L 19 Local Anesthetics

Question 1

Two main types of local anesthetics in terms of chemical structure

Answer 1

Esters: earlier forms of anesthetics, shorter duration, but more toxic
Amides: more recently developed drugs

Question 2

How do local anesthetics work?

Answer 2

They bind Na channels to prevent their function thereby preventing transmission of pain signals
They bind to the intracellular side of the receptors by first crossing the membrane in the non-ionized form and then binding in the ionized form.
Higher affinity to the more active neurons

Question 3

How does extra-cellular Ca and K affect mechanism of action for local anesthetics?

Answer 3

Increased extracellular Ca => increase in membrane potential and a decrease in block

Increase in extracellular K => depolarized membrane and a more active neuron and the block is enhanced

Question 4

Which local anesthetics last longer or shorter?

Answer 4

Short: Procaine

Medium: Cocaine, Mepivacaine, Lidocaine

Long: Tetracaine, Bupivicaine, Ropivicaine

Question 5

What determines duration of action for LA’s?

Answer 5

Lipid solubility => increased time at site of action and therefore longer duration of action.

Question 6

Metabolism and Excretion of Amides and Esters

Answer 6

Amides: CYP450 in liver, metabolites excreted in kidney

Esters: metabolized in the plasma

Question 7

Oder of sensitivity of nerve fibers

Answer 7

Sympathetic > Sensory > Touch > Motor
(Usually)

Small, unmyelinated are more sensitive to block
Faster nerves are less sensitive to block

Question 8

Potential adverse effects of local anesthetics

Answer 8

Cardiovascular: can act on the heart Na channels => arrhythmias–Bupivacaine, Cocaine

CNS: depression of inhibitory pathways => nystagmus, twitching, convulsions, death

Allergic: PABA from ester metabolism can => hypersensitivity

Blood: Prilocaine can => methemoglobinemia

Neural injury locally

Transient Neuro Symptoms: pain, dysthesia

Question 9

Procaine (Novocaine)

Answer 9

Ester
Short duration (few minutes)
PABA => allergic response
Infiltration anesthesia and diagnostic nerve blocks
Minimal toxicity

Question 10

Tetracaine (Pontocaine)

Answer 10

Ester
Longer lasting than Procaine
Slow onset of action > 10  min
16x more potent and toxic than procaine
Good for ophthalmological use
Spinal anesthesia

Question 11

Benzocaine (Americaine)

Answer 11

Ester
Unique low pKa=3.5 means transported well but binds poorly to Na channel
Topical only for sunburns, pruritis
Risk of methemoglobinemia

Question 12

Cocaine

Answer 12

Ester
Short acting
Topical use
Can reduce bleeding
Causes euphoria in CNS
Cardiovascular: HTN, CVD, thyrotoxicosis

Question 13

Lidocaine (Xylocaine)

Answer 13

Prototype Amide drug
Rapidly absorbed, intermediate duration 1.6hr half-life
More potent and longer than procaine
Preferred for infiltration blocks and epidural anesthesia
Not for spinal blocks

Question 14

Prilocaine (Citanest)

Answer 14

Amide group
Highest rate of clearance of the amides
Known to cause Methemoglobinemia
Used mostly in dentistry

Question 15

Bupivacaine (Marcaine)

Answer 15

Amide group
Long duration
Used post-op for pain
Greater degree of cardiotoxicity
More potent sensory block than motor block
Preferred as epidural block for labor and delivery

Question 16

Ropivacaine (Naropin)

Answer 16

Amide
Long acting
Enantiomer to Bupivacaine
Less lipid soluble and cleared more quickly than Bupivacaine, also less likely to cause cardiac toxicities
CYP3A4 metabolism
Used for peripheral epidural blocks
Unique in that it has a vasoconstricting effect and doesn’t need epinephrine co administration

Question 17

Mepivacaine (Carbocaine)

Answer 17

Amide similar to bupivacaine
Intermediate duration
Not used in labor

Question 18

Etidocaine (Duranest)

Answer 18

Amide
Long duration
Reverse differential block–motor before or without sensory

Question 19

Articaine (Septocaine)

Answer 19

Amide with an additional ester group
Subject to metabolism like amides and esters => decreased half-life
Use in dental medicine
Large therapeutic window
May cause persistent paresthesias

Question 20

Dibucaine (Nupercainal)

Answer 20

Amide

Used primarily to measure cholinesterase activity, differentiates between mutations and deficiencies