Local Anesthetics

Question 1

Two classes of local anesthetics?

Answer 1

Ester, Amide

Question 2

Ester anesthetics?

Answer 2

Procaine, Cocaine, Benzocaine, Tetracaine (Pros do Coke in Benzs while playing Tetris)

Question 3

Amide anesthetics?

Answer 3

Mepivicaine, Lidocaine, Dibucaine, Prilocaine, Ropivicaine, Bupivicaine (Mark Leets Dubious Past Reeks Bad)

Question 4

Cocaine?

Answer 4

Ester

Question 5

Lidocaine?

Answer 5

Amide

Question 6

Mepivicaine?

Answer 6

Amide

Question 7

Bupivicaine?

Answer 7

Amide

Question 8

Procaine?

Answer 8

Ester

Question 9

Benzocaine?

Answer 9

Ester

Question 10

Prilocaine?

Answer 10

Amide

Question 11

Tetracaine?

Answer 11

Ester

Question 12

Ropivicaine?

Answer 12

Amide

Question 13

Dibucaine?

Answer 13

Amide

Question 14

The aromatic ring of LAs determines? What portion of the LA is this?

Answer 14

Potency, Duration of Action. This portion is lipophilic.

Question 15

The intermediate linkage of LAs determines?

Answer 15

The class: Ester or Amide

Question 16

The terminal amine of LAs determines? What portion of the LA is this? What form of the LA is active? What form can cross membranes? How does this relate to pKa & pH? What happens as pKa increases? What happens in an acidic (abscess, inflammation) environment? Why would we mix an LA with sodium bicarbonate?

Answer 16

Onset of action. This portion is hydrophilic. The ionized form is active but the unionized form is the form that can cross membranes. So, the onset of action is ultimately related to the pKa of the LA & the pH of the local environment. All LAs have pKas greater than physiological pH (7.4). As pKa increases, more ionized form exists, meaning less unionized form, meaning less diffusion into cells, meaning longer time of onset. In an acidic environment, the ionized form is favored even greater, so onset is prolonged even more. Adding sodium bicarbonate will reduce acidity of the local environment, favor the unionized form, and speed onset.

Question 17

What are ester LAs limited by? These are metabolize by?

Answer 17

Metabolized by plasma esterases. Limited by short duration (hydrolysis is rapid) & allergies (derivatives of PABA – a known allergen).

Question 18

Amides are metabolized by?

Answer 18

Hepatic amidases

Question 19

What is the MOA of LAs?

Answer 19

Bind and block the intracellular portion of the inactivated voltage gated sodium channel.

Question 20

What is the time of onset in terms of nerve fibers? What other factors determine onset of block?

Answer 20

B (temperature) > C (pain) > Ad (pain) > Ag (proprioception) > Ab (touch & pressure) > Aa (motor). Size (smaller diameter, quicker), Meyelination (myelinated, quicker), Firing frequency (more often, quicker).

Question 21

Absorption of LAs is determined by? Distribution? Metabolism/Excretion?

Answer 21

Absorption: Site (highly vascular? – ^), Vasoconstrictor (epinephrine? – v), LA used (highly protein bound? – v). Distribution: Perfusion, Tissue/Blood coefficient. Metabolism: Esterase, Amidase, Both classes excreted in kidney.

Question 22

Systemic toxicity can affect which systems? List affects & treatments.

Answer 22

CNS. Cardiovascular . CNS: decreased inhibition, sensory disturbances, muscle twitching, seizures, coma, respiratory depression. Treat with ABCs, reverse seizures with benzodiazepines. Cardio: vasodilation, depresion, bradycardia, v.fib., arrest. Reverse with intralipid emulsion. Methemoglobinemia can also occur (tx with methylene blue).

Question 23

Local toxicity can manifest as?

Answer 23

Transient neurological symptoms (TNS), Neuronal injury.