Local Anesthetics Flashcards
definition of local anesthetic
an agent that reversibly prevents transmission of nerve impulse in the region to which it is applied, without affecting consciousness.
what was the first local anesthetic?
cocaine
ion levels in intra and extracellular fluid
intracellular fluid has an abundance of potassium ions, while extracellular has an abundance of sodium ions
what is the charge of the interior of a neuron
negative
how do nerves conduct?
opening of voltage gated Na channels transiently, Na rushes into cell and depolarizes. Na channels close, and then voltage gated K channels open resulting in repolarization. Both K and Na channels close resulting in resting state.
preemptive analgesia
nerve block is performed prior to the incision
where do local anesthetics bind?
reversibly bind to the intracellular portion of sodium channel and inactivate the channel. as more and more sodium channels are blocked, more action potential is needed to send a nerve impulse. eventually impulse is completely blocked
resting state
during the resting nerve period, where there is an absence of stimulus. no sodium is moving
active state
starts immediately on depolarization. sodium is moving and gates are open
inactivated state
refractory to repeat stimulus. repolarizing is happening to bring you back to resting state.
is blockade of sodium channels voltage dependent, time dependent, or both?
both! effects are more marked in an activated state rather than in a resting or inactivated state. therefore, the effect of drug is more marked in rapidly firing axons
greater lipid solubility = ?
greater potency. need to be lipid soluble to pass through the nerve sheath!
esters mechanism
hydrolyzed by enzyme in plasma, pseudocholinesterae. rapid metabolism to water soluble metabolites. genetically abnormal pseudocholinesterase exists, causing long lasting ester effects. CSF lacks the enzyme.
amides mechanism
transformed by hepatic carboxyl esterases and CYP-450 enzymes. slow metabolism. liver disease may lead to accumulation and toxicity. low hepatic blood flow can lead to prolonged effects
terminal amine
can be tertiary form (lipid soluble) or quaternary form (water soluble). acts as on-off switch allowing the local anesthetic to exist in either lipid soluble or water soluble conformations
what does onset of action depend on?
depends on what percentage of the drug exists in the active ionized form
how do you get drug to exist in ionized form?
the greater the difference between pKa of a drug and pH of the body fluid, the more the drug will exist as ionized form and will not be able to penetrate membranes. this makes it less potent
pain is transmitted by what types of nerve fibers?
A delta and C. C is non-myelinated
rank the types of nerve fibers from fast to slow and diameter
A alpha, A beta, A delta, C. works for speed and diameter
are proximal or distal fibers blocked first
proximal
what does absorption of local anesthetics depend on ?
site of injection (vascularity), dose of drug, drug’s intrinsic properties, addition of epinephrine (reduces blood flow around injection site)
cauda equina syndrome
reported with continuous spinal catheters and high dose lidocaine usage. severe back pain in the setting of motor deficit, sensory deficit, and loss of bowel/bladder control
transient neurologic symptoms
transient pain or dysesthesia linked to the use of lidocaine for spinal anesthesia. not related to dose. increased risk with certain positions. increased risk with ambulatory anesthesia. found with procaine and mepivacaine, bot not bupivacaine or chlorprocaine
what drug has worst side effects
bupivocaine