Local Anesthetics Dr. Pond

Question 1

What do local anesthetics have in common structurally?

Answer 1

-lipophillic group -> aromatic ring)
-hydrophillic domain -> usually a tertiary amine
connected by an alkyl

Question 2

How does the pH affect local anesthetics?

Answer 2

the protonation of the tertiary amine depends on the pKa of the compound and the local pH

Question 3

Which form of the local anesthetic is preferred in order to work? Protonated or unprotonated?

Answer 3

There must be a balance between the two

the target is the inner site of the voltage-gated Na+channel -> so it has to cross the membrane first

-unprotonated form to cross the membrane
-protonated form to actually bind to the inner part of the receptor

Question 4

How are the different local anesthetics categorized?

Answer 4

by the type of intermediate chain (alkyl chain) that connects the lipophilic aromatic ring to the hydrophilic tertiare amine

-Ester intermediate chain
-Amide intermediate chain

Question 5

What are the Ester local anesthetics?

Answer 5

Cocaine
Tetracaine
Procaine/Chloroprocaine !!!
Benzocaine!!!

Question 6

What are the Amide local anesthetics?

Answer 6

Mepivacaine
Ropivacaine
Lidocaine !!!
Bupivacaine !!!
Prilocaine !!!

Amides have an “i” before -caine

Question 7

How might Ester local anesthetics be broken down and what is it is the metabolic product?

Answer 7

plasma esterases
-> product: para-aminobenzoic acid (PABA)
-> CAUTION: with allergies

-> can’t sterilize it repeatedly, bc not as stable

Question 8

Where are Amide local anesthetics metabolized?

Answer 8

in the liver by CYP enzymes
-can undergo repeated high temperature sterilization without losing potency

Question 9

Where are local anesthetics usually administered?

Answer 9

by injection into the
-dermis
-the soft tissue
-> in the area of the nerves

Question 10

What is affected by the absorption and distribution of local anesthetics?

Answer 10

-Duration of action
-Toxicity

the onset is not affected bc we apply it locally and it works pretty quickly

Question 11

What affects the absorption of local anesthetics?

Answer 11

Vascularization (amount of blood vessels)
-> fe the mouth isvery vascular

Question 12

What might be given additionally to local anesthetics when applied to a vascular area of the body?

Answer 12

Vasoconstrictor
-alpha-1-agonist (like Epinephrine)
-> Reduce systemic absorption
-> prolongs the duration of action
-> reduces toxicity

Question 13

What is the MOA of local anesthetics?

Answer 13

it blocks voltage-gated Na+channels
-crosses the membrane and binds the inner part

Question 14

Which state of the Ca2+ channel is preffered by local anesthetics?

Answer 14

the activated and inactivated state
-when depolarized

-it prefers more rapid-firing neurons

Question 15

REMINDER route of pain signal

Answer 15

-REMINDER: the nocireceptor receives pain signal and forwards it along the axon -> to the dorsal root ganglion (DRG) -> to the dorsal horn of the spinal cord -> secondary neuron -> to the brain

Question 16

Where exactly on the neuron do local anesthetics work?

Answer 16

on the axon along the primary afferent neuron
-> blocking voltage-gated Na+ channels (inner part) -> prevents depolarization and the action potential transmission

Question 17

Which type of axons are primarily sensitive to local anesthetics?

Answer 17

Type C: small sized (diameter)
Type B: somewhat bigger -> some myelination are more sensitive local anestheitcs

Question 18

Which drugs are usually used for surface anesthesia?

Answer 18

Benzocaine -> mucous membranes (mouth, nose, throat)
Cocaine -> cornea

other surface: skin

Question 19

What does infiltration anesthesia refer to?

Answer 19

injection of local anesthetic into the affected area without the need to target nerve tracks
-> dentis for example

Question 20

What does nerve block anesthesia refer to?

Answer 20

injecting the local anesthetic into or adjacent to the peripheral nerves and plexuses

-> larger area of action
-> the entire area distal to the site of injection is affected
-> for patients with chronic pain

Question 21

Which parts of the body will affected when local anesthetics are injected intrathecally?

Answer 21

-anesthetize a large fraction of the lower body

injection into the CSF (Cerebrospinal fluid) around the spinal cord
minimal plasma level -> so less toxicity

Question 22

Where in the spinal cord is the CSF located?

Answer 22

between the Dura mater and Pia mater
-> subarachnoid space

Question 23

How is Epidural anesthesia different from an intrathecal injection?

Answer 23

it is injected above the dura mater into the epidural space
-> more likely to be absorbed into the bloodstream from the epidural space

Question 24

What is a possible complication of the Epidural injection?

Answer 24

Wet tap
-> when puncturing the dura it can leakage of spinal fluid -> creating a killer headache

Question 25

What are the adverse effects of local anesthetics?

Answer 25

-cardiovascular: bradycardia, hypotension
-GI: metallic taste, N/V
-CNS: drowsiness, dizziness, nervousness, blurry vision

-> should be minimal since applied locally and low systemic absorption

Question 26

What are possible (rare) CNS toxicites when applying high concentrations of local anesthetics?

Answer 26

-neural toxicity

-twitching followed by tonic-clonic convulsions
->due to depression of cortical descending inhibitory pathways

Question 27

What are possible cardiovascular toxicities of local anesthetics?

Answer 27

at high doses:
-slow conduction in atria and ventricles
-reduced excitability of heart muscle
-> can cause cardiac arrest
-may also depress the strength of cardiac contraction -> arteriolar dialtion (body reacts to low BP and creates less resistance for increased blood flow)

exception: cocain -> which is a stimulant