Ch. 10 Local Anesthetics- Nagelhout Questions
and Answers 100% Solved
*what are the 2 classes of local anesthetics - ANSWER-esters and amides (also have
miscellaneous
*how to differentiate esters and amides - ANSWER-one "i" in the generic name for
esters and two "i"s in the generic name for amIde
first local ever used; what makes this guy so special? - ANSWER-cocaine; naturally
occurring from coca leaf
*for a drug to have local anesthetic properties, what 3 chemical compounds - ANSWER-
1. lipophyllic portion (lipid soluble) usually a benzene ring
2. water soluble portion (the nitrogen containing molecule in the structure)
3. lipid soluble and water soluble portions must be separated by a certain distance and
this is either by an ester or amide chemical chain
*explain the structure of an ester local anesthetic; explain for amide structure -
ANSWER-ester is C==O, O and both the Os are negative (-);
amide is C==O, N where the N is positive (+) and O is negative (-) and brings closer
together and makes harder to break
(== reads as "double bond"
*what is the significance for both the Os being negative in a ester bond - ANSWER-both
negative means they push away from each other and make bond easier to break
(metabolism)
*how are esters metabolized - ANSWER-plasma and tissue cholinesterases via
hydrolysis that occurs throughout the body and is rapid (they are metabolized right in
the tissue they are in bc water and cholinesterase are everywhere)
*what is special about tetracaine? - ANSWER-we mostly used amides. Esters tend to
be short acting, but tetracaine is the longest acting ester we have
talk about what we need to know regarding the esters and amide locals and allergies to
them - ANSWER-local anesthetic allergies are uncommon, yet esters are more
commonly associated with allergies than the amides (99%). if you have an allergy to an
ester, then you most likely have allergy to all the other esters (cross allergy within
class). Though very unlikely, if you're allergic to an amide, then there is no cross allergy
and the other amides will be okay.
, how are amides metabolized - ANSWER-in the liver by CYP1A2 and CYP3A4 (would
take longer than the esters and therefore higher blood levels may develop with rapid
absorption)
between esters and amides, which are shorter acting? why? - ANSWER-esters are
shorter acting because they are readily metabolized by esterases throughout the entire
body and at the tissue where they are injected. amides are longer acting bc they are
more lipophilic and protein bound and require transport to liver for metabolism
why are esters more associated with allergy? - ANSWER-the lipophilic group of ester is
called PABA (paraminobenzoic acid) which is a component of a los of cosmetics and
some food products that we are exposed to. then when get the local they experience
the allergy
what is the MOA of the local anesthetics? - ANSWER-block Na+ channels in nerves.
what happens when you block motor nerve; sensory nerve; autonomic nerve? -
ANSWER-no movement; no feeling; vasodilation or whatever the autonomic function of
that nerve is
how do the local anesthetics block Na Channels? (go through the whole MOA starting
w/ placing local in skin) - ANSWER-local anesthetics outside the body are equal parts
lipid soluble and water soluble. they are weak bases. place local in tissue > depending
on the pH of the tissues and pKa of the drug then some will ionize and some will stay
non-ionized. the non-ionized portion will be lipid soluble and WILL cross the nerve
membrane and enter the axoplasm of the nerve. The ionized (water soluble) portion will
not cross in. Once inside the cell, the non-ionized portion will reach a new equilibrium in
the nerve axoplasm pH. some of the drug will stay non-ionized and some WILL ionize.
this time the water soluble (ionized) portion will go into the sodium channel and attach to
the local anesthetic receptor and block the Na channel.
what determines the ionization of a local? - ANSWER-the pH of the tissue its going in
and the pKa of the drug itself
how does blocking the Na channel cause nerve block? - ANSWER-bc blocking the Na
channel causes inability to depolarize the nerve can't transport action potential
why must local anesthetic have a lipid soluble and water soluble portion? - ANSWER-
needs to be lipid soluble to get into the nerve itself and then needs to use the water
soluble portion to enter the actual Na channel and attach to local anesthetic receptor to
block depolarization and nerve conduction
local anesthetics can't just enter from the outside of the nerve cell and attach to the Na
channel. what is the ONE exception to this rule? - ANSWER-benzocaine
and Answers 100% Solved
*what are the 2 classes of local anesthetics - ANSWER-esters and amides (also have
miscellaneous
*how to differentiate esters and amides - ANSWER-one "i" in the generic name for
esters and two "i"s in the generic name for amIde
first local ever used; what makes this guy so special? - ANSWER-cocaine; naturally
occurring from coca leaf
*for a drug to have local anesthetic properties, what 3 chemical compounds - ANSWER-
1. lipophyllic portion (lipid soluble) usually a benzene ring
2. water soluble portion (the nitrogen containing molecule in the structure)
3. lipid soluble and water soluble portions must be separated by a certain distance and
this is either by an ester or amide chemical chain
*explain the structure of an ester local anesthetic; explain for amide structure -
ANSWER-ester is C==O, O and both the Os are negative (-);
amide is C==O, N where the N is positive (+) and O is negative (-) and brings closer
together and makes harder to break
(== reads as "double bond"
*what is the significance for both the Os being negative in a ester bond - ANSWER-both
negative means they push away from each other and make bond easier to break
(metabolism)
*how are esters metabolized - ANSWER-plasma and tissue cholinesterases via
hydrolysis that occurs throughout the body and is rapid (they are metabolized right in
the tissue they are in bc water and cholinesterase are everywhere)
*what is special about tetracaine? - ANSWER-we mostly used amides. Esters tend to
be short acting, but tetracaine is the longest acting ester we have
talk about what we need to know regarding the esters and amide locals and allergies to
them - ANSWER-local anesthetic allergies are uncommon, yet esters are more
commonly associated with allergies than the amides (99%). if you have an allergy to an
ester, then you most likely have allergy to all the other esters (cross allergy within
class). Though very unlikely, if you're allergic to an amide, then there is no cross allergy
and the other amides will be okay.
, how are amides metabolized - ANSWER-in the liver by CYP1A2 and CYP3A4 (would
take longer than the esters and therefore higher blood levels may develop with rapid
absorption)
between esters and amides, which are shorter acting? why? - ANSWER-esters are
shorter acting because they are readily metabolized by esterases throughout the entire
body and at the tissue where they are injected. amides are longer acting bc they are
more lipophilic and protein bound and require transport to liver for metabolism
why are esters more associated with allergy? - ANSWER-the lipophilic group of ester is
called PABA (paraminobenzoic acid) which is a component of a los of cosmetics and
some food products that we are exposed to. then when get the local they experience
the allergy
what is the MOA of the local anesthetics? - ANSWER-block Na+ channels in nerves.
what happens when you block motor nerve; sensory nerve; autonomic nerve? -
ANSWER-no movement; no feeling; vasodilation or whatever the autonomic function of
that nerve is
how do the local anesthetics block Na Channels? (go through the whole MOA starting
w/ placing local in skin) - ANSWER-local anesthetics outside the body are equal parts
lipid soluble and water soluble. they are weak bases. place local in tissue > depending
on the pH of the tissues and pKa of the drug then some will ionize and some will stay
non-ionized. the non-ionized portion will be lipid soluble and WILL cross the nerve
membrane and enter the axoplasm of the nerve. The ionized (water soluble) portion will
not cross in. Once inside the cell, the non-ionized portion will reach a new equilibrium in
the nerve axoplasm pH. some of the drug will stay non-ionized and some WILL ionize.
this time the water soluble (ionized) portion will go into the sodium channel and attach to
the local anesthetic receptor and block the Na channel.
what determines the ionization of a local? - ANSWER-the pH of the tissue its going in
and the pKa of the drug itself
how does blocking the Na channel cause nerve block? - ANSWER-bc blocking the Na
channel causes inability to depolarize the nerve can't transport action potential
why must local anesthetic have a lipid soluble and water soluble portion? - ANSWER-
needs to be lipid soluble to get into the nerve itself and then needs to use the water
soluble portion to enter the actual Na channel and attach to local anesthetic receptor to
block depolarization and nerve conduction
local anesthetics can't just enter from the outside of the nerve cell and attach to the Na
channel. what is the ONE exception to this rule? - ANSWER-benzocaine
