General and Anatomy Flashcards
What do local anesthetics bind to? What does the binding do?
The bind to sodium channels in NERVES to BLOCK NERVE TRANSMISSION.
What is the difference between myelinated and non-myelinated?
with myelinated need to block ~3 nodes of Ranvier (longer with NON myelinated)
Spinal/epidural anesthesia, which is easiest to block?
sympathectomy (B)>sensory (pain)>motor (MOST challenging to block)
Electrophysiology of Nerve conduction
- AP activates voltage gated sodium channels..more depolarization
- voltage fated sodium channels: M (activated) and H (INactivated)…3 distinct states of channel
What type of voltage gated sodium channels do LA bind ti?
Preferentially to inactivated and open states…freqeuncy dependent blockade
What is the frequency dependent blockade theory
In very active nerves, lots of opening and closing will be more quickly blocked (LA is not going thru the channel)
Ester Drugs
Cocaine
Procaine
Tetracaine
Benzocaine
Amides
Lidocaine Mepivacaine Bupivicaine Levobupivacaine Ropivacaine
PK/PD of LA: Where does binding occur?
On the cytoplasmic (inside) side of the receptor
UNcharged vs. Charged
UN-cross
Charged-ACTIVE
need an equilibrium
pH and pKa
Artificially raise the pH of the solution can generate more UNCHARGED LA molecules to drive them across to the inside of the cell more quickly. SODIUM BICARB can help SPEED UP the onset of the block.
Lipid solubility
PRIMARY determinant of potency. more lipophilic=give LESS of the LA, can cross membrane easier.
Protein Binding
LOCAL TISSUE PROTEINS that LA can bind to and creat a sink of LA that can be slowly released to the nerve (NOT talking about albumin). Bind protein longer=will last longer
Clinical uses for LA
- IV; arrythmias Beir block
- Epidural
- Caudal
- Intrathecal (spinal)
- peripheral Nerve (brachial plexus, sciatic, femoral)
- SQ
- Topical
We usually dont want LA in vascular space, what is the one exception?
LIDOCAINE in lower doses can treat arrythmias, causes toxicity if given too much.
Anatomy of Neuraxial Anethesia
Where does spinal cord end?
- adult: L1-2
- infant: 2-3
NEED TO BE LOWER THAN THE CORD
High spinal with respiratory arrest
NEVER from paralyzed phrenic nerves
results from hypoperfusion of respiratory center in 4V. rx: vasopressors and supportive ventilation
PK
vascularity: ICE (intercostal, caudal, epidural)–watch out for toxicity
drug properties (protein binding, lipid solubility)
renal failure: low hemoglobin, to compensate for drug delivery INCREASE CO=INCREASED blood flow=MORE absorption
acidosis: weak bases will get protonated and be easier to absorb
How are esters eliminated
BuChE
How are amides elimnated
liver, hydrolysis by Cyp450
Max recommended Doses Bupivicaine
BUPIVICAINE:
-highly protein bound, so adding epi wont change its absorption
3 mg/kg
2.5mg/kg neonates
LIDOCAINE:
5 mg/kg plain
7 mg/kg with EPI
Neurotoxicity–what happens when there is inhibition of inhibitory neurons?
Inhibit the inhibitor will lead to excitatory neurons.
Signs/Symptoms of Neurotoxicity
lightheadedness, peri-oral numbness, *TINNITUS, seizures
What worsens neurotoxicity?
Acidosis (respiratory or metabolic)
-resp acidosis decreases prot binding in the blood which increases free fraction of drug delivered to the brain. HIGH CO2 in blood, more blood flow in brain and drug flow to brain.
CV toxicity of LA
neurotoxicity occurs before CV
CV: 4x neuro dose with LIDOCAINE
2x neuro dose with BUPIVICAINE-dissociate from cardiac Na channels more slowly than LIDOCAINE
Prevention is key in the tx of LA Toxicity
use epi as intravascular marker, DO NOT USE LIDOCAINE
tx: 20% intralipid-very lipophilic can absorb and sequester LA (creates a sink)
