M & M CH 16 Local Anesthetics Flashcards
Na channels exist in at least three resting states
Resting (nonconducting)
Open (conducting)
Inactivated (nonconducting)
What are the subunits of Voltage-gated sodium channels
One large alpha subunit
One or two Beta subunits
Sensitivity of nerve fibers to inhibition by LAs is influenced by
Axonal diameter
Myelination
And other factors
LA potency correlates with
Octanol solubility
Ability for LA to penetrate lipid membranes
(T/F) Adding large alkyl groups to LAs decrease potency
FALSE it increases potency
(T/F) LA potency can be measured with MAC (minimum alveolar conc.)
FALSE no clinical measurement of LAs potency that is comparable to MAC exists
Factors that affect onset of action of LA
lipid solubility
relative conc of the nonionized (free-base) form (B) and the ionized water-soluble form (BH+)
The pKa is the pH at which there is an ____
fraction of ionized and nonionized drug
equal
What is the significance of the pKa in LA?
pKa represents the pH at which there is an equal fraction of ionized and nonionized drug
*plays a crucial role in determining the onset of action.
Mepivacaine and Lidocaine have (faster/slower) onset than more potent more lipid-soluble agents like ropivacaine or bupivacaine
Faster
*lipid soluble agents have a longer DOA but slower onset of action bec they slowly diffuse from lipid rich environment to aq. bloodstream
How do less potent and less lipid-soluble LAs compare in terms of onset?
Less potent and less lipid-soluble LAs have a faster onset compared to more potent, more lipid-soluble LAs
What determines the elimination and toxicity of local anesthetics in the blood?
pharmacokinetic profiles of LAs in blood are important in determining their elimination and toxicity.
Rank order of LA conc in blood and absorption r/t vascularity of site of injection
intravenous (or intraarterial) > tracheal > intercostal > paracervical > epidural >
brachial plexus > sciatic > subcutaneous
Which injection site has the highest systemic absorption?
Intravenous (or intraarterial) injections
Ester LAs are metabolized by
pseudocholinesterase
Amide LAs are metabolized by
(N-dealkylation and hydroxylation) by microsomal P-450 enzymes in the
liver.
(T/F) In awake pt’s, rising LA conc in CNS produce signs of LA tox
True
(T/F) Major cardiovascular toxicity usually requires about three times the
local anesthetic concentration in blood as that required to produce
seizures
True
Intravascular injection of this LA can cause cardiovascular toxicity. Including left
ventricular depression, av heart block, v-tach and v-fib
Bupivacaine
Hypersensitivity RXN’s (w/IgG & IgE) to LA are uncommon but can occur with
Ester compounds (i.e. procaine, benzocaine)
*PABA derivative compounds
resting membrane potential
-60 to -70 mV
transport of three sodium (Na) ions out of the
cell for every two potassium (K) ions it moves into the cell
sodium–potassium pump
(Na+-K+-ATPase)
creates a conc gradient that favors movement of K ions from intracellular to extracellular and movement of Na ions in opposite direction
sodium–potassium pump
(Na+-K+-ATPase)
(T/F) cell membrane is much more “leaky” to Na
ions than to K ions, so a relative excess of negatively charged ions (anions)
accumulates intracellularly.
FALSE
There are more “Leaky” K ions than Na ions
*combined effects of Na+-K+-ATPase and K
ion leak account for the negative resting membrane potential