Local Anesthetics

Question 1

When LA is injected around a nerve, which fibers are blocked first? How does this manifest clinically?

Answer 1

Fibers on outer surface are blocked first, before more central fibers. This means anesthesia generally occurs first in more proximal areas of an extremity.

Question 2

With increasing concentration of LA, which types of nerve fibers are blocked? (what order?)

Answer 2

Autonomic > sensory > motor

Question 3

What does the pKa of a LA say about the ionization of the LA in the body?

Answer 3

The lower the pKa, the more likely the LA exists in an uncharged state.

Question 4

Why is bicarbonate added to LA solutions?

Answer 4

Bicarbonate increases the unionized fraction of LA and can hasten onset of anesthesia.

Question 5

Why does LA cause a use-dependent/frequency dependent block?

Answer 5

LA binds better to sodium channels in the active or inactivated-closed state relative to the resting closed state. More depolarization of the nerve leads to better binding.

Question 6

How do LA block conduction?

Answer 6

Binding to sodium channels and not allowing depolarization of nerves

Question 7

What state must a LA be in to successfully reach its receptor?

Answer 7

Unionized (to cross lipid membrane)

However, it becomes charged in axoplasm after crossing and this form binds and blocks the ion channel

Question 8

What are the three structural components of a LA?

Answer 8

Aromatic head (lipophilic)
Linking hydrocarbon chain
Terminal Amine

Question 9

How are esters and amides structurally different?

Answer 9

In the hydrocarbon chain, ester LAs have ester linkages and amide LAs have amide linkages

Question 10

What does lipid solubility of a LA correlate with?

Answer 10

More lipid soluble > more potent, longer duration of action, POSSIBLY shorter time to onset

Question 11

LAs generally vaso_______

Answer 11

Dilate

Question 12

How are ester LAs metabolized?

Answer 12

Plasma ester hydrolysis

Question 13

How are amide LAs metabolized?

Answer 13

Liver (hepatic microsomal enzymes)

Question 14

What does addition of a vasoconstrictor do to LAs?

Answer 14

Limits systemic absorption, prolongs duration of action. Alerts you to intravascular injection. NO effect on onset

Question 15

What is the toxic dose of lidocaine?

Answer 15

5 mg/kg

7 mg/kg with epi

Question 16

What is the toxic dose of bupivacaine?

Answer 16

2.5 mg/kg

Question 17

What are warning signs of intra vascular LA injection?

Answer 17

Circumoral numbness, facial tingling, restlessness, vertigo, tinnitus, slurred speech, tonic-clinic seizures

Question 18

What are first line /readily available drugs to use for LA induced seizures?

Answer 18

Benzos, propofol

Question 19

Why do high plasma concentrations of LA cause hypotension?

Answer 19

Relaxation of arterial vascular smooth muscle + direct myocardial depression

Question 20

How does cardiac toxicity from LA manifest on the EKG?

Answer 20

Prolonged PR interval and widened QRS

Question 21

Why do LAs cause cardiovascular toxicity?

Answer 21

Binding to cardiac sodium channels

Question 22

Are allergic reactions to LAs common?

Answer 22

No.

Most will be to esters rather than amide, due to reaction to PABA.

Question 23

Tetracaine is commonly used for ______ anesthesia and not _______ anesthesia because _________

Answer 23

Used for spinal not epidural because of slow onset, profound motor blockade, and toxicity at high doses

Question 24

Duration of action of chloroprocaine in epidurals is relatively _______

Answer 24

Short

Question 25

Why is epidural use of chloroprocaine sometimes avoided? (hint: interferes with…)

Answer 25

Impairs the anesthetic/analgesic action of epidural bupivacaine or opioids used concurrently or sequentially

Question 26

What is a concern with using lidocaine in a spinal?

Answer 26

Neurotoxicity (cauda equina syndrome)
-or-
Transient neurological symptoms in up to 1/3 of people getting spinal lidocaine - pain and dysethesia (onset 12-24 hours postop not associated with sensory loss, motor weakness, or bowel/bladder dysfunction)

Question 27

How does mepivacaine compare to lidocaine? (duration, vasoactive property?)

Answer 27

Mepivacaine is similar to lidocaine but with less vasodilation and slightly longer duration of action. Ineffective as topical agent. Still has some risk of TNS in spinals.

Question 28

Which LAs cause methemoglobinemia?

Answer 28

Prilocaine and benzocaine

Question 29

Major features of bupivacaine (3)

Answer 29

Long duration of action, great sensory blockade relative to motor blockade, increased risk of cardiac toxicity compared to lidocaine.

Question 30

Ropivacaine produces ______ vasoconstriction compared to bupivacaine

Answer 30

More

contributes to reduced cardiac toxicity

Question 31

Why is Ropivacaine said to be safer and more efficacious than bupivacaine?

Answer 31

Less binding of cardiac sodium channels, and better differential blockade of sensory > motor (disputed)

Question 32

What two LAs are found in EMLA?

Answer 32

Lidocaine and prilocaine