Local Anesthetics

Question 1

local anesthetcis

Answer 1

a drug that temprarily eliminates sensation, especially pain, at a specific site when they are locally applied without affecting consciousness

sodium channel as the primary means of action potential generation, block is reversible

Question 2

chemistry of local anesthetics

Answer 2

contain hydrophobic and hydrophilic groups

hydriohobic aromatic ring

hydrophilic group defines the pKa of the molecule

ester or amide linkage determines the mode of metabolic degradation

Question 3

benzocaine

Answer 3

exception to general formula of local anesthetic

no terminal amino group

always neutral, uncharged because it has a pKa of 3.5

only used for topical anesthesia

Question 4

alkyl substitutions of anesthtics

Answer 4

enhances potency dramatically

does not increase therapeutic index

Question 5

intrinsic properties that affect local anesthetic action

Answer 5

lipid solubility of a local anesthetic affects ability to cross membrane and related to potency

pKa of a local anesthetic important as well

Question 6

pH of local anesthetic and function

Answer 6

alters the ratio of the uncharged to charged form

uncharged neutral form penetrates the membrane

charged cationic form blocks the Na channel

Question 7

Explain how the charged and uncharged form of a local anesthetic acts in the body.

Answer 7

uncharged form helps drug diffuse into axons where the charged form can act on the cytoplasmic side of the sodium and potassium channels

Question 8

the effects of pH on local anesthetic action

Answer 8

local anesthetics have higher pKa so a greater pH will lead to more ions being trapped in the site of action

Question 9

What happens after repetitive injections of local anesthetic?

Answer 9

decreases local anesthetic action because the tissue buffer capacity is reduced

Question 10

What part of the action potential do local anesthetics block?

Answer 10

sodium channels responsible for the upstroke

Question 11

What is the role of the alpha subunit of the sodium channel?

Answer 11

forms the pore of the channel, receptor for local anesthetic

fourth transmembrane segment senses voltage

Question 12

What is the role of the beta subunits of the sodium channels?

Answer 12

modulates expression and channel functions

Question 13

use-dependent block

Answer 13

repetitive depolarization enhances sodium channel blocking action by lidocaine

this is because binding site is only accessible when the channel is open, so repetitive stimulation opens the channel more often and enhances the local anesthetic block

Question 14

frequency-dependent block

Answer 14

an increase int he frequency of repetitive activity enhances the extend of use-dependent block

less drug molecules escaping form the channel when the inter-pulse interval is short

Question 15

significance of use- and frequency- dependent block of Na+ channels

Answer 15

high frequency of firing enhances the block

Question 16

membrane potential-dependnt block of local anesthetics

Answer 16

the avialability of Na channels decreases when the membrane is depolarized

curve is shifted to the hyperpolarizing direction by local anesthetics, increasing the effectiveness of the block

ex. in damaged tissues there are fewer channels, so the block is more effective

Question 17

differential nerve block

Answer 17

the phenomenon that different nerves and biological resposnes are blocked at different rates when local anesthetic is applied

Question 18

factors that influence differential nerve block

Answer 18

size of the nerve fibers - smaller fibers more sensitive

myelinated vs. unmyelinated fibers of the same size - myelinated fibers more sensitive

firing frequency - snesory fibers fire at high frequency, enhancing block

anatomical arrangement - circumferentially located fibers are blocked first

Question 19

size effects on nerve block

Answer 19

large fibers have smaller surface-to-volume ratios than small fibers

also large fibers take longer to be saturated with anesthetic, so when the drug is washed off, the large fibers recover faster

Question 20

critical exposure length for blocking of myelinated fibers

Answer 20

three consecutive nodes of Ranvier must be blocked for suppressing conduction completely

explains why epidural blocks can leave motor function intact but relieve parturition pain, not enough length inhibited for the motor neuron

Question 21

anatomic arrangment of nerve fibers and anesthetic block

Answer 21

core contains sensory fibers at most distal sites, whereas surface innervates proximal sites

anesthetic placed outside of nerve bundles will anesthetize proximal fibers first before getting to the distal

Question 22

How are ester-type local anesthetics hydrolyzed?

Answer 22

pseudocholinesterase

Question 23

How are amide-type local anesthetics hydrolyzed?

Answer 23

metabolized by the liver microsomal P450 enzymes (N-dealkylation and hydroxylation)

Question 24

para-aminobenzoic acid (PABA)

Answer 24

a metabolite of the ester-type local anesthetics

can be used to compromise antibacterial activity of soulfonamides

antibacterial action depends on blocking folate synthesis from para-aminobenzoic acid

Question 25

sulfanilamides

Answer 25

structural analogs of PABA, competitively prevents bacterial utilization of PABA to synthesize folic acid

Question 26

clinical uses of local anesthetics

Answer 26

topical anesthesia

infiltration

regional block

Question 27

topical anesthesia

Answer 27

used for nose, mouth, and tracheobronchial tree and urethra procedures

also used for cosmetic surgery

benzocaine 20% spray is common

lidocaine/prilocain (EMLA) most commonly used for venipuncture

Question 28

infiltration

Answer 28

injected under the skin of the surgical site

Question 29

regional block

Answer 29

injection near a nerve or plexus proximal to the surgical site, which includes spinal or epidural anesthesia

Question 30

spinal anesthsia - three major sites

Answer 30

spinal nerve block

epidural or peridural nerve block

caudal block

onset is rapid, minimal amount needed

Question 31

most important derminants of sensory level blockade

Answer 31

baricity of the solution and patient position

Question 32

lumbar epidural anesthesia

Answer 32

lumbar, thoracic, or cervical levels - most often at the lumbar level

drug is deposited outside the dura, requiring a much larger amount of drug

1:200,000 of epinehprine used in test injection to make sure there is no intravascular injection

Question 33

What type of anesthetic is used for delivery?

Answer 33

local anesthetics such as chloroprocaine - preferred because it is quickly hydrolyzed by plasma cholinesterase

very little drug reaches the fetus

Question 34

caudal anesthesia

Answer 34

agent is introduced through the sacral hiatus above the coccyx, useful in perineal and rectal procedures

Question 35

intravenous regional anesthesia (Bier’s block)

Answer 35

a large volume of local anesthetic is injected into a peripheral vein after circulation is interrupted using a tourniquet

anesthetic is limited to the area and excluded from blood circulation, quickly resolved once circulation is restored

Question 36

short-acting local anesthetics

Answer 36

ester-type: procaine and chloroprocaine

Question 37

intermediate local anesthetics

Answer 37

lidocaine, mepivacaine and prilocaine

Question 38

long-acting local anesthetics

Answer 38

tetracaine, bupivacaine, levobuprivacine, and ropivacaine (mostly amide-type)

Question 39

factors that influence choice of local anesthetics

Answer 39

method of anesthesia

duration of action

neurotoxicity

allergic reactions

Question 40

effects of vasoconstrictors on anesthetic function

Answer 40

small quanitites of epinephrine can be added to reduce blood flow

increases duration and reduces risk of systemic toxicity, gives time for blood to clear anesthetic

Question 41

local anesthetic systemic toxicity (LAST)

Answer 41

always due to excessive blood concentratino of local anesthetics, especially amide-type ones

includes CNS and CV toxicities:

CNS - lightheadedness, dizziness, seizures, etc. treated with GABA(A) receptor-mediated inhibitory response

CV - myocardial depression and vasodilateion, fall in blood pressure

use intralipids to emulsify and decrease blood levels

Question 42

effects of cocaine

Answer 42

blocks monoamine reuptake

produces euphoric effects due to inhibition of dopamine uptake

causes vasoconstriction and hypertension peripherally due to norepinephrine reuptake inhibition

Question 43

methemoglobinemia

Answer 43

when heme iron is oxidized from the ferrous to ferric state

hemoglobin is transformed to methemoglobin

does not bind to oxygen, results in functional anemia and hypoxia

caused by the presence of oxidizing agents such as benzocaine and prilocaine

treat with methylene blue IV

Question 44

allergic reactions to local anesthetics

Answer 44

symptoms such as bronchospasm (sudden constriction of muscles of the bronchile walls) and uticaria (hives)

occur more often with ester-type local anesthetics

caused by derivatives of p-aminobenzoic acid, a metabolite of the ester-type local anesthetics

Question 45

tetrodotoxin (TTX)

Answer 45

found in puffer fish, selectively blocks sodium channels - reversible block

blocks from axoplasmic side of the excitable membranes