Unit 3 - Local Anesthesia Flashcards
what is the definition of local anesthesia?
drug-induced reversible blockade of pain sensation in a specific part of the body that doesn’t alter consciousness or block sensation in other parts
what are the ideal properties of local anesthetics?
- fast onset
- minimal absorption
- minimal distribution
- predictable and reversible action
- large margin of safety
what are the three parts of local anesthetics?
- aromatic ring (lipophilic portion)
- intermediate linkage (ester or amide)
- terminal amine (hydrophilic portion)
what is the aromatic ring/head of local anesthetics the primary determinant of?
lipid solubility, potency, and duration of action
- highly lipid soluble anesthetics are less likely to be cleared by blood flow and have a high degree of plasma binding, so elimination is prolonged
- greater lipid solubility enhances diffusion through nerve sheaths and neural membranes of individual axons which commprise a nerve trunk
- potency and lipid solubility increase with size
what is the middle part of a local anesthetic?
ester or amide link (creates the 2 classifications)
what are ester anesthetics metabolized by? examples? limits?
old fashioned
- metabolized by plasma esterases (but some patients have slow and fast metabolism)
- ex: cocaine, procaine, benzocaine, chloroprocaine, tetracaine
- limits: allergic potential and short duration
what are amide anesthetics metabolized by? examples? limits?
newer ones; maxed desirable properties (longer duration and sooner onset of action)
- metabolized by hepatic amidases
- ex: lidocaine, mepvivocaine, bupivicaine, etidocaine, prilidocaine, ropivicaine, dibucaine
- limits: less than esters
what does the terminal portion of a local anesthetic determine? types?
determines onset of action and how quickly it can cross a membrane
- can be tertiary form (lipid soluble) or quaternary form (positively charged, water soluble)
- depends on pKa and tissue pH (how much is converted to lipid soluble form)
- -RNH- RN + H+
what state is a local anesthetic in when injected? which part is active?
water soluble
- charged part is active, but then can’t cross lipid cell membrane
- much change to uncharged form to become lipid soluble
- time for onset is thus determined by how much of it converts to lipid soluble form when exposed to physiologic pH
what is the ideal pKa of a local anesthetic? what is actually the case?
- ideal is 7.4, so that 50% of the molecular structure outside the cell is uncharged, and rapid diffusion across the lipid bilayer could occur
- actual are much higher, causing lower concentration of diffusable form in injection, and longer time for local anesthetic to take effect
what does the pKa of a local anesthetic determine?
how much of it is in a diffusible form on injection, and thus determines time of onset
-higher the pKa –> lower concentration of uncharged (diffusible) base, longer it takes to work
what happens to local anesthetic in an acidic environment? example?
pushes equation to left (RNH+), thus making less of diffusable form available, and slower onset of effect
- much of LA may be metabolized or taken away by circulation before it converts to lipid soluble form
- more ionized form is available, so less unionized form can diffuse
- ex: abscesses
what happens to local anesthetic in an basic environment?
shifts equation to right (RN + H+), thus making more unionized diffusible form available to cross membrane
- faster onset of block
- ex: C-sections (mix with Na bicarb)
recall what the concentrations of sodium and potassium are in the resting neuron?
more sodium outside the membrane (positive charge) and more potassium inside the membrane (negative charge)
how do local anesthetics affect action potentials?
bind to and block intracellular portion of inactivated voltage gated Na channels, thus blocking conduction
-LA reduces Na influx and K+ efflux, thus inhibiting depolarization along nerve
