LOCAL ANESTHETICS [tan] Flashcards
branch of medicine/dentistry that deals with the study and administration of anesthesia
Anesthesiology
a drug that causes unconsciousness or deadens physical sensation
Anesthetic
the partial or total loss of sensation due to an anesthetic
Anesthesia
loss of sensation in a circumscribed area of the body caused by depression of excitation in the nerve endings or an inhibition of nerve conduction
Local Anesthesia
The self-propagated passage of an electrical current along nerve fibers
Nerve Conduction
drugs that reversibly block nerve conduction when applied to a circumscribed area of the body without inducing loss of consciousness
LOCAL ANESTHETICS
LOCAL ANESTHETICS work on___?
general anesthesia work on the _____?
peripheral nerves
CNS
Cocaine (1884)
A. First Local Anesthetic
B. First Synthetic LA
C. First Amide
A
Kollar: opthal surgeon
A. First Local Anesthetic
B. First Synthetic LA
C. First Amide
A
“erythroxylon cola”
A. First Local Anesthetic
B. First Synthetic LA
C. First Amide
A
→ Procaine (1905)
A. First Local Anesthetic
B. First Synthetic LA
C. First Amide
B
Einhorn
A. First Local Anesthetic
B. First Synthetic LA
C. First Amide
B
Lidocaine (1943)
A. First Local Anesthetic
B. First Synthetic LA
C. First Amide
C
Lofgren
A. First Local Anesthetic
B. First Synthetic LA
C. First Amide
C
DESIRABLE PROPERTIES OF LOCAL ANESTHETICS [11]
(1) Non-irritating to tissues
(2) Action must be reversible
(3) Low degree of systemic toxicity
(4) Rapid (short) time of onset
(5) Duration of action must be sufficient or long enough to
permit completion of procedure yet not too long to require
extended recovery
(6) Effective whether injected into tissues or applied locally on
the mucous membrane
(7) Should have potency sufficient to give complete anesthesia
without the use of harmful concentration
(8) Relatively free from producing allergic reactions
(9) Stable in solution
(10) Undergoes biotransformation within the body
(11)Sterile or capable of being sterilized by heat without
undergoing deterioration
PARTS OF ANESTHETIC MOLECULE [3]
aromatic ring
intermediate linkage
terminal amine
Having both a lipophilic (hydrophobic) and hydrophilic part, an anesthetic molecule is considered _____.
amphiphilic
→ largest part
A. aromatic ring
B. intermediate linkage
C. terminal amine
A
from benzoic acid or aniline
A. aromatic ring
B. intermediate linkage
C. terminal amine
A
lipophilic
A. aromatic ring
B. intermediate linkage
C. terminal amine
A
RN / free base / uncharged
A. aromatic ring
B. intermediate linkage
C. terminal amine
D. AMINO GROUP
E. A &D
E
colorless crystalline solid
BENZOIC ACID
simplest aromatic carboxylic acid
BENZOIC ACID
Uses of BENZOIC ACID
o preservative
o foods such as sauces and pickles
o artificial flavors
volatile organic aromatic amine compound
ANILINE
manufacture of precursors to polyurethane and other industrial chemicals
ANILINE
used as a dyeing agent in the cloth industry
ANILINE
a hydrocarbon with either an ester or amide linkage
A. aromatic ring
B. intermediate linkage
C. terminal amine
B
formed when a carboxylic acid and an alcohol react
A. ESTER LINKAGE
B. AMIDE LINKAGE
A
a water molecule is removed
A. ESTER LINKAGE
B. AMIDE LINKAGE
A
formed when a carboxyl group of one amino acid molecule reacts with the amino group of the other amino acid molecule, causing the release of a molecule of water
A. ESTER LINKAGE
B. AMIDE LINKAGE
B
formed when a carboxyl group of one amino acid molecule reacts with the amino group of the other amino acid molecule, causing the release of a molecule of water
A. ESTER LINKAGE
B. AMIDE LINKAGE
B
an amino derivative of ethyl alcohol or acetic acid
AMINO GROUP
T/ F
AMINO GROUP is hydrophilic
T
Local Anesthetics should be able to diffuse to the ______. Being weak bases, it has to be combined with acids to form salts. Anesthetic acidic salt is dissolved in sterile water or saline making them injectable fluids.
nerve fiber
other term is dissociation constant of the acidic form of a drug
pKa
pH that will produce an equal number of ionized state (RNH)
and the unionized stage (RN+ H+)
pKa
range value is from 7.5 to 9.0
pKa
pKa of Lidocaine
7.7
Percent Base (RN) at pH 7.4 of Lidocaine
29
FACTORS INVOLVED IN THE ACTION OF LOCAL ANESTHETICS [2]
(1) Diffusion of the local anesthetics through the nerve sheath
(2) Binding of the local anesthetic at receptor sites at the nerve membrane
The binding site is inside the channels and drugs have to cross the _____.
lipid-rich membrane
conversion of the water-soluble part of the anesthetic compound into the fat-soluble form
DEPROTONATION
→ tissue alkalinity (7.3 to 7.4) needed
→ allows anesthetic solution to penetrate the lipid-rich membrane
DEPROTONATION
T/ F
DEPROTONATION should be alkaline
T
T/ F
DEPROTONATION.
As it passes through the nerve membrane, it has to be the lipophilic part . To bind with the receptor sites, it must be the _______ part. Receptor sites close the sodium channels (spiky sites)–an action of nerve conductio
T, hydrophilic
DEPROTONATION.
100 molecules of anesthesia 75% RNH : 25% of RN
↓
Deprotonation of RNH part
↓
Diffuses through nerve membrane
↓
Re-equilibration of RNH to bind at receptor sites
↓
Suppressed nerve conduction
PROPOSED SEQUENCE FOR MECHANISM OF ACTION OF ANESTHESIA [7]
(1) Calcium ions at phospholipid receptor sites are displaced
(2) Local anesthetic molecule binds at receptor sites
(3) Na channels are blocked
(4) Depressed/decrease depolarization
(5) Firing potential is not reached
(6) Propagated action potential does not develop
(7) Block of nerve conduction
type of nerve block produced by local anesthetics
NON-DEPOLARIZING NERVE BLOCK
bi-molecular lipoprotein layer of the nerve membrane
A. Primary Site of Action
B. Primary Effect
C. Primary Action
A
NON-DEPOLARIZING NERVE BLOCK (3)
A. Primary Site of Action
B. Primary Effect
C. Primary Action
decreases the permeability of the nerve membrane to Na
A. Primary Site of Action
B. Primary Effect
C. Primary Action
B
to stabilize the nerve membrane in a polarized state
A. Primary Site of Action
B. Primary Effect
C. Primary Action
C
THEORIES THAT EXPLAIN THE MODE OF ACTION OF LOCAL ANESTHETICS (5)
(1) Surface Charge Theory
(2) Acetylcholine Theory
(3) Calcium Displacement Theory
(4) Specific Receptor Hypothesis
(5) Membrane Expansion Theory
CLASSIFICATION OF ANESTHETICS (2)
ACCORDING TO RECEPTOR SITES
ACCORDING TO THE INTERMEDIATE GROUP
ACCORDING TO THE INTERMEDIATE GROUP (2)
ESTER, AMIDE
ACCORDING TO RECEPTOR SITES (4)
Class A
Class B
Class C
Class D
ACCORDING TO RECEPTOR SITES (4)
Class A, B,C,D
toxins (ex.: scorpion, pufferfish)
Class A
Class B
Class C
Class D
Class A, B
topicals (remain on the surface)
Class A
Class B
Class C
Class D
Class C
injectables
Class A
Class B
Class C
Class D
Class D
ACCORDING TO THE INTERMEDIATE GROUP:
ESTER
Give the Benzoic Acid (4)
tetracaine
butacaine
cocaine
benzocaine
ACCORDING TO THE INTERMEDIATE GROUP:
ESTER
Give the PABA grp.
procaine
chloroprocaine
propoxycaine
ACCORDING TO THE INTERMEDIATE GROUP:
What’s under AMIDE? (4)
lidocaine
mepivacaine
prilocaine
bupivacaine
T/F
Amides have two “i’s”
while esters have only one “i”.
T
An exception to the rule is ___ which is an ester and Articaine which is both an ester and amide but is classified more as an amide.
Piperocaine
T/ F
there should be a lipophilic part, the nerve membrane, and a hydrophilic part, the receptor sites
T
