Local Anesthesia

Question 1

LA MOA

Answer 1

impair nerve signal transmission by blocking VG Na channels

Question 2

Amino-esters

Answer 2

• metabolized by pseudocholinesterase except cocaine
• ester linkage connects aromatic ring to tertiary amine
• cocaine, procaine, chloroprocaine, tetracaine

Question 3

Amino-amides

Answer 3

• metabolized by liver
• amide linkage connects aromatic ring to tertiary amine
• lidocaine, lignocaine, mepivacaine, prilocaine, bupivacaine, levobupivacaine, ropivacaine

Question 4

structure of LA

Answer 4

• aromatic ring is lipophilic
• tertiary amine is hydrophilic
• more hydrophobic compounds are more portent and produce longer blockade

Question 5

procaine

Answer 5

Duration: 45-60 min
pka 8.9
nonionized (7.2) 2; (7.6) 5
-low potency, slow onset, short duration

Question 6

chlorprocaine

Answer 6

Duration: 30-45 min
pka 8.7
nonionized (7.2) 3; (7.6) 7
short duration, fast onset

Question 7

Tetracaine

Answer 7

Duration: 60-180 min
pka 8.5
nonionized (7.2) 5; (7.6) 11
more potent, long duration, slowly metabolized
too toxic for use in peripheral blocks
OK for long acting spinal blocks

Question 8

lidocaine

Answer 8

Duration: 60-120 min
pka 7.9
nonionized (7.2) 17; (7.6) 33
rapid absorption parenteral, GI, respiratory
-intermediate duration
-1.5-2% for most regional blocks for surgery
-more dilute concentrations for pain management (no motor block)

Question 9

mepivacaine

Answer 9

Duration: 90-180 min
pka 7.6
nonionized (7.2) 28; (7.6) 50
-intermediate duration
-similar to lidocaine
-similar onset, longer duration than lidocaine
-toxic to neonates

Question 10

bupivicaine

Answer 10

Duration: 240-480 min
pka 8.1
nonionized (7.2) 11; (7.6) 24
-longer duration LA (longer with EPI)
-slow onset, longer/variable duration
-2-3 hr for spinal dose, 12-24 for peripheral nerve block
-cardiotoxic (direct injection into medulla will producce arrhythmias, difficult to dissociate bupivacaine from na+ channels)
-periph in dilute concen (0.5)
cont infusion usually 0.1% w or w/o opioid
-careful use in OB epidurals (0.25)

Question 11

levobupivicaine

Answer 11

Duration: 240-480 min
pka 8.1
nonionized (7.2) 11; (7.6) 24
-single enantiomer version of bupiv
-less well studied
-appears to work in similar fashion to ropivicaine, less toxic than bupivacaine, similar onset and duration as bupivacaine

Question 12

prilocaine

Answer 12

Duration: 60-120 min
pka 7.9
nonionized (7.2) 17; (7.6) 33
-intermediate duration
-pharmacology similar to lidocaine
-lacks vasodilation, increased Vd, limits CNS toxicity
-causes methemogloinemia (req dose 8 mg/kg, rx with methylene blue 1-2 mg/kg)
-uncommon for peripheral nerve blocks

Question 13

ropivacaine

Answer 13

Duration: 180-360 min
pka 8.1
nonionized (7.2) 11; (7.6) 25
S–enantimor of bupivicaine: lower cardiac toxicity
-slower uptake and thus lower blood levels
-extensive hepatic metabolism
-less potent than bupivacaine at lower concentations (0.5%)
- at > 0.5% dense block with slightly shorter DOA than bupiv
at 0.75% onset is fast, CNS and cardiotoxicity are reduced, motor block is less than bupiv
-very popular for peripheral blocks

Question 14

What partially determines DOA of LA

Answer 14

-pro binding fraction

bupivicane > etidocaine > ropivacaine > mepivacaine > lidocaine > procaine > 2 chloroprocaine

Question 15

What other tertiary amines block Na channels

Answer 15

meperidine, morphine, codeine, heroin, TCA, amitryptyline, pufferfish toxin (blocks from outside)

Question 16

Rate of diffusion across nerve sheath is determined by:

Answer 16

• concentration of LA
• degree of ionization
• hydrophobicity
• physical characteristics of tissue surrounding the nerve

Question 17

Why are motor fibers blocked before sensory in large trunks

Answer 17

-due to location on outer portion of the nerve bundle

Question 18

increased lipid solubility….

Answer 18

• increases potency and duration of LA

- increases toxicity and decreases TI

Question 19

duration of a block is determined by:

Answer 19

• lipid solubility
• vascularity of the tissue
• presence of vsoconstrictors which prevent vascular uptake

Question 20

order of loss of nerve sensations:

Answer 20

autonomic functions
pain
cold
warmth
touch
pressure
vibration
proprioception
motor function

Question 21

cocaine

Answer 21

• blocks nerve impulses
• ester LA
• local vasoconstriction d/t inhib of local norepinephrine reuptake
• euphoria 2/2 blockade of dopamine reuptake in CNS
• good for LA in nasal passages

Question 22

allergies to LA

Answer 22

-rare, but sometimes happens with esters or additives like PABA

Question 23

etidocaine

Answer 23

• longer duration
• onset like lidocaine, duration like bupivicaine
• alkyl substitution on aliphatic group between hydrophilic amine and amide linkage increases lipid solubility with increases potency and increases duration
• prolonged motor blocks that outlasts sensory block
• not useful for peripheral nerve blocks

Question 24

plasma concentration of LA is determined by:

Answer 24

• dose of drug administered
• rate of absorption of drug (systemic: interscalene, humeral, paravertebral, psoas, intercostal, femoral, sciatic more than superficial and intracutaneous)
• site of injection
• biotransformation and elimination of the drug

Question 25

symptoms of LAST

Answer 25

drowsy–>parasthesias of mouth/tongue>tinnitis/auditory hallucinations > seizures > coma > resp arrest > cardiac arrest

Question 26

rx of LAST

Answer 26

1) airway mangement/seizure precautions

2) BLS/ACLS (avoid lidocaine, Ca+ blockers, vasopressin, beta blockers, reduce epi doses to