Local Anesthesia

Question 1

Using the Henderson-Hasselbalch equation, what are the two basic rules about the acid form versus the basic form of a drug?

Answer 1

1. The acid form will have a proton that is lacking in the basic form.
2. Either the basic form is negatively charged OR the acid form is positively charged.

Question 2

Take a look at the 4th slide for how to figure out how much of the drug is in the basic form

Answer 2

Sure thing boss.

Question 3

If your pH is 1 unit higher than your pka (for example, say your pka is 4 and your pH is 5) then how much more acid than base will you have? What about for 2 units? 3 units?

Answer 3

10 times
100 times more
1000 times more acid

Question 4

If your pka and your pH are the same, how much acid and base will you have?

Answer 4

Equal amounts

Question 5

What does the aromatic group do to the local anesthetic?

Answer 5

It makes it lipophilic.

Question 6

The local anesthetics favored in dental practice have what type of linkage between the aromatic part and the amine part?

Answer 6

Amides

Question 7

The general structure of local anesthetics can be described as having three parts. What are they?

Answer 7

1. Aromatic region (to make it lipophilic)
2. Ester or amide linkage (this means it will be short lived in the blood due to enzymatic activity) (amide linkages are favored in dentistry)
3. The amine group

Question 8

T/F ester linkages are more allergenic than amides?

Answer 8

True

Question 9

Amide (linkages) will have an I in their name somewhere prior to ‘caine’ such as Lidocaine.

Answer 9

Truth

Question 10

Will ester linkages have an ‘I’ in their name somewhere prior to caine?

Answer 10

Nope. An example is procaine

Question 11

T/F, The acidic and basic forms of the local anesthetic are important for the intended function? Why?

Answer 11

True.
The uncharged basic form allows for the local to get inside the nerve. Once inside, the charged version has a better ability to bind to the Na+ channel and inhibit the conduction of a nerve impulse.

Question 12

T/F- in a chiral molecule, the S-, R-, and Racemic mixes of the drug have the same effect?

Answer 12

False- they can have similar or different pharmacokinetic and/or pharmacodynamic properties.

Question 13

What is the basic mechanism of action for a local anesthetic?

Answer 13

Local anesthetics cross the axon membrane and interact with the open and inactivated forms of the Na+ channel, blocking sodium conduction. No more sodium ions can come in and the drug remains in the inactive sodium channel.

Question 14

Is local anesthetic effective outside the axon?

Answer 14

Nope

Question 15

Which form of the local anesthetic can pass through the membrane? Which form is better at blocking the channel?

Answer 15

Basic or uncharged form

Acidic or charged form

Question 16

T/F, myelinated and unmyelinated axons are susceptible to local anesthetics?

Answer 16

True

Question 17

We care about which types of nerve fibers? Why these ones?

Answer 17

A delta and C fibers.

Because they deal with pain and temperature.

Question 18

When a local anesthetic is acting on C fibers (pain) compared to acting on A beta fibers (touch and pressure), which fiber returns to normal function slowest?

Answer 18

Pain. This is good for us!

Question 19

Local anesthetics bind to the open form of the sodium channel. Will the nerve block occur faster on rapidly firing or slowly firing nerves?

Answer 19

Rapidly firing

Question 20

T/F, B and C fibers are more easily influence by drugs than A fibers? Why?

Answer 20

True.

Because A fibers are really big compared to B and C fibers. The drug has to diffuse over a longer distance on A fibers.

Question 21

What must happen to achieve total nerve block? How is that achieved?

Answer 21

Activity at several nodes must be blocked

This is achieved by further diffusion of the anesthetic.

Question 22

T/F the faster a fiber is blocked, shorter it takes to recover?

Answer 22

False, the longer it takes to recover.

Question 23

T/F inflamed tissue is more difficult to anesthetize? Why?

Answer 23

True.
This is because the cells release things in inflammation that lower the pH, making it more difficult to get the drug inside the axon (remember that the uncharged or basic version of the drug is best at getting inside the axon)

Question 24

Which type of drug has a longer duration- lipophilic or hydrophilic? Why?

Answer 24

Lipophilic because it is going to be bound to a protein and protected from clearance in the blood. Hydrophilic drugs will go in the blood very well and be more susceptible to enzymatic clearance.

Question 25

The pKa can’t stray too far from physiological pH. Why?

Answer 25

Because if you do, then you’re only going to get one form of the drug. You need both the acidic (charged) and basic (uncharged) forms in order for the local anesthetic to work properly.

Question 26

Sometimes the pH is lowered from biological pH (6-7) to a pH of 4 or 5 to stabilize epinephrine. Why is it not a great idea to add a bunch of NaHCO3 to increase the concentration of free base?

Answer 26

Because you can precipitate out the local anesthetic

Question 27

T/F, local anesthetics can readily pass from the periphery to the CNS?

Answer 27

True

Question 28

Are CNS neurons sensitive to local anesthetics?

Answer 28

Yes, very.

Question 29

T/F concentrations of local in the blood stream that won’t affect the peripheral activity also won’t affect CNS activity?

Answer 29

False. Those concentrations will affect the CNS

Question 30

What happens if you inject some local directly into a vein?

Answer 30

You can block cardiac Na+ or Ca++ channels… clearly that is bad. This depresses pacemaker activity, excitability, and conduction, and contractility and this can produce hypotension. Yes, you could die!

Question 31

What does epinephrine do?

Answer 31

It’s a vasoconstrictor. So this makes the success rate and intensity better. The toxicity of the anesthetic is also reduced.

Question 32

T/F all local anesthetics will get absorbed into the blood stream? What should you do about that with lidocaine and procaine?

Answer 32

True

You should administer a vasoconstrictor with them because those drugs produce potent vasodilation

Question 33

Are unbound drugs free to diffuse to various tissues, like the CNS or placenta once they’re in the blood?

Answer 33

Indeed they are.

Question 34

How does the body keep the concentration of amide local anesthetics low?

Answer 34

The liver takes care of business

Question 35

What enzyme breaks down ester locals?

Answer 35

Pseudocholinesterase

Question 36

Just don’t do some inadvertent intravascular injections. How do you prevent this?

Answer 36

After inserting the needle you aspirated a little bit- this means you pull out on the plunger and see what you suck up into the tube. If there’s no blood, you’re good. If you suck up blood, then don’t inject your anesthetic there.

Question 37

The most serious side effects of local anesthetics are a result of what?

Answer 37

2 things- operator error:

1. inadvertent intravascular injection
2. excessive amounts of the drug

Question 38

What are some possible adverse side effects (the most serious ones) of local anesthetics?

Answer 38

the most serious are convulsions, respiratory arrest, and cardiovascular collapse

Question 39

What do you do if your patient is in respiratory distress?
Hypotension?
Cardiac function disruption?

Answer 39

Respiratory distress- ventilation, oxygen
Hypotension- epinephrine
Cardiac function disrupted- cardiopulmonary resuscitation

Question 40

What about using local anesthetic during pregnancy?

Answer 40

Lidocaine and prilocaine are category B drugs so they’re okay, but you might not want to use articaine because it’s category C