Local Anesthetics

Question 1

What are local anesthetics (LA)?

Answer 1

Drugs that reversibly block conduction of electrical impulse along nerve fibers
- removal of drug is followed by spontaneous and complete return of nerve conduction, without evidence of structural damage to nerve fibers

Question 2

What is the ability of LA to produce reversible blockade of impulses along pathways dependent on?

Answer 2

• physiochemical properties of LA

- anatomy of nerves being blocked

Question 3

What is the difference in myelinated vs unmyelinated nerves?

Answer 3

• Unmyelinated: lacks fatty myelin sheath, charge can leak, impulse can slow down as it goes
• myelinated: impulse can jump, no electrolyte leaking, IMPULSE SPEEDS UP
  
  • Na+ propagates action potential

Question 4

How does an action potential work along axons?

Answer 4

Exactly the same way as a muscle cell action potential, with Na+ and Ca++ moving into the cell and K+ moving out, only the resting membrane is -70mv

Question 5

What factors of nerve fibers influence sensitivity to LA?

Answer 5

Diameter and myelination
SIZE effects susceptibility more than myelination
- smaller= more susceptible than myelin

Question 6

Do different types of fibers (myellin/demyelinated) send a different type of pain impulse?

Answer 6

Yes

Question 7

In spinal nerves, sensitivity to LA is:

Answer 7

1st: autonomic nerve fibers
2nd: sensory nerve fibers
3rd: motor nerve fibers

Question 8

LA mechanism of action?

Answer 8

• reversibly block Na+ Chanel’s
• receptors, located on inside of cell have a greater affinity for charged from of LA
  
  • BUT first must penetrate cell membrane, much easier in uncharged state

Question 9

How does LA get into cell to work on the receptors?

Answer 9

• LA is given as a weak base
• when injected into the body will stay in same form (body is a weak base too) and diffuse into cell
• once inside the neuron- acidic environment separates LA into ionized and unionized forms
  
  • cation (ionized form) binds with receptor on inside of neuron

Question 10

All LA have a similar structure of an aromatic ring with an amine group at the very end? What splits LA into 2 groups?

Answer 10

The intermediate group:

• can either be an ester linkage or an amide linkage
  
  • clinically important as it affects metabolism and allergy potential

Question 11

Which LA are esters?

Answer 11

Procaine
Chloroprocaine
Tetracaine
Cocaine

Question 12

Which LA are amides?

Answer 12

* If you remove the “caine” their is an “i” in all Am”i”des**
Lidocaine
Prilociane 
Levobupivicaine
Mepivacaine
Bupivacaine
Ropivacaine
Etidocaine

Question 13

The onset of action depends on:

Answer 13

• lipid solubility* —> main determinant in amount of LA that is in non-ionized form
• pka is the pH of LA where amount of ionized and non-ionized form of drug are equal
• LA with pka closes to physiologic pH will have HIGHER CONCENTRATIONS of non-ionized form that can readily pass through nerve cell membrane

Question 14

What is ion trapping and what is it caused by?

Answer 14

Loss of penetration into nerve

• occurs when injecting into an acidic area (ischemia)
• a weak base injected into an acidic environment converts to ionized form and cannot enter cell*
  
  • will not work to control pain

Question 15

Duration of action:

Answer 15

• correlates with lipid solubility
• higher lipid solubility = longer duration —> less likely to be cleared by blood flow (stored in lipid depot)
• higher lipid soluble are typically highly protein bound
  —> adding large chemical radicals to amide results in greater protein binding

Question 16

Which LA have a duration of 200 + minutes?

Answer 16

Robivicane and bupivicine

- tetracaine duration is 200 minutes

Question 17

Which LA have a duration of 30-60 or 30-90 minutes?

Answer 17

Lidocaine: 30-60 minutes
Prilocaine: 30-90 minutes

Question 18

Which LA have duration in the 40 minutes range?

Answer 18

Mepicacaine: 45-90 minutes
Procaine: 40 minutes
Chlorpromazine: 45 minutes

Question 19

How long until the onset of action in most LA?

Answer 19

5-15 minutes

Question 20

If you have a 1% solution of lidocaine, what does that mean?

Answer 20

1G/100mL

Question 21

How are LA distributed?

Answer 21

Unlike most meds, LA are meant to remain in area of injection/application

• the HIGHER the CONCENTRATION of drug that REMAINS AT THE AREA of the nerve, the FASTER the ONSET OF ACTION
• Systemic absorption = offset and termination of drug effect

Question 22

How do LA leave the area of injection?

Answer 22

If close to blood vessels —> swept away more quickly
Sits in fatty tissue longer
- does not get metabolized in place-needs to dissipate away to be metabolized

Question 23

What does systemic absorption depend on?

Answer 23

• Blood flow
• specific agent
  
  • highly lipid soluble
  • intrinsic vasodilation properties

Question 24

What does adding vasoconstrictors (epi) to the mix do?

Answer 24

• decreases vascular absorption
• increases nerve cell uptake
• enhances quality of anesthesia
• prolongs duration of action
• limits toxic effects *

Question 25

Why do you add epi to LA?

Answer 25

All LA, except cocaine, relax vascular smooth muscle—> vasodilation—> systemic absorption - epi counters the vasodilation - cocaine is the only one that doesn’t dilate—> strong vasoconstrictor (alpha and beta adrenergic stimulator)

Question 26

Once LA is absorbed systemically, how is it distributed?

Answer 26

Initially to highly perfused organs-> brain, lungs, liver, kidneys, heart - slower distribution to moderately perfused organs - muscles and gut (muscles d/t large mass)

Question 27

How are LAs with ester linkages metabolized?

Answer 27

Mainly by pseudocholinESTERase - targets “Ester” linkage - ester hydrolysis is a rapid process - H2O soluble metabolites are excreted in the urine - pts with genetically abnormal pseudocholinesterase are at risk for toxic side effects (you won’t know until you give the med)

Question 28

What enters have metabolites that can cause allergic reactions?

Answer 28

Procaine and Benzocaine | Metabolized to PABA, which causes an allergic reaction

Question 29

How are amides metabolized?

Answer 29

By CYP 450- liver takes longer than breaking ester linkages - decreased liver function decreases metabolism—>increases toxicity - metabolism depends on renal clearance

Question 30

Which LAs create metabolites that convert to methemoglobin?

Answer 30

Prilocaine and benzocaine

Question 31

What does methemoglobin do to the body?

Answer 31

Produces a left shift - brownish gray cyanosis - tachypnea - met. Acidosis * Severs s/s: tissue hypoxia, HA, irritability, LOC *

Question 32

What is the treatment for methemaglobinemia?

Answer 32

Methylene blue: immediate reversal

Question 33

Is methemoglobinemia an issue in healthy patients?

Answer 33

No, becomes a problem with anemia or CHF- pts that can’t tolerate decrease in O2 carrying capacity

Question 34

What does adding opioids, NaHCO3,and epi to LA do?

Answer 34

added to increase safety, quality, intensity, duration, and rate of anesthesia

Question 35

Toxicity of LA occurs when:

Answer 35

- accidental IV administration | - excessive dose

Question 36

What will you see in toxicity?

Answer 36

Cardiac and cerebral effects * famous lidocaine side effects with systemic absorption—> gibberish, tinnitus, confusion, seizures, metallic Tate - will see HR and BP increase then both will drop * high death rate if significant toxicity - combo of bradycardia, heart block, and low BP cause cardiac arrest

Question 37

What is the treatment for systemic LA toxicity?

Answer 37

Lipid infusion: binds lipophillic med

Question 38

If you need to give LA and you pt has had an allergic reaction in the past what do you do?

Answer 38

Find out which one and if it’s an amide or ester-> then use one from the other class

Question 39

What is EMLA?

Answer 39

Mix of lido and prilocaine Dermal pain receptors, lipophillic - about 1 hours to onset of analgesia

Question 40

Can topical anesthetic absorb systemically?

Answer 40

Yes: avoid high blood flow membranes

Question 41

What is topical cocaine used for?

Answer 41

ENT- excellent in nasal surgery—> Shrinks nasal mucosa | - produces vasoconstriction by blocking norepinephrine and epinephrine uptake int adrenergic nerve endings

Question 42

What can happen if epinephrine is injected into nasal mucosa prior to cocaine admin?

Answer 42

Toxic effect of epi may occur since cocaine blocks epi reuptake —>life threatening arrhythmias