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Flashcards in Local Anesthetics Deck (52):
1

Local Anesthetic effect on neural electrophysiology

Increases excitation threshold
Slows impulse conduction
Decreases action potential rate of rise
Decreases action potential amplitude

2

LA Site of Action

Voltage-gated Na+ channels

3

*Characteristics of Nerve Fiber sensitivity to LA blockade

*Nerve fibers differ greatly in their sensitivity to LA blockade based on the fibers: D.E.P.F
1. Diameter-small fibers are first to be blocked
2. Effects on other excitable membrane- weak NMB, antiarrythmic properties (lidocaine), potential for lethal arrhythmias (Bupivacaine)
3. Position in nerve bundle- peripheral nerves of bundle are blocked first
4. Firing frequency- blockade more pronounced at higher frequencies

4

*Classification of Nerve Fibers based on sensitivity to LA blockade

Autonomic Sympathetic B-fiber nerves-Most senstitive to blockade
Autonomic Sensory C fibers-Highly sensitive to blockade
Somatic sensory/motor nerve fibers Aa Ab-least sensitive
Clinically, LA produce sequential loss of:

Autonomic fx>>>Sensory fx>>>Motor fx

5

Structurally, All LA have a similar structure that consists of:

Lipophilic, Hydrocarbon, Hydrophilic portions

6

The hydrocarbon portion of LAs vary and can be classified as either:

Esters or Amides

7

Amide LA include:

Mepivacaine, Etidocaine, Prilocaine, Lidocaine, Bupivacaine, and Ropivacaine

8

Rapid acting Amide LAs include

Mepivacaine
Etidocaine
Lidocaine
Prilocaine

9

Ester LA include:

Chloroprocaine-Rapid
Procaine-Slow
Tetracaine-Slow

10

LA acid/base properties

Local anesthetics, all of which have a pKa > 7.4, become more charged at neutral or acidic pH (i.e. they accept protons when the pH is ~ 7.4), and are less charged at more basic pH (able to cross cell membrane)

11

Why is the acid/base properties of LA important?

This is important because the uncharged base forms are more soluble in lipid environments, and lipid solubility is correlated with potency

12

Because LAs are prepared in acidic HCL salts (pH 4-7), they tend to be

highly ionized & water soluble
this means a vial contains equal mixtures fo nonionized, lipid-soluble (free base) & ionized water-soluble (cationic) molecules

13

the uncharged base in LA is the most important molecule because

It readily crosses the lipid bilayer, and is the reactive species.

14

What does the uncharge base in LA react to once inside the cell

Intracellular Hydrogen Ions to form an ammonium ion complex

15

What does the newly formed LA ammonium complex react

Sodium channels

16

LA's exert it's effect on neurons by binding to Na channels and prolonging entry of sodium ions which -------

repolorization, and therefore subquent depolorization of the cell

17

Increased Lipid Solubility (Pka >7.4) of LA correlates to

Increased potency

18

the solubility/potency relationship of LA is similar to what anesthetic

Inhalation agents

19

Cm is defined as:

the lowest drug concentration required for conduction blockade

20

Cm is influenced by

nerve fiber:
Size
Type
pH
Frequency of Action Potential

21

Larger nerves have lower or higher Cm

Higher

22

Increased pH ------Cm

lowers

23

Increased Action Potential frequency---Cm

lowers

24

pKa of LA determines

Onset of action

25

Protein binding determines

Duration of action
the greater the protein binding, the longer the duration of action

26

Predict the following LAs DOA based on their protein binding %
Chlorprocaine 0%
Lidocaine 65%
Mepivacaine 78%
Bupivacaine 96%
Ropivacaine 93%

Clor.. (< 30 min-Short)
Lido.. (1hr-Medium)
Mepiv...(1 hr-Medium)
Bupiv...(>2 hr-Long)
Ropiv...(>2 hr-Long)

27

**LA systemic absorption varies by site of injection, name the order from greatest to least absorptive sites

ITIC.PEB.SFS
Intravenous>Tracheal>Intercostal>Caudal>
Paracervical>Epidural>Brachial Plexus>Sciatic/Femoral>Subcutaneous

28

Common additives used to Increase LA activity include:

Sodium Bicarbinate
Opioids
Alpha-adrenergic agonist (Clonidi/Dexmed)
Epinephrine

29

Epinephrine added to LA

useful for local and epidural analgesia where epinephrine can reduce the peak local anesthetic concentrations in blood and also serve as part of a test dose to detect acccidental intravenous injection of local anesthetic.
It can also prolong the duration of regional blocks

30

Sodium Bicarbonate added to LA

Raises the pH of the mileau, thus less of the LA is charged, and more of it is lipid soluble. DO NOT ADD TO BUPIVACAINE (as precipitation may occur).

31

Ester LA metabolism

Rapid hydrolysis by plasma cholinesterase
Chloroprocaine>Procaine>Tetracaine

32

Amides LA metabolism

Undergoe pulmonary extraction (Lidocaine, Bupivacaine, Prilocaine)
Hepatic metabolism
*Caution with sever liver dx

33

Systemic toxicity and LA

Systemic toxicity (CNS and/or CVS)

Local Toxicity- nervous tissue injury

34

CNS toxicity and LA

(tinnitus, paresthesias, agitation, lethargy, seizures, and coma)

* Neurologic manifestations precede cardiovascular manifestations
* Hypoxia, Acidosis, Hypercapnea potentiate LA toxicity

35

CVS toxicity and LA

A-V block, arrhythmias, myocardial depression, cardiac arrest

*bupivacaine being the most cardiotoxic
*Hypoxia, Acidosis, Pregnacny, HyperKalemia can exacerbate both cardiac toxicities

36

LA toxicity: Maximum Safe Doses (mg/kg)

Lidocaine (3-5) x2 w/ epi
Bupivacaine (1-2.5) 3 w/ epi
Ropivacaine (3) 3.5 w/ epi
Chloroprocaine (20-22)

37

LA (local) toxic effects

Transient Neurologic Symptoms (M-S lower back pain, buttocks, & post. thighs) begin within 36 hours after recovery from spinal anesthesia, but self-limiting

Cauda Equina Syndrome
-diffuse lumbar sacral injury with bowel/bladder sphincter dysf., & paraplegia.
-Assoc. with hyperbaric 5% lidocaine via continuous spinal microcatheters
* increased risk w/ lidocaine and the lithotomy position.

38

LA and Allergic rxns

Occurs with esters>amides

*cross -sensitivities do not exist between classes of LA

39

LA and Adverse Effects

Methemoglobinemia-seen w/ Prilocaine use
* avoid in OB use
*Tx w/ Methylene Blue IV

- Amide- can cross the placental barrier and can cause Ion-trapping in fetus.
-Esters don't cross PB

40

Lidocaine

- Most widely used
- Rapid onset
-Immediated action and toxicity
*Lidocaine toxicity (and all local anesthetic toxicity) can cause circumoral numbness, facial tingling, restlessness, vertigo, tinnitus, slurred speech, and tonic-clonic seizures. Local anesthetics are actually CNS depressants, thus tonic-clonic seizures are thought to be caused by depression of inhibitory pathways.
- Used in liposuctions, and ETT to blunt sympathetic response

41

*Lidocane's dose-dependent (mcg/mL) systemic effects

1-5 mcg/mL>>> Analgesia
5-10 mcg/mL>>>light headed,tinnitus, circum. numbness, muscle twithing, hypoten, myocardial depress.
10-15 mcg/mL>>> Seizures,unconscious.
15-25 mcg/mL>>> Coma, Resp. arrest
>25 mcg/mL>>> CV depression

42

Mepivacaine

-Rapid onset
-In contrast to lidocaine, no Vasodilator properties

43

Bupivacaine

-Slow onset (need to work)
-Long DOA
-Highly Toxic

44

Ropivacaine

- (S)- enatiomer of bupivacaine
-Less Cardiotoxic than Bupivacaine
-Less potent & DOA than Bup..
-Less Moter blockade than Bup..

45

LevoBupivacaine

-(S)- enatiomer of Bupivacaine
-Identical physio-chemical properties of Bu.
-Less systemic/cardiotoxicity than Bu.

46

Etidocaine

-similar to bupivicane
-More potent motor block than sensory block

47

Cocaine

-ONSET slow
-DOA short
-Significant SNS stimulation-blocks presynaptic reuptake of NE & Dopamine
**Avoid in HTN, CAD, patients receiving catecholamines
-TOPICAL use ONLY

48

Cocaine Toxicity

Nitroglycerin
Beta-adrenergic blockers
Alpha-adrenergic blockers
Benzodiazeines

49

Procaine

-DOA short
-ONSET slow
-Hydrolyzed to PABA by cholinesterase

50

Chloroprocaine

-ONSET rapid
-DOA short
-Metabolized rapidly by plasma cholinesterase- reason for low toxicity profile
-Preservatives>>neurotoxicity

51

Of the Esters Tetracaine

has highest potency, but onset slow

52

Of the Amides, Lidocaine

has the lowest potency, but onset most Rapid