Local Anesthetics Flashcards
local anesthetcis
a drug that temprarily eliminates sensation, especially pain, at a specific site when they are locally applied without affecting consciousness
sodium channel as the primary means of action potential generation, block is reversible
chemistry of local anesthetics
contain hydrophobic and hydrophilic groups
hydriohobic aromatic ring
hydrophilic group defines the pKa of the molecule
ester or amide linkage determines the mode of metabolic degradation
benzocaine
exception to general formula of local anesthetic
no terminal amino group
always neutral, uncharged because it has a pKa of 3.5
only used for topical anesthesia
alkyl substitutions of anesthtics
enhances potency dramatically
does not increase therapeutic index
intrinsic properties that affect local anesthetic action
lipid solubility of a local anesthetic affects ability to cross membrane and related to potency
pKa of a local anesthetic important as well
pH of local anesthetic and function
alters the ratio of the uncharged to charged form
uncharged neutral form penetrates the membrane
charged cationic form blocks the Na channel
Explain how the charged and uncharged form of a local anesthetic acts in the body.
uncharged form helps drug diffuse into axons where the charged form can act on the cytoplasmic side of the sodium and potassium channels
the effects of pH on local anesthetic action
local anesthetics have higher pKa so a greater pH will lead to more ions being trapped in the site of action
What happens after repetitive injections of local anesthetic?
decreases local anesthetic action because the tissue buffer capacity is reduced
What part of the action potential do local anesthetics block?
sodium channels responsible for the upstroke
What is the role of the alpha subunit of the sodium channel?
forms the pore of the channel, receptor for local anesthetic
fourth transmembrane segment senses voltage
What is the role of the beta subunits of the sodium channels?
modulates expression and channel functions
use-dependent block
repetitive depolarization enhances sodium channel blocking action by lidocaine
this is because binding site is only accessible when the channel is open, so repetitive stimulation opens the channel more often and enhances the local anesthetic block
frequency-dependent block
an increase int he frequency of repetitive activity enhances the extend of use-dependent block
less drug molecules escaping form the channel when the inter-pulse interval is short
significance of use- and frequency- dependent block of Na+ channels
high frequency of firing enhances the block
membrane potential-dependnt block of local anesthetics
the avialability of Na channels decreases when the membrane is depolarized
curve is shifted to the hyperpolarizing direction by local anesthetics, increasing the effectiveness of the block
ex. in damaged tissues there are fewer channels, so the block is more effective
differential nerve block
the phenomenon that different nerves and biological resposnes are blocked at different rates when local anesthetic is applied
factors that influence differential nerve block
size of the nerve fibers - smaller fibers more sensitive
myelinated vs. unmyelinated fibers of the same size - myelinated fibers more sensitive
firing frequency - snesory fibers fire at high frequency, enhancing block
anatomical arrangement - circumferentially located fibers are blocked first
size effects on nerve block
large fibers have smaller surface-to-volume ratios than small fibers
also large fibers take longer to be saturated with anesthetic, so when the drug is washed off, the large fibers recover faster
critical exposure length for blocking of myelinated fibers
three consecutive nodes of Ranvier must be blocked for suppressing conduction completely
explains why epidural blocks can leave motor function intact but relieve parturition pain, not enough length inhibited for the motor neuron
anatomic arrangment of nerve fibers and anesthetic block
core contains sensory fibers at most distal sites, whereas surface innervates proximal sites
anesthetic placed outside of nerve bundles will anesthetize proximal fibers first before getting to the distal
How are ester-type local anesthetics hydrolyzed?
pseudocholinesterase
How are amide-type local anesthetics hydrolyzed?
metabolized by the liver microsomal P450 enzymes (N-dealkylation and hydroxylation)
para-aminobenzoic acid (PABA)
a metabolite of the ester-type local anesthetics
can be used to compromise antibacterial activity of soulfonamides
antibacterial action depends on blocking folate synthesis from para-aminobenzoic acid
sulfanilamides
structural analogs of PABA, competitively prevents bacterial utilization of PABA to synthesize folic acid
clinical uses of local anesthetics
topical anesthesia
infiltration
regional block
topical anesthesia
used for nose, mouth, and tracheobronchial tree and urethra procedures
also used for cosmetic surgery
benzocaine 20% spray is common
lidocaine/prilocain (EMLA) most commonly used for venipuncture
infiltration
injected under the skin of the surgical site
regional block
injection near a nerve or plexus proximal to the surgical site, which includes spinal or epidural anesthesia
spinal anesthsia - three major sites
spinal nerve block
epidural or peridural nerve block
caudal block
onset is rapid, minimal amount needed
most important derminants of sensory level blockade
baricity of the solution and patient position
lumbar epidural anesthesia
lumbar, thoracic, or cervical levels - most often at the lumbar level
drug is deposited outside the dura, requiring a much larger amount of drug
1:200,000 of epinehprine used in test injection to make sure there is no intravascular injection
What type of anesthetic is used for delivery?
local anesthetics such as chloroprocaine - preferred because it is quickly hydrolyzed by plasma cholinesterase
very little drug reaches the fetus
caudal anesthesia
agent is introduced through the sacral hiatus above the coccyx, useful in perineal and rectal procedures
intravenous regional anesthesia (Bier’s block)
a large volume of local anesthetic is injected into a peripheral vein after circulation is interrupted using a tourniquet
anesthetic is limited to the area and excluded from blood circulation, quickly resolved once circulation is restored
short-acting local anesthetics
ester-type: procaine and chloroprocaine
intermediate local anesthetics
lidocaine, mepivacaine and prilocaine
long-acting local anesthetics
tetracaine, bupivacaine, levobuprivacine, and ropivacaine (mostly amide-type)
factors that influence choice of local anesthetics
method of anesthesia
duration of action
neurotoxicity
allergic reactions
effects of vasoconstrictors on anesthetic function
small quanitites of epinephrine can be added to reduce blood flow
increases duration and reduces risk of systemic toxicity, gives time for blood to clear anesthetic
local anesthetic systemic toxicity (LAST)
always due to excessive blood concentratino of local anesthetics, especially amide-type ones
includes CNS and CV toxicities:
CNS - lightheadedness, dizziness, seizures, etc. treated with GABA(A) receptor-mediated inhibitory response
CV - myocardial depression and vasodilateion, fall in blood pressure
use intralipids to emulsify and decrease blood levels
effects of cocaine
blocks monoamine reuptake
produces euphoric effects due to inhibition of dopamine uptake
causes vasoconstriction and hypertension peripherally due to norepinephrine reuptake inhibition
methemoglobinemia
when heme iron is oxidized from the ferrous to ferric state
hemoglobin is transformed to methemoglobin
does not bind to oxygen, results in functional anemia and hypoxia
caused by the presence of oxidizing agents such as benzocaine and prilocaine
treat with methylene blue IV
allergic reactions to local anesthetics
symptoms such as bronchospasm (sudden constriction of muscles of the bronchile walls) and uticaria (hives)
occur more often with ester-type local anesthetics
caused by derivatives of p-aminobenzoic acid, a metabolite of the ester-type local anesthetics
tetrodotoxin (TTX)
found in puffer fish, selectively blocks sodium channels - reversible block
blocks from axoplasmic side of the excitable membranes
