4.5 Local anesthetics Flashcards
Local anesthetics
reversible loss of sensory perception, spedcifically of pain, in a restricted area of the body upon local injection or topical application, blocks the generation and conduction of impulse at all parts of neuron where it comes in contact, abolishes sensory and motor activity in a limited area without producing unconsciousness
local anesthetic structure
weak bases and have 3 structural domains. Hydrophobic (lipophilic group)–aromatic residue, hydrophilic group–amine, both are linked by ester or amide bond
LA block
Na channels, prolonging the inactivated state –> inhibit further activation, inhibit propogation of impulse through the nerve
LA suffix
caines
LA has a hydrophobic domain so
it enters cell
two types
ester local anesthetics or amide local anesthetics
ester local anesthetics
benzocaine, cocaine, procaine, chloroprocaine
amide local anesthetics
bupivacaine, lidocaine (most common), prilocaine, mepivacaine, ropivacaine
ester lined LA have
shorter duration of action (metabolized by cholinesterases), less intense analgesia, higher risk of hypersensitivity — hense rarely used for infiltration or nerve block, but are still used on mucous membranes
amide linked LA have
longer duration of action, more intense analgesia, less risk of hypersensitivity, no cross sensitivity with ester lined Las
LA short duration
Procaine, Chloroprocaine
LA intermediate duration
Lidocaine, Prilocaine, Mepivacaine
LA long duration
Bupivacaine, ropivacaine
Surface anesthetics (LA)
cocaine, lidocaine, tetracaine, benzocaine, oxetacaine (oxethazaine)
LA can be produced by cooling such as
application of ice, CO2 snow, ethyl chloride spray
Mechanism of LA
block nerve donduction by inhibiting voltage gated Na channel keeping it in the inactive form, increasing the thresholed for excitation and refractory period is prolonged. Las interact with the receptor situated within the voltage sensitive Na channesl and raise threshold of channels opening, i.e. Na permeability fails to increase in response to an impulse or stimulus (pain) 50-100X duration of normal closure
LA entry and binding
in basic environment, drug is non ionized to enter the cell, then inside the cell it has to be ionized again bc cell is a little acidic and the ionized form binds the receptor, binds at the activated and inactivated state but not in resting state (more the inactivated) on its inner aspect, hence blocks sodium current and slows recovery and propagation of action potentials —use dependant block –the more the channels are used the more will be the block
Modulated Receptor hypothesis
the different states of Na channels bind LA with different affinities –Las have higher affinity for the open and inactivated states than for the closed state —used dependent block—thus a resting nerve is rather resistant to blockade, and the block develops rapidly when the nerve is stimulated repeatedly
Tetrodotoxin/Saxitoxin
block Na outer gate
Scorpion venom
prevents inactivation causing massive depolarization
LA actions on nerves
blockage not only limited to loss of pain sensation, sensory and motor nerve fibers (high conc.) are both sensitive to LA, somatic as well as autonomic nerves are blocked – spinal anesthesia
blockage of autonomic nervsou system
motor n. block–>respiratory paralysis; autonomic block –>hypotension
sensitiveity of the nerve fiber ti the blockade is determine dby
the diameter and mylation of the fibers, smaller fibers are more sensitive than the larger fibers, non-mylinated fibers are blocked more easily than myelinated fibers –> differential functional blockade
small fibers blocked first
B and C > Adelta
block of modalitties
pain sensation first than other modality
fibers with high firing rate
more marked block
actions on modalities
sensory>motor. Adelta > A alpha
order of sensitivity to LA
B and C> A delta> Abeta and A gamma > Aalpha —- recovery in REVERSE order
block of autonomic fibers by LA
more succeptible than somatic fibers
somatic afferent blockade order is
pain-temperature-touch-deep pressure (differential blockade)
LA applied to tongue
bitter taste is lost followed by sweet and sour, and slaty taste last of all
nonmylinated and small diameter fibers
more intensely blocked – type B and C –pain and autonomic (slide 27)
nonionized part
responsible for crossing the lipid membrane
ionized part
responsible for binding to specific Na channel
absrobtion
most surface anesthtics are absorbed from the mucosa membranes and abraded arease—absorption through intact skin is poor
Ester linked LA metabolism
rapidly hydrolyzed by plasma pseudocholinesterase and the remaining by esterases in the liver,
after oral admin, both procaine and lidocaine
undergo extensive first pass metabolism so wont give orally, give thorugh IV
Amide lined LA metabolism
are degraded mainly in the liver by microsomal cyp-450 (dealkylation and hydroxylation)
Absorbpion dependent on
dosage, site of action, drug tissue binding, vasoconstrictor used
Epinephrine/Phenylephrine
LA causes vasodialation so some amount can be absorbed and less drug will be available at the site of cation so you need more frequent administration to provide the persistent pain control—so using EPI will decrease absorption allwing more neuronal uptake and more anesthesia, so less is required bc more amount of drug remains in the tissues, leading to decrease in systemic toxicity —>provides a relativley bloodless field for surgery
EPI/Phenylephrine actions with LA
prolongs the duration of anesthesia bc more of drug will remain in tissue, reduces the requirement of LA, and reduces the systemic toxicity of LA
Combination contraindicated in
end artery orgains – fingers, toes, pinna, tip of penis—never use vasoconstirtors with end artery organs
