local anesthesia

Question 1

Na, Cl, K, HCO3: intra or extracellular higher?

Answer 1

Na: out
K: in
Cl: out
HCO3: out

Question 2

Pain Threshold:

Answer 2

– The least experience of pain which a subject can recognize

Question 3

• Pain Tolerance:

Answer 3

– The greatest level of pain which a subject is prepared to tolerate

Question 4

when is pain tolerance highest? lowest?

Answer 4

highest: morning
lowest: late afternoon

Question 5

axoplasm and axolemma

Answer 5

plasm: nn cyto
lemma; nn cell mem

Question 6

electrochemical gradients for Na and K

Answer 6

both are into the nn, but K favors out due to concentration

Question 7

AP basic diagram

Answer 7

Question 8

Where do local anesthetics work?

Answer 8

nn membrane

Question 9

SPECIFIC RECEPTOR theory

Answer 9

– Local anesthesia bind to specific receptor on the voltage gated Na channel

Question 10

What about Myelinated Nerve Fibers?

Answer 10

conduction much faster with saltatory conduction possible (a-a and a-d fibers)

Question 11

Myelinated Nerve Fibers
insulation from?

Answer 11

• Myelin sheath insulates axons electrically and pharmacologically
• Nodes of Ranvier=Sodium channel is abundance

Question 12

Ensuring effective anesthesia on myleinated fibers
what must be blocked, length?

Answer 12

– 2 or 3 nodes needs to be blocked
– 8-10 mm length needed

Question 13

How Local Anesthesia Work?

Answer 13

• Decrease permeability of ion channels to Na
• Nerve block by local anesthesia is a Non-depolarizing block

Question 14

Basic Structure of Local
Anesthetics

Answer 14

EXCEPT BENZOCAINE

Question 15

Active Forms of Local Anesthetics
exceptions?
hydrophobic/philic? exception?
what has weak LA properties?

Answer 15

• Majority are Tertiary amine, some esters
– Except prilocaine and hexylcaine ( 2nd amine)
• All local anesthetics are amphipathic except…benzocaine
• Antihistamine and anticholinergics have weak local anesthetic properties

Question 16

2 Types of local anesthetics, hydrolysis?

Answer 16

– Amide
• Resist hydrolysis, excrete unchanged in urine
– Ester
• Readily hydrolyzed in aqueous solution

Question 17

naming trick to local anesthetics

Answer 17

all amides have an i before -caine

Question 18

benzocaine structure

Answer 18

Benzocaine doesn’t have hydrophilic group
Therefore, its not suitable for injection but nice topical !!

Question 19

Dissociation of Local Anesthesia, equilibrium and shifts?

Answer 19

• Local Anesthesia are weak basic compounds
– They combine with acids to form local anesthetic salt (HCl)

• RNH+ ↔ RN + H+

– RNH+ ← RN + H+
Excess H+ (low pH), equilibrium shifts to the left RNH+

– RNH+ → RN + H+
Decrease of H+ (high pH), equilibrium shifts toward free base

Question 20

• pKa
equation, rearranged to pH?
when pH=pKa?

Answer 20

(dissociation constant)
– Relative proportion of ionic form depends on pKa
Log(Base/acid) = pH - pKa
pH = Log(Base/acid) + pKa

When pH of solution = pKa, you have 50/50 RN/RNH+

Question 21

Two Factors involved in the action of local anesthesia

Answer 21

– 1) Diffusion through nerve sheath
– 2) Binding at receptor site

Question 22

diffusion and binding of local anesthesia

Answer 22

only free base can diffuse but only cationic form can bind receptor

Question 23

Etidocaine example of diffusion and action
at 7.4 RN=25%

Answer 23

• Etidocaine @ normal tissue pH 7.4
– 25% free base (RN), 75% cation (RNH+) (RNH+ ↔ RN + H+)
• Let’s say we have 1000 molecules available
– 250 lipophilic RN WILL diffuse through membrane
• Once at intracellular level, 250 will re-equilibrate into
– 70 RN and 180 RNH+
• This process will continue until all gone

Question 24

pKa influence on onset of action, why is benzocaine not injected?

Answer 24

– ↑ pKa translate to slow onset
• b/c few free base molecule available to diffuse
– ↓ pKa will have faster onset
• Remember, once intracellular, we need RNH+ to bind the receptor.

i.e. Benzocaine isn’t all that cool for injection purpose! (doesn’t form cation)

Question 25

Clinical Implication: Extracellular pH and local anesthesia

Answer 25

Extracellular pH determines the ease for nerve blockade
• Inflamed or infected tissue is much more difficult to get
adequate anesthesia b/c lower pH or ↑H+ (shift to cation and less free base to diffuse)

Question 26

Local Anesthetic Solution pH (injected and topical forms)
what is added to injected forms?
why are topical forms prepared this way?

Answer 26

• Keep low pH equates ↑effective shelf live of local anesthesia
• Most local anesthesia have pH 5.5 to 7
– Sodium bisulfite (antioxidant) is added with vasoconstrictor
– Slower onset with vasoconstrictor vs “plain”

• Most topical Anesthesia is prepared in more concentrated form compared to injectable local anesthesia (1% or 2 % lidocaine)
– This is due to poor buffering capacity of mucous membrane

Question 27

barrriers to diffusion

Answer 27

• Endoneurium, Perineurium, Epinerium
• Perineurium is greatest barrier for diffusion
– Slower diffusion is dependent on the thickness

Question 28

mantle and core fibers innervate?

Answer 28

• Mantle fiber tends to innervate proximal region (molars)
• Core fiber innervates more distal points (incisors)

Question 29

Complete conduction blockade requires

Answer 29

– Volume and Concentration in correct region

Question 30

What happens to injected drug?

Answer 30

Absorbed by nonneural tissue
– Diluted by interstitial fluid
– Removed by capillaries and lymphatic system
– For Ester-type: immediate enzymatic hydrolysis

Question 31

lower pKa?

Answer 31

faster onset

Question 32

greater lipid solubility effect?

Answer 32

more potent (rapid diffusion)

Question 33

increased protein binding effect?

Answer 33

increased duration of action

Question 34

Recovering from nerve block

Answer 34

– “reverse” of anesthetic induction pattern
– Intraneural concentration exceeds extraneural concentration, diffusion out

Question 35

Recurrence of Immediate profound anesthesia
reduced concentration where?
what should be done?

Answer 35

– Reduced concentration at mantle fibers= reinjection
– Residual local + newly deposited supply = immediate profound anesthesia

Question 36

Difficulty reestablish profound anesthesia when?

Answer 36

– Surgical procedure outlasts effectiveness of med
– Tachyphylaxis

Question 37

Tachyphylaxis, factors?

Answer 37

– ↑ Tolerance to drug after repeated administration
• Factors
– Edema
– Localized hemorrhage
– Clot formation
– Transudation
– Hypernatremia
– ↓pH of the tissue

Question 38

what do lipid solubility, pro binding and pKa influence?

Answer 38