18 – Local Anesthetics and Nerve Blocks

Question 1

Local anesthetic drugs are designed to

Answer 1

• Penetrate peripheral nerve barriers
• Interrupt nerve conduction

Question 2

Conduction of electrical impulses in excitable membranes requires

Answer 2

• Flow of SODIUM ions through ion selective channels
  o Occurs in response to depolarization of the nerve cell

Question 3

Resting membrane potential

Answer 3

• At rest: concentration of Na ions is HIGHER OUTSIDE than inside the nerve
• RMP=-70mV

Question 4

What is the role of Na during depolarization?

Answer 4

• Permeability of membrane to Na ions increases transiently
• Na ions pass through the membrane by way of Na selective ion channels that first open and then close in response to depolarization of the membrane

Question 5

What is the role of K during depolarization?

Answer 5

• Membrane permeability to K ions increases
• normally: K is much higher inside than outside
• K efflux and membrane REPOLARIZATION occurs

Question 6

Action potential is completed in

Answer 6

• Approximately 1-2 msec

Question 7

How are peripheral nerve fibers classified?

Answer 7

• According to:
  o Fiber size
  o Physiological function
  o Rate of impulse transmission

Question 8

Myelin

Answer 8

• Phospholipid layer that surrounds and INSULATES axons of many neurons
• INCREASES speed of impulse propagation along the nerve
• Increases the fiber diameter
• *nonspecific binding site for local anesthetic molecules
• Relatively impermeable to local anesthetics

Question 9

Na channel receptor number and internodal distances

Answer 9

• *less numerous as the internodal distances INCREASES

Question 10

Myelin: increases axon diameter

Answer 10

• Contribute to a DELAY in onset of motor nerve blockage by local anesthetics

Question 11

Rate of local anesthetic blockade in C vs A fibers

Answer 11

• FASTER in unmyelinated C fibers than A fibers
• *fewer diffusion barriers around C fibers than A fibers

Question 12

A delta fibers: function, myelination, order of blockage and signs of blockade

Answer 12

• Fast pain, temperature
• Myelinated
• SECOND
• Pain relief, loss of temperature sensation

Question 13

C fibers: function, myelination, order of blockage and signs of blockade

Answer 13

• Slow pain, autonomic, postganglionic, sympathetic, polymodal nociceptors
• Unmyelinated
• SECOND
• Pain relief, loss of temperature sensation

Question 14

Mechanisms of action of local anesthetics

Answer 14

• Diffusion through nerve cell membrane
• Enter Na channels
• Inhibit influx of Na ions
• Interrupt nerve conduction

Question 15

What are the chemical properties that determine local anesthetic effect? (4)

Answer 15

• Lipid solubility
• Dissociation constant
• Chemical linkage
• Protein binding

Question 16

Lipid solubility

Answer 16

• POSITIVE correlation exists between degree of lipid solubility and inherent anesthetic POTENCY

Question 17

Lipid solubility: low

Answer 17

• High pKa
• Penetrate lipid membranes of large myelinated nerve fibers slowly
• Little conduction block develops
• Ex. Procaine

Question 18

Lipid solubility: high

Answer 18

• Low pKa
• Penetrate diffusion barriers around A-alpha nerves relatively easily
• Produce good motor blockade
• Ex. Mepivicaine

Question 19

Dissociation constant

Answer 19

• Determines the portion of an administered dose that exists in the lipid-soluble (uncharged), tertiary molecular state at a given pH
• *most local anesthetics have a pKa slightly greater than physiological pH

Question 20

Low pKa (dissociation constant)

Answer 20

• Greater proportion of drug that is in the diffusible (lipid-soluble) state
• Shorter ONSET OF ACTION

Question 21

What happens when the pH is equal to the drugs pKa?

Answer 21

• 50% of drug in in ionized form (active)
• 50% of drug is in unionized form

Question 22

Local anesthetic drugs are BASES that consist of 3 essential components

Answer 22

• Lipophilic aromatic ring
• Intermediate ESTER or AMIDE chain
• Terminal amine

Question 23

What is the classification of local anesthetics determined by?

Answer 23

• INTERMEDIATE LINKAGE (ester vs. amide)
  o *notable effect on chemical stability and METABOLISM

Question 24

Esters: chemical linkage

Answer 24

• Metabolized rapidly by plasma cholinesterases
• Shorter half-lives when stored in solution w/o preservatives

Question 25

Amides: chemical linkage

Answer 25

• Stable for LONGER periods of time
• Cannot be hydrolyzed by cholinesterase
• Enzymatically bio transformed in liver

Question 26

Esters examples

Answer 26

• Cocaine
• Benzocaine
• Procaine
• Tetracaine

Question 27

Amides examples

Answer 27

• Lidocaine
• Mepivacaine
• Bupivacaine
• Ropivacaine

Question 28

What does protein binding correlate with?

Answer 28

• DURATION OF ACTION
  o High affinity of local anesthetic for plasma proteins
  o Increased ability to bind Na channels
  o Prolonged duration of neural blockade

Question 29

Potency and toxicity: order of drugs lowest to highest toxicity

Answer 29

*increased potency=increased risk of toxicity
1. Lidocaine
2. Mepivacaine
3. Ropivacaine
4. Bupivacaine
5. Cocaine

Question 30

Therapeutic concentrations are clinically useful for

Answer 30

• Treatment of cardiac arrhythmias
• Lowering infectable and inhalant anesthetic drug requirements
• Producing promotility of GI effects
• Treating shock

Question 31

Negative effects of local anesthetics

Answer 31

• May potentiate CNS depressant effects of sedatives and opioids causing vasodilation and hypotension
• Higher concentrations can induce seizure activity (due to inhibition of CNS inhibitory tracts)

Question 32

Lidocaine vs. Bupivacaine and first signs of toxicity (+onset and duration)

Answer 32

• Lidocaine: CNS depression, ataxia, seizures
  o Onset: 5mins
  o Duration: 30-45mins
• Bupivacaine: arrhythmias
  o Onset: 10-20
  o Duration: 2-6hours

Question 33

Ways to potentiate (increase action/duration) of local anesthetics

Answer 33

• Vasoconstrictors
• Hyaluronidase
• pH adjustment

Question 34

Vasopressors combined with local anesthetics to produce

Answer 34

• local VASOCONSTRICTION
  o provide local hemostasis
  o delay the absorption of local anesthetic
• Ex. dexmedetomidine

Question 35

What is hyaluronic acid?

Answer 35

• tissue cement or ground substance of the mesenchyme

Question 36

What does hyaluronidase do?

Answer 36

• Depolymerizes hyaluronic acid
  o Aids in LOCAL spread of the anesthetic agent
• Not used as much anymore (more precise where we inject)

Question 37

What are most local anesthetics marketed as (pH adjustment)?

Answer 37

• Mildly acidic HCL salts to MAXIMIZE water solubility and improve stability

Question 38

What does raising pH of lidocaine, mepivacaine, and bupivacaine by adding Na-bicarbonate before injection do?

Answer 38

• Accelerate the onset of epidural analgesia and anesthesia
• Alkalinizer=decreases smell

Question 39

What does adjusting the local anesthetic pH toward physiological range do?

Answer 39

• Increase amount of anesthetic base available for diffusion through axonal membranes
• *should not affect duration of action

Question 40

Inflammation and local anesthetics

Answer 40

• Inflamed tissue=acidic
• Greater proportion of molecules is in water soluble form
• UNABLE TO CROSS CELL MEMBRANES
• DECREASED EFFECTIVENESS
• Ex. inflammation in dentals

Question 41

What are some techniques to improve success of nerve blocks?

Answer 41

• Nerve stimulator
• Ultrasound guidance