Neuro: Local Anesthetics

Front 1

Name the three stimuli that activate nociceptors.

Back 1

1. high temperature
2. mechanical trauma
3. harsh chemicals

Front 2

Where are the cell bodies of nociceptors located?

Back 2

DRG
Trigeminal ganglion

They synapse in the dorsal horn of spinal cord.

Front 3

What are some ways nociceptors get sensitized?

Back 3

1. Bradykinin, serotonin, prostaglandins, K+ ions released by damaged cells.
2. substance P and calcitonin gene related peptide(CGRP) released by activated nociceptors.
3. histamine and serotonin released by mast cells that are activated by substance P and CGRP.

Front 4

Describe the process in nociceptor activation.

Back 4

1a. stimuli activate polymodal nociceptors.
1b. nearby damaged cells release bradykinin, prostaglandins, serotonin, and K+ which stimulate nociceptors.
2. nociceptor activation
3. activated nociceptors release substance P and CGRP.
4. blood vessel dilation(white cell recruitment) and mast cell degranulation(histamine, serotonin) in response to substance P and CGRP.

Front 5

Firing rate of nociceptors correlates with ____.

Back 5

stimulus intensity (eg. pain)

Front 6

Which type of nerve fibers are most susceptible to local anesthetics?
A. Aα, Aβ fibers
B. Aγ fibers
C. Aδ fibers
D. C fibers

Back 6

D: smallest diameter, unmyelinated, slow conducting.

Front 7

T/F: Small unmyelinated nerve fibers are blocked before larger myelinated nerve fibers.

Back 7

T.

Front 8

How does local anesthetics work on myelinated nerve fibers?

Back 8

Local anesthetics work in Na+ channels that are located at Nodes of Ranvier.
Three successive nodes must be blocked to halt impulse propagation.

Front 9

In myelinated nerve fibers, how many successive nodes must be blocked to stop the impulse transmission?

Back 9

Three

Front 10

Rank the following in the sequence of loss of function in response to local anesthetics:
A. cold, warmth, touch, deep pressure
B. pain sensation and autonomic response
C. somatic motor functions

Back 10

B
A
C

Front 11

Do local anesthetics change resting membrane potential in neurons?

Back 11

No.

Front 12

Thermal nociceptors are activated at temperature above ___ degrees or below ___ degrees.

Back 12

Above 45 and below 5 degree C.

Front 13

What are the two uses(effects) of lidocaine?

Back 13

1. local anesthetics
2. anti-arrhythmic agent

Front 14

At high doses, the toxicity of local anesthetics is due to what?

Back 14

Other channels that are also affected by the local anesthetics (such as K+, Ca2+ channels, nicotinic and muscarinic receptors).

Front 15

First pain is conducted by ___ fibers, where as the second pain is conducted by ___ fibers. Which pain is slower arriving? Which pain is sharp and which is diffuse?

Back 15

First pain: Aδ fibers
second pain: C fibers

Second pain is slower arriving because C fibers are smaller diameter, unmyelinated, and slow conducting.

Sharp pain: 1st pain
diffuse pain: 2nd pain.

Front 16

Which pain is more sensitive to local anesthetics? (1st or 2nd)

Back 16

2nd pain: conducted by C fibers.

Front 17

T/F: Small sensory fibers with high frequency, long action potentials are blocked before low frequency, short action potential motor fibers.

Back 17

T.

Exception: in large mixed nerve, circumferential motor fibers are blocked before sensory fiber in the center of the bundle.

Front 18

Where are sensory fibers located in a large mixed nerve bundle?

Are they blocked first by local anesthetics?

Back 18

In the center.
No. Circumferential motor fibers are blocked first in this case.

Front 19

Where do you find Aδ in highest density?

Back 19

finger tips
face
lips

Front 20

What are the components of peripheral nerve(mixed nerve)?

Which components do local anesthetics block?

Back 20

1. A,B,C nociceptor fibers
2. efferent fibers: somatic motor and autonomic nerve fibers

Local anesthetics block all of these components.

Front 21

What are the three layers of protective sheath of periphery nerve fibers?

Which layer is local anesthetics usually injected?

Back 21

1. epineurium
2. perinurium
3. endoneurium

LA is normally injected outside epineurium.

Front 22

Why do the proximal areas of the body become numb first?

Back 22

Because proximal areas are innervated by superficial fibers.

Front 23

Rank the following item in local anesthetic blockade order:
first pain
second pain
touch
temperature
skeletal muscle tone
proprioception
voluntary tension

Back 23

first pain
second pain
temperature
touch
proprioception
skeletal muscle tone
voluntary tension

Front 24

What is the difference in type of nerve block between local anesthetics and lidocaine?

Back 24

LA: block sensory without producing motor blockade.

Lidocaine: blocks both Aα and Aγ motor fibers.

Front 25

Name the two types of LA.

Back 25

Esters: Procaine
Amides: Lidocaine

Front 26

Procaine
What enzyme metabolizes procaine?

Back 26

butyrylcholinesterase (pseudocholinesterase)

Front 27

Procaine
Why is it not used for spinal anesthesia?

Back 27

Spinal fluid lacks metabolizing enzymes.

Front 28

Procaine
What is its drug-drug interaction?

Back 28

Procaine can not be used with sulfonamide: procaine metabolite PABA reduces effectiveness of sulfonamides, sulfonamides inhibit synthesis of PABA.

Front 29

Lidocaine
Where is lidocaine metabolized?

Back 29

Liver: all amides are metabolized here.

Front 30

Which produces longer toxicity, procaine or lidocaine?

Back 30

Lidocaine: metabolized more slowly in the liver.

Front 31

For elderly, alcoholics, and newborns, higher or lower dosage of lidocaine should be adminstered?

Back 31

Lower: because of their impaired liver function.

Front 32

Where is the site of action of LA? extracellular side or cytoplasmic side?

Back 32

Cytoplasmic

Thus drug need hydrophobicity for effective activity.

Front 33

Where are neutral or weakly phydrophobic LAs accumulate?

Back 33

In the acqueous extracellular interstitial fluid.

Front 34

Where are strongly phydrophobic LAs accumulate?

Back 34

They are trapped in the lipid bilayer.

Front 35

Which phydrophobic type of LA will be able to cross cell membrane?
A. neutral
B. weakly hydrophobic
C. moderately hydrophobic
D. highly hydrophobic

Back 35

C.

Front 36

Name other two toxins that blocks Na+ channels in a similar fashion as LA.

Back 36

marine toxins: tetrodotoxin, saxitoxin

Front 37

Name two biological toxins that blocks Na+ channel inactvation thus causing prolonged influx of Na+.

Back 37

1. veratridine
2. scorpion venom

Front 38

What does veratridine do to Na+ channels?

Back 38

Blocks Na+ channel inactvation thus causing prolonged influx of Na+.

Front 39

What does scorpion venom do to Na+ channels?

Back 39

Blocks Na+ channel inactvation thus causing prolonged influx of Na+.

Front 40

What does tetrodotoxin do to Na+ channels?

Back 40

Blocks Na+ channel by binding to cytoplasmic side of the receptor.

Front 41

What does saxitoxin do to Na+ channels?

Back 41

Blocks Na+ channel by binding to cytoplasmic side of the receptor.

Front 42

T/F: LA blocks Na+ channel in a time and voltage dependent fashion.

Back 42

T.

Front 43

Compare the pH of LA in the following places:
1. in formulation
2. in interstitial fluid

Back 43

Supplied as water soluble, stable hydrochloride salts of weakly basic amines.
1. in formulation: completely ionized pH 4.5-6, dissociates into +charged quaternary amine and uncharged tertiary amines.

2. in interstitial fluid: pH 7

Front 44

What happens when you administer LA repeatedly at the same site?

Back 44

Depletion of local tissue buffers, this leads to tachyphylaxis.

Front 45

Which form of LA crosses cell membrane? Charged or uncharged?

Back 45

Uncharged. So raising pH enhances LA penetrance: more drug is non-ionized.

Front 46

What percentage of lidocaine is non-ionized at pH 7?

Back 46

20%.
Lidocaine: pKa 7.86

Front 47

Which is more fast acting, lidocaine or procaine?

Back 47

Lidocaine: 20% non-ionized at pH7.4 where as 2% non-ionized for procaine. Thus more % of lidocaine crosses lipid bilayer.

Front 48

Why should you wait for treatment of inflammation before doing anesthetic procedures?

Back 48

Inflammation reduces interstitial pH which then lowers penetrance of LAs(more ionized form).

Front 49

T/F: Resting nerve much less sensitive to LAs than acitivated ones.

Back 49

T.

Front 50

Describe LAs' progression of effects on Na+ channel.

Back 50

1. increased threshold for excitation
2. slowed impulse conduction
3. decreased rate of rise of action potential
4. decreased action potential amplitude
5. ability to generate an action potential
6. abolished propagation of Na+ current along the axon.

Front 51

How does LA block the opening of Na+ channels after it makes the way to the receptor site on the cytoplasmic side?

Back 51

LAs act by attaching to 2 anionic phosphate tails and this causing a bridge across the membrane, which no longer opens.

Front 52

The Na+ channel is consisted of ___ domains, each having ___ transmembrane segments.

Of the segments:
____ form the voltage sensing elements needed to open the M gate.
___ and ___ line the pore.

Of the domains:
___ and ___ make up the H gate.
___ is targeted by the LAs.

Back 52

4 domains, each having 6 transmembrane segments.

Of the segments:
S4 form the voltage sensing elements needed to open the M gate.
S5 and S6 line the pore.

Of the domains:
III and IV make up the H gate.

S6 of domain IV is targeted by the LAs.

Front 53

Which protein segment is targetd by LAs?

Back 53

S6 of domain IV is targeted by the LAs.

Front 54

Which protein segement(s) line the ion channel pore?

Back 54

S5 and S6

Front 55

Which Na+ channel protein segment contains the voltage sensing elements?

Back 55

S4

Front 56

H gate is made up of which two domains of the Na+ channel protein?

Back 56

III and IV

Front 57

What are two ways that LA make it to the receptor on S6 of domain IV in Na+ channel?

Back 57

1. aqueous route(charged) when channel is open.

2. through membrane (uncharged) when gate is inactivated.

Front 58

T/F: The higher frequency of recent stimulation, the lesser the blockade.

Back 58

F. The higher the frequency, the greater the blockade. (phasic block)

Front 59

Which of these 2 has high firing rate and a relatively long action potential duration?
1. sensory pain fibers
2. motor fibers

Back 59

sensory pain fibers(A delta)

Front 60

What are some factors of LA absorption extent and rate? (4)

Back 60

1. vascularity of injection site
2. LA concentration
3. addition of vasoconstrictor
4. properties of LA

Front 61

How are amide-linked LA metabolized?

Back 61

Travel to the lung first and then metabolized by P450 in the liver.

Front 62

What factors affect LA binding to tissue, glycoprotein, albumin, and erythrocytes?

Back 62

1. hydrophobicity of the LA: the more lipophilic, the greater the tissue binding
2. plasma pH: the higher the pH, the greater the binding.

Front 63

Which has a larger Vd, more or less lipophilic LA?

Back 63

more lipophilic LA has larger Vd, and are also eliminated slowly.

Front 64

How are ester-linked LA metabolized?

Back 64

by tissue and plasma esterases, excreted by kidney.

Front 65

Which drug has liver toxicity, amide- or ester-linked LA?

Back 65

Amide-linlked: because P450 is needed for its metabolization.

Front 66

What type of patients should not use ester-linked LAs?

Back 66

People who has atypical pseudocholinesterase.

Front 67

Which of the following space should you not inject ester-linked LAs?
A. Interstitial space
B. Subarachnoid space

Back 67

B: because CSF do not contain esterase to metabolize it.

Front 68

What condition/technique would lead to ester-linked toxicity? (2)

Back 68

1. People who has atypical pseudocholinesterase.
2. Injection into CSF: CSF do not contain esterase to metabolize it.

Front 69

What conditions would lead to amide-linked toxicity? (2)

Back 69

1. overdose
2. elderly and newborn: decreased liver function(P450) to metabolize the drug.

Front 70

What can cause allegic reactions to LAs? (4)

Back 70

1. overdose
2. epinephrine as a vasoconstrictor
3. hypersensitivity to methyl paraben (preservative).
4. nervousness, fright, needles, pain, position.

Front 71

What drugs can be used to treat allegic reactions to LAs?

Back 71

1. diphenhydramine
2. epinephrine
3. external cardiac message
4. IV dextrose in water
5. hydrocortisone (slowly)

Front 72

T/F: LA toxicity can be both excitatory and depressive.

Back 72

T.
Excitatory: yawning, restlessness, apprehension, disorientation, nausea, vomit, tremor, convulsions.

Depressive: loss of consciousness, loss of reflexes, decreased BP, decrease HR, decreased RR.

Front 73

What are some management of LA toxicity?

Back 73

1. maintain airway
2. ventilate with O2
3. administer diazepam(sedative)
4. fluids nad vasopressors

Front 74

Which type of LA is more likely to cause allergic reactions?

Back 74

ester type: more likely topically.

Front 75

Is LA with vasoconstrictors contraindicated in hypertesive patients?

Back 75

Not if they are well controlled and LA carefully administered.

Front 76

When is LA with vasoconstrictors contraindicated?

Back 76

1. uncontrolled hypertension, hyperthyroids.
2. patients receiving cyclopropane, halogenated hydrocarbons.

Caution with MAO inhibitors, phenothiazines, antidepressants.
Caution in patients on propranolol.

Front 77

Why should you wear gloves when adminstering LAs?

Back 77

Topical application is more likely to cause allergic reactions (contact dermatitis).

Front 78

What are some ways to avoid adverse reactions to LAs? (7)

Back 78

1. avoid overdose
2. avoid IV injections
3. avoid multiple vials
4. use regional block needles
5. limit vascular absorption by using vasoconstrictors.
6. keep pCO2 low (keep patients well ventilated)
7. used diazepam to elevate convulsive threshold

Front 79

Rank the following sites in decreasing order of LA absorption:
A. peripheral nerve
B. epidual
C. caudal
D. intercostal

Back 79

D, C, B, A

Front 80

Why is pure alpha agonist contraindicated in LAs?

Back 80

Cause circulatory collapse and reflex bradycardia.

Front 81

In dentistry or in patients with cardiac dysfunction, what drug should be used to vasoconstrict?

Back 81

self-aspirating system of injection, or drugs other than catecholamines.

Front 82

How is potency related to lipid solubility in vitro and in vivo?

Back 82

In vitro: potency is directly related to lipid solubility.

In vivo: not clear because of variable degree of vasodilation.

Front 83

T/F: The more close to 7.4 the pKa of LA is, the more onset of analgesia.

Back 83

T. More uncharged LAs to get through cell membrane.

Front 84

Which of the following produces least vasodilation?
A. Mepivacaine
B. Prilocaine
C. Lidocaine
D. Procaine

Back 84

A.B.

C: cause more vasodilation
D: cuase most vasodilation

Front 85

What is the drug that produces pain-free childbirth without the mother losing lower limb motor control?

Back 85

Bupivacine: long acting LA with differential sensory and motor blocking ability.

Front 86

Name 2 ester type LAs.

Back 86

1. procaine: most vasodilation, hydrolyzed to PABA(allergen), used for infiltrating anesthesia and in dental procedures.

Tetracaine: long acting, used in spinal and topical anethesia.

Front 87

Name the amide type LAs.

Back 87

Lidocaine: rapid onset, long duration.
Mepivacine: not effective topically.
Dibucaine: most toxic and potent, used for people with pseudocholinesterase.
Prilocaine
Bupivacaine

Front 88

Which drug should be used when epinbephrine is contraindicated?

Back 88

Prilocaine.

Front 89

Which drug should be used in people with atypical pseudocholinesterase?

Back 89

Dibucaine

Front 90

Routes of LA administration.

Back 90

1. spinal block
2. paravertebral block
3. epidural block
4. caudal block

Front 91

Which LAs can be used topically?

Back 91

cocaine
benzocaine
lidocaine+prilocaine (EMLA)

Front 92

Which LAs can be used for infiltration anesthesia?

Back 92

procaine
lidocaine

Infiltration anesthesia: intradermal, subcutansous

Front 93

Which LAs can be used for peripheral nerve anesthesia (conduction block)?

Back 93

procaine
lidocaine

Front 94

Where is spinal anesthesia injected?

Back 94

subarachnoid space between 2nd and 5th lumbar vertebrae.

Front 95

What are the factors that determine the diffusion of LA during spinal block? (5)

Back 95

1. specific gravity
2. position of patients
3. curvature of spine
4. movement or coughing
5. size of subarachnoid space

Front 96

What are some advantages and disadvantages of intrathecal anesthesia?

Back 96

Advantages: complete muscle relaxation, loss of conscious, useful for lower extremety operations.

Disadvantages:
hypotension
unpredictability
nausea, vomit
traumatize nerve roots, spinal cord or meninges
loss of CSF causes headache

Front 97

What are some advantages and disadvantages of epidural anesthesia?

Back 97

Advantage: avoid suarachnoid space, more predictable.

Disadvantage:
difficult to perform
longer time to onset
require large amount of drug
systemic absorption may be significant

Front 98

What is a Bier's block?

Back 98

Intravenous regional anesthesia: after applying a tourniquet to an elevated extremity, a LA is injected IV in extremity to provide local anethesia.

Front 99

Name an example of a epidual block.

Back 99

Caudal block.