physical properties of local anesthetics
- weak bases
- lipophilic group (usually a benzene ring)
- hydrophilic group (usualy a tertiary amine)
- these groupas are connected by a ester or amide (this is the classifying factor)
differentiating amides and ester LA’s
- amides have 2 “i” in there generic name
- esters have 1
metabolism of esters
- metabolized by plasma/pseudocholinesterase which is found in the blood
- short systemic half life of about 1 minutes
- degraded into p-aminobenzoic acid
metabolism of amides
- metabolized by the CYP450 enzyme in the liver
- elimination half life is 2-3 hours
- N-dealkylation of amide link via hydrolysis
LA effect on action potential
- impairs the porpogation of action potential
- rate of rise of action potential is decreased, the threshold is not reached
- no effect on the resting or threshold potential
LA cellular effect
- when in an uncharged state (unbound from a H+), the LA will move into the neuron by crossing the lipid bilayer
- once in the neuron, it binds a H+ and becomes charged again
- this allows the anesthetic to block the Na+ channel thereby blocking the propogation of action potential
local anesthetics work better in a “blank” environment
-basic
the pka of the acid to closely associated with
- the onset of action
- the closer the LA’s pka is to physiological pH, the faster the LA will act
- however, a higher pH of LA solution, the faster the onset as well
lipid solubility of the LA is associated with
- LA potency
- this is related to their abiility to cross nerve membranes easily
LA protein binding is most closely associated with
- duration of action
- higher protein binding increases duration of action
- they say that this is due to the binding reducing the ability of the blood to wash away the anesthetic but the prof said that this is probably wrong
lidocaine duration of action
-short acting
etidocaine duration of action
-long acting
blocking unmyelinated verus myelinated nerve fibers
myelinated are easier to block
-LA gets concentrated at a node and stops the action potential right there
clinical effects of LA’s
- sympathetic block (vasodilation, skin temp)
- loss of pain and temperature sensation
- loss of proprioception
- loss of touch and pressure
- loss of motor function
order of clinical effects when giving LA
- sympathetic blockade
- sensori blockade
- motor blockade
- this have to do with how deep the nerves are within the nerve bundle
Neuro (tissue) toxicity of LA’s
- rare but can occur if the concentration rises too high in a muscle
- in high concentrations, these are directly neurotoxic and inhibit nerve growth
- TRI or TNS are clinical syndromes of local toxicity following intrathecal injection of LA in clinical doses
systemic toxicity of LA
- presence of toxic LA levels in the blood either due to IV injection or massive absorption
- CNS toxicity occurs before respiratory arrest and cardio tox
symptoms of CNS tox
- metallic taste in mouth
- tinnitus
- light-headedness
- numbness of lips and tongue
- muscle fasciculations
- LOC
- seizures
- coma
CVS symptoms of tox
- negative inotropy
- refractory cardiac arrhythmias
- loss of vasomotor tone
- CV collapse: often difficult to treat
- exacerbated by acidosis, hypercarbia, hypoxia
- narrow therapeutic margin for bupivaccaine
fact about bupivicaine
- narrow therapeutic margin
- we do not give 0.75% solutions to pregnant women becasue of the increased risk for maternal cardiac arrest
LA tox and pregnancy
- more sensitive to bupivicaine
- less LA produces hypotension, resp arrest, and circulatory collapse
treatment of systemic LA tox
- apply oxygen: low oxygen worsens the effects
- hyperventalate (make blood more basic): acidosis and hypercarbia worsen effects of LA tox
- intrralipid 20% IV solution: seperats the LA from the sodium channel and binds it, works as a lipid sink and facilitates cario pulmonary resuscitation
benzocaine
- topical agent only
- oxidizer that can induce methemoglobin if it is used systemically
prilocaine
- metabolized to ortho-toludine
- ortho-toludine can oxidize hemoglobin to methemoglobin
- may occur in prilocaine doses greater than 600mg
