Pain Basics Flashcards
(157 cards)
1
Q
Pain most paitients feel in the perioperative period
A
Protective physiologic pain from tissue damage
2
Q
Peripehral nociceptive neuron stimulated by noxious stimuli asrnd signal to CNS - brain and spinal cord for input and sensation of pain
A
Protective physiologic pain from tissue damage
3
Q
firing of a neuron that is not indicative of of physical damage, but is a pathalogical firing
A
Neuropathic pain
4
Q
Pain out of proportion to noxious stimuli
A
Hyperalgesia
5
Q
Pain evoked by a non-noxious stumuli
A
Allodynia
6
Q
pain with no apparent stimuli - it is NERVE pain
A
spontaneous pain
7
Q
Peripheral nociceptive neuron activated by intense noxious stimimuli (tissue damage) via
A
- Mechanical
- thermal
- chemical
8
Q
slow conduction, dull, burning, diffuse
A
non-mylinated C fibers
9
Q
fast conduction - sharp and well localized
A
A-delta fibers
10
Q
nociceptiv impulse depends on the balance between
A
excitatory and inhibatory receptors
11
Q
excitatory catioon channel activated by:
- Protons
- heat
- capsaisin
- Endovanilloids
A
TRIP1
12
Q
Blocking this TRPV1
A
Pain medicine too good, lost protective mechanism ad could not perceive pain
13
Q
- inhibatory
- Bind to GPCR to initiate cascade (PKA)
- increase K conductance hyperpolarizing the cell
A
Opioids
14
Q
hyperpolarizing the cell with opioids means
A
cells will need a stronger stimulus to fire
15
Q
Locations of opioid receptors
A
- Peripheral tissues
- dorsal horn of spinal cord
- Brain (this is wher opioids work)
16
Q
promotes depolarization and stimulates pain
A
Bradykinin and Prostaglandins
17
Q
Area of dorsal horn that is very rich in opioid peptides and receptors
A
substantia geletinosa
18
Q
Synapse in dorsal horn at lamina I, II, III, V
A
A-delta fibers
19
Q
Synapse in dorsal horn at lamina I and II
A
C-fibers
20
Q
Located in lamina II and III
A
Substantia gelatinosa
21
Q
what is in the substantia gelatinosa
A
- short inhibatory neurons that receive afferent fibers from A-delta and C fibers
- descending pathways that are moculating pain signals (they are inhibatory)
22
Q
Determine weather a pain signal is sent to the higher centers for processing or modulated
A
Internurons
23
Q
sends pain signals to the thalamac which then sends pain signals to the somatosensory cortes
A
neospinothalamic tract
24
Q
responsible for the experience of pain
A
neospinathalamic tract
25
sends pain signals to the brainstem which then signals to the thalamus, hyptothalamus and elsewhere
peleospinothalamic tract
26
Causes the stress response to pain
paleaospinothalamic tract
27
tract we want to supress with pain that causes the SNS to release a ton of cortisol
paleospinothalamic tract
28
Opioids releive not only the ____________ aspect of pain, it also releves the ___________ aspect thereby preventing ___________ or _____________ from the exaggerated stress response.
1. somatosensory
2. physiologic
3. MI
4. prolonged healing
29
descending _____________ pathways originate in the \_\_\_\_\_\_\_\_\_\_\_\_/ __________ including areas such as \_\_\_\_\_\_\_\_\_\_\_\_\_, \_\_\_\_\_\_\_\_\_\_\_\_, \_\_\_\_\_\_\_\_\_\_\_, \_\_\_\_\_\_\_\_\_\_\_\_\_\_
1. inhibatory
2. midbrain/brainstem
3. Periaquaductal gray
4. amygdala
5. corpus striatum
6. Hypothalmus
30
In descending pathways neurons from the midbrain/brainstem project into the \_\_\_\_\_\_\_\_\_\_\_\_\_\_which then sends its descending neurons __________ to synapse in the \_\_\_\_\_\_\_\_\_\_\_\_
1. nucleus raphe magnus
2. down the spinal cord
3. substantia gelatinosa
31
opioids and the brain
act pre and post synaptically to activate descending inhibatory pathways
32
opioids and the spinal cord
work directly on the dorsal horn of the spinal cord
33
opioids and the periphery
act on peripheral teminals of nociceptive neurons
34
why is the perception of noxious stimuli not the same as pain?
it is lacking the emotional component
35
Opioids can change patients __________ without necessarily changing the patients ability to __________ noxious stimuli
1. tolerance of pain
2. perceive
ie- they can still tell you where the wound is
36
Opioids are effective for both ________ and _______ pain
somatic and visceral
37
The main use of opioids on anestehsia
Attenuate the SNS response to noxious stimuli- Laryngoscopy
38
During inductons opioids are used to \_\_\_\_\_\_\_\_\_\_\_\_\_and causes the patient to have \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
1. maintain stable hemodynamics
2. less Cardiovascualr comprimise
39
If opioids are not given to someone with coranary artery disease durring laryngoscopy
could have an **MI** with a really **fast heart rate**
40
opoids and inhaled anesthetics
act as an **adjunct** allowing for less use of inhaled agent
41
cardiac anestheisia and opioids
opioids are used as a sole anesthetic
42
**natrurally** occuring drugs **derrived** from opium from the poppy plant
Opiate
1. Morphine
2. Codeine
43
**Natural** and **synthetic** substances that bind to opioid receptors and produce and **agonist** effect
1. Opioid
1. anything that acts like an opiate
44
Term for DEA regualtions
narcotics
45
**therepeutic agents** with the general opioid structure
Opioid**s**
46
Opioids produce analgesia without loss of
1. Touch
2. Propioception
3. Conciousness
47
Unique characteristics that set opioids apart
1. no ceiling effect or max dose
2. tolerance and cross tolerance
48
Tolerance with opiods is associated with ____________ but not necessarily __________ - this is expected
1. Physical dependance
2. psychological
49
naturally occuring opioids
1. Morphine
2. Codeine
50
**semisynthetic**: analogs of morphine
1. **heroine** and **dihydromorhone**
2. **heroine** and **fentanyl** are very structurally similar
51
**Synthetic** Opioids
1. Exogenous
2. Has 4 classifications
1. agonist
2. partial aginist
3. mixed agonist/antagonist
4. antagonist
52
Synthetic antagonist
Narcan
53
1. can reach maximum eficacy on dose response curve
2. their potency is what varries
Synthetic agonists (full)
54
1. will have a ceiling effect
2. cannot reach maximum effect on dose response curve
Synthetic partial agnosts
55
Synthetic opioid **agonist / antagonist**
1. agonist at kappa receptors
2. antagonist and mu receptors
56
if their is any potential you will need to switch to a full agonist you want to start with
a parial agonist and **NOT** an agonist / antagonist
57
OPIOIDS MECHANISM OF ACTION
Activate **\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_** and act
1. **\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_**to directly decrease neurotransmission by:
1. increase K conductance (**\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_)**
2. Ca++ channnel inactivation (**\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_**)
3. inhabitionof **\_\_\_\_\_\_\_\_\_\_\_\_ (\_\_\_\_\_\_\_\_\_\_\_\_\_\_)**
4. Modulation of\_\_\_\_\_\_\_\_\_\_\_- signaling cascade for phospholipase C
2. **\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_**
1. Decrease **\_\_\_\_,\_\_\_\_\_\_\_\_\_\_,\_\_\_\_\_\_\_\_**and **\_\_\_\_\_\_\_\_\_\_\_**
2. anytime you hyperoplarize a membrane you decrease **\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_**
OPIOIDS MECHANISM OF ACTION
Activate **stereo-specific G-protein coupled receptors** and act
1. **post-synaptically** to directly decrease neurotransmission by:
1. increase K conductance (**hyperpolarization)**
2. Ca++ channnel inactivation (**decreased NT release**)
3. inhabitionof **adenylate cyclase (decreased cAMP)**
4. Modulation of **phospinositide**- signaling cascade for phospholipase C
2. **Pre synaptically**
1. Decrease **ACh, dopamine, norepi** and **Substance p release**
2. anytime you hyperoplarize a membrane you decrease **NT release**
58
anytime you hyperpolarize a cell you
decrease neurotransmitter release
59
Opioids POST-synaptic mechanism of action
1. increase K conductance (hyperpolarization)
2. Ca++ channel inactivation (decreases NT release)
3. Modulationo of phospinositide- signaling cascade for phospholipase C
4. Inhabition of adenlyate cyclase (decrese cAMP)
60
Opioids PRE-synaptic mechanism of action
1. inhibits the release of excitatory neurotransmitters
1. ACh
2. Dopamine
3. Norepi
4. Substance P
61
Opioid receptors
1. Mu (agnoist binding site)
2. Kappa (antagonist binding site)
3. Delta
62
When opioids bind to receptors they
activate endogenous pain modulating systems
63
All endogenous and exogenous opiois agonists work at these receptors
Mu-1 and Mu-2
64
May actually cause immunosupression and accelerate some types of cancer
Mu-3
65
Mu receptors location
1. brain- supraspinal
2. spinalcord
3. periphery
66
**Supraspinal** is thought to be the principal site of action but also works at spinal cord and periphery
Mu-1
67
Mu-1 receptor activation causes
1. euphoria
2. miosis pupil constriction
3. Bradycardia
4. Urinary retention
5. hypothermia- impairment of thermal regulation
68
Mu-2 receptor activation effects
Most of the bad effects
1. Hypoventilation
2. physical dependence
3. constipation
69
receptor that principal site of action is the spinal cord, but also has some supruaspinal action as well
Mu-2
70
opioid agonist/antagonists have principal site of action
kappa receptor
71
responsibe for supraspinal , spinal and peripheral analgesia
Kappa receptor
72
Kappa receptor activation effects
1. Dysphoria
2. sedation
3. Miosis- pupillary constriction
4. Diuresis
73
dysnorphins act on these receptors
Kappa receptors
74
endogenouas ligand of enkephalin
Delta receptor
75
Main site of action is peripheral (but also acts supraspinal and spinal)
Delta Receptor
76
receptors involved in hypoventilation from opioids
Mu-2 and Delta
77
Delta receptor activation
1. Peripheral analgesia
2. Hypoventilation
3. Constipation
4. Urinary Retention
78
Located on Chromosome 6q24-q25
Mu opoid receptor
79
aspartated in place of asparagine
10-20% of the population
1. Nucleotide 118 polymorphism
2. Gene Effects agonist binding to Mu receptor
80
valine in place of alanine
1-10% of population
1. Nucleotide 17 polymorphism
2. Gene Effects agonist binding to Mu opioid receptor
81
Why are opioids more of an art than a science
1. there are polymorphisms that effect opioid binding
2. incidences can vary with racial/ethnic groups
82
Two things genetics can influence
1. Receptors
2. CYP 450 metabolism
83
5 common polymorphisms can alter the metabolism of codine
CYP2D6
84
Codine is a \_\_\_\_\_\_\_\_\_\_\_\_\_\_.
Its active form is \_\_\_\_\_\_\_\_\_\_\_\_.
Black box warning with \_\_\_\_\_\_\_\_\_\_\_\_\_.
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ dont get adequate pain controll and may get increased nausea.
\_\_\_\_\_\_\_\_\_\_\_\_\_ get a build up of morphine and can have respiratory depression
1. Prodrug
2. Morphine
3. Children
4. Fast Metabolizers
5. Slow Metabolizers
85
Increased metabolizers associated with the CYP2D6 gene may have increased nausea and decreased pain controll with...
1. Oxycodone
2. Hydrocodone
3. methadone
86
Codine has unpredictable pharmacokinetics and half lives due to
CYP2D6 gene polymorphisms
87
Opioid least likely to be impacted by genetic variability. Predictable pharmacokinetics.
Fentanyl
88
side effect rate can be influenced by ....
The rate of metabolism
89
Ultra-rapid metabolizers are at risk for
PONV
90
Prototype for Opioids
Morphine
91
Opioids and Perioperative **cardiovasucular** effects (4)
1. **Minimal impairment of CV function** but has **additive effect** with other analgesics
2. profound **vasodilation/ decrease SVR-** most evident in patients with hypovolemia
3. **Dose dependant bradycardia**- via **vagal** stimulation (nuclei in medula) and**Direct SA/AV nodal depression**
4. **I****mpairmennt of SNS response**and baseline tone**orthostatic hypotension** that is pronounced with hypovolemia
92
morphine and meperedine and cardiovascular effects
Have a **dose dependant histamine release**
1. risk more vasodilation - decreased BP and SVR
2. risk bronchospasm
93
Why is meperidine an exception to the CV effects of opioids
It will cause tachycardia - due to its atropine like structure
94
When a large dose of opioids are given and the BP drops what is it likely due to?
Hypovolemia with vasodilation it is NOT likely a contractility isusse, Opioids are pretty cardiac stable
95
Opioids and HR
1. Dose dependant bradycardia
1. Central vagal stimulation
2. act directly on SA/AV nodal depression
96
Opioids and vascualture
Vasodilation/ Decreased SVR
1. decreased SNS response and baseline tone
2. decreased CO and venous pooling = **orthostatic hypotension**
3. Pronounced effect on vasculature
97
What opiods do we want to avoid in astmatics? Why?
**Morphine** and **meperidiene**-
1. dose and infusion rate dependant **histamine release**
2. causes more vasodilation and **BRONCHOSPASM**
98
Do opioids produce amnesia
No
99
Opioids and patients with increased ICP
1. Must have ventilations controlled prior to giving opioids
2. Hypoventilation and Increased CO2 will cause cerebral vasodilation and increased ICP
100
As long as **\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_** Opioids will cause a modest decrease in ICP
1. **ventilations are controlled**
101
Opioids and urination
1. Increased **Uregency** and reduced **ability to void**
2. Increased tone and peristaltic activity of ureter
3. incresed tone of detrusor
102
Opioids can cause a spasm of the \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_and ____________ contraction with ____________ billiary pressure. This smooth muscle contraction may feel like an _____ and can be releived with __________ or \_\_\_\_\_\_\_\_\_\_\_. __________ will make the patient vomit.
1. Sphincter of Oddi
2. gallbladder
3. increased
4. MI
5. Glucagon
6. Nitroglycerine
7. Glucagon
103
Constipation, decreased gastric motility and prolonged gastric emptying are caused by
**Spasm of GI smooth muscle** from opioids
104
Why do opioids cause nausea and vomiting
1. decreased gastric emptying
2. stimulation of chemoreceptor zone of the 4th ventricle
1. balanced depression of medulary vomiting center
105
Puritis and Opioids
cause is **unknown**, could be the **histamine release** with **morphine and meperidine**, but fentanyl it is unknown
1. **fentanyl nose itch**
106
**drugs** that cause adverse affect: **muscle rigidity** in chest, abdomen, jaw and extremeties
1. Fentanyl
2. Sufentanyl
3. Hydromorphone (Dilaudid)
107
issues with adverse affect: **muscle** **rigidity** from opioids
1. **High** **airway** **pressures** from increased intrathoracic pressure and decreased veonus return
2. difficult/impossible to **Venltilate**
3. only releived my **non**-**depolarizing** muscle relaxant
4. glottic **rigidity** and closure reported
108
Increased Tidal voume and decreased RR
Smaller dose of opioids
109
Increased CO2 and decrease O2
Ventilatory effects of smaller doses of opioids
110
Decreased TV and Decreased RR
Larger dose of opioids
111
decreased ventilation and decreased response to CO2
Hypercarbia
112
Perioperative ventalitory effects of opioids
1. **Dose dependant** respiratory depression
2. Decreased chest wall **compliance**
3. **constriction** of pharyngeal and laryngeal muscles
4. **cough** supression
5. Dramatically **decreased** response to **hypercarbia** and **hypoxia**
113
Factors that increase the magnitude and duration of opioid induced respiratory depression
1. **more pain** = **less** respiratory depression/sedation
2. **Intermittent boluses** have higher degree of respiratory depression than **contiuous infusion**
3. **Speed** of injection
4. **Concurrent admin** with other anesthetics
5. Decreased **clearance-** active metabolites build up
6. **Age**- older an younger
114
consiterable first pass effect - dose seems really large
Morphine
115
Abuse of this very bad because of the APAP component
Vicodin / Hydrocodone
116
1/2 live 3-4 hours, then converted to an active metablolite
1. Morphine
2. converted to **morphine-6-glucuroninde**
117
prodrug- active form is morphine
Codeine (3-methylpmorphine)
118
1. Long plasma half life 8-59 hours or 13-100, sources vary
1. High variability among individuals
Methadone
119
Oxycodone
1. long acting
2. with acetomenophen
3. with ASA
1. Oxycontin
2. Percocet
3. Percodan
120
Hydrocodone is ALWAYS combined with
1. APAP
2. ASA
3. Ibuprofun
4. antihistamine
121
Antitussive affects reamin without conversion- lower doses needed
Codeine (3-methylmorphine)
122
No active metabolites - safer in patients with renal dysfunction
1. Oxycodone
2. Methadone
123
Ineffective in 10% caucasions and 30% asians due to the lack in 2D6
Codeine (3-methymorphine)
124
dosed QD for opioid addiction treatment
Methadone
125
Synthetic opioid
Methadone
126
Combined with
1. APAP
2. Gusifenesin
3. promethazine
Codeine (3-methyl-morphine)
127
analgesic and antitussive
Hydrocodone Vicodin
128
mild paine relief
Codiene (3-methylmorphine)
129
used for chronic pain
Hydrocodone/vicodin
130
severe acute pain
morphine
131
Moderate to severe pain, chronic pain and post op pain
oxycodone
132
1. chronic pain syndrome treatmentbecause of its long half life
2. dosed BID or TID (q 4-8 hours) to maintain steady plasma concentrations
Methadone
133
Used for neuropathic pain
Methadone
134
At risk for respiratory depression **secondary to its long unpredictable half time**
Methadone
135
How long does it take to develop **tolerance** to opioids?
48 hours - need to taper
136
Timeline of tolerance
1. reduction of **adverse effects**
2. shorter **duration** of analgesia
3. decrease in **effectiveness**
4. **does not work**
137
how can tolerance be surmounted?
increase the dose
138
in addition to tolerance of analgesic effects, tolerance also occurs to
**Respiratory** and **CNS** adverse effects
139
**\_\_\_\_\_\_\_\_\_\_\_\_** exists amung all **\_\_\_\_\_\_\_\_\_\_\_**, but it is not 100% so when switching drugs start at **\_\_\_\_\_\_** **\_\_\_\_\_\_\_\_\_\_\_\_\_** dose
**Cross-Tolerance** exists amung all **full agonists**, but it is not 100% so when switching drugs start at **half the** **equianalgesic** dose
140
switching opioid tolerant patients to _______ may improve pain releif
Methadone
141
What side effect dies NOT go away with tolerance
**Constipation**- a stimulant laxative w/ or without stool softener should be started early in treatment
142
With tolerance __________ and _________ effects go away
sedative and emetic
143
causes abstinance symptoms on sudden d/c
dependence
144
addiction involves ___________ , \_\_\_\_\_\_\_\_\_\_\_\_, and ___________ factors
1. psychological dependence
2. Biologic
3. social
145
Dosages of opioids
No minimum or maximum unless they have APAP or ASA
146
what type of dosong should be used in chronic pain
sustained release- so they tond have peaks and valleys
147
among individuals a __________ varioation of analgesia is obtained with a single dose
10 fold
148
Neuralaxial analgesia (diffusion)
1. Cross the **dura** onto **mu** receptors to the **substantia geletinosa**
2. difuses into the **vascularture** to get **systmeic** effect
149
given neuroaxial: very lipid soluable
fentanyl
150
Given neuroaxial: very water soluable - will circulate with CSF
Morphine
151
Opioids in the epeidural space may diffuse into
1. \_\_\_\_\_\_\_
2. \_\_\_\_\_\_\_
3. \_\_\_\_\_\_\_
1. fat
2. systemic absorbtion (vasculature)
3. CSF
152
Cephalad movemnt of ipoid in CSF depends on \_\_\_\_\_\_\_\_\_\_\_\_.
Lipid solubility
153
Fentanyl which has ____________ will be _____________ by uptake into the spinal cord,
Where as, _________ opioid will \_\_\_\_\_\_\_\_\_\_fro transfer to the cephald location such as \_\_\_\_\_\_\_
1. lipid solubility
2. limited in migration
3. les soluable
4. remain in CSF
5. Morphine
154
More lipid soluabel = \_\_\_\_\_\_\_\_\_\_\_\_
Quicker peak in CSF and systemic concentration
155
Why is the dose for an epidural 5x higher than that for a spinal?
Because the spinal is directly at the site
156
Using local anesthesia such as spinals and epidurals may decrease
overall anesthetic requirements
157
