Local Anesthetics

Question 1

Most local anesthetic agents consist of a lipophilic group (eg, an ___ ring) connected by an intermediate chain (___ or ___) to an ionizable group (eg, a ___ ___).

Answer 1

aromatic; ester; amide; tertiary amine

Question 2

Because ester links are more prone to ___ by pseudocholinesterases than amide links, esters usually have a ___ duration of action. Which is favored in dental practices?

Answer 2

hydrolysis; shorter; amides

Question 3

Why do amides have a longer half life in the plasma?

Answer 3

local anesthetics with an amide linkage will be metabolized by P450 enzymes in the liver, thereby they’ll have a longer half life in the plasma

Question 4

Which are more allergenic, esters or amides?

Answer 4

esters

Question 5

T/F. Amides will have an ‘i’ in their name somewhere prior to ‘caine’ (eg, lidocaine) but esters won’t (eg, procaine).

Answer 5

True.

Question 6

Primary, secondary and tertiary amines will exist in equilibrium between basic and acidic forms. What are type of amine are local anesthetics used in dentistry?

Answer 6

secondary or tertiary amines

Question 7

Are both forms, acidic and basic, of local anesthetics important for function? Why?

Answer 7

Yes, the uncharged BASIC form will cross the cell membrane. Therefore, local anesthetics produce their block from ‘inside’ the nerve.

Once inside the nerve, the charged acidic form will bind better to the Na+ channel and inhibit conduction of the nerve impulse.

Question 8

In the case of optically active agents such as ___, the R(+) isomer can usually be shown to be slightly more ___ than the S(-) isomer (___).

Answer 8

bupivacaine; potent; levobupivacaine

Question 9

Local anesthetics cross the axon membrane and interact with the ___ and ___ forms of the Na+ channel, blocking Na+ conductance.

Answer 9

open; inactivated

Question 10

Axons are either myelinated or unmyelinated. Which form conducts nerve impulses more rapidly?

Answer 10

myelinated

Question 11

Peripheral nerves consist of bundles of nerve fibers encased by ___ tissue. Which of these tissue covering is found in the outermost layer, surrounding fasicles, and surrounding individual nerve fibers?

Answer 11

Connective tissue

Epineurium - outermost layer
Perineurium - surrounds fasicles
Endoneurium - surrounds individual nerve fibers

Question 12

A ___ is a organized bundle of nerve fibers.

Answer 12

fasicle

Question 13

A-alpha fibers are ___ and involved in somatic ___ and ___ at muscle spindle (Ia) and golgi tendon organ (Ib).

Answer 13

myelinated; motor; proprioception

Question 14

C fibers are ___-___ and are involved in ___ from the dorsal root or serve as ___ sympathetic fibers.

Answer 14

non-myelinated; pain; postganglionic

Question 15

What is the relative size and susceptibility to block of nerve fibers?

Answer 15

1. pain
2. cold
3. warmth
4. touch
5. deep pressure
6. motor

Recovery in reverse order.

Question 16

T/F. Because local anesthetics bind to the open form of the sodium channel, they produce a more rapid nerve block on axons with a more rapid firing rate.

Answer 16

True.

Question 17

Functions served by ___ and ___ fibers are more readily disrupted by local anesthetics than the motor functions served by (larger) ___ fibers.

Answer 17

B; C; A

Question 18

Sensory neurons are heterogeneous in size and sensitivity. When senses are most sensitive to least sensitive?

Answer 18

Most sensitive → least sensitive
pain
cold
warmth
touch
deep pressure

Question 19

T/F. The slower the fiber is blocked, the longer it takes to recover.

Answer 19

False, the FASTER a fiber is blocked, the longer it takes to recover.

First on, last off

Question 20

T/F. Local anesthetics block more rapid with rapidly firing nerves.

Answer 20

True.

Question 21

___ produces sensory anesthesia at ___ the concentration required for motor blockade. ___ shows no selectivity. Which would be favored for epidural anesthesia during childbirth (maintain uterine muscle contractility)?

Answer 21

Bupivacaine; 1/3; Etidocaine

Bupivacaine

Question 22

T/F. Inflamed tissue is more difficult to anesthetize.

Answer 22

True.

Products released by cells in inflamed tissue lower pH, making it more difficult to get sufficient levels of anesthetic inside the axon.

Question 23

Anesthetic must be sufficiently ___ to diffuse to its site of action, but once at the site, the more ___ local anesthetics have a longer duration of action (increased protein binding, decreased clearance by local blood flow).

Answer 23

hydrophilic; lipid-soluble

Question 24

Why can’t the pKa of the anesthetic stray too far from the physiological pH?

Answer 24

Most local anesthetics are prepared as a water soluble HCl salt (pH of solution around 6 or 7). If epi is included, the pH is frequently lowered to 4 or 5 to stabilize the epi. The buffering capacity at the injection site neutralizes this.

Question 25

What is added prior to injection of an epi-containing preparation to increase the concentration of free base but runs the risk of precipitating the local anesthetic?

Answer 25

NaHCO3

Question 26

T/F. Local anesthetics can readily pass from the periphery to the CNS and affect the CNS causing light headedness, dizziness to death.

Answer 26

True.

Question 27

What are the direct effects that local anesthetics have on the heart?

Answer 27

block cardiac Na+ channels
block cardiac Ca2+ channels (much higher concentrations)
Depress pacemaker activity, excitability, conduction

Question 28

What effects do local anesthetics have on the autonomic nervous system of the heart?

Answer 28

By inhibiting the sympathetic response

• depress contractility
• produce hypotension

Question 29

What local anesthetic is cardiotoxic?

Answer 29

Bupivacaine

Question 30

T/F. Allergic reactions are significant for ester local anesthetics not amide local anesthetics. Amides are usually used in dentistry.

Answer 30

True.

Question 31

What are the benefits and concerns with using Epi as a vasoconstrictor?

Answer 31

benefits: success rate and intensity better, toxicity of anesthetic reduced, less blood loss
concerns: excess dosing or inadvertent intravascular injection possible and can lead to cardiovascular side effects

Give 40ug instead of 200ug in a compromised patient

Question 32

All local anesthetics will get ___. Lidocaine and procaine produce potent ___ and are more readily absorbed. It is important to supply a ___ with these drugs.

Answer 32

absorbed; vasodilation; vasoconstrictor

Question 33

Name two plasma proteins that local anesthetics bind to as they are being distributed in the body.

Answer 33

alpha-1 glycoprotein

albumin

Question 34

Unbound drugs can ___ to various tissues, including the CNS and ___. Absorption (and subsequent metabolism) by ___ is important to keep systemic concentrations of ___ local anesthetics low.

Answer 34

diffuse; placenta; liver; amide

Question 35

___ local anesthetics are metabolized by a combo of ___ in the plasma and tissue (liver metabolism). The t1/2 for procaine hydrolysis is less than ___ min and less than ___% of the drug leaves the kidneys unhydrolyzed.

Answer 35

Ester; pseudocholinesterase; 1; 2

Question 36

T/F. Amides with p-aminobenzoic acid hydrolyzed very rapidly by pseudocholinesterase.

Answer 36

False, ESTERS withp-aminobenzoic acid hydrolyzed very rapidly by pseudocholinesterase.

Question 37

___ local anesthetics undergo complex biotransformation in the liver, which includes ___ by cytochrome P450 isozymes.

Answer 37

Amide; dealkylation

Question 38

Which two amide local anesthetics are inactivated more rapidly?

Answer 38

prilocaine (secondary amine, dealkylation not required, extrahepatic metabolism)

articaine (inactivated by blood esterase)

Question 39

What is the cause of the most serious side effects?

Answer 39

operator error

Question 40

What does operator error result from?

Answer 40

• excessive concentrations in the blood caused by inadvertent intravascular injection
• administration of excessive quantities of drug

Question 41

What are the results of operator error?

Answer 41

convulsions, respiratory arrest, cardiovascular collapse

Question 42

What are the three guiding principles when administering local anesthetics?

Answer 42

• administer the smallest dose that is effective
• use proper injection technique
• use a vasoconstrictor-containing solution unless contraindicated

Question 43

How do you treat convulsions, respiratory distress, hypotension and disrupted cardiac function?

Answer 43

convulsions: benzodiazepine, barbituate (thiopental), succinylcholine (treats symptoms only)
respiratory distress: ventilation, oxygen
hypotension: sympathomimetic agents
cardiac function disrupted: cardiopulmonary resuscitation

Question 44

What is the dermatological and anaphylactic shock treatment?

Answer 44

dermatological: antihistamines

anaphylactic shock: epi???

Question 45

What local anesthetics can be used during pregnancy?

Answer 45

lidocaine, prilocaine category B, articaine, mepivacaine, bupivacaine category C

Question 46

Why are local anesthetics generally safe in dentistry?

Answer 46

doses are low
low fatalities
adverse effects (pallor, unrest, swating, palpitation, nausea) difficult to quantitate from anxiety.