Local Anesthetics

Question 1

3 structural components of local anesthetics

Answer 1

Lipophilic side (benzene ring)
Hydrophilic side (quarternary amine)
Intermediate chain linkage
-Ester or
-Amide

Question 2

Ester metabolism

Answer 2

Via cholinesterase, rapid

Tend to be shorter acting than amides

Question 3

Ester allergies

Answer 3

Higher potential than amides

If allergic to one ester, all esters should be avoided

Question 4

Amide metabolism

Answer 4

In liver by CYP1A2 and CYP3A4
Longer acting generally because they’re more lipophilic and protein bound and require transport to the liver for metabolism

Question 5

Amide allergies

Answer 5

Extremely rare
No cross allergy among class or with esters

Question 6

Nerve Fibers A alpha, A delta, B, and C function

Answer 6

A alpha: Motor
A delta: Fast pain
B: Preganglionic SNS
C: Slow pain

Question 7

Side of chemical structure of local anesthetic that can be ionized or not (Lipophillic or hydrophilic)

Answer 7

Hydrophillic side

-Can be ionized (charged) or nonionized (not charged)

Question 8

Mechanism of action of local anesthetics

Answer 8

• Nonionized portion (lipid soluble) enters the nerve
• Drug reequilibrates
• Ionized fraction attaches to receptor on the inside of the sodium channel, blocking it

Question 9

Protein binding of local anesthetics determines:

Answer 9

Duration of action

• Higher percent protein binding = longer duration of action
• Binding stronger to proteins ~=binding stronger to tissues/nerves

Question 10

Lipid solubility of local anesthetics determines:

Answer 10

Potency
Lipid solubility means they are nonionized and able to penetrate the myelin/nerve bilayer to get into the nerve to ionize and work

Question 11

pKa of local anesthetics determines:

Answer 11

Onset of action
Lower pKa = faster onset
-Closer to 7.4 means theres a larger fraction that nonionized to enter the nerve
*Exception: Chloroprocaine has a high pKa but its fast because it’s given in such high concentrations

Question 12

Effects on local anesthetics when epinephrine is added

Answer 12

• Shorter onset time (faster) *Except during spinal anesthesia
• More depth motor and sensory blockage
• Longer duration of blockade
• Larger area of blockade
• Lower peak plasma concentration (less toxicity)

Question 13

Ester name

Answer 13

1 I

Question 14

Amide name

Answer 14

2 I’s

Question 15

Ropivacaine characteristics

Answer 15

Similar to bupivacaine but doesn’t have the cardiac effects/risks

Question 16

Bupivacaine problem, max dose

Answer 16

Preferentially binds to cardiac cells over others, can cause sudden cardiac arrest

• .75% no longer allowed in US
• Max dose = 3mg/kg

Question 17

Lidocaine max dose

Answer 17

With epi: 7mg/kg

Question 18

Cocaine max dose

Answer 18

Only topical: 200mg

Question 19

Procaine max dose

Answer 19

14mg/kg

Question 20

Chloroprocaine max dose

Answer 20

14mg/kg

Question 21

Tetracaine max dose

Answer 21

1mg/kg (most toxic)

Question 22

Mepivacaine max dose

Answer 22

7 mg/kg

Question 23

Prilocaine max dose

Answer 23

8.5 mg/kg

Question 24

Ion trapping CNS toxicity

Answer 24

• Local anesthetic overdose -> respiratory depression -> hypoxia, acidosis
• Increased ionized fraction in cerebral circulation (b/c of acidosis, decreased pH)
• Unable to cross the blood/brain barrier to exit cerebral circulation and reenter systemic circulation

Question 25

Ion trapping in fetal circulation

Answer 25

Fetal pH is lower than maternal pH | -Local anesthetic crosses the placental barrier to fetus, ionizes and is unable to cross back to maternal circulation

Question 26

Local anesthetic use in infected tissues

Answer 26

Ineffective because tissue is more acidotic | -Local anesthetic is more ionized, not lipid soluble and cannot be absorbed into the nerve

Question 27

Carbonation of local anesthetics

Answer 27

Speeds onset of action and intensity of block - CO2 diffuses into the nerve and makes the inside more acidotic - LA inside the nerve will ionize more = higher concentration of active form in the neuron at the sodium channel

Question 28

Adding sodium bicarbonate to local anesthetics

Answer 28

Speeds onset of action - Increases the concentration of the non-ionized (lipid soluble) form of the drug on injection - Improved diffusion of local anesthetic through the neuronal membrane * Also takes away stinging feeling initially felt by patient on injection

Question 29

LAST (local anesthetic systemic toxicity) is a concern with which class of LA?

Answer 29

Amides | -Won't happen with esters because they're metabolized so fast by cholinesterases

Question 30

Signs of LAST (and lidocaine plasma level they will occur at)

Answer 30

Lidocaine plasma concentration up to 5mcg/mL is therapeutic -Lightheaded, tinnitus, circumoral (mouth) and tongue numbness -Visual disturbances -Muscular twitching (like fasciculation's) -Convulsions -Unconsciousness, coma -Respiratory arrest -CV arrest Bupivacaine goes strait to cardiac arrest

Question 31

Most common CNS sign of LAST

Answer 31

Seizure - Self limiting, happening because of disinhibition - Inhibitory parts of brain are asleep, seizure happens until pt goes deeper to coma

Question 32

Most common time after injection that LAST occurs

Answer 32

<1 minute (~50%)

Question 33

Primary goal in treating LAST (and why)

Answer 33

Prevent hypoxia and acidosis: they will potentiate LAST | -Rapidly halt seizures with benzos (succs if that doesn't stop them)

Question 34

ACLS modifications for LAST

Answer 34

- Use smaller doses of epi (10-100mcg) - Vaso isn't recommended - Avoid calcium channel blockers and beta blockers - Treat ventricular arrhythmias with amiodarone (not lidocaine or procainamide)

Question 35

Lipid emulsion therapy for LAST, and what to do if it doesn't work

Answer 35

1.5 mL/kg bolus of 20% lipid emulsion Infusion of 0.25mL/kg/min for at least 10 mins after circulatory stability If circulatory stability isn't attained consider another bolus of 0.5mL/kg/min ^If this doesn't work -> cardiopulmonary bypass

Question 36

Pregnancy affect on local anesthetics

Answer 36

- Pregnancy enhances the effect of local anesthetics = dosage should be reduced - Elimination of amides are longer in newborns than their mothers (greater volume of distribution) - Fetus/newborn isn't more vulnerable to toxic effects of local anesthetics than adults - Combining neuraxial LA with an opioid increases the block density and allows for administration of lower total dose of LA and side effects - Spinal bioavailability of fentanyl/sufentanil (lipophilic) is better than morphine/hydromorphone (hydrophilic)

Question 37

Mixing local anesthetics

Answer 37

- Done to make onset faster but keep duration of action long (can make sure you're in the right space for a longer block since they're onset sometimes isn't for 30-40 minutes) - Max doses is additive, not individual

Question 38

Tumescent Anesthesia

Answer 38

Technique used by plastic surgeons during liposuction - SQ injections of large volumes of dilute local anesthetics combined with epi, saline, and sodium bicarbonate - Max safe dose of lidocaine w/ epi = 35-55mg/kg

Question 39

Hyaluronidase

Answer 39

"Spreading factor" - Breaks down the tissue matrix so things can spread/move around to surrounding tissue - Makes onset of action faster but duration shorter - Used mostly in opthamology (so once injection in the eye can be done and it'll spread instead of moving needle in the eye)

Question 40

Cocaine unique properties

Answer 40

Blocks reuptake of norepinephrine in the sympathetic nervous system: Has sympathomimetic effects -Easily toxic, only used topically now

Question 41

EMLA

Answer 41

``` Mixture of lidocaine and prilocaine -Topical anesthetic -Used primarily in peds for IV starts Max doses 0-3 months: 1g 3-12 months: 2g 1-6 years: 10g 7-12 years: 20g -Has potential for mehemoglobinemia ```