Hsf: Nerve Pharmocology

Front 1

Name 4 local anesthetics

Back 1

-Lidocaine
-Tetracaine
-Procaine
-Benzocaine

Front 2

3 Features that All Local Anesthetics Share

Back 2

1. A Liphophilic End (usually a modified benzene ring)
2. A Hydrocarbon chain that connects the hydrophobic end to the amine part
3. Amine part of the molecule

Front 3

Most local anesthetics are _______ _____ and so exist in solution in both protonated (positively charged) and neutral forms.

What is the one exceptions?

Back 3

-Tertiary Amines
-Benzocaine

Front 4

How do the local anesthetics prevent the initiation and propagation of action potentials?

Back 4

-By interacting with Na channels-->clinically and physiologically more important
-May have small effects on K channels

Front 5

The local anesthetics exert their effect by blocking _____ ion movement .....

Back 5

-Na+
-through the pore in Na channels

Front 6

Local Anesthetics: 2 Pathways to the Binding Site

Back 6

1. Uncharged (unprotonated) form of the anesthetics reach the site by a HYDROPHOBIC PATHWAY through the lipid bilayer of through the hydrophobic parts of the channels
2. Charged (protonated) local anesthetics can reach this site only from the AXOPLASMIC SOLUTION and only when the channel is in its "OPEN" conformation

Front 7

Na Channel: 3 Conformations

Back 7

1. Resting, closed conformation
2. Open, ion-conducting conformation
3. Inactivated, non conducting one

Front 8

Local anesthetics tend to stabilize the Na channels in the ______ state.

Back 8

-Inactivated

Front 9

The more often a channel is in the inactivated state, the _____ the probability it will be stabilized in that state by the anesthetic.

Back 9

-Highly

Front 10

When does the charged form of the anesthetic have access to the Na channel site?

Back 10

-When the channel is in the open conformation

Front 11

Describe the "use-dependent block"

Back 11

-When local anesthetics are more effective on axons with high action potential firing rate compared to ones with lower firing rates

Front 12

Why does the "use dependent block" occur?

Back 12

-The more often a channel is "used" (higher action potential rate) the more often the channels will go through their conformational cycle (including inactivated state)
-These channels are more likely to be "blocked" by the anesthetic

Front 13

Why are chronically depolarized nerve fibers more sensitive to local anesthetics than normal ones?

Back 13

-More Na channels in the inactivated conformation and a smaller "safety-factor" for action potential initiation
-The channels that are already activated are stabilized in that state by the local anesthetics; blocking only a few of the rest of the channels can cause failure of action potential initiation

Front 14

Are externally applied quaternary (permanently charge) local anesthetic analogs effective? Why or why not?

Back 14

-No, they are not effective.
-Charged molecules do not have access to binding site from the external solution

Front 15

Tetrodotoxin

Back 15

-Prevalent in puffer fish
-Binds outer vestibule of the Na+ pore and blocks it

Front 16

Saxitoxin

Back 16

-Highly selective Na channel inhibitor
-From Red Tide

Front 17

Microcurrents

Back 17

-local currents around the myelin and nodes of Rainvier
-Can generate local potential

Front 18

What does "Use"-dependent do concerning depolarization?

Back 18

-Stabilizes inactive form
-Lengthens absolute refractory period

Front 19

Where does the "use" dependent bind?

Back 19

-In the interior of the cell

Front 20

Metabolism of Local Anesthetics: Amide Local Anesthetics

Back 20

-metabolized by liver enzymes
-relatively long acting

Front 21

Most metabolites are ________

Back 21

-inactive