Local Anesthetics

Question 1

What are the effects of local anesthetics on sensation and on consciousness?

Answer 1

produce loss of sensation (and can cause paralysis) in a localized region without loss of consciousness or vital functions

Question 2

Can their effects be targeted to a particular body part? If so, what determines the site of effect?

Answer 2

Yes, the location of application determines the site of effect

Question 3

Name 4 short-acting local anesthetics

Answer 3

procaine
chloroprocaine
benzocaine
cocaine

Question 4

Name 3 intermediate-acting local anesthetics

Answer 4

lidocaine
articaine
mepivacaine

Question 5

Name 3 long-acting local anesthetics

Answer 5

bupivicaine
ropivicaine
tetracaine

Question 6

Name the target of all local anesthetics (type of channel)

Answer 6

alpha subunit of voltage-gated sodium channels

Question 7

Effect of local anesthetics on its target and overall effect on conduction of nerve impulses

Answer 7

blocks the influx of sodium ions into the cell, decreasing the propagation of the action potential down the nerve; nerve conduction fails

Question 8

4 factors that can affect potency of local anesthetics

Answer 8

1. intrinsic responsivity of various nerve fibers (smaller diameter and myelinated nerves are more easily blocked; lower conc required to achieve a given level of block)
2. fraction of the dose that reaches the target nerve fiber, which depends on proximity to the site of action and the lipophilicity of the agent
3. pKa of the agent and local pH (i.e. ionization state)
4. Tissue pH

Question 9

What is the relationship between nerve stimulation frequency and efficacy? Why?

Answer 9

frequency-dependence: nerves that are more frequently stimulated present more opportunities for local anesthetics to bind

Question 10

4 factors that influence duration of action

Answer 10

1. degradation of plasma esterases
2. lipid solubility of anesthetic agent
3. vascularity of the tissue
4. use of an adjunct vasoconstrictor

Question 11

Which type (esters vs amides) tends to have shorter plasma half-life? Why?

Answer 11

ester local anesthetics have a shorter half-life because choline esters in the blood are rapidly hydrolyzed by plasma cholinesterase

Question 12

What is the relationship between lipid solubility and duration of action? Why?

Answer 12

drugs that partition more into lipid myelin sheath remain near the site of action longer

Question 13

What is the relationship between tissue vascularity and duration of action?

Answer 13

more tissue vascularization = more rapid clearance of drug from the site of action

Question 14

What are the effects of a vasoconstrictor?

Answer 14

a vasoconstrictor is added to decrease rate of absorption from administration site into blood (localizes the drug at desired site)

Question 15

3 types of rare but severe toxicities of local anesthetics

Answer 15

1. allergic reactions
2. CNS toxicity
3. cardiovascular toxicity

Question 16

Major mechanism underlying allergic reactions to local anesthetics

Answer 16

procaine and benzocaine are metabolized to an antigenic metabolite (PABA)

Question 17

Symptoms associated with CNS toxicity and why they occur

Answer 17

-lightheadedness and numbness and at high doses: seizures and coma
-thought to occur as a result of preferential depression of central inhibitory tracts which allows excitatory neurotransmission to increase to unsafe levels

Question 18

How does system exposure affect CNS and CV toxicity?

Answer 18

-route/site of administration (accidental IV injection can be lethal)
-under use of measures to confine drug (e.g. epinephrine)
-impaired metabolism ability