Local Anesthetics Flashcards by B -

Local Anesthetics:

what is the determinant for the speed of onset?

amount of LA in NON-Ionized form

AKA– the pKa

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Local Anesthetics: Onset (pKa)
agents w/ ______ pKa are MORE NON-Ionized at a pH of 7.4. (the more non-ionized the faster it penetates the lipid bilayer.

LOWER

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Local Anesthetics: Onset (pKa)

Agents w/ a high pKa have a _______ onset

slower onset

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Local Anesthetics: Onset (pKa)

Agents with a low pKa have a _____ onset

faster

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Local Anesthetics: Onset (pKa)

why is it that a lower pKa has a faster onset

bc if you remember the line and place the pKa on it it will be more non-ionized.
Also if pH is 7.4 and pKa is 9 then obviously less than 50% is non-ionized, but if pKa is 7.4 then 50% is non-ionized

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Local Anesthetics: Onset (pKa)
place these in order from slowest onset to fastest onset
Drug        pKa 
Procaine 8.9
Mepivacaine 7.6
Lidocaine 7.7
Tetracaine 8.6
Etidocaine 7.7
Ropivacaine 8.1
Bupivacaine 8.1
Chloroprocaine 9.1

onset           % non-ionized (just to visualize)
Procaine 8.9       3        
Tetricaine 8.6      14
Bupivacaine 8.1    17
Ropivacaine 8.1    17
Chloraprocaine 9.1 2 (the one exception) fastest
Lidocaine 7.7        24
Etidocaine 7.7       33
Mepivacaine 7.6   39

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Local Anesthetics: Onset (pKa)
in general, the LOWER the pKa of the LA, the greater the proportion of LA in the NON-IONIZED form at pH=7.4, and the _______ the onset of the conduction block.

faster

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LA block nerve conduction by blocking (impairing) propagation of the action potential along axons. the block is accomplished by directly acting on _______ channels and inhibiting ____ influx

Sodium Channels

Na++

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the ____ of the LA determines the speed of onset?

pKa

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A LA that has a HIGH lipid solubility is very ____. Lipophilic LA more readily cross nerve membranes

potent

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Local anesthetics the are highly ____ ____ will have a prolonged duration of action.

Protein Bound

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pKa relates the what?
Lipid solubility relates to what?
Protein binding relates to what?

pKa - onset (low pKa fast onset)
Lipid solubility - potency (more lipid soluble more potent)
Protein binding - duration (more bound longer duration)

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what is the determinant for potency?

lipid solubility

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Local Anesthetics: Lipid Solubility (potency)

what is a good measure of lipid solubility?

oil:water partition coefficient

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Local Anesthetics: Lipid Solubility (potency)

the greater the oil:water partition coefficient the ____ the lipid solubility

greater

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Local Anesthetics: Lipid Solubility (potency)
place in order from least to most potent
LA            Oil: water partition Coefficient
Etidocaine 140
Chloroprocaine 1
Mepivacaine 1
Tetracaine 80
Lidocaine 4.0
ropivacaine

Drug  least potent to most potent
Chloroprocaine 1
Mepivacaine 1
Lidocaine 4
Tetracaine 80
Bupivacaine 30
Ropivacaine

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Local Anesthetics: Lipid Solubility (potency)

explain the potency as it applies to our anesthetics like Lidocaine and Bupivacaine

Lido is less potent oil:water is 4.0. we need large amounts when we use it for ex usually comes in 1%, 2%, 4% etc
Bupivacaine is more potent, oil:water is 30. we need small amounts when we use it for ex usually comes in 0.25%, 0.5%, 0.75%

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Local Anesthetics: Lipid Solubility (potency)

In general the more lipid soluble the LA the greater it’s _____

potency

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what determines the duration of action of a LA

both protein binding and lipid solubility (but primarily we are concerned w/ protein binding)

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Local Anesthetics: Duration of action

what is the MOST important factor in determining the duration of action of a LA

Protein binding

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Local Anesthetics: Duration of action

the greater the protein binding the _____ the duration of action

longer

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Local Anesthetics: Duration of action

how does protein binding control the duration of a LA

immediately after injection of LA, much of the agent binds to proteins in the vicinity of the injection site. as the unbound anesthetic diffuses from the injection site, some protein bound LA is released and becomes available to diffuse to nerve axons. thus proteins serve as storage depots for the LA

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Local Anesthetics: Duration of action
so we already discussed that duration is primarily dependent on Protein binding, but what is the other factor that plays a role in duration of action?

Lipid solubility

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Local Anesthetics: Duration of action

agents w/ greater lipid solubility tend to have ____ durations of action

longer

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Local Anesthetics: Duration of action | How does lipid solubility control duration of action of a LA?

After the LA is injected some of it will dissolve in lipids in and around the site of injection. Agents w/ higher lipid solubility will dissolve to a greater extent in surrounding tissue (lipids). thus the lipid act as a reservoir for lipid soluble agents, just as proteins act as a reservior for agents that bind to proteins. As the LA diffuses away from the site of injection, LA will diffuse out of the lipid compartment down the concentration gradient and will act on the nerve to maintain he nerve block.

Local Anesthetics: Duration of action | what single change in property of a LA will result in more POTENT and LONGER acting agent?

an increase Lipid solubility. An Increase in lipid solubility will increase the duration of action and the potency

Weak Bases ( Benzos, LA, Opioids, Ketamine) bind to what protein?

Alpha 1 - glyco protein

Weak acids (thiopental, Propofol, barbiturates) bind to what protein?

Albumin

Local Anesthetics: Duration of action the duration of action is greatest for LA that exhibit the greatest _______ and highest _____ . However ______ is more important when it comes to duration of action

Protein Binding and Lipid solubility | Protein binding

Determinants of blood concentration of LA: | blood concentration is determined by what 4 things

pressance or absence of vasoconstrictor tissue blood flow concentration of injection number and frequency of injections

Determinants of blood concentration of LA: | loss of LA from injection site is primarily by what?

vascular absorption

Loss of LA from injection site is primarily by vascular absorption. the rate of absorption of LA from the injection site is influenced by what 2 things

Presence of vasoconstrictor | High blood flow to tissue

Determinants of blood concentration of LA: | what does the presence of a Vasoconstrictor to?

decreases the rate of absorption

Determinants of blood concentration of LA: | what does high blood flow to the tissue do

the greater the blood flow the faster the agent is absorbed into circulation and washed away from the site. this higher blood flow = reduced duration of action

rank the bodies tissues from highest to lowest blood flow . Or think of it as what area or routes are where the most LA will be absorbed systemically into the blood circulation to the least

``` IV Tracheal Intercostal Caudal Paracervical Epidural Brachial plexus SA/ Sciatic/ femoral Subcutaneous ``` Mnemonic I Think I Can Push Each Bolus SSlowly For Safety

Factors unrelated to Physoichemical Properties that prolong Block: how does presence of vasoconstrictor prolong block

decreases blood flow and slows the removal of the LA

Factors unrelated to Physoichemical Properties that prolong Block: how does concentration of LA prolong block

greater concentrations increase block duration

Factors unrelated to Physoichemical Properties that prolong Block: how does blood flow prolong block

the lower the blood flow the slower the removal of LA

Mechanism of Action of Local Anesthetics: | LA block what channels

Na+

Mechanism of Action of Local Anesthetics: | what form of the LA diffuses into the nerve axon?

NON-ionized

Mechanism of Action of Local Anesthetics: | what form of the LA binds to the receptors on the Na+ channel

Ionized

Mechanism of Action of Local Anesthetics: | explain how the LA works on the Na+ channel

this a LA (LAH+ LA + H+ ) the LAH+ breaks down in the body to LA + H+. the non-ionized part ( LA ) crosses the lipid bilayer into the nerve cell. there the LA binds with free floating H+ to again form an IONIZED for LAH+. the LAH + binds to the Na+ channel on the inside of the nerve axon.

Must Know: | for mylinated axons __-__ nodes of ranvier must be blocked to stop nerve conduction

2-3

Must Know: | conduction block if frequency dependent. explain that.

the greater the frequency of the action potential, the faster the nerve is blocked. B/c the LA must attach to the Na+ channel in the inactive state; the faster the nerve is firing, the more opportunities the LA will have to "catch" the Na+ channel in the inactive state

Must Know: | is the ionized or non-ionized form of the LA needed to block nerve conduction?

both non-ionized and ionized forms are required for a conduction block

Must Know: | Voltage gated Na+ channels are only found in the nerves ____

axon

____ block is 2-6 dermatomes HIGHER than the sensory block

Sympathetic

____ block is 2 dermatomes LOWER than the sensory block

Motor

state the order of the 3 blocks that occur following a SA spinal injection

Sympathetic Sensory Motor

Metabolism of LA: | Ester LA are metabolized how?

plasma pseudocholinesterases

Metabolism of LA: | Amides are metabolized how?

``` the liver (CYP450) (think AMiDE and LiVER) ```

Toxicity of LA: | what 2 LA can cause methemoglobin?

Benzocaine | Prilocaine

Toxicity of LA: | Methemoglobin is Ferric what?

Ferric 3 (Fe3)

``` Toxicity of LA: is Fe2 (ferrous) good or bad? ```

good

``` Toxicity of LA: is Fe3 (ferric) good or bad ```

bad causes methemoglobin

Toxicity of LA: | if you have methemoglobin (Fe3) what drug do you give to treat it

Methylene blue 1-2 mg/kg IV | Converts Fe3 back to Fe2

what is the ONE ester that is metabolized via the liver?

Cocaine

Toxicity of LA: MAX DOSES | Lidocaine and Mepivacaine plain and w/ epi

Plain 4.5 mg/Kg or 300mg W/ epi 7 mg/Kg or 500mg think of 2, 4.5 + 2 is almost 7 then 300 + 2oo =500

Toxicity of LA: MAX DOSES | Bupivacaine and Ropivaceine plain and w/epi

Plain 2.8 mg/Kg or 175 mg w/ epi 3.2 mg/kg or 225 mg just think 3 its in the middle of both

Toxicity of LA: MAX DOSES | max of procaine and chloroprocaine

12 mg/kg

Toxicity of LA: MAX DOSES | Cocaine and tetracaine

3 mg/kg

Toxicity of LA: MAX DOSES | max of benzocaine spray

N/A

Toxicity of LA: | what is the drug for treatment

``` lipid emulsion (20% intralipid) 1.5 mL/kg followed by infusion of 0.25 mL/kg/min ```

Toxicity of LA: | name how to treat

``` Airway Breathing Circulation Intralipids Benzo (for seizures) ```

Toxicity of LA: | what drugs do you want to avoid if toxicity occurs

Vasopressin CCB BB LA

Manifestation of Toxicity of LA: | what is the therapeutic plasma level of lidocaine?

2-4mcg/mL

Manifestation of Toxicity of LA: LIDOCAINE Name SE (SE progress in this order for ALL LA) 1-5 mcg/mL (x1)

analgesia | therapeutic

Manifestation of Toxicity of LA: LIDOCAINE Name SE (SE progress in this order for ALL LA) 5-10mcg/mL (x2)

``` Lightheaded tinnitus visual disturbance Numbness of tongue Muscle twitching ```

Manifestation of Toxicity of LA: LIDOCAINE Name SE (SE progress in this order for ALL LA) 10-15 mcg/mL (x3)

Seizures | CONVULSIONS

Manifestation of Toxicity of LA: LIDOCAINE Name SE (SE progress in this order for ALL LA) 14-25 mcg/mL (x4)

unconsciousness COMA respiratory arrest

Manifestation of Toxicity of LA: LIDOCAINE Name SE (SE progress in this order for ALL LA) > 25 mcg/mL (x5)

CARDIOVASCULAR depression

Manifestation of Toxicity of LA: | state the order on which toxic manifestations occur

Light headed/ tinnitus/ numbness tongue Convulsions (SZ) Coma CV collapse

Manifestation of Toxicity of LA: | what is the plasma concentration of Lidocaine at which early S/S of toxicity are elicited

5-10mcg/mL | 2 Xs the therapeutic dose

Miscellaneous facts and Issues: | how do u tell amides from esters

amides have 2 i's (bupIvacaIne, ropIvacaIne, prIlocaIne) | esters only have 1 i (cacaIne, tetracaIne, procaine)

Miscellaneous facts and Issues: | what is the LA that all others are compared to?

Lidocaine

Miscellaneous facts and Issues: | the actions of Ester LA would be prolonged in a pt with what disorder

atypical pseudocholinesterase

``` Miscellaneous facts and Issues: chronic therapy with what drug class prolongs the action of Ester LA bc they depress pseudocholinesterase function ```

Acetlycholinesterase inhibitors (edrophonium, neostigmine)

``` Miscellaneous facts and Issues: which class ester or amide is higher risk for allergic reaction ```

ester

Miscellaneous facts and Issues: | what is the metabolic end-product of ester metabolism (also the cause of why there is an increased in allergic reaction)

Para-aminobenzoic acid (PABA)

Miscellaneous facts and Issues: | what LA differs from all other LA in that it is a vasoconstrictor and it is naturally-occurring?

Cocaine

``` Miscellaneous facts and Issues: what class of LA doesn't accumulate in the blood? why? ```

Ester LA | bc they are metabolized be pseudocholinesterase (plasma cholinesterase, butyrocholinesterase)

Miscellaneous facts and Issues: what LA is suitable for OB bc it is rapidly metabolize by plasma cholinesterases, thus the plasma level will normally be kept low. it is important b/c LA cross the placental barrier.

Chloroprocaine

Miscellaneous facts and Issues: | what depresses the activity of pseudocholinesterase?

dibucaine

Miscellaneous facts and Issues: | if pseudocholinesterase is normal dibucaine will depress the activity of pseudocholinesterase by how much?

70-85%

Miscellaneous facts and Issues: | the % that dibucaine depressed pseudocholinesterase is called what?

dibucaine #

Miscellaneous facts and Issues: | what is normal dibucaine # and what does it mean?

80 = 80% (75-85) | it means that it causes 80% depression

Miscellaneous facts and Issues: | if the dibucaine # is 20, what disorder is the pt said to have

homozygote atypical pseudocholinesterase

Miscellaneous facts and Issues: | if the dibucaine # is b/t 30-70 the pt is said to have what

heterozygote atypical pseudocholinesterase

Miscellaneous facts and Issues: | what is the major problem with atypical pseudocholinesterase

incapable of hydrolyzing SCh | (the lower the Dibucaine # the slower hydrolysis of SCh an date longer duration of SCh

Miscellaneous facts and Issues: | the likely cause of bradycardia after SA injection is what?

blockade of cardiac sympathetic preganglionic fibers. (T1-T4)

Miscellaneous facts and Issues: | if a pt becomes nauseous 5 min after spinal what likely is the cause

Hypotension

Miscellaneous facts and Issues: | the dose of LA administered Epidurally is reduced what % in the parturient?

25-50%

Miscellaneous facts and Issues: | what is responsible for the hypotension associated with spinal and epidural anesthesia

blockage of sympathetic preganglionic nerves