogenous opioid is hyperalgesic?
Dynorphin
322
Opioid receptors
Mu- mediates most of morphines effects
Delta- analgesia
Kappa- in spinal cord mediates analgesia
323
Which receptor is morphine selective for?
Mu
324
Which receptor(s) are endorphins and enkephalins selective for?
Mu and delta
325
Which receptor is dynorphin selective for?
Kappa
326
What effects does the mu receptor have?
Analgesia, resp. depression, constipation, sedation, euphoria
327
What effects does the delta receptor have?
Analgesia
328
What effects does the kappa receptor have?
Analgesia, constipation, sedation, psychosis
329
What does activation of DOC and MOR do?
activates the inhibitory subunit of the G-protein coupled receptor and alters neuronal excitability through 2 mechanisms.
1. ) increases K conductance causing membrane hyperpolarization and supressing depolarization (makes neuron less likely to fire)
2. ) decreases ca activity, decreasing release of neurotransmitters, particularly glutamate.
330
Do opioid receptors alter inflammatory response?
no
331
Inhibition of cough by opioids
Both the d and L isomers are antitussive.
The L isomer is also analgesic
D isomer does not cause dependence.
332
Which opioid effects have a high tolerance?
Analgesia, euphoria/dysphoria, mental clouding, sedation, respiratory depression, antiduresis, N/V, cough suppression
333
Which opioid effects have minimal/none tolerance?
Miosis
Constipation
Convulsions
334
Where is functional selectivity (biased signaling) located?
GPCR
