Local Anesthetics

Question 1

Drug that reversibly blocks impulse conduction along nerve axons and other excitable membranes that utilize voltage gated sodium channels as the primary means of action potential generation

Answer 1

Local Anesthetic

Question 2

What are the three common structural features of local anesthetics?

Answer 2

Aromatic ring, Intermediate chain (Ester or amide), and ionizable group (usually a tertiary amine)

Question 3

Are weak bases, therefore, the more acid the pH, the greater the [BH+]; the more basic, the greater the neutral [B] form

Answer 3

Local Anesthetics

Question 4

Required to diffuse to the site of action

Answer 4

Neutral form of local anesthetic

Question 5

Required for activity

Answer 5

The charged form of a local anesthetic

Question 6

The more acidic the extracellular medium, the higher the proportion of the

Answer 6

Charged form

Question 7

Block Na+ channels in excitable membranes without changing resting potential

Answer 7

Local Anesthetics

Question 8

By doing this, local anesthetics reduce the aggregate

Answer 8

Inward sodium current

Question 9

Neutral form of LA required to enter membrane, binding site is on the

Answer 9

Cytoplasmic face of channel

Question 10

The charged LA is required for binding to the

Answer 10

Channel Site

Question 11

LA binding is a function of the conformational state of the channel, i.e., different kinetics/affinities for different conformational states. This is called the

Answer 11

Modulated Receptor Hypothesis

Question 12

In the modulated receptor hypothesis, LA’s have a higher affinity for the receptors in the activated & inactivated states, less affinity for the receptor in the

Answer 12

Resting state

Question 13

Fibers that fire at a faster rate are more susceptible to the effects of

Answer 13

Local Anesthetics

Question 14

Repeated depolarizations produce more effective

Answer 14

Anesthetic Binding

Question 15

Repeated depolarizations produce more effective anesthetic binding. This phenomenon is known as

Answer 15

Frequency Dependent Block

Question 16

High potency, highly hydrophobic drugs tend to be highly bound to

Answer 16

Serum and Tissue Proteins

Question 17

The greater the degree of protein binding, the longer the

Answer 17

Duration

Question 18

In clinical practice, incremental increases in local anesthetic concentration result in progressive interruption of (in order of sensitivity)

Answer 18

Autonomic/pain fibers, Sensory Fibers, and Motor Fibers

Question 19

This is probably a result of a combination of geographic arrangement of nerve fibers and the intrinsic sensitivity of the nerve fiber types

Answer 19

Nerve Sensitivities to LA’s

Question 20

In neuraxial blockade, the order of loss is

Answer 20

Autonomic/pain, Sensory, and Motor

Question 21

In a peripheral blockade

1. ) Motor Fibers are
2. ) Sensory Fibers are

Answer 21

1. ) Peripheral

2. ) Central

Question 22

Of the sensory fibers:

1. ) Proximal are?
2. ) Distal are?

Answer 22

1. ) Outside

2. ) Inside

Question 23

In peripheral blockade, motor block occurs before

Answer 23

Proximal sensory loss which occurs before distal sensory loss

Question 24

The absorption of local anesthetics is

Answer 24

Site dependent

Question 25

What are the common sites for LA’s?

Answer 25

ICE-BS

-Intercostal, Caudal, Epidural, Brachial Plexus, and Sciatic Nerve

Question 26

Decrease absorption of LA’s irrespective of site of injection

Answer 26

Vasoconstrictors (epinephrine and phenylephrine)

Question 27

Particularly effective for short and medium acting drugs. Increase tissue binding responsible for duration of action of long acting drugs

Answer 27

Vasoconstrictors

Question 28

Vasoconstrictors are intrinsically analgesic in

Answer 28

Neuraxial blockade

Question 29

Low concentration of epinephrine added to LA; Small dose injected before therapeutic dose; Heart rate increases within 2 minutes (15% increase) if LA is injected

Answer 29

Intravascularly

Question 30

Usually have a shorter duration of action

Answer 30

LA esters

Question 31

How are the LA amides excreted?

Answer 31

Liver via cytochrome P450

Question 32

Low flow states to liver (portal hypertension, CHF, etc.) decreases delivery of LA’s to liver, decreasing amide LA metabolism, increasing

Answer 32

Lifetime and serum concentration

Question 33

Results from effects of LA on excitable membranes and tissues other than target nerves

Answer 33

Systemic Toxicity

Question 34

Manifests first as CNS toxicity and then cardiotoxicity

Answer 34

Systemic Toxicity

Question 35

The range of effects of systemic toxicity are directly proportional to

Answer 35

Serum LA concentration

Question 36

Tinnitus, perioral numbness, blurred vision, metallic taste, change in MS, and convulsions are signs of

Answer 36

Systemic Toxicity

Question 37

Systemic acidosis or hypercarbia increase sensitivity to

Answer 37

LA toxicity

Question 38

Rescue of systemic toxicity is via

Answer 38

IV lipid emulsion

Question 39

High concentrations of LA’s for extended periods can lead to

Answer 39

Nerve tissue destruction

Question 40

High concentrations of LA’s for extended periods can lead to nerve tissue destruction via membrane damage, cytoskeletal disruption, etc. but not due to blockade of the

Answer 40

Na Channel

Question 41

Motor and sensory losses are seen (e.g. cauda equina syndrome) and paralysis and paresis may result from

Answer 41

Local (Neural Tissue) Toxicity

Question 42

Transient pain syndrome associated with spinally administered Lidocaine and certain surgical positions (e.g. lithotomy)

Answer 42

Transient Neurological Symptoms (TNS) from Local Toxicity

Question 43

TNS is not associated with

Answer 43

Motor or sensory loss

Question 44

A self limited neuropathic pain syndrome

Answer 44

TNS

Question 45

When prilocaine metabolites (O-toluidine) act as an oxidizing agent to convert Hb++ to Hb+++

Answer 45

Methemoglobinemia

Question 46

Which two LA’s can cause methemoglobinemia?

Answer 46

Prilocaine and Benzocaine

Question 47

Characterized by chocolate colored blood and a pulse oximeter with 85% saturation

Answer 47

Methemoglobinemia

Question 48

How do we treat methemoglobinemia?

Answer 48

Methylene Blue

Question 49

Can cause allergic reactions due to hapten formation via PABA

Answer 49

Ester LA’s

Question 50

A long duration, potent ester primarily used for spinal anesthesia, toxic at relatively low doses

Answer 50

Tetracaine

Question 51

The exception to the short acting ester rule

Answer 51

Tetracaine

Question 52

Quick onset, short duration, hypersensitivity reactions, TNS implication (rarely used)

Answer 52

Procaine (Novocain)

Question 53

Quick onset, moderate duration and toxicity, TNS implication

Answer 53

Lidocaine

Question 54

Longer duration than lidocaine, lowest pKa of injectable LA’s, acts as a vasoconstrictor

Answer 54

Mepivacaine

Question 55

Associated with methemoglobinemia, component of EMLA

Answer 55

Prilocaine

Question 56

Excellent long duration LA with devastating potential for cardiac toxicity. Sensory block>Motor block

Answer 56

Bupivacaine

Question 57

Single enantiomer long duration LA with properties similar to bupivacaine but with less cardiotoxicity; vasoconstrictor

Answer 57

Ropivacaine

Question 58

Eutectic Mixture of Local Anesthetic Prilocaine/Lidocaine for topical anesthesia

Answer 58

EMLA