Exam 3 - Lecture 26 Local Anesthetics

Question 1

What is local anesthesia?

Answer 1

Remove sensation from a specific location in the body

Question 2

Local Anesthesia

Answer 2

small area of the body, ie tooth

Question 3

Regional Anesthesia

Answer 3

a portion of the body, such as a limb

Question 4

Major forms of local anesthetic

Answer 4

Topical
Infiltration
Epidural
Spinal

Question 5

Why use local anesthesia?

Answer 5

Cheaper and often safer than general anesthesia

Patient can remain fully awake or be sedated, removes risks

Fewer post-op concerns

Decreased incidence of DVT

Question 6

Infiltration Technique

Answer 6

Most common Dental anesthesia

Goal is to get as close to nerve as possible in general area, not into actual nerve

Question 7

Epidural

Answer 7

Goes into epidural space

Harder to find than just going into spinal cord

Question 8

Epidural info

Answer 8

Dose is high
Onset is slow
Does not cause significant neuromuscular block
Multiple dosing possible
Can be given at various points along backbone

Infiltration technique

Question 9

Spinal info

Answer 9

Dose is low
Onset is fast
dose cause significant neuromuscular block
single dose
Can only be given at specific point along the backbone to avoid damaging the spinal cord

Must choose to where it needs to act

Question 10

Cocaine MoA

Answer 10

Blocks the reuptake of catecholaminergic neurotransmitters from the synaptic cleft

Causes increase in amount in synaptic cleft

Topically: application directly to myocytes will cause change in sodium channel current…will increasingly decrease current over time course of application

Question 11

2 classes of synthetic local anesthetics

Answer 11

Aminoester - O double bond to C-O

Aminoamide - O double bond to NH

Question 12

Mechanism of Action Local Anesthetics

Answer 12

charged form becomes turns into uncharged form, then will cross membrane into cell.

They become charged inside the cell, acting on Nav channels preventing Na to go through

Question 13

Local Anesthetics potency

Answer 13

As lipophilicity increases, so does potency

Bupivacaine > Lidocaine

Question 14

Local Anesthetics onset of action

Answer 14

Decreasing pKa speeds up onset

Bupivacine > Lidocaine

speed depends on water/lipid interface and pH of aqueous phase

Question 15

Ester class….

Answer 15

Often not used as epidural

Tend to have higher pKa

Question 16

Amide class….

Answer 16

Used both spinal and epidural

Tend to have lower pKa values = faster onset

Question 17

Chloroprocaine (Nesacaine)

Answer 17

MoA: State dependent block of Nav channels

FDA approval: epidural but not spinal use

Pharmacokinetics: developed for rapid, short acting spinal anesthesia

Ester, so rapidly metabolized by esters

Rapid onset of action

safe fetal = obstetric

Question 18

Lidocaine (xylocaine / Lignocaine)

Answer 18

MoA: State dependent block of Nav channels

Suitable for infiltration, block and surface anesthesia but not caudal (caudal canal spine) and epidural. Primary dental anesthetic

Rapid onset, intermediate duration of action

Pharmacokinetics: CYP3A4 dealkylation, ~100min 1/2 life

1st amino amide local anesthetic

Anti-arrhythmic

Question 19

Bupivicaine (Marcaine)

Answer 19

MoA: State dependent block of Nav channels

Rapid onset, long duration of action (~3hr)

One of mot common local anesthetics in clinical practice.

Suitable for infiltration, epidural and all types of nerve block

Question 20

Ab - fibers

Answer 20

typically myelinated, faster “5G”

associated with light touch, proprioception (unconsciously know where parts of your body are)

Question 21

C - fibers

Answer 21

typically unmyelinated, slower “3G”

Pain fibers, thermal, mechanical, chemical nociceptors

Question 22

Puffer fish and blue ringed octopus

Answer 22

Tetrodotoxin (Bacterial)

doesn’t move around body well

Question 23

Snakes

Answer 23

Inland Taipan: Taipoxin

Black mamba: dendrotoxins

Question 24

Spiders

Answer 24

Brazilian wandering spider
PhTx3 - blocks Ca2 channel + Glut release
Tx2-6 activates NOS - painful, long boner
Tx2-6 used in study of ED

Question 25

Scorpions

Answer 25

Health stalker scorpion: multiple peptide Na+ and K+ channel blockers

Chlorotoxin: small conductance Cl- channel blocker in glioma cells

Question 26

Mambaglins

Answer 26

Small protein

Acid-sensitive ion channels (ASICs), are activated by acidity and elicit a pain response in sensory neurons

Mambaglins block ASIC channels, more potent analgesic than morphine

Question 27

Zinconotide (Prialt)

Answer 27

Cav2.2 channel blocker used for chronic pain

From cone snail

Question 28

Eptifibatide (integrilin) and Tirofiban (aggrastat)

Answer 28

components of snake venom that target aIIIbB3 intern receptor antagonists, use in numerous acute cardiovascular conditions

Question 29

Bivalirudin (Angiomax)

Answer 29

thrombin inhibitor from leech, used to treat coagulation

Question 30

Exenatide (Byetta)

Answer 30

GLP1 receptor agonist from Gila monster used in type 2 diabetes

Question 31

Batroxobin

Answer 31

factor Xa inhibitor for preoperative bleeding from pit viber

Question 32

Magician’s cone

Answer 32

w-conotoxin - MVIIA

A specific blocker of Ca2.2 (N-type) channels

Used as an intrathecal analgesic - Prialt/ Ziconitide

Used for pain in morphine tolerant patients

1000X more potent than morphine

Question 33

Role of Cav2.2 in pain transmission

Answer 33

Noxious stimulation will activate N-type calcium channel in Ad/C fiber. Ziconotide blocks channel, removing the influx of calcium that causes Glutamate release.

This reduces Glutamate release, thus AMPA and NMDA channels in Dorsal Horn neuron will not let calcium in leading to no depolarization and thus no pain signal

Question 34

Sodium channels we want to target

Answer 34

1. 7, 1.8, 1.9
2. 8 found heart = be careful
3. 7 = pain channel, C fibers