Local Anesthetics

Question 1

At what point in the pain pathway do local anesthetic work?

initiation, transmission, perception, or reaction?

Answer 1

transmission of the pain signal

Question 2

What is a distinguishing characteristic of local anesthetics and how is their goal different from other pain management techniques?

Answer 2

the distinguishing characteristic is that they can provide complete loss of all sensory modalities

they’re unique in that other forms of pain control want to try to be systemic, but local anesthetics try really hard to just be local

Question 3

What are the three structural components of a local anesthetic:

Answer 3

the hydrophobic aromatic ring

the ester or amide linker

the hydrophillic amine

Question 4

As the hydrophobicity of the aromatic ring increases, what happens to the LA’s potentcy, duration of action, and toxicity?

Answer 4

potency goes up

duration of action begins sooner and lasts longer

toxicity also increases unfortunately

Question 5

What are hte two types of linker bonds in LAs and how are the two classes different?

Answer 5

ester bonds or amide bonds

they are different in that they are metabolized differently

esters are more rapidly broken down in the plasma and also have a higher potential for allergic sensitization

Question 6

What does the hydrophilic amine of an LA determine?

Answer 6

the pK of the drug - basically how much of the drug will be ionized at physiological pH

Question 7

Are most local anesthetic weak acids or weak bases? What does this mean in terms of concentration of ionized drug?

Answer 7

weak bases with pK about 8-9

It means that at physiologic pH of 7.4, most of the drug will be ionized

Question 8

Why are both the ionized and unionized form of the anesthetic necessary for the effect?

Answer 8

in order to enter the cell, the drug must be unionized

but in order to be effective and block the sodium channels, the drug must be ionized

Question 9

So will a drug with a lower pK or higher pK have faster action?

Answer 9

lower pK

at lower pK you’ll have less of the drug in the ionized form, so more will be able to cross the cell membrane into the neuron

Question 10

Local anesthetics have higher affinity for the sodium channels when they are n what states? What does this means in terms of what neurons are most affected?

Answer 10

higher affinity for open and inactive states

less affinity for resting states

This means that neurons that are especially active will be affected first.

Question 11

Why do local anesthetics block pretty much all transmission?

Answer 11

they block sodium channels, and literally all nerves use sodium channels

so it can block anything with a sufficient concentration of the drug

Question 12

Do LAs preferentially block smaller diameter or larger diameter nerve fibers? Myelinated or unmyelinated?

Answer 12

will block small diameter nerve fibers faster

will block myelinated nerves faster than unmyelinated nerves of the same diameter

Question 13

In what order are the modalities of sensation and motor function affected by LAs?

Answer 13

1. pain
2. cold
3. warmth
4. touch
5. deep pressure
6. motor function

Question 14

What effect do LAs have on the cardiovascular system? Why is this a bad thing in terms?

Answer 14

they block Na+ channels in vascular smooth muscle, resulting in vasodilation

this is a bad thing because it counterintuitively promotes removal of the LA form the site of application, which decreases effectiveness and increases risk of toxicity

Question 15

How do you pharmacologically circumvent the vasodilation effects of the LAs?

Answer 15

you give them with a vasoconstrictor like epinephrine to prolong action, decrease toxicity

also helpful because it decreases bleeding

Question 16

What are some of the adverse CNS side effects of LAs?

Answer 16

tongue numbness (at even low concentrations)

dizziness

visual disturbances

tinnitus

slurred speech

generalized convulsions

eventual coma

Question 17

What cardiovascular adverse effects will the LAs have if they diffuse to the heart?

Answer 17

these are really bad - potentially fatal

hemodyanmic instability

decreased myocardial electrical excitability

decreased conduction rate/decreased force of ocntractions

cardiovascular collapse

Question 18

In what type of LAs are hyeprsensitivity reactions more common? Why?

Answer 18

the esters

they are metabolized rapidly and one fo the metabolites - PABA - is easy to develop a hypersentivity to

Question 19

What are the two reasons you don’t want systemic distribution of a LA?

Answer 19

distribution decreases teh effectiveness because it dilutes the drug

distribution is associated with toxicity because ou don’t want Na+ channels blocked in the CNS or CV systems

Question 20

What is the negative impact of using a vasoconstrictor like epinephrine with LA when closing significant wounds?

Answer 20

they can have a negative impact by reducing blood flow, which makes healing ultimately harder

Question 21

Why might LAs be less effective when injected to inflammed/pruritic areas?

Answer 21

inflammaton and pus formation makes the area more acidic, with a pH about 5.5-6.5

this means that the vast majority of the drug will be ionized right away and less likely to enter the neuron, reducing the anesthetic effect

Question 22

Which form: esters or amides distribute more widely?

Answer 22

the amides, since they take longer to metabolize

Question 23

What enzyme hydrolyzes the esters and where?

Answer 23

the pseudocholinesterases in the plasma

Question 24

How and where are the amides metabolized?

Answer 24

they are hydrolyzed in the liver by mixed-function oxidases

Question 25

How are LA metabolites excreted?

Answer 25

urine

Question 26

What is EMLA?

Answer 26

It’s a eutetic mixture of local anesthetics

lidocaine and prilocaine

it’s an oil at room temp, so you put it on intact skin to numb the area over where you’re going to do an LP, venipuncture, or skin graft harvesting

Question 27

What is the most common route of administration for the LAs? What do you need to be careful for with this route?

Answer 27

infiltration anesthesia - injected subcutaneous or submucosal for minor surgery or dental procedures

you need to be careful that you don’t inadvertently inject it into the vascular system - you dont want systemic action

Question 28

How would you administer an LA if you wanted to block nerve conduction in a bigger area like the finger or the arm?

Answer 28

a nerve block

injection into thte brachial plexus will anesthetize the whole extremity

Question 29

What’s another name for an intravenous regional block and when can you use it/what’s the danger?

Answer 29

A bier block

You can only use it on the extremities because you need to block the diffusion fo the drug by placing a touniquet and leaving it on for at least 15 minutes

Question 30

How does an epidural work and what nerves does it primarily work on?

Answer 30

you inject LA into the epidural space of the spinal cord - primarily works on spinal nerve roots

Question 31

Why is there a concern for systemic distribution with epidural injections?

Answer 31

they can diffuse into the blood stream following absorption from the epidural space

so give with epinephrine and use a dilute solution fo bupivacaine during labor to avoid respiratory depression in the neonate

Question 32

Why are spinal local anesthetics helpful sometimes?

Answer 32

they are best at anesthetizing very large regions - you inject it into the CSF of the lumbar space

nice because it doesn’t really get into the blood at all with this route

Question 33

Is procaine an ester or amide? What does that mean for it’s duration of action and metabolism?

Answer 33

it’s short acting because it’s rapidly metabolised in the plasma - thus not useful as a topical anesthetic

Question 34

What is the most widely used local anesthetics?

Answer 34

lidocaine

Question 35

Is lidocaine an ester or amide?

Answer 35

amide - metabolized in the liver

Question 36

What is lidocaine used for besides as a LA?

Answer 36

an antiarrhythmic agent

Question 37

lidocaine OD can produce death due to….

Answer 37

ventricular fibrillation or cardiac arrest

Question 38

What local aneshetic works very similar to lidocaine, but with a longer duration of action?

Answer 38

mepivacaine

Question 39

What is the major pro to bupivacaine?

Answer 39

it’s very potent and long-acting, making it perfect for epidural blocks and prolonged surgery

Question 40

What is the benefit to ropivacaine over bupivacaine?

Answer 40

it has fewer CVS and CNS toxicities

Question 41

What LA is common used for topical anesthesia of the eye, nose, and throat?

Answer 41

tetracaine

Question 42

What is the added benefit that is unusual to cocaine?

Answer 42

It actually has vasoconstrictor action instead of vasodilation - so it’s great at numbing areas and stopping bleeding

(especially in the mucosal membranes - so cut lips)