Unit II week 2 Flashcards
1
Q
Receptor (generator) potential
A
stimulus elicited change in membrane potential (depolarization or hyperpolarization) → release of NT from synaptic end (typically glutamate)
2
Q
Short sensory receptor cells
A
(less than 0.1 mm or 100 um in length) → receptor potential spreads to synaptic end via passive electrotonic transmission
-Regenerative APs not necessary
EX) rod photoreceptor cells, auditory hair cells
3
Q
Long sensory receptor cells
A
(>1mm in length) → regenerative AP used to carry info from receptive ending to synaptic release site
EX) skin mechanoreceptors
4
Q
Depolarizing receptor potentials
EX) ?
A
increase in nonspecific cation conductance in receptive area membrane
EX) Muscle mechanoreceptors - mechanosensitive nonselective cation channels that open in response to stretch → depolarize sensory ending
5
Q
Hyperpolarizing receptor potentials
EX) ?
A
substantial number of resting cation conductance channels open in receptive area → stimulus → receptive area cation channels close = hyperpolarization
EX) Rod photoreceptor
6
Q
Rod photoreceptor resting state
A
resting membrane potential around -40mV due to high cGMP concentrations under resting conditions that maintain cGMP-gated cation channels open
7
Q
What happens when light hits a rod photoreceptor?
6 steps
A
1) Light hits RHODOPSIN → 1-CIS-RETINAL bound to rhodopsin absorbs light → changes conformation to 1-TRANS-RETINAL
2) → causes rhodopsin to change conformation → METARHODOPSIN
3) Metarhodopsin stimulates TRANSDUCIN (g-protein) → activate cGMP PHOSPHODIESTERASE
4) → cGMP breakdown → closure of cGMP-gated nonselective cation channels
5) → HYPERPOLARIZATION
6) → Fewer NTs released
8
Q
Transduction channel
-how is it different from voltage-dependent channel?
A
NOT voltage-dependent
Sensitive only to the adequate stimulus - allows channel to encode stimulus intensity as a graded increase in magnitude of receptor potential
9
Q
Sensory systems convey information about what five attributes of a stimulus
A
1) Modality
2) Intensity
3) Quality
4) Duration/Frequency
5) Location
10
Q
Modality is encoded how?
A
LABELED LINES
Conscious appreciation of sensory modality is determined by specific neuronal connections from sensory organs through thalamus to cerebral cortex
Separate pathways for different sensory systems → separate chain of neurons (separate labeled line) for each sensory system
Stimulus modality is coded by which nerve cells are active
EX) visual info relayed via LGN of thalamus → visual cortex in occipital lobe
EX) auditory info relayed via MGN of thalamus → auditory cortex in temporal lobe
11
Q
All sensory information goes through the _______ except for __________
A
everything goes through THALAMUS, except for OLFACTION
12
Q
How is Intensity coded?
A
the magnitude of the generator potential increases as intensity of stimulus is increased (more depolarized OR more hyperpolarized = increased generator potential)
The fraction of time the transduction channel spends in the open (or closed) state is a function of the intensity of the stimulus
13
Q
C-fibers
A
small, unmyelinated axons, 1 um in diameter, slow conduction velocity
Warm temperature, burning pain, itch, crude touch
14
Q
A-fibers
A
myelinated fibers
Alpha, Alpha
Alpha, Beta
Alpha, Delta
15
Q
Alpha, Alpha fibers
A
most rapidly conducting, largest diameter
Ia → muscle spindle afferent
Ib → tendon organ afferent
16
Q
Alpha, Beta fibers
A
slower and smaller diameter than Aa, but still fast
Mechanoreceptors of skin, secondary muscle spindle afferents
17
Q
Alpha, Delta fibers
A
slower and smaller diameter than AB
Sharp pain, cool temperature, extreme hot temperature
18
Q
Merkel’s Disk
A
Sensory Receptors of the Skin
- slowly adapting, small receptive field
- High density of receptors
- Support fine tactile sense of fingertips
A-Beta fibers
19
Q
Meissner’s Corpuscle
A
Sensory Receptors of the Skin
rapidly adapting, small receptive field
High density of receptors
Shallow depth in skin
Fine touch (fingertips)
20
Q
Pacinian corpuscle
A
Sensory Receptors of the Skin
- rapidly adapting, large receptive field
- High sensitivity to skin deformation over a wide area
- Very deep in skin
- Vibratory stimuli
21
Q
Ruffini Endings
A
Sensory Receptors of the Skin
slowly adapting, large receptive field
Free nerve ending,
Info on how skin is stretched
A-Beta fibers
22
Q
Hair follicle receptors
A
Sensory Receptors of the Skin
bending of hair shaft activates nerve terminals
Rapidly adapting
23
Q
Somatotopy
A
precise and orderly mapping of body surface onto cortex
Preservation of nearest neighbor relationships: neighboring cells in nucleus cuneatus or within thalamus have receptive fields near to one another in skin
Distorted “homunculus” due to differences in innervation density
24
Q
Cortical Barrel
A
idea that cells innervating the same thing (e.g. one whisker) all project to the same place in somatosensory cortex
Circular arrangements of cells run throughout cortical depth
All cells within that barrel respond to movement of that “whisker”
Morphological specialization of cortex that reflects a functional organization
25
Columnar Organization
vertical arrangement of functionally related cells (barrels)
Seen in vertical segregation of cells by response to modality
6 layers of cortex within a column each project to different areas of brain → cortical columns serve as computational modules that transform information received from the thalamus and redistribute it to other brain regions
26
Dorsal Column/Lemniscal System
1) sensory cell receptors bodies in _________ → enters spinal cord → __________
2) → local branches project to ________ for spinal reflexes
→ ascending branches enter __________ = _________ (upper limbs) and __________ (lower limbs)
3) Ascending branches then...
1) Dorsal root ganglia, Bifurcate
2) dorsal horn
dorsal (posterior) columns
fasciculus cuneatus
fasciculus gracilis
3) → ascend spinal cord to nucleus cuneatus/gracilis in medulla
27
Dorsal Column/Lemniscal System
4) → second-order neurons ____________ after synapsing in _______ = __________ Pathway
5) → synapse in __________ complex of ___________
_____ nucleus = trunk and limbs
______ nucleus = head
6) → Ventrobasal complex projects to areas ____, ____ and _____ on posterior bank of ______ → primary motor cortex
4) cross midline, medulla, Medial Lemniscal
5) ventro-basal, thalamus
VPL nucleus = trunk and limbs
VMP nucleus = head
VPL + VPM = ventrobasal complex
6) 3, 1, and 2, Central sulcus
28
Trigeminal Lemniscal Pathway
lemniscal system for head
Afferent information regarding touch, proprioception, pain, and temperature on face and head flow through trigeminal nerve
29
Trigeminal Lemniscal Pathway
1) Cell bodies located in _______________ → synapse in _________
2) → second order cells then _________ and join __________ pathway
3) First-order afferents may also branch upon entering ______ and send a branch into ________ and other branch into nucleus
4) →_______ nucleus of thalamus → ______ area of somatosensory cortex
1) trigeminal ganglion
principal nucleus
2) cross midline
medial lemniscus
3) pons, descending spinal tract
4) VPM, face
30
Anterolateral System
includes what 3 tracts
ascending pathway for pain and temperature information, axons of dorsal horn second order neurons that cross midline and ascend anterolaterally
Includes: spinothalamic, spinoreticular, and spinomesencephalic tract
31
Spinothalamic tract
pain pathway to thalamus
Cell bodies in dorsal horn --> Projects to nuclei of ventrobasal thalamus (includes VPL) --> somatosensory cortex
Processes information related to localization of pain
-CONSCIOUS information on skin temperature
32
Spinoreticular tract
pain pathway that leads to forebrain arousal and elicits emotional/behavioral responses
second order axons end information via reticular formation to hypothalaumus
Connects to limbic system
Terminates in pons and medulla
33
Spinomesencephalic tract
projects to midbrain periaqueductal gray region (PAG)
Descending control of pain
34
Anterolateral system have cell bodies in the _______ or __________
DRG (trunk and limbs)
Trigeminal ganglia (head and neck)
35
primary neurons in anterolateral system synapse in __________ or __________
dorsal horn of spinal cord OR spinal trigeminal nucleus
36
Trigeminal System
pain and temperature input from head and neck
Axons enter CNS at level of pons, first synapse in spinal trigeminal nucleus
37
Cool receptors
(10-37 degrees C)
10x more than warm receptors
A-delta fibers
Decrease temp = increased AP frequency
38
Warm receptors
(30-48 degrees C)
C fibers
Increase temp = increased AP frequency
39
Within range of ____-___ degrees C we sense changes in skin as cooling/warming - outside this range = PAIN
Neutral ____ deg C, cold/warm receptor afferents have same firing rate
10-48
33
40
Are we wired to detect rapid change or gradual change in temperature?
RAPID change
Transient AP frequency followed by a steady state change after a rapid step change in temperature
41
Thermal nociceptors
fiber type?
stimulated by what?
extreme temperatures (less than 5C or >43C)
Ad = extreme hot, (opposite of normal)
C fibers = extreme cold, (opposite of normal)
42
Mechanical nociceptors
fiber type?
stimulated by what?
intense pressure (not touch)
Ad fibers
43
Polymodal Nociceptors
fiber type?
stimulated by what?
3 examples
high-intensity mechanical, chemical, or thermal stimuli (C fibers)
1) Vanilloid Receptors (e.g. VR1 Capsaicin receptor)
2) P2X receptors: ionotropic receptors opened by ATP
3) ASIC receptors: acid sensing channels
44
Types of nociceptors (3)
1) thermal nociceptors
2) mechanical nociceptors
3) Polymodal nociceptors
45
First pain
fiber type
localization
sensation
Ad fibers → detect tolerable, localized, “pricking pain”, tolerable
- Alerts you, well-localized
- Faster conduction velocity than C fibers
Smaller receptive field = better localized spatial discrimination
46
Second pain
fiber type
localization
sensation
intolerable, diffusely localized, “burning” pain
Slower conduction velocity than Ad fibers
Larger receptive field = dull, aching, poorly localized pain
47
As increasing pressure applied around arm, nerve fibers are lost in what order? (e.g. BP cuff)
Most metabolically active, large diameter Aa and AB fibers become nonconductive first → lose touch, vibration, joint position/movement
Next Ad fibers blocked → only burning sensation remains
Next C fibers blocked → no sensation remains
48
Anesthetics affect nerve fibers in what order and blocks what sensations?
Low dose → preferentially block small C fibers (suppress burning pain)
Higher doses → block pricking pain
Even high dose → block touch and motor
49
Pain activators (4)
Bradykinin
Potassium
Acid
Serotonin (5-HT)
50
Activators vs. sensitizers
Activators: lead to direct activation of nociceptors
Sensitizers: decrease threshold for activation of nociceptors
51
Bradykinin is an activator for ____ and ____ fibers and increases the synthesis of _______
→ Ad and C fiber activator
Also increases synthesis of prostaglandins (Sensitizer)
52
Primary hyperalgesia
sensitization of nociceptors
53
Allodynia
sensitization extreme enough to allow non-noxious stimuli to trigger painful sensation
54
VR-1 Receptor
capsaicin receptor, non selective cation channel (activation = depolarization)
Strongly activated by capsaicin and weakly activated by acids
55
Modality Segregation
afferents conveying different modalities segregate to different positions within dorsal horn/trigeminal nucleus
EX) C fiber terminate in substantia gelatinosa (Rexed’s lamina II)
56
Referred pain
convergence of visceral and somatic inputs in dorsal horn neuron
Injury to internal organ perceived as injury to cutaneous site
57
Glutamate function at first synapse in pain pathway
primary NT released by nociceptive sensory neurons at site of first synapse in dorsal horn
Bind AMPA and NMDA ionotropic receptors → generate both fast and slower excitatory responses
58
Substance P role at first synapse in pain pathway
stored in vesicles in dorsal horn
Released by C fibers in response to strong repetitive stimulation in CNS at site of first synapse
59
What happens when substance P is released by C fibers at the first synapse in pain pathway?
→ binds Neurokinin 1 receptor (NK-1) → close K+ channel, depolarization
-Leads to enhancement and prolongation of glutamate actions
Takes longer to diffuse out of synapse → broad central sensitization at level of dorsal horn
60
Gate Control Theory
determine if you perceive pain based on balance of excitation and inhibition at the first synapse in dorsal horn
61
Why do you stroke or rub an area evoking pain?
Activation of non-nociceptive (A-Beta) fibers → activation of dorsal horn INHIBITORY INTERNEURONS that in turn inhibit synapses activated by nociceptive fibers
AB fibers excite inhibitory interneurons that decrease efficacy of nociceptive dorsal horn synapses
Elimination of AB fiber input → increase in pain sensitization (hyperalgesia)
62
Aspirin as an analgesic
COX inhibitor
Prevents conversion of arachidonic acid to prostaglandin → prevent nociceptor sensitization
63
Opiates as an analgesic (Morphine and Codeine)
Bind G-protein coupled opiate receptors → activation leads to inhibition of neuron on which they are found
High concentration of opiate receptors in PAG
64
What happens when PAG is activated?
PAG → nucleus raphe → spinal cord inhibitory interneuron
PAG especially sensitive to opiates → greater excitatory output from PAG → increased excitation of enkephalinergic inhibitory interneuron
65
Endogenous opiates include _________ and __________
Enkephalins, B-endorphin and Dynorphins (endorphins)
66
Naloxone
inhibitor of opiate receptor, blocks placebo effect too!
67
Cannabinoids effects
interact with opiate system (activate PAG) and immune system
→ Decrease secretion of proinflammatory cytokines, and increase secretion of anti-inflammatory cytokines
68
What kinds of things activate the PAG (midbrain)
1) cognitive factors (e.g. placebo effect) via frontal cortex and insular cortex
2) Systemic morphine
3) Stress (via hypothalamus)
4) Emotions (via amygdala)
69
Triple Response
occurs as a result of injury = reddening, wheal, and flare
70
What generates the redness and wheal during triple response?
Tissue damage → Bradykinin local production → activator, vasodilator (heat, redness), increased permeability (edema)
71
Flare
pink zone around inflamed area
72
Generating a flare
Bradykinin → activate C fiber nociceptors → AP propagates in 2 directions
1) towards cell body
2) along collaterals toward peripheral sites in neighboring skin regions
→ Substance P released into surrounding wound region
→ vasodilation, sensitization
73
What is the adaptive benefit if the triple response?
These physiological changes promote behavioral changes that minimize contact with wound, and allow better repair of wounded area
74
Without innervation from the nervous system what happens to the triple response?
→ only get red center, and wheal, no flare, no sensitization
75
Substance P
Released by C fibers in response to repetitive stimulation in CNS at site of first synapse
Acts as a sensitizer
Released by collateral terminals in neighboring skin regions to tissue damage → Flare production
Causes vasodilation (less than bradykinin) → pink instead of red
→ Flare region shows enhanced response to noxious stimuli
76
What is the pathway that allows pain to be controlled by descending inputs?
1) __________ stimulated in midbrain
2) --> ___________ in medulla
3) → project to spinal cord via __________ and release ________ (NT)
4) ______ (NT) in spinal cord → inhibit second-order neurons by exciting __________________
5) Interneuron secretes NT _________ → presynaptic inhibition (block _______________) AND postsynaptic inhibition (open ____________)
1) Periaqueductal Gray Region (PAG) stimulated in midbrain
2) PAG --> nucleus raphe magnus in medulla
3) Nucleus raphe neurons → project to spinal cord via dorsal lateral funiculus and release serotonin
4) Serotonin in spinal cord → inhibit second-order neurons by exciting enkephalinergic inhibitory interneurons
5) Interneuron secretes NT enkephalin → presynaptic inhibition (block voltage gated Ca2+ channels) AND postsynaptic inhibition (open K+ channels)
77
When the PAG is stimulated what sensation is attenuated, and what sensation persists?
PAG stimulation in midbrain → analgesia (pain sensation attenuated) while touch, pressure and temperature sensation persists
78
Placebo Effect
physiologic response evoked by administration of inert drug
Activity in neocortex and/or limbic system → PAG activation via increased secretion of endorphins → inhibition of second-order neurons in dorsal horn of pain pathway
BLOCKED by nalaxone (opiate receptor blocker) --> indicates important role of PAG in this process
79
Stress-Induced Analgesia
adaptive response of individual to stressful conditions
Stress → increased limbic system activity (amygdala + hypothalamus) → activation of PAG
→ inhibition of second-order neurons in dorsal horn of pain pathway
80
Neuropathic pain
peripheral vs. central mechanism generally include what?
persistent pain syndrome resulting from peripheral or central nervous system damage
1) Peripheral = Na+ channels
2) Central = GABA content/receptors, sprouting/rewiring, glia and immune system
81
Peripheral mechanism for causing neuropathic pain
Following nerve damage, expression, distribution, and function of Na+ channels profoundly altered → spontaneous discharge of pain primary afferents
causes chronic pain patients to experience pain in absence of any stimuli
82
Types of sodium channels involved in neuropathic pain (3)
Na1.7 = TTX sensitive
Na1.8 and 1.9 = TTX resistant
83
What happens if you have a mutation in Na1.7 channel?
Na1.7 = TTX sensitive
Familial primary erythermalgia = mutation in SCN9A gene that encodes this channel → pain, warmth, redness in hands/feet
84
Familial primary erythermalgia
mutation in SCN9A gene that encodes this channel → pain, warmth, redness in hands/feet
85
What happens if you have a mutation in Na 1.8 or 1.9?
Na1.8 and 1.9 = TTX resistant
Lack this current → higher pain thresholds
86
Role of GABA in Central mechanism of neuropathic pain generation
Damage → neuronal loss, reduction in GABA content, decreased number of GABA and opiate receptors
→ reduce inhibition of dorsal horn neurons → increase their excitability (sensitization)
87
Role of sprouting and reqwiring in Central mechanism of neuropathic pain generation
Following injury to C fibers, AB afferents sprout and invade substantia gelatinosa (formerly region with only pain neurons synapse)
→ second-order neurons in SG that are normally activated only by pain input are now also activated by non-noxious stimuli (allodynia)
88
Role of glial and immune cells in Central mechanism of neuropathic pain generation
Macrophages in DRG secrete _________ which binds ____________ and activate __________
Microglia in spinal cord secrete ________ which causes what?
Inflammatory reaction to peripheral injury at lesion site, DRG, and spinal cord
Macrophages in DRG: secrete TNF → bind TNF-R1 on sensory neurons → activate TTX-resistant sodium channels
Microglia in spinal cord → secrete BDNF → change chloride reversal potential → GABA receptor activation = excitation, NOT inhibition
89
Epidemiology of headache
Complaint of more than half of patients seeking medical advice from physician
more common in women
90
Primary headache (3 kinds)
no known cause (e.g. migraines) (>90%)
Episodic (coming and going) or chronic (present most days for > 3 months)
Includes:
1) Migraine
2) Tension headache
3) Cluster headache
91
Secondary headache
attributed to a systemic or cephalic disorder
Constant
Associated with underlying cranial or systemic pathology in temporal relationship with onset of headache
92
Migraine criteria (3)
1) at least 5 recurring headaches that last 4-72 hours
2) with at least 2 of the following (unilateral in location, pulsating in character, moderate or severe intensity, pain increases with physical activity)
3) and must also be associated with nausea/vomiting or photo/phonophobia
93
Aura
neurologic symptoms preceding headache - visual, sensory, language, motor, brainstem, retinal changes
Migraine may or may not have aura associated
94
Abortive treatment of migraines (5)
1) *Ibuprofen, *Naproxen, *Acetaminophen
2) Combo: ibuprofen or acetaminophen + caffeine/ASA
3) Triptans (*sumatriptan)
4) Ergotamine derivatives (*Dihydroergotamine, DHE)
5) Dopamine receptor antagonists (for nausea and vomiting) = *Metoclopramide
95
Prophylactic treatment of migraines (6)
1-3) Antihypertensives: *B-blockers (propanolol), *Ca2+ blockers (verapamil), *ACEIs/ARBs (lisinopril / -sartans)
4) tricyclic antidepressants (SSRIs)
5) anti-epileptics/convulsants
6) botox
96
Pain pathway of migraine
_______ + ________ --> trigeminal activation at ____________
--> pain signal transduction to ____________ --> ________ then _________
Vasodilation + peptide release
→ trigeminal activation at trigeminal ganglion
→ pain signal transmission to trigeminal nucleus caudalis
→ thalamus and cortex
97
Cluster headache criteria (3)
| aka Trigeminal autonomic cephalalgias
1) at least 5 episodes of severe, unilateral periorbital and/or temporal pain that lasts 15-180 min
2) Pain should recur at least every other day up to 8x per day
3) Ipsilateral, conjunctival injection, lacrimation, nasal congestion, rhinorrhea, eyelid edema, ptosis, miosis, facial swelling, ear fullness, restlessness/agitation
98
Tension type headache criteria (3)
1) at least 10 episodes of headache lasting 30min-7 days
2) each episode characterized by at least 2 of the following (pressing or tightening sensation, mild/moderate in severity, bilateral, not aggravated by physical activity)
3) Patients must NOT have nausea, vomiting, photophobia or phonophobia
**FEATURELESS headache
99
Trigeminal Neuralgia criteria (3)
primary or secondary headache
1) very brief pain in trigeminal nerve distribution lasting less than 1 second up to 2 min.
2) Intense, sharp, superficial, or stabbing pain
3) Triggered by sensory stimulation of particular area within trigeminal sensory innervation or by factor such as chewing/brushing teeth
100
Red flags indicating dangerous condition could be causing headache
SNOOP
1) Systemic symptoms (fever, weight loss) or secondary risk factors (HIV, systemic cancer)
2) Neurologic symptoms (confusion, impaired alertness/consciousness)
3) Onset sudden, abrupt
4) Older patient with new onset and progressive headaches
5) Previous history: Change in headache frequency, severity, or clinical features
101
Meningitis
features of headache + other signs
Acute pain (hours for bacterial, 1-2 days for viral)
Associated FEVER, stiff neck (meningismus), nausea/vomiting, altered consciousness, signs of meningeal irritation (Kernig, Brudzinski signs)
102
Traumatic injury to head
features of headache + other signs
Pain develops within 7 days of injury, resolves by 3 months
Dizziness, poor concentration, irritability and insomnia
103
Subarachnoid hemorrhage
features of headache + other signs
Severe “thunderclap” headache, sudden onset, +/- impaired consciousness or focal neurologic signs
Neck stiffness, photophobia, nausea, vomiting, neurologic signs, depressed arousal, obtundation
Aneurysm rupture accounts for 80% of cases
104
Giant cell arteritis symptoms
jaw claudication, temporal artery region scalp tenderness, joint pain, constitutional symptoms (fever, malaise, weight loss)
Usually in older patients (>60 years)
105
Giant cell arteritis diagnosis
Elevated ESR and CRP
Must biopsy temporal artery to confirm dx
106
Giant cell arteritis treatment
IMMEDIATE steroid treatment
107
Increased intracranial pressure
features of headache + other signs
headache that occurs/worsens with exertion, retro-orbital pain, nausea/vomiting, pulsatile intracranial noises, transient visual obscurations, photopsias, diplopia, vision loss
Headache worse when first awaking from sleep
- 6th nerve palsies
- Papilledema (edema of optic nerve), vision loss from optic nerve dysfunction
- Possible neurologic exam findings
108
Idiopathic Intracranial Hypertension
1) normal CSF constituents
2) normal neuroimaging
3) normal neuro exam EXCEPT for PAPILLEDEMA and 6th NERVE PALSIES
4) no other causes to explain increased ICP
109
Cluster headache prophylaxis (3)
Lithium, methysergide (ergo), verapamil
110
Cluster headache abortive treatment (5)
```
ergotamine (DHE)
glucocorticoids
lidocaine
oxygen
sumatriptan
```
111
Tension Headaches prophylaxis (2)
TCADs (amitriptyline)
SSRIs
112
Tension headaches abortive treatment (2)
NSAIDs
| Acetaminophen
113
Medication overuse headache
dull or migraine-like headache present for at least 15 days a month, associated with overuse of analgesics
114
High risk drugs that can cause medication overuse headache (3)
butalbital combinations
ASA-acetaminophen-caffeine
opioids
115
Moderate risk drugs that can cause medication overuse headache (2)
triptans, ergots
116
Low risk drugs that can cause medication overuse headache (1)
NSAIDs
117
Pathogenesis of Migraine (5 steps)
1) Trigeminal Neurovascular Dysfunction
2) Trigeminal neurovascular activation
3) Release of vasoactive peptides (substance P + calcitonin and prostaglandins)
4) Neuroinflammation (including PG release) and Vasodilation of pial and dural vessels
5) Moderate to severe pain of migraine
118
Serotonin in Migraines
serotonin=primary target in migraine treatment
5HT-1B receptors → Gi/o → Presynaptic inhibition, pulmonary vasoconstriction
Inhibits presynaptic release of vasoactive peptides
5HT-1D receptors→ Gi/o → Presynaptic decrease release, cerebral vasoconstriction
Inhibits vasodilation of pial/dural vessels
119
“-triptans” (sumatriptan / zolmitriptan)
mechanism of action and 3 main effects that reduce migraine
Agonist activity at 5HT-1B/1D receptors →
1) Vasoconstriction of cerebral vessels → reverse vasodilation-induced throbbing headache
2) Inhibit release of vasodilatory, neuroinflammatory, and pain causing peptides
3) Prevent activation of pain fibers in trigeminal nerves
120
Triptans should be avoided in which patients?
Avoid use in patients with uncontrolled HTN, cerebrovascular, coronary, or arterial disease
DO NOT use within 24 hrs of ergot alkaloid or concurrently with MAOI→ vasoconstriction additive
121
Side effects of triptans (4)
1) Tingling, flushing dizziness, drowsiness, fatigue
2) Coronary vasospasm, angina MI, cardiac arrhythmia
- -> Heaviness/tightness/pressure in chest
3) Stroke and death
4) Increased risk of serotonin syndrome → too much serotonin activity → neuromuscular effects (clonus), ANS changes, mental status changes (Agitation, delirium, hypervigilance)
122
Triptans are used for what?
first line drug for moderate/severe migraines
123
NSAIDs (ibuprofen / naproxen / Celecoxib / ASA / Acetaminophen)
are used for what kinds of headaches?
mild/moderate episodes of migraine without nausea or disabling symptoms
124
Mechanism of action of NSAIDs in headache
inhibits COX-2
Interrupts inflammatory mediator synthesis/release initiated by CGRP (calcitonin gene-related peptide)
125
NSAIDs should be avoided in what kinds of patients?
should be avoided in patients with acute gastritis, peptic ulcer disease, renal insufficiency, and bleeding disorders
126
Ergot alkaloids (dihydroergotamine, DHE) use for what kinds of headaches
terminating moderate/severe migraine attacks
127
Ergot alkaloids (dihydroergotamine, DHE) mechanism of action
agonist at 5HT-1B/1D receptors
Similar to triptans
1) Vasoconstriction of cerebral vessels → reverse vasodilation-induced throbbing headache
2) Inhibit release of vasodilatory, neuroinflammatory, and pain causing peptides
3) Prevent activation of pain fibers in trigeminal nerves
128
Side effects of Ergot alkaloids (dihydroergotamine, DHE)
More toxic and less effective than triptans - NOT FIRST LINE
Mild effects = nausea, vomiting → treat concurrently with antiemetic
Serious effects = vascular occlusion and gangrene due to stimulation of a1-adrenergic receptors
129
Ergot alkaloids should NOT be used in what kinds of patients?
AVOID USE WITH non-selective B-blockers or other vasoconstrictors (→ severe peripheral ischemia)
AVOID USE in patients with ischemic vascular disease
130
When to use prophylaxis treatment of migraines? (7)
1) Severe
2) frequent (>4/month)
3) long lasting (>12 hours)
4) disabling
5) Failure-overuse of acute therapies
6) Contraindications to vasoconstrictor therapies
7) Adverse drug events
131
Local anesthetics cause
Loss of sensation, particularly pain, in circumscribed region of body
No loss of consciousness
132
Mechanism og local anesthetics
Block AP initiation and conduction via block of voltage-gated Na+ channels in peripheral nerve
133
Method of application of local anesthetic determines ____
body region and size of region affected
134
Where can local anesthetics block Na channels
Anywhere!
Including CNS and heart
135
Tripartite structure of local anesthetics consists of:
1. Lipophilic aromatic portions
2. intermediate alkyl chain
Hydrophilic amine portion
136
What are the two types of local anesthetics?
1. amide
| 2. ester
137
What part of the tripartite structure do amide and ester local anesthetics differ in?
Intermediate alkyl chain
138
Amides have how many i's in their name?
2
| Lidocaine, Bupivacaine
139
Esters have how many i's in their name
one
| Cocaine, procaine, benzocaine, tetracaine
140
Amide local anesthetics: duration of action and termination
Duration of action: A1-acid glycoprotein (plasma protein) → readily binds amide local anesthetics → amides typically have longer duration of action
Termination: Metabolized by liver → excreted via kidney
141
Ester local anesthetic: Termination
Termination: Hydrolyzed in plasma by esterase (pseudo cholinesterase), also hydrolyzed in liver → excreted via kidney
142
Effective of pH in determining effectiveness of local anesthetics
Local anesthetics = weak bases: pKa=7.7-9.0 → partly ionized at pH 7.4
1. Cationic (+) form → bind better to local anesthetic binding site
2. Neutral form → cross plasma membrane to reach site of action
ii. In cases with increased tissue acidity (e.g. infection), need to give increased dose, because will decrease amount of neutral local anesthetic present
143
binding of Neutral form of local anesthetics
a. Bind site when channel is OPEN via intracellular pore entrance
b. Can cross plasma membrane even when channel is closed/inactivated
c. Much slower rate
144
binding of Cationic form of local anesthetics
a. Enters OPEN channel and binds
b. High affinity for Na+ channel pore
c. Enters/exits channel when channel is in OPEN state, but NOT when channel is closed or inactivated
145
Local anesthetics exhibit ___ dependent blockage
use
146
Use-dependent block
the more Nav channel is open/used, the greater degree of local anesthetic binding and block
i.UNBLOCK is also use dependent - channel must be open
147
Which form (neutral or cationic) are needed for local anesthetic blockage of Na channel?
Both
148
Local anesthetics and the inactivated state of Na channels
Local anesthetics can also increase stability of inactivated state of channel → prolong refractory period of nerve
149
Local anesthetics preferentially block which fibers?
Preferential conduction block of small fibers: Conduction block occurs at LOWER DOSES for SMALL DIAMETER axons (shorter internodal distance, more rapid AP firing rate) than in large diameter axons
1.Best block conduction in small-diameter, myelinated and unmyelinated axons, such as C fibers → pain sensation first functionality lost
150
Physicochemical properties of local anesthetics that determine potency
determined by lipid solubility→higher lipid solubility = higher potency
151
Physicochemical properties of local anesthetics that determine speed of onset
determined by pKa
Lower pKa → more uncharged → more easily get across cell membranes → faster speed of onset
152
Physicochemical properties of anesthetics that determine duration of action
determined by protein-binding capacity
More bound to plasma protein → longer duration of action
153
Topical application of local anesthetics: 3 drugs, used for what, and disadvantage
tetracaine, lidocaine, cocaine
1. Superficial anesthesia
2. Disadvantage = considerable absorption into circulation
154
Injection of local anesthetic into tissue: 3 drugs, uses, and disadvantage
lidocaine, procaine, bupivacaine
1. Superficial anesthesia, function of underlying organ unaffected
2. Disadvantage: need large dose, significant absorption into circulation
155
Nerve block: what is it, two drugs used, what is it used for
injection of high concentration near peripheral nerve/nerve plexus
1. Lidocaine (2-4 hours), bupivacaine (longer duration)
2. Anesthetize larger body regions
156
Intravenous regional anesthesia AKA ___?
What is it and drug used?
Bier's block
tourniquet applied, inject anesthetic via catheter for limb anesthesia
1.Lidocaine
157
Spinal anesthesia: 3 drugs used with duration of action
inject into CSF
1. Anesthetize large body areas with low plasma level of drug
2. Lidocaine (shorter procedures), Bupivacaine (intermediate), and tetracaine (long lasting, ester-linked drug)
a. No plasma esterase activity in CSF → long duration of action
158
Epidural anesthesia
inject just outside dura-enclosed spinal canal
1. Allows repeated/continuous anesthetic application
2. Higher plasma level of anesthetic than spinal anesthesia
3. Lidocaine (shorter), bupivacaine (longer procedures)
159
Often times, ____ are used with local anesthetics
vasoconstrictors
160
Why are vasoconstrictors used with local anesthetics
prolongs duration of conduction blockade by reducing blood flow in vicinity of injection
i.Retards systemic absorption of anesthetic
EX) Epinephrine = vasoconstrictor
iii.Local anesthetics typically reduce SNS activity → vasodilation
161
7 side effects of local anesthetics
i. OD → convulsions due to action on inhibitory interneurons of CNS (cross BBB)
ii. Interfere with ANS function (give with epinephrine to avoid this)
iii. Block cardiac Na channels → Cardiovascular effects, proarrhythmic
iv. Vasodilation via action on vascular smooth muscle
v. Can cross placenta and enter fetal circulation
vi. Inhibit neuromuscular transmission
vii. Allergic reactions - hypersensitivity reactions
162
Tetrodotoxin
toxin found in puffer fish, newts, and frogs
i. Block extracellular entrance of voltage-gated Na+ channel
1. VERY high affinity for Nav channel
ii. Cause death by paralyzing respiratory muscles, not by action on heart
163
Saxitoxin
toxin found in dinoflagellates (red tide) eaten by clams/shellfish
i. Block extracellular entrance of voltage-gated Na+ channel
ii. Cause death by paralyzing respiratory muscles, not by action on heart
164
Paresthesia
abnormal sensation - burning, pricking, tickling, tingling, pins and needles
165
Dysesthesia
impairment of sensation short of anesthesia
166
Hyperesthesia
abnormal acuteness of sensitivity to touch, pain or other sensory stimuli
167
Paresis
decreased strength
168
Plegia
complete loss of strength
169
Dermatome
cutaneous area served by an individual SENSORY ROOT
170
Myotome
muscles innervated by an individual MOTOR ROOT
171
Radiculopathy
sensory and/or motor dysfunction due to injury to a nerve root
172
Myelopathy
disorder resulting in spinal cord dysfunction
173
Nerve root
combined sensory (dorsal) and motor (ventral) rami of spinal cord
31 pairs of nerve roots (8 Cervical, 12 Thoracic, 5 Lumbar, 5 Sacral, 1 Coccygeal)
Vertebral body number is different from underlying cord segment
174
Intervertebral foramen
opening formed by 2 adjacent vertebral bodies through which nerve roots travel
175
Spinothalamic tract
(pain and temperature)
first synapse in substantia gelatinosa (dorsal horn of spinal cord) and crossing via anterior white commissure in spinal cord
176
Posterior/Dorsal columns
(vibration and position)
first synapse in medulla at nucleus gracilis/cuneatus and crossing in medulla after synapse
177
Lateral Corticospinal tract
motor (extremities, head/neck)
crossing in medulla at pyramid, first synapse in ventral horn of spinal cord on alpha motor neurons
178
At what level do the nerve roots exit?
C1,2,3,4,5,6,7 exit ABOVE same numbered vertebra
(Only have 7 cervical vertebrae, but 8 cervical roots)
-->
C8 and below exit BELOW same numbered vertebra
179
Anterior cerebral artery
supplies ventral spinal cord
(created by two branches of vertebral artery that come together to form single midline artery)
Gets contributions from radicular branches at each level
180
Spinal cord level each vertebral body overlies
```
Upper cervical
Lower cervical
Upper thoracic
Lower thoracic/lumbar
Conus medullaris
```
Upper cervical: vertebra # overlies same cord segment #
EX) C2 vertebra overlies C2 spinal cord segment
Lower cervical: vertebra # overlies cord segment # + 1
EX) C6 bone, C7 cord
Upper thoracic: vertebra # overlies cord segment # + 2
EX) T4 bone, T6 cord
Lower thoracic/lumbar: vertebra # overlies cord segment # + 2-3
EX) T11 bone → L1-2 cord
Lower edge of L1 vertebral body overlies cord tip (conus medullaris)
181
Somatotopic organization of tracts
Dorsal column: _____ is most medial, _______ is most lateral
Corticospinal and spinothalamic tracts: ______ is most medial, _______ is most lateral
Dorsal column: sacral (medial) → cervical (lateral)
Corticospinal and spinothalamic tracts: sacral (lateral) → cervical (medial)
182
Signs/symptoms of radiculopathy
Pain = shooting, burning, tingling, numbness
-Radiates to dermatome or myotome
Spurling's sign
Lasegue's sign
183
Spurling’s sign
foraminal compression test
Turn head towards a narrowed neural foramen → tight foramen can cause acute pinching of nerve root → pain radiates out with nerve root into arms
sign of radiculopathy
184
Lasegue’s sign
straight leg raising test
Sciatic nerve test - if sciatic nerve roots are under compression → shooting shock like sensation down legs
sign of radiculopathy
185
Common causes of radiculopathy
compression by degenerative joint disease or herniated disc (posterior/lateral direction) near intervertebral foramen
186
Lhermitte’s symptom
pain syndrome arising due to disease of spinal cord
Neck flexion results in “electric shock” sensation down back and/or arms
Due to posterior column disease
Indicative of myelopathy
187
Polyradiculopathy
impingement of collection of nerve roots within cauda equina (in lumbosacral spine below conus medullaris) → can cause problems with bowel/bladder function
188
Spinal shock
physiologic disruption of all spinal cord function
Loss of all neurological activity below level of injury, including loss of motor, sensory, reflex, and autonomic function
-no bulbocavernosus reflex
189
Bulbocavernosus reflex
indicates when spinal shock has resolved
Tug on the tip of the dick, if your asshole squeezes tightly, then reflex is present
If BC reflex is present and patient still is not moving/no sensation → anatomic transection of fibers
190
Neurogenic shock
disruption of descending sympathetic outflow
No sympathetic response and unopposed vagal tone
Cardiovascular instability
Treated with dopamine drip
191
Extramedullary lesions
arise from outside cord
EARLY PAIN and UMN signs
Pain and temperature sensation evolves in ASCENDING fashion (affects sacral, lumbar, then thoracic, etc.)
192
Intramedullary lesions
arise within cord
Cause early bladder dysfunction with only LATE development of PAIN
Loss of pain and temperature progresses in DESCENDING fashion (Cervical → thoracic early, then lumbar → sacral later)
193
Upper motor neuron signs (3 reflex signs)
hyperreflexia
- Babinski sign
- Hoffman's sign
- Crossed adductor response
194
Babinski sign
Plantar response: normal = flexion of toes
Babinski sign = extension of big toe, fanning of other toes → HYPERREFLEXIA
195
Hoffman’s sign
hyperreflexia in upper extremity
196
Complete Cord Transection
tracts affected?
deficit?
Tracts: all ascending and descending
Deficit: sensory + motor levels below lesions
→ Spinal shock, followed by UMN signs
197
Central lesions
tracts affected?
deficit?
EX) syringomyelia (fluid filled cavity in cord)
Tracts: initially involve CROSSING SPINOTHALAMIC tract
Deficit: pain/temp loss at level of lesion with sparing of position sensation
→ “Cape-like” distribution if in C-spine
198
Posterior Column Syndrome
tracts affected?
deficit?
EX) Tabes dorsalis (neurosyphilis)
Tracts: DORSAL (posterior column)
Deficit: bilateral loss of position and vibration sensation
199
Combined anterior horn cell-pyramidal tract syndrome
tracts affected?
deficit?
Tracts: CORTICOSPINAL and LMN cells in cord
Deficit: loss of bilateral strength + UMN/LMN signs
-Fasciculations, atrophy, decreased or increased deep-tendon reflexes, normal sensation
200
Brown-Sequard (hemi-section)
tracts affected?
deficit?
Tracts: crossed spinothalamic, uncrossed dorsal column, crossed corticospinal
Deficit:
Below lesion, loss of: contralateral pain/temp, ipsilateral, position and strength
201
Posterolateral column syndrome
tracts affected?
deficit?
EX) B12 deficiency
Tracts: DORSAL column, CORTICOSPINAL tract
Deficit: bilateral loss of position, vibration, strength
202
Anterior Horn Cell Syndrome
tracts affected?
deficit?
Tract: none - lower motor neurons only
Deficit: bilateral loss of strength
-Fasciculations, decreased tone, decreased deep-tendon-reflexes
*Spares sensory tracts and bladder functions
203
Anterior Spinal Artery Occlusion
tracts affected?
deficit?
Tracts: SPINOTHALAMIC and CORTICOSPINAL tract
Deficit: bilateral loss of strength, pain/temp
*Spare position sense
204
Pyramidal Tract Syndrome
tracts affected?
deficit?
Tract: CORICOSPINAL tract
Deficit: bilateral UMN weakness with spastic gait
-Increased deep-tendon-reflexes
*Complete sparing of all sensory tracts and bladder function
205
Myelopathy with Radiculopathy
tracts affected?
deficit?
Tracts: any or all 3 tracts
Deficit: bilateral UMN syndrome with spastic gait
-Increased DTRs + ipsilateral or contralateral root signs
*Possible bladder dysfunction
206
Conus medullaris syndrome
- pain = early vs. late
- muscle weakness where?
- symmetric vs. asymmetric?
- early vs. late bladder/bowel dysfunction
S3-S5, tip of cord
Supplies bladder, rectum, and genitalia
LATE pain in thighs and buttocks
Pelvic floor muscle weakness
SYMMETRIC “saddle” anesthesia numbness
EARLY bladder dysfunction
EARLY bowel and sexual dysfunction
207
Cauda equina
- pain = early vs. late
- muscle weakness where?
- symmetric vs. asymmetric?
- early vs. late bladder/bowel dysfunction
ROOTS L1-S5
EARLY root pain radiating to legs
Leg weakness and decreased DTRs (LMN sign)
Patchy, ASYMMETRIC “saddle”
LATE bladder dysfunction
LATE bowel and sexual dysfunction
208
Detrusor (smooth) muscle innervated by what?
activated by preganglionic parasympathetic outflow from S2-S4 (pelvic nerve)
209
Involuntary (smooth) sphincter innervated by what?
controlled by sympathetic outflow, T10-L2 (hypogastric nerve)
210
Skeletal (voluntary) muscle of pelvic floor innervated by what?
innervated by alpha motor neurons, S2-S4 (Pudendal nerve)
211
Forebrain (medial frontal) role in micturition
voluntary inhibition of pontine center AND relaxation of voluntary sphincter
212
Pontine micturition center
coordination of sympathetic and parasympathetic centers in spinal cord
213
Flaccid Bladder
bladder does not contract → overflow incontinence
Parasympathetic lower motor neuron injury, axon compression/disruption
214
Spastic Bladder
Descending pathways cut or injured (BILATERALLY) → UMN injury = initial flaccidity of bladder, then spasticity
Problems with coordination between sympathetic outflow (inhibited during voiding) and parasympathetic outflow (activated during voiding)
Urinary frequency and urgency
215
What dermatome covers the nipple line?
T4 dermatome
216
What dermatome covers the xiphoid process?
T6 dermatome
217
What dermatome covers the umbilicus?
T10 dermatome
218
C5 nerve root
motor function
reflex
usual disc involved
motor function = deltoid, infraspinatus, biceps
reflex = biceps
usual disc involved = C4-C5
219
C6 nerve root
motor function
reflex
usual disc involved
motor function = wrist extension, biceps
reflex = biceps, brachioradialis
usual disc involved = C5-C6
220
C7 nerve root
motor function
reflex
usual disc involved
motor function = Triceps
reflex = triceps
usual disc involved = C6-C7
221
L4 nerve root
motor function
reflex
usual disc involved
motor function = Psoas, quads
reflex = patellar
usual disc involved = L3-4
222
L5 nerve root
motor function
reflex
usual disc involved
motor function = foot dorsiflecion, big toe extension, foot eversion and inversion
reflex = none
usual disc involved = L4-L5
223
S1 nerve root
motor function
reflex
usual disc involved
motor function = foot plantar flexion
reflex = achilles
usual disc involved = L5-S1
224
C5 nerve root
sensory zone
shoulder, upper/lateral arm
225
C6 nerve root
sensory zone
1st and 2nd digits of hand
226
C7 nerve root
sensory zone
3rd digit (middle finger)
227
L4 nerve root
sensory zone
Knee
| medial leg
228
L5 nerve root
sensory zone
dorsum of foot
| great toe
229
S1 nerve root
sensory zone
lateral foot
small toe
sole of foot
230
Opioid indications/uses (5)
1) Relief of moderate to severe pain (best for NOCICEPTIVE pain - NOT effective for NEUROPATHIC pain)
2) Cough suppression (lower dose)
3) Diarrheal conditions (Loperamide - local GI tract actor)
4) Pulmonary edema associated with cardiac dysfunction
5) Effects on cardiovascular system: MI → analgesia, decrease cardiac load
231
Opioid contraindications (7)
1) Respiratory dysfunction of any cause: emphysema, asthma, sleep apnea, severe obesity
Pathological:
2) Suspected head injury (opioids cause cerebral vasodilation → problem if pt has increased ICP)
3) Hypotension → lower BP even more
4) Shock → makes shock worse
5) Histamine release
6) Hypothyroidism
7) Impaired hepatic function → increased bioavailability and accumulation of toxic metabolites
232
Behavioral effects of opioids (4)
1) Euphoria
2) Dysphoria (hallucinations)
3) Sedation, lethargy, confusion
4) Behavioral excitation (sign of acute toxicity)
- Due to buildup of toxic metabolites)
233
Adverse interactions of opioids with other drugs (3)
1) CNS Depressants:
- Barbiturates: additive or synergistic CNS depression
2) Antipsychotics (Phenothiazines)
- Increase opioid analgesia, but increase respiratory depression
- Increase hypotensive effect of opioids
3) MAO Inhibitors and Tricyclic Antidepressants:
- Increase respiratory depression
- Can induce CNS excitation, delirium, and seizures
234
Major/life-threatening side effects of opioids (5)
1) Respiratory depression = **MOST dangerous side effect of opioids
* *Avoid by avoiding use with head injury patients, and patients with compromised respiratory function
2) Nausea and vomiting
3) Pupillary Constriction (Miosis) - pinpoint pupils
4) Constipation
5) Anaphylaxis (rare)
- Cause histamine release (typically managed with antihistamines)
235
μ , mu receptor
endogenous agonists?
Agonist drugs?
target of most clinically useful drugs - e.g. morphine
endogenous agonist = B-endorphin
236
Three types of opioid receptors
1) μ , mu
2) d, delta
3) K, kappa
237
μ , mu receptor activation causes ______ and ______.
This is accomplished what what 3 mechanisms?
analgesia (central) and respiratory depression
DECREASE neuronal excitability
1) Inhibit presynaptic voltage-gated Ca2+ channels → inhibit NT release
2) Activate potassium channels → membrane hyperpolarization
3) Inhibit cAMP synthesis
238
Opioid Analgesics produce analgesia through what three mechanisms?
1) Inhibit spinal cord/ascending pain pathway
2) Activate “descending” pain pathway
3) Reduce subjective response to pain
239
How do opiates inhibit the ascending pain pathway?
Inhibit spinothalamic “ascending” output neurons
Inhibit presynaptic excitatory NT release from primary afferent terminals in dorsal horn of spinal cord (substance P, glutamate)
240
How do opiates activate the "descending" pain pathway?
Activate descending inhibitory output system in medulla, PAG, and locus coeruleus mediated by 5-HT and NE
Inhibiting GABA-ergic neurons → increase descending output
241
Tolerance
Decreased response to drug as a result of previous exposure
- Need increased dose to produce same pharmacological effect
- Does not develop to all opioid effects equally (pupillary constriction, and constipation issues do not develop tolerance - resp depression does)
Tolerance can “generalize” to similar drugs (all mu agonists)
Tolerance reverses following withdrawal
242
Dependene
physical and psychological
Produced by opioids in patients abusing opioid drugs and long-term therapy to treat chronic pain
Continued use of drug to prevent withdrawal
Different mechanism than tolerance
243
Withdrawal
Occurs with cessation of opioid following prolonged use
Symptoms of withdrawal: OPPOSITE to those caused by acute opioids
--> “Flu-like”, dilated pupils, insomnia, restlessness, yawning, rhinorrhea, sweating, diarrhea, nausea, cramps, chills
Withdrawal not life-threatening with opiates
Clonidine (a2-agonist) can be used to treat withdrawal symptoms
244
What are the main sites of opioid action?
Analgesia (3 sites)
Limbic and motor CNS regions (3 sites)
Reinforcement regions (2 sites)
Gut (1)
Analgesia:
1) Periaqueductal gray (descending pain)
2) Medulla nuclei (side effect respiratory depression)
3) Spinal cord dorsal horn (ascending pain)
Limbic and motor CNS regions:
Amygdala, hippocampus, striatum (affective response to pain)
“Reinforcement” Regions in CNS:
Ventral tegmentum, nucleus accumbens (addiction-abuse)
Gut: myenteric plexus (side effect-complication)
245
Classes of endogenous opioids
1) Enkephalins = NT in brain/spinal cord
2) Endorphins = NT and neurohormone
3) Dynorphins
4) Endomorphins
246
μ agonists include...(9)
1) Morphine
2) Heroin
3) Hydrocodone
4) Oxycodone
5) Codeine
6) Tramadol
7) Fentanyl
8) Loperamide
9) Dextromethorphan
247
Morphine
μ agonists
Use: severe post-op pain and in acute trauma (IV/IM), also available in oral sustained release for chronic pain
248
Heroin
μ agonists
not medicinal, schedule 1 drug
249
Hydrocodone
μ agonists
aka Vicodin
Use: antitussive, weak analgesic, similar to codeine
250
Oxycodone
μ agonists
aka Oxycontin, Percocet
Use: equipotent to morphine
oxycontin has highly abused currently
251
Codeine
μ agonists
most commonly used opioid analgesic, also an antitussive
Less potent than morphine
Often combined with acetaminophen or ASA
10% metabolized to morphine by CYP2D6 metabolism, but some patients don’t have CYP2D6 → not effective in everyone
252
Tramadol
μ agonists AND monoamine re-uptake inhibitor (potentiate descending pain pathway)
253
Fentanyl
μ agonists
Extremely potent - 100x more potent than morphine
Use: perioperative and postoperative pain management
Adjunct to surgical anesthesia
Requires mechanical ventilation at high doses
254
Loperamide
μ agonists
Anti-diarrheal (oral)
Low abuse potential
255
Dextromethorphan
μ agonists
aka robitussin DM
cough suppresant
256
Bupenorphine
Partial μ agonist
can precipitate mild withdrawal because partially antagonizes effects of morphine
257
Naloxone
aka narcan
μ antagonist
Competitive antagonist
Short duration, may require readministration in tx of OD with long-acting agonists
258
Drugs to treat constipation side effects (4)
Bisacodyl-senna (stimulant laxative)
Docusate (stool softener)
Magnesium hydroxide (osmotic laxative)
Polyethylene glycol (osmotic laxative)
259
Methadone
mu agonist
used to alleviate symptoms of withdrawal
260
Acute pain
short duration, resolves
Primarily NOCICEPTIVE (somatic more common than visceral)
261
Chronic pain
pain that persists for longer than would be expected
Pain persists beyond normal healing time for acute injury → NEUROPATHIC
Related to a chronic disease → NOCICEPTIVE
Without identifiable organic cause → FUNCTIONAL
Associated with cancer
262
Nociceptive pain
“normal” pain from activation of nociceptive nerve fibers
either somatic or visceral
263
Somatic pain
arising from skin, bone, joint, muscle or CT
Throbbing, well-localized
264
Visceral pain
arising from internal organs
Can be referred pain or well-localized
265
NSAIDs use in nociceptive pain
inhibit COX-2 and PG synthesis → reduce peripheral and central sensitization
Reduce PG synthesis from tissue damage
Reduce PG release in central sensitization
266
Celecoxib
COX-2 reversible inhibitor (can be used for analgesic and anti-inflammatory injury)
May increase risk of clotting
267
Acetaminophen
COX-2 reversible inhibitor, CNS ONLY (no anti-inflammatory action, only analgesic)
Risk of hepatotoxicity
Safest one for patients with kidney dysfunction or gastric ulcers
268
Ibuprofen
COX-½ reversible inhibitor
| → can have GI side effects
269
Aspirin
COX-½ irreversible inhibitor
→ causes antiplatelet (bleeding)
→ can have GI side effects
270
Local anesthetics (lidocaine) use in nociceptive pain
block voltage-sensitive Na+ channels → reduce nociceptive stimuli AP
Block noxious mechanical pain transmitted via Ad fiber and noxious heat/chemical pain in C fiber
(as well as non-noxious mechanical stimuli of AB fibers)
271
NMDA receptor antagonists (Ketamine) use in nociceptive pain
block glutamate receptor depolarization at 2nd order neuron → decreased transmission of nociceptive stimuli
272
Mu opioid receptor agonists (morphine) use in nociceptive pain
block glutamate-substance P release from primary neuron
AND
hyperpolarizes 2nd order neuron → reduce excitation of 2nd order neuron → decreased transmission of nociceptive stimuli
273
A2-adrenergic receptor agonists (clonidine) use in nociceptive pain
block glutamate-substance P release from primary neuron → reduce excitation of 2nd order neuron → decreased transmission of nociceptive stimuli
274
Neuropathic Pain/Functional pain (whats the difference?)
persists, disengaged from noxious stimuli or healing process
Typically chronic
Burning, tingling, shock-like/shooting
Hyperalgesia + allodynia
Neuropathic → result of nerve damage
Functional → abnormal operation of nervous system (fibromyalgia, IBS, tension type headache)
275
Multimodal management of acute pain
Use of different classes of analgesics that act via different pathways
→ greater analgesic efficacy from synergistic actions of agents with different mechanisms
→ Synergism allows LOWER DOSES → REDUCE dose-related SIDE EFFECTS
Typically have comparable EFFICACY (equal analgesia) within a mechanistic class
276
Mechanistic approach to treatment of chronic pain (neuropathic mostly):
Non-opioid and adjuvant medications emphasized for treatment of chronic-persistent pain
→ NSAIDs, Acetaminophen
→ Anticonvulsants, antidepressants, and local anesthetics (neuropathic pain only)
→ Tricyclic antidepressants
Opioid analgesics reserved for moderate to severe pain that adversely impacts function or quality of life
277
Brodmann's areas 3, 1, and 2
make up somatosensory cortex
3b → primary somatosensory cortex
3a → proprioception (contralateral information)
1 and 2 → receive input from 3b, and detect complex features of somatosensory stimulation
278
________ stroke is most likely to transform into homorrhage
embolic
279
Stroke protocol for evaluation and treatment
Noncontrast head CT --> look for contraindication for TPA
Perfusion CT (with IV contrast) to determine complete infarct of penumbra
Give TPA in less than 4.5 hours, consider IA thrombolytics (mechanical intracranial embolectomy)
280
Perfusion CT imaging:
shows decreased blood volume = ?
shows normal or increased blood volume = ?
shows decreased blood volume = complete infarct
shows normal or increased blood volume = brain at risk (penumbra)
