Intro/neuro - Lec 1&2

Front 1

Methods of inducing LA (do not want to do these things)

Back 1

Mechanical trauma
low temp
anoxia
chemical irritants
neurolytic agents
chemical agents

Front 2

LA

Back 2

Loss of sensation WITHOUT loss of consciousness (unlike GA)

Must be TRANSIENT and completely REVERSIBLE

Front 3

Desirable Properties of LA

Back 3

Low Allergenicity
Low systemic Toxicity
Fast onset (non-irritating, effective via all routes, suitable duration of action, potency without deleterious effects)
Stable in solution and readily undergo biotransformation in body
Sterile
Ability to be sterilized
Completely reversible

Front 4

Desired Action of LA

Back 4

To prevent both the generation and conduction of a nerve impulse

Front 5

LA Neurophysiology

Back 5

Motor: V3-Muscles of Mastication
Sensory: V1, V2, V3
Sensory neurons transmit pain (Dendritic zone of free nerve ending, axon, cell body)
Impulse or electrical action potential are brief membrane depolarizations

Front 6

Sensory Neuron

Back 6

Dendritic Zone: free nerve endings, most distal segment, impulse
Axon: cable like, synapse to CNS
Cylinder of neural cytoplasm (axoplasm), covered by the nerve membrane (axolemma)
Continuous nerve membrane separates axoplasm from ECF

Front 7

Biologic Membranes (axolemma)

Back 7

Block diffusion of water-soluble molecules
Selectively permeable by pores/channels
Transduce info by protein receptors responsive to chemical or physical stimulation by neurotransmitters, chemicals, physical stimuli

Front 8

Biologic Membranes

Back 8

Bilipid layer of phospholipids
Proteins, lipids, carbs
Proteins are primary organizational element of membrane
Transport proteins or receptor sites
Channel proteins (passive ion flow, gated)

Front 9

Impulse Transmission

Back 9

rapid depolarization-reversal of electrical potentail across nerve membrane +40
Absolute refractory period, relative

Front 10

Action of LA

Back 10

Specific Receptor Theory: Direct
LA acts by binding to specific receptors on the sodium channel

Front 11

Active forms of LA

Back 11

Majority of injectale LA are tertiary amines
Secondary amines (Prilocaine)

Front 12

Typical Structure of LA

Back 12

Amino esters of Amino amides
Lipophilic and hydrophilic part (amphipathic)
Intermediate chain

Front 13

True or False question

Back 13

LAs are basic compounds, dispensed as salts (weakly basic/combined with acids - LA dispensed as salts, most commonly with HCl salts, dissolved in sterile H2O or saline

Front 14

Acidification of tissue

Back 14

decreases LA effectiveness, pain
Normal pH = 7.4
Inflamed pH = 5-6

Front 15

Alkalinization of LA

Back 15

Speeds onset of action, decreases discomfort
Sodium bicarb/CO2, more comfort and faster onset

Front 16

pH

Back 16

high H+ = low pH
low H+ = high pH
pKa = dissociation constant, affects rate of onset of LA and Diffusion

Front 17

Clinical Implications of pH

Back 17

LA containing a vasopressor are acidified to retard oxidation of the vasoconstrictor
Sodium bisulfate 0.05% 0.1%
pH = 5.5-4.2 (Lidocaine alone, pH = 6.8)
Slows onset of action based on buffering capacity of tissue

Front 18

Diffusion

Back 18

Diffusion through nerve sheath and binding to receptor site
RN - free base form - diffusion
RNH+ cationic - binds to sodium channel receptor
The pH of the ECF determines the ease which LA moves from site of deposition to axoplasm

Front 19

Endoneurium

Back 19

covers the axons

Front 20

Perineurium

Back 20

binds nerves tobether into bundles or fasiculi

Front 21

Diffusion Barriers

Back 21

Perilemma - innter surface of perineurium = main barrier
Epineurium - contains fasiculi (LA readily diffuses)
Increased thickness of perineurium = diffusion barrier

Front 22

What is the main barrier of diffusion of LA into the nerve?

Back 22

Perilemma = the inner surface of perineurium

Front 23

Onset of LA

Back 23

Diffusion into the nerve
Depends on: Drug form (RN vs RNH+)
Ability to penetrate anatomical barriers
Conc. gradient

Front 24

Normal physiological pH

Back 24

Normal pH = 7.4

Front 25

2 forms of LA

Back 25

Base form (RN) - NOT active
Cation form (RHN+) - Active

Front 26

What is the main factor determining the effectiveness of LA

Back 26

ECF pH
Large buffering capacity - slows process

Front 27

&darr pH

Back 27

&darr pH = &uarr RHN+ form
abscess (lower pH)
Poor anesthesia

Front 28

&uarr pH

Back 28

&uarr RN (base) form = &uarr diffusion across nerve sheath = &uarr onset of LA

Front 29

pKA

Back 29

Controls the rate of onset (diffusion) - but is minimal

Front 30

Factors NOT under clinician's control

Back 30

Diffusion of anesthetic-conc. gradient
Penetration of anatomic barriers

Front 31

Factors under clinician's control

Back 31

Volume of LA
Conc. of LA
Technique/Anatomy

Front 32

Mantle Bundles

Back 32

Outer bundles of nerve are easily blocked due to their peripheral location and exposure to higher conc. of LA

Reach more proximal areas (molars, premolars)

Front 33

Core Bundles

Back 33

Inner bundles of nerve
More difficult to block due to their central location oand exposure to a lower conc. of LA

Reach more distal areas (canines, incisors)

Front 34

What are the greatest anatomic barriers to diffusion?

Back 34

Perineurium and Perilemma

Thickness of Perilemma (inner most layer of the perineurium) is the main barrier to diffusion

Front 35

Physical Properties of LA

Back 35

Lipid solubility
RN form more lipohilic
RNH+ form binds to receptor site

Front 36

Lipid Solubility of LA

Back 36

&uarr Potency
More rapid penetration into nerve
Can use lower conc./vol.

Front 37

RN form more lipophilic

Back 37

Protein binding
&uarr duration of action of LA

Front 38

Vascoactivity of LA

Back 38

Most cause vasodilation
&uarr blood flow and removal of drug from site
&darr conc. and shortens duration of action

Front 39

Vasoconstrictors and LA

Back 39

&uarr local vasoconstriction
&darr local blood supply
Maintain conc. of AL locally
Prolong duration of LA
Less systemic absorption (&darr systemic toxicity)

Front 40

Biotransformation

Back 40

Depends on type of LA (amide or ester)

Front 41

Esters

Back 41

hydrolyzed rapidly in plasma by pseudocholinesterase (short acting)

Front 42

Amides

Back 42

metabolized in liver by MAO and COMT (longer acting)

Front 43

Reinjection Phenomenon

Back 43

Rapid and profound LA
Tachyphylaxis

Front 44

Tachyphylaxis

Back 44

Increased tolerance to drug
More likely to occur if anesthesia is lost before reinjection

Front 45

Causes of Tachyphylaxis

Back 45

Edema, Hematoma/clot, Transduration, Hypernatremia (drowning patient)
&darr pH - from previous injection of acidic LA

Front 46

Duration of LA

Back 46

Protein Binding
Vascularity of the injection site
Presence or absence of vasoactive substances

Front 47

Duration and Protein binding

Back 47

the stronger the binding, the slower they are released from the Na+ channel receptors the the longer the duration

Front 48

Factors affecting LA Action

Back 48

pKa - onset
Diffusion - onset
Protein Binding - duration
Lipid solubility - Potency
Vasodilator activity - potency and duration

Front 49

How do pKa and Diffusion affect LA action?

Back 49

Onset

Front 50

How does protein binding affect LA action?

Back 50

duration

Front 51

How does lipid solubility affect LA action?

Back 51

potency

Front 52

How does vasodilator activity affect LA action?

Back 52

potency and duration