local anesthetics Flashcards
Local anesthetics are the most important drug group in dentistry.
• All local anesthetics in use today share similar chemical structures
and can be categorized as being either _ or _
esters or amides.
local anesthetics mechanism of action is by blockade of the propagation
of peripheral nerve impulses through binding to their receptor
within _ channels.
• Their duration of anesthetic action is determined by _, not metabolism.
• Most local anesthetics cause vasodilation, necessitating addition of
a vasoconstrictor to provide appropriate duration of action for use
in dentistry.
•
sodium channels.
duration - redistribution
away from the site of action
local anesthetics
The most common adverse reaction is _ in nature,
manifested as syncope.
• Toxicity can occur with excessive doses or by intravascular
injection.
• Pediatric patients are most susceptible to overdose.
psychogenic
Henderson-Hasselbalch - redux
rules:
1) acid form has a proton that is lacking in the basic form - One more positive charge in the _ form compared to the _ form so
2) either the _form is negatively charged OR the _ form is positively charged.
acid form has a proton that is lacking in the basic form - One more positive charge in the ACID form compared to the BASICform so
2) either the BASIC form is negatively charged OR the ACID form is positively charged.
if the pKa is close to 7 (like most local anesthetics) what is the distribution of the acidic and basic forms of the drug
something close to 50-50 at pH 7.4
both forms being represented
it is essential that local anesthetics cross the neuronal membrane (and the _ form of a local anesthetic facilitates this). Once inside, it is the _ form of the local anesthetic that blocks axonal conduction.
Thus, both forms of the anesthetic must exist at physiological pH and local anesthetics are _ based with a pKa close enough to the physiological pH(7.4).
basic- to cross membrane
acidic - blocks axonal conduction
amine based
we need uncharged molecule to cross and then become charged when inside the cell (acidic form inside)
Local anesthetics are Amides. At physiological pH(7.4) they are in equilibrium so that both the basic form and the acid form are represented
_ form crosses membrane
_ form blocks Na+ channels
Basic form crosses membrane
Acidic form blocks Na+ channels
General structure of the local anesthetics
3 important components
_- renders the local anesthetic lipophilic
_- linkage, where hydrolyzes takes place
_- furnishes water solubility.
aromatic group - benzyl ring stucture - lipophilic
ester or amide linkage - the esters (-COO-)(more allergenic) and the amides (-NHCO-)(favored) .
amine group = water solubility secondary and tertiary, no quat because can’t cross membranes
Local anesthetics with an _ linkage will be hydrolyzed by pseudocholinesterase and have a very short half life in the plasma
Local anesthetics with an _ linkage will be metabolized by P450 enzymes in the liver and have a longer half life in the plasma.
Esters are generally more allergenic.
Amides will have an ‘i’ in their name somewhere prior to ‘caine’ (e.g. lidocaine). Esters won’t (e.g. procaine).
The local anesthetics favored in dental practice are _ .
ester - pseudocholinesterase - short 1/2 life
amide - P450 - liver
amides are favored in dental practice - stick around a little longer
General structure of the local anesthetics:
Primary, secondary and tertiary amines will exist in equilibrium between basic and acidic forms (Local anesthetics used in dental practice are _ and _ amines).
The uncharged basic form will cross cell membranes. We will see that local anesthetics produce their block from the ‘_’ of the nerve. Therefore, the ability to cross the membrane is an essential property.
Once inside the nerve, the charged acidic form will bind better to the Na+ channel and inhibit conduction of the nerve impulse.
Thus, the acidic and basic forms are both important to the functioning of the local anesthetic
secondary or tertiary (number of carbons)
from the inside of the nerve
Molecular Mechanism of Local Anesthetic Action
site?
Local anesthetics cross the axon membrane and interact with the _ and _ forms of the Na+ channel, blocking Na+ conductance. They are not effective outside the axon.
site - Voltage sensitive states of the Na+ channel
open and inactivated forms of the Na channel
Both the ionized (_ and non-ionized (_) forms of a local anesthetic are important
Basic form crosses membrane
Acidic form blocks sodium channel
Both the ionized (acidic) and non-ionized (basic)
