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5 items that do nociceptive activation and sensitization (in addition to various ions and other biochemical mediators that do this)
- histamine,
- substance P,
- prostaglandins,
- serotonin,
- bradykinin
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Substance P is made by cells of the spinal ganglia, and found at peripheral terminal of unmyelinated primary afferent fibers. Plays a role in ...?
increasing pain from GI, ureters, and urinary bladder
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C fibers conduct what pain, how
- dull and burning pain
- slow conduction velocity, bc they're unmyelinated
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A fibers conduct what pain, how?
fast, sharp, -- they're myelinated
from muscles, joints, bone
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A and C ascending nociceptive fibers synapse with neurons where?
dorsal horn
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Dorsal horn has neurons that get hyperexcited by distinct types of stimuli from primary afferent nociceptors (A and C). There are 3 classes of cells responding here. What are they, what do they respond to?
- class I - respond to low threshold mechanical and thermal impulse
- class II - have a wide dynamic range
- class III - respond to stim only from tissue damage
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anterolateral pathway transmits what kind of sensory info?
temp, pain, crude touch, tickle, itch
does sensory that doesn't require speed, precise localization, or fine gradations of intensity from signal source
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anterolateral fibers originate where? then do waht?
- dorsal horns
- then cross in the anterior commissure to the opp. ant and lat white columns
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upper terminus of anterolat pathway
- throughout the reticular nuclei of brainstem
- ventrobasal and introlaminar nuclei of thalamus
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5 classes of pain meds
- non-opiate analgesics
- steroidal anti-inflam
- opiate analgesics
- local anesthetics
- skeletal muscle relaxants
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when to use opioids? what do they mix well with and why?
- in refractory cases or pts w severe pain
- use with NSAIDs bc they can enhance opioid analgesia and produce "dose sparing"
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acetylsalicyclic acid, aka __
aspirin
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how does aspirin/ acetylsalicylic acid exert its therapeutic effect?
inhibit synth of eicosanoides
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3 eicosanoides
- prostaglandines
- thromonxanes
- leukotriens
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4 basic effects of eicosanoides (prostaglandines, thromboxanes, leukotriens)
- inflam (increase local blood flow, capillary permiability, and effects of histamine)
- pain (increase sensitivity of receptors)
- fever
- thrombus formation
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4 times to use aspirin or other NSAIDs
- mild to mod pain
- fever
- vascular disorders (nsaids inhibit thrombus formation)
- certain cancers (decreases risk of GI cancer)
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aspirin side effects
- Reye's syndrome (brain and liver damage)
- irreversible inhibition of platelet aggregation
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choline magnesium trisalicylate (an NSAID) - side effects?
- minimal bleeding
- peptic ulcer potential
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diflunisal (NSAID) 2 notes
- antacids may decrease absorption
- convenient dosing
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ibuprofin -- what type of drug? does what?
- nonopioid
- reversibly inhibits platlet aggregation
- same gastric effects as aspirin but w less severity and incidence
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naproxen
- same mechanism as acetaminophne
- reversibly inhibits platlet aggregation
- same gastric effects as aspirin but with less severity
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what pain killer irreversibly inhibits platelet aggregation? what 2 do it reversibly?
- aspirin
- ibuprofen and naproxen
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indomethacin -- pain killer with higher risk of what
GI sie effects
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4 potentitial adverse effects of nonopioids
- renal failure
- hepatic dysfunction
- bleeding
- gatric ulceration
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use nonopioids cautiously in these populations
- geriattrric
- renal, heart, liver porblems
- hypovolemia
- elevated angiotensin II or catecholamine levels
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what do aspirin and aspirin like drugs do that acetaminophen does too? what doesn't acetominophen do? advantages of aceto?
- both are analgesic and antipyretic
- acetaminophen doesn't do anti-inflam or anticoagulant
- aceto has minimal bleeding risk, no GI irritation, no Reye's, doesn't decrease uric acid secretion
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acetaminophen, 5 points
- low anti-inflam activity
- low plasma protein binding
- minimal bleeding / peptic ulcer potential
- doesn't ecacerbate volumen overload
- synergistic w narcotic analgesics
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histamine's impact on inflammation
vasodilation
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prostaglandine's impact on inflammation
platelet aggregation
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leukotrien's impact on inflammation
vasoactive properties (affects diameter of vessels)
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lymphokine's impact on inflammation
chemotactic properties (causing cells to exit the blood stream and enter tissue?)
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main category of corticosteroid drugs used for inhibition of inflammatory process
basic role?
- glucocorticoids
- decrease of pain receptor activation
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5 jobs of glucocorticoids (the main category of corticosteroid drugs)
- inhibit fibroblast activation (prevent walling off of infection)
- inhibit phospholipase A2 and reduce release of arachidonic acid from phospholipids
- reduce formation of eicanosides - leukotriens (high conc are found in synovial fluid in RA) thromoxanes, and prostaglandinsstabilize lysosomal membrane and inhibit breakdown of lysosomes
- inhibit rel of interleukin-1
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downsides of glucocorticoids
- they treat the symptoms but don't address the disease -- could mask the severity of the disease, leading to serious or fatal delay in diagnosis
- inhibit body's own production of glucocorticoids from adrenal cortex
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does the body produce glucocorticoids?
adrenal cortex (can atrophy and shut down in response to taking to much of the drug)
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side effects of glucocorticoids
- skin atrophy
- muscle weakness
- weakening connective tissues
- osteoporosis
- reduced wound healing
- increase susceptibility to infection
- peptic ulcers
- hyperglycemic reactions (esp troublesome for diabetics)
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how to administer glucocorticoid drugs?
orally for short term episodes or directly by injection into the inflamed tissue or joint
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3 conditions where you'd use glucocorticoid drugs?
- inflammation in ankylosing spondylitis
- RA
- soft tissue inflam
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how to administer dexamethasone?
- iontophoresis, pushing it into inflamed areas with the negative electrode
- (it's a glucocorticoid)
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acting at the different levels of the CNS, system opioids induce analgesia by
- mimicking the actions of endogenous neurotransmitters at the opioid-receptor binding sites
- specific receptors in the encephalon and spinal cord are activated by the interaction with opioid agent --> stim or depression of diff neurons
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at level of spinal cord, opioids do what?
inhibit transmition of nociceptive impulses from periphery to CNS
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at level of basal ganglia, opioids
activate the descending antinociceptive pathway by interaction btwn opioids and recepters in the periaqueductual gray matter of the brain stem
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mu opioid receptor effects include
- analgesia
- nausea
- vomiting
- constipation
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kappa opioid receptors mediate
- sedation
- spinal analgesia
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delta opioid receptors mediate
- analgesia
- may potentiate morphine analgesia
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morphine binds to what opiate receptor?
- mu
- but also kappa and delta
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