NAGELHOUT LOCAL ANESTHETICS CHAPTER
10 QUESTIONS AND ANSWERS
*what are the 2 classes of local anaesthetics - 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 anaesthetic properties, what 3 chemical compounds -
ANSWER 1. lipophilic 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
*describe the structure of an ester local anesthetic; describe 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 implication 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 thus 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
10 QUESTIONS AND ANSWERS
*what are the 2 classes of local anaesthetics - 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 anaesthetic properties, what 3 chemical compounds -
ANSWER 1. lipophilic 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
*describe the structure of an ester local anesthetic; describe 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 implication 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 thus 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
