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local anesthtics can reversibly block generation and propagation of nerve impulses in ALL excitable cells.
True, any sodium channel may be blocked
gate control theory
rub your arm after stubbing toe
Is pain an unpleasant sensory AND emotional experience with actual or POTENTIAL tissue damage
what are the two aspects of pain?
sensory and affective(escape threshold-varies, reaction, variable, unpleasnatness)
what are the processes (4) involved in pain experience?
transduction, transmission, modulation, perception.
physical to electrical
peripeheral to CNS
attentutaiton of pain info
actual pain experience
potentially tissue damaging thermal or mechanical energy on Adelta or C fiber nerve endings.
pain from the head
do not go through spinal cord, jus thte trigemeinal nerve
what nerve does local anesthesia hit?
nerve endings at the local site the lower neuron before it crosses over.
diff b/t facial and trigeminal
pain in different areas of the head
- main sensory info- sensory nucleus
- pain info- spinal nucleus caudalis
- proprioceptive info- mesencephalic nucleus
somatotropic info from dermatomes
slide 19, area 1 mouth at the first segment
what segment is not innvervated by CN V
types of LA
- infiltration-injected into an area to be treated
- regional nerve block- injected close proximity to nerve supplying the area to be anesthesized
injected in CSF in lumbar subarachnoid space (sugery of lower body)
injected into epidural space, spinal anestheisa but less likely to accidently rise to high segment
injected into venous system of a limb, distal to point of circulation, DISTAL to the point of ciculation
tratment of pain cause of reflec symp dystrophies for intractable pain (carminoma of pancrease or upper abdomen)
- stellate gangion- upper arm, head, neck
- celiac pleus- pancreas pain
- lumbar symp- lower legs
what receives signals
are myelin sheaths in periphery called
what is the membrane that surrounds nerves?
oligodnedrocytes in CNS surround/....
more than one axon is wrapped
which peripheral fibers to nerves are fast?
- larger the diameter Aaphla
- alpha delta
- c fibers are the slowest smallers diameter (1 m.sec)
C is unmyelinated (dull throbbing pain)
peripheral nerves are mixed with diff types of fibers
voltaged gated channels depend on the membrane potentia. What are the three diff states?
closed, open, inactive
what is the structure of local anesthetic?
lipophillic, amlide/ester, hydrophillic
what form crosses the membrane and what form blocks the sodium channel?
non-ionized and ionized
How do LA work on blocking impulse conduction
- inhibit sodium channel
- decrease rate and degree of depolarization
- failure to achieve action potential
LA are weak bases pKa>7.4. What does onset depend on?
pKa 50% of drug is ionized and only the nonionized form crosses into the nerve membrane
which has a faster onset? Lidocaine or bupivacane
- Lidocane because lower pKa
- acidic tissue b/c of bacterial infection has slow entry into membrane
what doe anestheitc potency depend on?
lipid solubility. Higher solubility can use lower concentration
what does duration of action depend on?
what does clearnace depend on?
- esters--hydrolysis via pseudocholineeserase
- amides via hepatic enzymes
are amides or esters more likely to be toxic?
amides(but stable chemially and faster onset of action)
LAs cause.....at local site.
- washout related to bldflow
vasoconstrictors are least effective when....
high lipid soluble LAs
LA effect on nerve fiber higher concentration for..
- position (easier to get mantle fibbers)
- Core fibers innervate distal nerves
what sensations are lost first?
- 1. pain/temp
- 2. proprioception
- 3. touch/pressure
- 4. motor function
during which phase are sodium channels converted from inactive to close?
rapid depolarization closes the....
how many subunits does the sodium receptor channel have?
4 alpha subunits
inactivation gate is the
pore is b/t
LA mode of action
LA bind to Na channel, the h gate actually closes, trapping the anestheic inside the channel.
LA possible mechanism
close...open...inactivated via h gate closing
LA will not inhibit permeability to Na.
LA can cause elevation of threshold and sowing of spread of conduction. Only occurs at nodes in mylination
What is 'critical length'?
A critical length needs to be covered for the blockade to occur
the smaller the nerve
the easier to block.
3 nodes of ranvier
LA action can be increase by repeated stimulation of nerve fiber because
- LA gaining more access to a binding site and having a greater affinity for it.
- Known as "use-dependent block or phasic block'
Toluidine and Thiophene derviatives(amides)
Prilocaine and atricane