Principles of local aneasthetics

Question 1

Recall the generation of action potnetial

Answer 1

cell normally polarised around-70mv
depolarised-slight-cause opening of Na channels open and Na enters cell
Rapid depolarisation phase to about 30mv
Na inactivate and K+ channels open-K+ leavs
repolarise
Na channels flip back to normal stage, K+ still open-repolarise to resting state but still refractory

then Na and K closed as normal-can repond to more stimuli

ALL or nothing-unlike NMJ that are graded–once triggered get the whole thing
Acts in 10-15ms (whole thing)

Question 2

What is the key thing to remember about structures of local aneathetics?

Answer 2

all have a aromatic region-like benzene
All have a basic amine side chain
Then either linked by a ester or amide bridging group—this is how you differentiate the 2 groups
all act very similar-just at different speed
Cocaine-esters, lidocaine-amide are 2 exemples studied here

all are weak bases (pKa 8-9)

Question 3

How do local aneathetics interact with sodium channels?

Answer 3

Nociceptive neuron firing-
Injected near connective tissue. Will form ionised and unionised
Hydrophilic pathway: immediatly, unionised can diffuse through-work from the inside (in there once again seperates from ionised to not)
CATion is the one that binds inside of Na channels-and blocks influx of Na into the cell
Channels need to be open for the cation to enter and bind
This is called the hydrophilic pathway-main one
Use-dependent as well (more used more/faster it gets blocked)-why select for sensory neurons in pain, and not act too much on motor neurons

Hydrophobic pathway–
FOr aneathetics with lipid solubility-as pass through the membrane, dissolve in it and can get acess to the channel that way directlty (still needs to form Cation) BUT can work on closed channels

Question 4

What are the effects of aneathetics on neurons?

Answer 4

Prevent generation and conduction of AP BUT DO NOT INFLUENCE RESTING MEMBRANE POTENTIAL
May also influence channel gating-recent evidence (may hold channel in inactive form before letting back to resting form)

selectively block small diameter fibres and de-myelinated fibres (and also select rapidely acting neurons-nociceptors)-sensory fibres
Always weak bases (pKa 8-9)-small amount will be ionised. But infected tissue tend to be acidic-even less is ionised and can enter

Question 5

What are the 6 main routes of administration of local aneathetics?

Answer 5

surface aneathesia-administered to mucosal surface (mouth, eyes, throat)–spray, powder, ointment
Need high concentrations–> can cause systemic toxicity

Inflitration aneasthesia
Directly into tissue via needle-> sensory nerve terminals (target). good for minor surgeries (suture, abcess drainage, cysts). dont want to give too much.
Adrenaline co-injection to reduce toxicity-vasoconstricts and limits spread to other parts of body. and can reduce bleeding if there. BUT not adrenaline in digits because they still need blood. might use vasopressin instead

Intravenous regional aneasthesia
IV-distally to a pressure cuff -cant leave that way
For smaller surgeries but on large areas -> Limb surgery, resetting bones,
can cause systemic toxicity if premature cuff release-at least 20 mins

Nerve block aneastesia
Close to nerve trunks-dental nerves-quite skillfull
Widely used-low doses, but slow onset
also co-administer with vasoconstrictor

Spinal aneathesia-
Into sub-arachnoid space-acts on spinal roots
Abdominal, pevlic, lower limb surgeries
Low doses
can cause low BP (ans can be affected) and prolonged headaches
Some people add glucose to increase specific gravity-doesnt move as much+ can control

Epidural aneathesia
In fatty tissue of epidural space (outside of dura)-spinal roots still affected
Uses same as spinal and painless childbirth
Slower onset and needs higher doses, but less effects on BP

Question 6

What are the different properties of cocaine and lidocaine

Answer 6

Cocaine-ester, Lidocaine-amide
Both well absorbed by mucous membrane
Plasma protein binding-lido (70%), cocaine (90%)
Metabolism-lido-Hepatic N-dealkylation. Cocaine-non specific esterase in liver and blood
Lido-2h half life
Cocaine-1h halflife

amide in general tend to have longer half lifes-be more stable

Question 7

What are the side effects of local aneathetics

Answer 7

all very similar. take exemple of lidocaine
Key:
CNS-systemic overdose: stimulation, restlessness, confusion, tremor. as increase conc dampen down CNS, but initally cause over activation (might inhbit GABA at first)
CVS-Myocardial depression, vasodilation, lower BP

cocaine-similar–CNS-euphoria, excitation
CVS-Cardiac output UP, vasocontriction, BP up
BECAUSE ALSO HAS A SYMPATHETIC ACTIVITY (stops monoamide reuptake)