Local Anesthesics

Question 1

Electrochemical gradients are maintained by

Answer 1

active transport (ATPase) and K+ leak channels (sets the negative membrane potential)

Question 2

Depolarization causes

Answer 2

1. opening of NaV channels, influx of cations and drive Vm to positive potentisl
2. KV channels open and conduct current in opposite direction, repolarizing Vm back close to EK

Question 3

What is the “m” gate and the “h” gate doing at a hyperpolarized resting membrane potential?

Answer 3

“m” gate is closed and the “h” gate is open

Question 4

What is the “m” gate and the “h” gate doing at a depolarized membrane potential?

Answer 4

“m” gate opens and sodium rushes into the cell; “h” gate is still open

Question 5

The two gates on the voltage-gated sodium channels

Answer 5

“m” gate (actual channel itself) and an “h” gate

Question 6

What does the “h” gate do shortly after the sodium channel opens?

Answer 6

the “h” gate closes; the “m” gate remains open; closure of the “h” gate precludes the channel from conducting current - inactivated

Question 7

Voltage-gated sodium channel inactivation occurs during which period?

Answer 7

occurs during the absolute refractory period

Question 8

Structure of the voltage-gated sodium channel

Answer 8

tetrameric structure though a single polypeptide

Question 9

Effects of Na+ channel block on the electrophysiology of a nerve cell

Answer 9

Na+ channel blockade will slow the upstroke rate and amplitude, sometimes to the point of abolishing the AP altogether; this slows or eliminates the conduction through nerve

Question 10

Factors affecting pharmacological action

Answer 10

1. Frequency of transmission
2. Size/class of peripheral axons
3. pH (acidic pH reduces efficacy of LA)
4. Vascularity of target tissue

Question 11

Size/class of peripheral axons related to anesthetics

Answer 11

small diameter axons are blocked better than large diameter axons; myelinated axons blocked better compared to unmyelinated fibers of same diameter because only a few nodes need to be blocked to halt transmission

Question 12

pH of environment related to strength of anesthetics

Answer 12

less effective when injected into infected (acidic) tissue becasue less is non-ionized versus at physiological pH and non-ionized is the form that penetrates biological membranes

Question 13

How does vascularity related to local anesthetics

Answer 13

greater blood flow results in faster/better absorption and higher blood concentration (an issue for toxicity)

Question 14

Slow-firing nerves

Answer 14

lower frequency; drug completely dissociates between AP spikes, activity is preserved

Question 15

Fast-firing nerves

Answer 15

high frequency; drug does not completely dissociate between spikes; block accumulates each spike; activity is suppressed

Question 16

Hyperpolarized nerves

Answer 16

hyperpolarized Vm; drug completely dissociates between spikes; activity is preserved

Question 17

Depolarized nerves

Answer 17

depolarized Vm prolongs drug interaction with channel; high percentage of channels are always blocked; activity is suppressed

Question 18

Why does local anesthetic block small fibers better than large ones?

Answer 18

large ones have the ability to overcome blockade at low LA concentrations whereas small fibers do not

Question 19

Why do you give alpha agonists with local anesthetics?

Answer 19

alpha adrenergic agonists are used with LA to locally constrict blood flow and prevent escape or large amounts of LA molecules into the circulation; this traps LA in the local area, increases its local concentration and can prolong its duration of action

Question 20

Where should a mixture of alpha agonists and LA be avoided?

Answer 20

should be avoided in areas poorly vascularized due to risk of necrotic tissue damage

Question 21

Why are LA often stored on the shelf at a low pH of 3 to 5 and why is bicarbonate often added immediately prior to injection of LA?

Answer 21

done to raise the pH closer to 7 which reduces pain on injection caused by low pH, and can enhance the onset of the LA

Question 22

Local anesthetic prototypes

Answer 22

1. Cocaine
2. Procaine
3. Lidocaine

Question 23

What must happen to LA in order for them to cross nerve sheaths into the nerve cell membrane itself

Answer 23

LA must become non-ionized (this occurs better for LA with a pKa closer to 7.4)

Question 24

What form of LA blocks channels?

Answer 24

ionized form blocks channels

Question 25

Amides

Answer 25

1. Bupivacaine
2. Etidocaine
3. Levobupivacaine
4. Lidocaine
5. Mepivacaine
6. Prilocaine
7. Ropivacaine

Question 26

Esters

Answer 26

1. Benzocaine
2. Chloroprocaine
3. Cocaine
4. Procaine
5. Tetracaine

Question 27

Properties of Amides

Answer 27

fast onset; med/long duration; slow half-life; hydrolysis by CYP system

Question 28

Properties of Esters

Answer 28

variable onset; short to long duration; rapid half life; hydrolysis by esterases

Question 29

Are amides or esters more likely to have a longer duration of action?

Answer 29

amides

Question 30

Local anesthetic cardiovascular toxicity

Answer 30

arrhythmias; depresses cardiac AP (rate and force, QRS spread)

Question 31

Local anesthetic neurotoxicity

Answer 31

CNS stimulation; respiratory depression, death

Question 32

Treatment of local anesthetic CNS stimulation toxicity

Answer 32

benzodiazepines

Question 33

LA routes of administration

Answer 33

1. Topical
2. Infiltration (local injection)
3. Nerve block (into neural plexus)
4. Spinal (sub-arachnoid, on top of pia)
5. Epidural (outside dura)
6. Caudal (sacral hiatus)

Question 34

Topical anesthetics

Answer 34

benzocaine, lidocaine, tetracaine

Question 35

Infiltration (local injection) anesthetics

Answer 35

lidocaine, procaine, bupivacaine

Question 36

Nerve block (into neural plexus) anesthetics

Answer 36

lidocaine, mepivacaine

Question 37

Spinal (sub-arachnoid, on top of pia) anesthetics

Answer 37

bupivacaine, tetracaine

Question 38

Epidural anesthetics

Answer 38

bupivacaine

Question 39

Caudal anesthetics

Answer 39

lidocaine, bupivacaine

Question 40

Infiltration route of administration used for

Answer 40

dental work, suturing etc

Question 41

Caudal route of administration used for

Answer 41

rectal procedures