Local anesthetics 1/9

Question 1

local anesthetics

Answer 1

substances that produce temporary blockade by blocking voltage-gated Na channels

Question 2

physical properties

Answer 2

weak bases,poorly water soluble

synthetic:derived from cocaine

have a hydrophilic(aromatic) and a lipophilic end(tertiary amine) joined by ester or amide linkage

made available clinically as salts to increase solubility and stability

Question 3

ester links

Answer 3

are more prone to hydrolysis than amide links.

that’s why esters have shorter duration of action

Question 4

mechanism of action:

disruption of membrane depolarization by

Answer 4

blocking Na channels

influx of K remains unchanged

cellular integrity and fx not affected

physical blockade or conformational change of Na channels by cationic form of LA appears to produce temporary dysfunction

Question 5

blockade of Na channels

Answer 5

concentration dependent

reversible and ends when concentration of LA falls below a critical minimum level

Question 6

frequency dependent block

Answer 6

refers to enhanced action of local anesthetic on a nerve which is being stimulated or is actively firing

nerves with higher firing frequency and more + membrane potential are more sensitive to LA (use-dependent block) because charged anesthetic molecules are more likely to access the binding sites in open Na channels

Question 7

pain fibers

Answer 7

have high firing rate and relatively longer AP–>more sensitive to lower concentration of LA

Question 8

pKa

Answer 8

is pH at which 1/2 of molecules are in charged quaternary form and 1/2 are in uncharged form

most LA are weak bases,thus charged cationic form will constitute large percentage at physiologic pH

benzocaine is exception.exists solely as nonionized base

Question 9

LA solutions

Answer 9

are acidic relative to their pKA to increase stability and shelf life

Question 10

nerve penetration

Answer 10

non-ionized base is necessary for this (charged form delays onset of action)

Question 11

receptor sites for LA

Answer 11

located at inner vestibule of Na channels

uncharged form is important for penetration, then formation of charged cation leads to binding at Na channels

Question 12

potency and lipid solubility

Answer 12

directly proportional

Question 13

duration of action

Answer 13

directly proportional to protein binding

longer protein binding, longer to wash out drug

higher protein binding, reduction amount of free drug,lower toxicity

Question 14

Esters metabolism

Answer 14

hydrolysis in blood by pseudo or butyrylcholinesterase.also red cell esterases

Question 15

metabolism of amides

Answer 15

liver enzymes (P450)

Question 16

considerable variations in rate of liver metabolism of amides

Answer 16

prilocaine>lidocaine>mepivacaine>ropivacaine>bupivacaine and levobupivacaine

Question 17

Absorption rates

Answer 17

1. intercostal block
2. caudal block
3. epidural block
4. brachial plexus block
5. sciatic and femoral nerve block

Question 18

LA toxicity:CNS initial

Answer 18

lightheadedness,peri-oral numbness,dizziness,tinnitis,disorientation,drowsiness

Question 19

CNS toxicity higher doses

Answer 19

muscle twitching,convulsions,coma,resp. depression,CV depression,often occur after initial CNS excitation followed by rapid depression

Question 20

cardiac toxicity

Answer 20

myocardial depression,dysrhythmias,cardiotoxicity in pregnancy

Bupivacaine is especially cardiotoxic

Question 21

peripheral effects of LA

Answer 21

vasoconstriction at low doses

dilation at higher doses

Question 22

hematological signs of LA

Answer 22

methemoglobinemia common with prilocaine and benzocaine

muscle necrosis

allergic reaction to ester LA. due to para-amino benzoic acid (PABA) which is a product of degradation

Question 23

Tx of bupivacaine-associated cardiac arrest

Answer 23

injecting 1mL/kg bolus of 20% lipid emulsion (intralipid)

Question 24

Tx methemoglobinemia

Answer 24

methylene blue

Question 25

cocaine

Answer 25

high local neural toxicity and potential for abuse

vasoconstrictive due to blockade of reuptake of catecholamines in sympathetic NS

Question 26

novocaine(procaine)

Answer 26

first ester to be synthesized

metabolized by pseudocholinesterase and excreted by kidneys

Question 27

tetracaine

Answer 27

slow onset due to high pKa,long duration

excellent topical anesthetic

Question 28

2-chloroprocaine

Answer 28

safest,rapid termination of effect

IV causes thrombophlebitis

Question 29

benzocaine

Answer 29

benzoic acid derivative

effective only in high concent

used mostly in mucous membranes

methemoglobinemia

Question 30

lidocaine

Answer 30

first amide LA

metabolized in liver

excreted by kidneys

LA which all others are compared

Question 31

dibucaine

Answer 31

high potency and toxicity

inhibitor of plasma cholinesterase

only for topical use and cream

Question 32

mepivacaine

Answer 32

similar to lidocaine but less vasodilation

useful in epidural,spinal,peripheral block and local infiltration

potential accumulation makes it unsuitable for prolonged epidural infusion

Question 33

bupivacaine

Answer 33

greater potency and duration

slower onset

good for spinal anesthesia as isobaric or hyperbaric solution

significant frequency-dependent block

Question 34

ropivacaine

Answer 34

almost pure S isomer

less potent and lasting than bupivacaine

less cardiotoxic

better frequency-dependent block

Question 35

prilocaine

Answer 35

most rapidly metabolized amide LA

produces methemoglobinemia

Question 36

epi(adjuvant)

Answer 36

may decrease absorption and prolong duration.

also used as monitor

Question 37

bicarb(adjuvant)

Answer 37

increases pH–>accelerates onset

may precipitate in ropivacaine and bupivacaine

Question 38

types of nerve block

Answer 38

topical

infiltration (local anesthetics)

nerve block (brachial)

IV limb block(Bier block)

neuraxis block(epidural,spinal)

Question 39

susceptibility as concent increases

Answer 39

pain>temp>touch>pressure>muscle