Exam 3 - Lecture 26 Local Anesthetics

Remove sensation from a specific location in the body

small area of the body, ie tooth

a portion of the body, such as a limb

Topical Infiltration Epidural Spinal

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

Most common Dental anesthesia Goal is to get as close to nerve as possible in general area, not into actual nerve

Goes into epidural space Harder to find than just going into spinal cord

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

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

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

Aminoester - O double bond to C-O Aminoamide - O double bond to NH

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

As lipophilicity increases, so does potency Bupivacaine > Lidocaine

Decreasing pKa speeds up onset Bupivacine > Lidocaine speed depends on water/lipid interface and pH of aqueous phase

Often not used as epidural Tend to have higher pKa

Used both spinal and epidural Tend to have lower pKa values = faster onset

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

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

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

typically myelinated, faster “5G” associated with light touch, proprioception (unconsciously know where parts of your body are)

typically unmyelinated, slower “3G” Pain fibers, thermal, mechanical, chemical nociceptors

Tetrodotoxin (Bacterial) doesn’t move around body well

Inland Taipan: Taipoxin Black mamba: dendrotoxins

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