Pain Flashcards
Where do local LA act at on the pain pathway
between transduction and transmission level
Transduction
Nerve/electrical impulses/signals start at the nerve endings
Transmission
Travel of nerve/electrical impulses to the nerve body connecting to the dorsal horn of the spinal cord.
Modulation
Process of altering (inhibitory/excitatory) pain transmission mechanisms at the dorsal horn to the PNS and CNS.
Perception
Thalamus acting as the central relay station for incoming pain signals & the primary somatosensory cortex serving for discrimination of specific sensory stimuli.
Nociception
transduction
transmission
modulation
perception
Where do the modulation of pain impulses occur?
Dorsal Horn
Location of Nociceptors
in periphery
Skin, muscles, joints, viscera, vasculature
Unmyelinated C- fiber
Afferent fibers; burning pain from heat and pressure from sustained pressure.
travels less than 2m/second
Myelinated A-fiber;
faster
Type I fibers ( Aβ & Aδ fibers): heat, mechanical, chemical
Type II fibers (Aδ fibers): heat
travels more than 2m/second
Peptides chemical mediators
Substance P, Calcitonin, Bradykinin [1st released w/ pain], CGRP
Lipids chemical mediators
Prostaglandins** (nsaids tx), Thromboxanes(nsaids tx),
Endocannabinoids (cannabis binds and causes no further transmission of pain))
Sensitization
increased sensitivity/ threshold is reached quicker
Hyperalgesia
Increased pain sensations to normally painful stimuli.
Allodynia
perception of pain sensations in response to normally non-painful stimuli
Primary Hyperalgesia
at the original site of injury from heat and mechanical injury.
Decreased pain threshold
Increased response to suprathreshold stimuli
Spontaneous pain
Expansion of receptive field
Secondary Hyperalgesia
uninjured skin surrounding the injury (only from mechanical stimuli(pressure/ injury/ inflammation).
Sensitization of central neuronal circuits
Spinal Dorsal Horn
Relay center for nociceptive & other sensory activity.
Lamina I (marginal layer):
afferent C Fibers
Lamina II
(substantia gelatinosa [opioids]): afferent C Fibers
Laminae I, IV, & VII, and ventral horn:
myelinated fibers (innervating muscles and viscera)
Laminae III & IV:
NKI (neurokinin) receptor with substance P
Gate open
pain is projected to supraspinal brain regions
Aδ (small diameter, myelinated) & C fibers (unmyelinated)
Gate closed
pain is not felt with simultaneous inhibitory impulses
Aβ fibers (large diameter, myelinated: faster) deliver information about pressure and touch (rubbing)
Limbic cortex and thalamus
Perception of motivational-affective pain components
Periaqueductal gray -rostral ventromedial medulla (PAG-RVM) system
Depress or facilitate the integration of pain info in the spinal dorsal horn towards the cns.
Excitatory impulses nt
Glutamate
calcitonin
neuropeptide Y
Aspartate
Substance P
Inhibitory impulses nt
GABA
Glycine
Enkephalin
sNE
dopamine
Ascending Pathways
Spinothalamic
Spinomedullary
Spinobulbar (hinebrain)
Spinohypothalamic
Where does the pain impulse originate if it is pertaining to the descending inhibitory tract?
PAG-RVM
Neuropathic pain
Persists after the tissue has healed -> allodynia and hyperalgesia
Increased risk: Cancer patients d/t chemo and radiation therapy
Treatment: symptomatic (opioids gabapentin, amitryptiline (antidepressant), cannabis)
Visceral Pain
Diffuse & poorly localized (referred to somatic sites: muscle & skin)- not specific
Causes: ischemia, stretching of ligamentous attachments, spasms, distention
Complex Regional Pain Syndromes
A variety of painful conditions following injury in a region with impairment of sensory, motor, and autonomic systems
Spontaneous pain, allodynia, hyperalgesia, edema, autonomic abnormalities, active and passive movement disorders, and trophic changes of skin & SQ tissues
Pain in Neonate and Infant
Pain perception at 23 weeks of gestation
Lower pain threshold & exaggerated pain responses
Opioid
All exogenous substances (natural & synthetic).
Narcotic
Greek word stupor, which has the potential to produce physical dependence
Phenanthrenes
Morphine, Codeine, & Thebaine
Benzylisoquinoline
Papaverine (used in arterial injection of barbituates) & Noscapine
Brain opioid receptors
Periaqueductal gray (PAG), locus ceruleus, rostral ventral medulla (RVM), & hypothalamus
Spinal Cord Opioid Receptors
Interneurons and primary afferent neurons in the dorsal horn (substantia gelatinosa).
Direct application -> intense analgesia.
Outside CNS Opioid Receptors
Sensory neurons and immune cells.
Intraarticular morphine after knee surgery.
Mu 1 effect
analgesia (supraspinal, spinal)
euphoria
low abuse potential
miosis
bradycardia
hypothermia
urinary retention
Mu 1 agonists
endorphins
Morphine
Sythetic opioids
Mu1, Mu2, Kappa, Delta antagonists
Naloxone
naltrexone
nalmefene
Mu 2 effect
analgesia (spinal)
depression of ventilation
physical dependence
constipation (marked)
Mu 2 agonist
endorphins
morphine
synthetic opioids
Kappa Effects
analgesia (supraspinal, spinal)
dysphoria
sedation
low abuse potential
miosis
Diuresis
Kappa agonist
Dynorphins
Delta effect
anaglesia (supraspinal, spinal)
depression of ventilation
physical dependence
constipation (minimal)
urinary retention
Delta Agonist
Enkephalins
Which receptor produces physical dependence?
Mu 2
Physostigmine effect on ventilation
increased CNS levels of Acetylcholine (Ach) ->antagonize ventilatory depression but not analgesia
Opioid side effects on chest wall and tx
Skeletal thoracic (chest wall) & abdominal muscle rigidity (looks like laryngospasm)
-Severe with mechanical ventilation
-Treatment: muscle relaxation or Naloxone
GI side effect of opioids
Spasm of biliary smooth muscle
Sphincter of Oddi spams
Fentanyl (99%), Morphine (53%), and Meperidine (61%)
Tolerance
the development of the requirement for increased drug doses (usually 2 to 3 weeks).
Morphine: 25 days
Cross-tolerance can develop between all opioids.
Downregulation
opioid receptors on the cell membrane surfaces become gradually desensitized by reduced transcription & subsequent decreases in numbers of opioid receptors….will need more to effect the lower number of the R.
Gold standard of opioids
morphine
morphine effects
:Analgesia, euphoria, sedation, & diminished ability to concentrate, nausea, feeling of body warmth, heaviness of extremities, dryness of the mouth, and pruritis (histamine release).
Relieves visceral, skeletal muscles, joints and integumental dull > sharp, intermittent pain
morphine dose
1-10 mg
morphine onset im and IV
10-20 min
Morphine IM peak
45-90 min
Morphine IV peak
15-30 min
morphine duration of action
4-5 hours
Morphine accumulates where
Accumulates rapidly in kidneys, liver, and skeletal muscles.
Morphine metabolism
Glucoronic acid conjugation in hepatic and extrahepatic sites.
Metabolites:
Morphine-3-glucuronide (75% to 95%) but inactive (long half life)
Morphine-6-glucuronide: active analgesic
Meperidine receptor effects
agonist at µ and κ opioid receptors
Meperidine analogues
Fentanyl
Sufentanil
Alfentanil
Remifentanil
Meperidine potency
1/10th as potent as morphine
Meperidine dose
12.5 mgs post op shivering
Meperidine duration of action
2 to 4 hours
meperieinde effects
sedation, euphoria, N/V, depression of ventilation
meperidine metabolism
90% hepatic ->normeperidine
Meperidine Protein binding
60% (elderly considerations)
Albumin level is decrease in Elderly = meperidine is 60% protein bound = sedate / higher effect on elderly because have less bound. Give less.
Meperidine use
intrathecal, IM for postop analgesia, postop shivering (_ receptors; potent agonist at _2 receptors)
Meperidine elimination 1/2 time
3 to 5 hours (35 hours with renal failure)
Meperidine S/E
: tachycardia & mydriasis with dry mouth, (-) inotropy, serotonin syndrome (MAOIs & TCAs), impaired ventilation, crosses placenta,
Withdrawal symptoms develop more rapidly > morphine
Fentanyl potency
75 to 125 times more potent > morphine
Fentanyl Blood:Brain Effect site equilibration
6.4 minutes
-Potent, rapid onset, very lipid soluble
Fentanyl metabolite
Norfentanyl
Fentanyl Vd
Large
IV (<5 mins 80% is gone)
->highly vascular tissues
->inactive tissue sites
Fentanyl context senstive half time
Context-Sensitive Half-Time is greater than Sufentanil
d/t saturation of inactive tissue ->return to plasma replaces those metabolized
Fentanyl analgesia dose
1-2 mcg/ kg IV
Fentanyl Induction dose
1.5 to 3 µg/kg IV 5 mins prior
Fentanyl Adjunct with inhaled anesthetics
2 to 20 µg/kg IV
Fentanyl Surgical Anesthesia (solo)
50 to 150 µg/kg IV
Fentanyl Intrathecal
25 mcg
Fentanyl Transmucosal (Oral)
5 to 20 µg/kg
Fentanyl 2 to 8 yo
15 to 20 µg/kg PO 45 minutes prior
Fentanyl mg compared to morphine
1 mg of PO Fentanyl = 5 mgs of IV Morphine
Fentanyl Transdermal
75 to 100 µg (18 hours steady delivery)
Fent cns s/e
Seizure like activity
SSEP and EEG (>30 µg/kg IV)
Modest increase in ICP (6 to 9 mmHg)
Sufentanil potency
5 to 12 times more potent > fentanyl
Sufentanil protein binding
92.5% protein binding (smaller Vd < fentanyl): α1-acid glycoprotein
Sufentanil first pass uptake
60% lung first-pass uptake
Sufentanil analgesia dose
0.1 - 0.4 µg/kg IV
Sufentanil induction dose
18.9 µg/kg IV
Sufentanil S/E
Bradycardia -> decreased cardiac output
Rigidity: chest wall and abdominal muscles
Alfentanil potency
1/5th less potent than fentanyl
Alfentanil onset
1.4 minutes > fentanyl & sufentanil
Alfentanil Metabolite
noralfentanil (hepatic P450 3A4)
Alfentanil Induction laryngoscopy
15 to 30 µg/kg IV (90 seconds prior)
Alfentanil Induction alone
150 to 300 µg/kg IV
Alfentanil Maintenance
25 to 150 µg/kg/hour IV with inhaled anesthetics
Remifentanil receptor
Selective µ opioid agonist
Remifentanil potency
15 to 20 times as potent as alfentanil (almost same as fentanyl)
Remifentanil metabolism
Because its ester structure
Hydrolysis by nonspecific plasma and tissue esterases
Remifentanil Onset
Brief action, rapid onset and offset (15 mins)
Precise and rapid titratable effect
Lack of accumulation
Rapid recovery when discontinued
Remifentanil dose based on
Dose in IBW
Remifentanil Peak effect site time
1.1 minute
Remifentanil Clearance
3L/min (8x more rapid > alfentanil)
Remifentanil Plasma Steady state with infusions
@ 10 minutes
Remifentanil Elimination half-time:
Elimination half-time: 6.3 minutes (99.8%)
Remifentanil induction
1 µg/kg IV over 60 to 90 seconds
0.5 to 1.0 µg/kg IV x 10 minutes
Remifentanil Maintenance
0.25 to 1 µg/kg IV or 0.005 to 2 µg/kg/min IV
Remifentanil S/E
Seizure-like activity
N/V
Depression of ventilation
Decreased BP and HR
Hyperalgesia d/t
Previous acute exposure to large opioid doses
Tolerance
Hydromorphone potency
5x more potent than Morphine
Hydromorphone dose
Dose 0.5 mg IV ->1 to 4 mgs total
Re-dose every 4 hours
Codeine Elimination half time
3 to 3.5 hours
only PO or IM
Codeine as Cough suppressant dose
15 mgs
Codeine Analgesia dose
60 mgs (120 mgs = 10 mgs of Morphine)
Tramadol potency
5 -10x less (morphine)
Tramadol receptor
µ with weak κ & δ
Tramadol dose
PO: 3 mg/kg
Interacts with Coumadin
Which pharmacokinetic category best describes onset of action
effect site of equilibration
