Local anesthetics and nerve blocks

Question 1

Local anesthetic design

Answer 1

-Penetrate peripheral nerve barriers
-interrupt nerve conduction

Question 2

Conduction of electrical impulses

Answer 2

Na ions flow through ion selective channels cause excitation due to depolarization of nerve cell

Question 3

Resting membrane potential

Answer 3

Rest: Concentration of Na ions higher outside than inside nerve

Resting membrane potential= -70 mV

Question 4

Na during depolarization

Answer 4

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

Question 5

K during depolarization

Answer 5

-Membrane permeability to K ions increases
-Normally K is higher inside than outside the nerve, but depolarization causes K efflux and membrane repolarization

Question 6

How to classify peripheral nerve fibers?

Answer 6

-Fiber size
-physiological function
-Rate of impulse transmission

Question 7

Myelin

Answer 7

A phospholipid layer that surrounds and insulates the axons of many neurons
-increases speed of impulse propagation along nerve
-increases fiber diameter-insulation barrier to anesthetics
-increases axon diameter- contributes to a delay in onset of motor nerve block by local anesthetics
-Na channels decrease in nuber as internodal distance increases

Question 8

Myelin and anesthetics

Answer 8

-Serves as a nonspecific binding site for local anesthetics molecules
-relatively impermeable to local anesthetics

Question 9

Rate of local anesthetic blocks on different fibers

Answer 9

Faster in unmyelinated C fibers than in A fibers

**because there are fewer diffusion barriers around the C fibers than A fibers

Question 10

A delta fibers

Answer 10

-fast pain and temperature

-myelinated
-second order of blockade; block will give pain relief and loss of temperature sensation

Question 11

C fibers

Answer 11

-slow pain, autonomic, post ganglionic sympathetic, polymodal nociceptors

-unmyelinated
-second order of block; block will provide pain relief, loss of temperature sensation

Question 12

Mechanism of action of local anesthetics

Answer 12

1.Diffusion through the nerve cell membrane
2.Enter Na channels
3. Inhibit influx of Na ions
4. Interrupt nerve conduction

Question 13

Chemical properties that determine local anesthetic effect

Answer 13

-lipid solubility
-dissociation constant
-chemical linkage
-protein binding

Question 14

Lipid solubility

Answer 14

Positive correlation exists between the degree of lipid solubility and inherent anesthetic potency

Question 15

Low lipid solubility

Answer 15

-High pKa
-penentrate lipid membranes of large myelinated nerve fibers slowly
-little conduction block develops

Question 16

High lipid solubility

Answer 16

-low pKa
-penetrate diffusion barriers around alpha A nerves relatively easily
-produce good motor blockade

Question 17

Dissociation constant

Answer 17

Determines the proportion of an administered dose that exists in the lipid-soluble (uncharged; unionized), tertiary molecular state at a given pH

**most local anesthetics have pKa slightly greater than physiological pH

Question 18

Lower pKa (dissociation constant)

Answer 18

The greater the proportion of drug that is in the diffusible (lipid-soluble) state
**shorter onset of action

Question 19

pH equal to drugs at pKa

Answer 19

Means 50% of drug in ionized form and 50% of drug in unionized form

Question 20

Three essential components of local anesthetic drugs

Answer 20

**BASES

1. Lipophilic aromatic ring
2. An intermediate ester or amide chain
3. A terminal amine

Question 21

Chemical linkage

Answer 21

Used to classify local anesthetics as it has an effect on their chemical stability and metabolism

Question 22

Ester linkages

Answer 22

-metabolized rapidly by plasma cholinesterases
-have short half lives when stored in solution without preservatives

Question 23

Amide linkages

Answer 23

-stable for longer periods of time
-cannot be hydrolyzed by cholinesterase
-enzymatically biotransformed in the liver

Question 24

Ester drugs

Answer 24

-cocaine
-benzocaine
-procaine
-tetracaine

Question 25

Amide drugs

Answer 25

-lidocaine
-mepivacaine
-bupivacaine
-ropivacaine

Question 26

Protein binding

Answer 26

Correlates with duration of action
-high affinity of local anesthetic for plasma proteins (alpha 1-acid glycoprotein)
-increased ability to bind Na channels
-prolonged duration of neural block

Question 27

Toxicity of local anesthetics

Answer 27

**increased potency=increased toxicity

Produce a dose dependent CNS depression proportional to their inherent local anesthetic potency

Question 28

Levels of toxicity of local anesthetic drugs

Answer 28

GREATEST
1. Cocaine
2.Bupivacaine
3.Ropivacaine
4. Mepivicaine
5. Lidocaine
LOWEST

Question 29

Therapeutic concentrations clinical uses

Answer 29

1. Treatment of cardiac arrhythmias
2. Lower injectable and inhalant anesthetic drug needs
3. Produce promotility GI effects
4. Treat shock

Question 30

Negative effects of local anesthetic use

Answer 30

-Potentiate CNS depressant effects of sedatives and opioids causing vasodilation and hypotension

-High concentrations can induce seizure due to inhibition of CNS inhibitory tracts

Question 31

Lidocaine vs. Bupivacaine toxicity

Answer 31

Lidocaine: first signs are CNS depression, ataxia, seizures

Bupivacaine: first signs of toxicity= arrhythmias

Question 32

Potentiation of local anesthetics

Answer 32

-Vasoconstrictors
-Hyaluronidase
-pH adjustment

Question 33

Hyaluronidase

Answer 33

Hyaluronidase depolymerizes hyaluronic acid (which is the tissue cement or ground substance of mesenchyme).

Results in the aiding of local spread of the anesthetic agent

Question 34

Vasoconstrictors

Answer 34

Local vasoconstriction is obtained by combining vasopressors and local anesthetics
-provides local hemostasis
-delay the absorption of the local anesthetic

Question 35

pH adjustment

Answer 35

Most local anesthetics are mildly acidic HCl salts to maximize water solubility and improve stability.

Therefore can raise pH (closer to physiological pH) of lidocaine, mepivacaine, bupivacaine by adding NaOH before injection can increase movement across membrane and the onset of epidural analgesia and anesthesia
*likely due to increasing anesthetic base available for diffusion through axonal membranes

Question 36

Inflammation and local anesthetics

Answer 36

-inflamed tissue is acidic and a greater proportion of molecule is in water soluble form. Means it is unable to cross cell membranes and effectiveness is decreased

Question 37

Techniques to improve success of nerve blocks

Answer 37

-Nerve stimulator

-Ultrasound guidance