Exam 3 - Lecture 26 Local Anesthetics Flashcards
What is local anesthesia?
Remove sensation from a specific location in the body
Local Anesthesia
small area of the body, ie tooth
Regional Anesthesia
a portion of the body, such as a limb
Major forms of local anesthetic
Topical
Infiltration
Epidural
Spinal
Why use local anesthesia?
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
Infiltration Technique
Most common Dental anesthesia
Goal is to get as close to nerve as possible in general area, not into actual nerve
Epidural
Goes into epidural space
Harder to find than just going into spinal cord
Epidural info
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
Spinal info
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
Cocaine MoA
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
2 classes of synthetic local anesthetics
Aminoester - O double bond to C-O
Aminoamide - O double bond to NH
Mechanism of Action Local Anesthetics
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
Local Anesthetics potency
As lipophilicity increases, so does potency
Bupivacaine > Lidocaine
Local Anesthetics onset of action
Decreasing pKa speeds up onset
Bupivacine > Lidocaine
speed depends on water/lipid interface and pH of aqueous phase
Ester class….
Often not used as epidural
Tend to have higher pKa
Amide class….
Used both spinal and epidural
Tend to have lower pKa values = faster onset
Chloroprocaine (Nesacaine)
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
Lidocaine (xylocaine / Lignocaine)
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
Bupivicaine (Marcaine)
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
Ab - fibers
typically myelinated, faster “5G”
associated with light touch, proprioception (unconsciously know where parts of your body are)
C - fibers
typically unmyelinated, slower “3G”
Pain fibers, thermal, mechanical, chemical nociceptors
Puffer fish and blue ringed octopus
Tetrodotoxin (Bacterial)
doesn’t move around body well
Snakes
Inland Taipan: Taipoxin
Black mamba: dendrotoxins
Spiders
Brazilian wandering spider
PhTx3 - blocks Ca2 channel + Glut release
Tx2-6 activates NOS - painful, long boner
Tx2-6 used in study of ED
Scorpions
Health stalker scorpion: multiple peptide Na+ and K+ channel blockers
Chlorotoxin: small conductance Cl- channel blocker in glioma cells
Mambaglins
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
Zinconotide (Prialt)
Cav2.2 channel blocker used for chronic pain
From cone snail
Eptifibatide (integrilin) and Tirofiban (aggrastat)
components of snake venom that target aIIIbB3 intern receptor antagonists, use in numerous acute cardiovascular conditions
Bivalirudin (Angiomax)
thrombin inhibitor from leech, used to treat coagulation
Exenatide (Byetta)
GLP1 receptor agonist from Gila monster used in type 2 diabetes
Batroxobin
factor Xa inhibitor for preoperative bleeding from pit viber
Magician’s cone
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
Role of Cav2.2 in pain transmission
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
Sodium channels we want to target
- 7, 1.8, 1.9
- 8 found heart = be careful
- 7 = pain channel, C fibers
