Local Anesthetic Flashcards
Local/regional anesthetics:
SNEIS: These are drugs used to prevent or relieve pain in specific regions of the body without loss of consciousness Reversibly block pain sensation by blocking nerve conduction 1. Surface /Topical 2. Nerve, Regional or Field/Conductive 3. Epidural 4. Infiltration 5. Spinal/Intrathecal
Amides and Esters
3 parts
Lipophilic: benzene ring
Intermediate
hydrophilic (lipophobic)
all amides have ____ while all esters have _____
2 i’s, 1 i
Esters have a half life of _____ metabolized by _______, while Amides have a half life of _____ and are metabolized by _____
seconds to minutes, plasma esterases, hours, microsomal p-450 enzymes in the liver
LAs are favored by:
depolization, open or inactivated Na channels, frequent impulses
LAs prefer to act upon:
rapidly-firing nerves, so-called “state-dependent blockade” so it is better to have the patient move their arm while you give them the numbing agent
the three types of nerve fibers are :
A (alpha, beta, gamma, delta) B, and C (Dorsal Root and Spinal thalamic)
The C fibers are ____ and ____ size is _____
smallest, both unmyelinated, and DR>Sym
The B fibers are _______ and are _____
myelinated, and are preganglionic autonomic fibers
the A fibers are ______ and the order is:
myelinated, proprioception>motor>touch/pressure>muscle spindles>pain and temp
S a mple Q: You just finishe d pla cing a S A B (spina l) in a 68 y o ma le for a urologic proce dure using 0.5%
bupivacaine. Which of the following is true concerning the sequence o f blockage by the local
anesthetic?
a ) S y mpa the tics > pa in > te mpe ra ture > touch > pre ssure > motor
b) S ma ll unmy e lina te d > sma ll my e lina te d fibe rs > la rge unmy e lina te d fibe rs> la rge my e lina te d fibe rs
c) A -fibe rs> B -fibe rs> C -fibe rs
d) A ll of the a bov e
A ns we r : A : C -S y m –> C -D R –> D e lta –> B e ta –> A lpha
(Sy m pa the tic ne r v e s , C ty pe fibe r s , a r e v e r y s m a ll)
- LA ‘s like myelinated fibers. LA ‘s also like small fibers.
- Small a regenerally blocked before large fibers.
- Size predominates over myelination.
S ympathetics > P ain > Temp > Touch > Pressure > Motor
(S- PT T P- M
Cha nne ls c a n e ithe r b e o p e n, c lo s e d o r
s o m e whe r e in b e twe e n.
This means that active channels (during use /AP propagation) are easier to block. In theory, if you wanted to block the brachial plexus the bes t thing to do would be to have the patient move their arm around while you administer the anesthesia (this is not done in practice ) because you want the channel to be in the depolarized state
at low pH, the LA does not work because:
it stays ionized and cannot cross the membrane (it is protonated )
A t a hig h p H, the LA will c r o s s the m e m b r a ne (unio niz e d
f o r m = m o r e l i p i d s o l ub l e ), b ut wi l l no t g a i n a f r e e H+ i o n
a nd wi l l no t b i nd the Na + c ha nne l s s o i t wi l l no t wo r k
e i the r .
will c r o s s the m e m b r a ne (unionized form = more lipid soluble ), but will not gain a free H+ i o n
and will no t b i nd the Na + channels s o it will not work
either .
The c lose r the ______ the more rapid the onset tim e . (pKa is the pH a t whic h ionized and unionized forms exist in equa l c onc e ntra tions ).
pKa of the LA is to tissue pH,
adding a vasoconstrictor:
epinephrine:
fingers, nose, penis, toes, using LAs are a no-go!
vasoconstriction:
slows the rate of systemic absorption, therefore a larger amount can be added to solution
Ester LAs - metabolized by
plasma esterases.
Amide LAs - metabolized (N-dealkylation and hydroxylation) by
microsomal P-450 enzymes in the liver.
Potency correlates with solubility, which in turn reflects the ability of LAs to permeate lipid membranes.
LAs are ______, with pKa’s ranging from ______.
weak bases 7.6 9.0; Both the ionic (protonated) and anionic forms are present at physiologic pH. Only the non-anionic form can cross the membrane and gain access to the intracellular domain of the Na+ channel. A low pH (acidotic environment) favors the ionized or ineffective form of theLA. Thus, it won’t work!
LAs bind a specific region of the α subunit and inhibit voltage-gated Na channels, preventing channel activation and the Na influx associated with membrane depolarization. LAs preferentially bind to the open Na+ channel; LAs prefer to act upon rapidly-firing nerves, so-called “state-dependent blockade.
Both the ionic (protonated) and anionic forms are present at :
physiologic pH.
Only the non-anionic form can cross the membrane and gain access to the
intracellular domain of the Na+ channel.
A low pH (acidotic environment) favors the
ionized or ineffective form of theLA. Thus, it won’t work!
LAs bind a specific region of the α subunit and
inhibit voltage-gated Na channels, preventing channel activation and the Na influx associated with membrane depolarization.
LAs preferentially bind to the
open Na+ channel; LAs prefer to act upon rapidly-firing nerves, so-called “state-dependent blockade.
