Local Anesthetics

Question 1

What compounds make up local anesthetics

Answer 1

Amide and ester compounds

Question 2

How does local anesthetics get to binding sites?

Answer 2

Diffuse across neuronal membranes via amine groups

Protonated = water soluble

Deprotonated = lipid soluble

Question 3

Why do local anesthetics have a wide variety of ADRs?

Answer 3

They target voltage gated sodium channels and these are found throughout the body, not just neuronal tissues

Question 4

Factors that determine fiber susceptibility to local anesthetics

Answer 4

Diameter
- smaller diameters make it easier to block nodes and prevent the signal propagation

Myelination
- assuming no diameter changes, myelinated fibers are easier to block since sodium channels are more concentrated in nodes of Ranvier in myelinated neurons

Fiber positioning
- fibers closest to the outside of the nerve bundle are easier to block since they get exposure to higher concentrations

Firing frequency of the fiber
- neurons that fire more frequent are more susceptible since their sodium channels are open more often, allowing more chances to block them

A(delta) and C fibers are the most susceptable to local anesthetics since they are smaller

Question 5

Ester -linked local anesthetics

Answer 5

Cocaine and its derivatives

• short acting with elimination half-life being less than 1 min

Breaks down rapidly in plasma -> water soluble compounds via butrylcholinesaes and pseudocholinesaterases

Question 6

Amide-linked local anesthetics

Answer 6

Contains lidocaine and its derivatives

Has longer half life and solubilized in the liver via CYP 450s

Question 7

Cardiotoxicity with local anesthetics

Answer 7

Produces negative chronotropic and inotropic effects
- only exceptions are lidocaine or procainamide low doses

Bupivacaine is super likely to experience cardiotoxicity since it is lipophilic
- can be reversed using IV infusions with lipid emulsifiers

Question 8

Hypotension with local anesthetics

Answer 8

Causes vasodilation and hypotension since sympathetic neurons have sodium channels

Cocaine however produces intense vasoconstriction (since it blocks NE receptors)

procaine is notorious for cardiovascular collapse potential

Question 9

Neurotoxicity with local anesthetics

Answer 9

Dose dependent

CNS effects:
1) low dose = antiarrhythmic and anticonvulsant effects, muscular twitching, unconsciousness

2) high dose = convulsions, coma, respiratory distress, CVS depression

Peripheral effects:
1) Low dose = urinary retention and urinary bladder paralysis

2) High dose = motor paralysis

Question 10

Hematologists effects of local anesthetics

Answer 10

Can produce methemoglobin at high doses (especially lidocaine or procaine)

Question 11

Pregnancy risk with local anesthetics

Answer 11

Bupivacaine has an increased chance of cardiac arrest in pregnant patients

Increased clearance occurs in pregnancy

Question 12

Why does accidentally placing local anesthetics into blood vessels so bad?

Answer 12

Because IV doses guarantee CNS toxicity

Question 13

Often coadministered compounds with local anesthetics

Answer 13

1) Sodium bicarbonate
- raises pH of target fissure to more closely match the PKA of a local anesthetic
- allows for lower dose to get desired action

2) epinephrine
- limits distribution into vasculature by vasoconstriction
- increases duration fo action and limits potential systemic toxicity
* increases chances of local toxicity chances, especially at injection site, so must be careful*