Flashcards in Local Anesthetics Deck (18):
Chemically, local anesthetics are weak ________.
Describe the basic structure of lidocaine and the other local anesthetics.
The have a benzene ring with methyl groups on either side of the active chain (usually). The active chain is either an amide or ester (the variant determines its pharmacokinetic properties) with an amine group at the terminus of the chain.
Dissecting the names of local anesthetics, what can you learn about the chemical structure of local anesthetics?
Amides have two Is (so lidocaine is an amide), while esters have only one (so cocaine is an ester).
As the pKa of local anesthetics goes up, the fraction that is effective is __________.
decreased; this happens because local anesthetics are weak bases, and plasma has a pH of 7.4. Thus, drugs with higher pKas will have a higher fraction of ionized form (the form that is not able to be distributed to neurons)
The gates in voltage-gated ion channels are on which side of the cell membrane?
The inside. They're often drawn on the outside, but this is incorrect.
Broad strokes: the local anesthetics that have _____________ will be more potent and longer-lasting.
lower pKas, higher lipid solubilities, and greater protein binding
Why does protein binding lead to longer-lasting effect?
Because the protein acts as a buffer that allows the drug to be released over time, which slows its metabolism
Do not use __________ local anesthetics in patients with hepatic insufficiency.
amides (because these are metabolized only in the liver)
Why is epinephrine co-administered with many local anesthetics?
With the exception of cocaine, most local anesthetics are sympathetic antagonists; as such, they will induce vasodilation. Vasodilation is an undesired state in giving local anesthetics, because it increases the likelihood of systemic effects. Giving epinephrine induces vasoconstriction and prevents some leakage of anesthetic into systemic circulation. This also prolongs the anesthetic effect.
Why is tetrodotoxin a poor anesthetic?
It binds extremely well regardless of activity of the channel. Thus, it lacks the selectivity of the local anesthetics (which, you'll recall, are use-specific and preferentially target channels that open frequently).
Local anesthesia results from block of ____________.
action potential conduction or initiation
How do the synthetic counterparts of cocaine differ from cocaine?
They are not able to inhibit the reuptake of catecholamines
Local anesthetics stabilize the _____________ state of voltage-gated sodium channels.
____________ are preferentially blocked by local anesthetics.
Small-diameter axons (such as C fibers)
Amide anesthetics tend to have ____________ duration of action.
longer (because a higher percentage is protein-bound)
What is different about tetrodotoxin (compared to local anesthetics)?
It binds the extracellular entrance to the protein pore, with a special preference for the NMJ – resulting in respiratory paralysis.
Toxicity of local anesthetic depends on the varying levels of _______________.