Week 1 Neuroanatomy 2 of 4 Flashcards
What is the spread of depolarization?
Opening of Na+ channels generates local current circuit that depolarizes adjacent membrane, opening more Na+ channels
Picture:
at rest
stimulated (depolarization)
spread of depolarization
spread of depolarization
Saltatory conduction: node to node jumping of depolarization
Un-ionizes form enter and ionized form blocks
Explain the action potential of local anesthetics.
Local anesthetics slow the rate of depolarization of the nerve action potential such that the threshold potential is not reached. As a result, an action potential cannot be propagated in the presence of local anesthetic and conduction blockade results.
Examples of Local Anesthetics.
A.Procaine, cocaine, lidocaine, bupivacaine
Mechanism of Action of local anesthetics.
- Local anesthetics are weak bases present in un-ionized form (LA) and ionized form (LAH+)
- Un-ionized form (LA) penetrates the cell membrane.
- The pH is slightly acidic inside the cells -> more ionized form (LAH+) produces.
- Ionized form (LAH+) blocks the Na+ channels (from inside)
- Inhibit conduction of pain impulses from periphery to CNS (afferent fibers)
When using local anesthetics how many nodes of Ranvier be blocked to stop nerve conduction?
A.For myelinated axon, 2-3 nodes of Ranvier must be blocked to stop the nerve conduction.
______ the frequency of action potential, the _____ the nerve is blocked by LA
D.Greater the frequency of action potential, the faster the nerve is blocked by LA
LA must attach to the ____________ when it is in the inactivated state
D.LA must attach to the sodium channel when it is in the inactivated state
____________ fibers are more sensitive to LA.
D.Small diameter fibers are more sensitive to LA.
_________ are relatively resistant to LA
D.C-fibers are relatively resistant to LA
What are LA normally used in?
D.Uses: minor surgical procedures, spinal anesthesia
Height of Sensory Versus Motor Block After Subarachnoid (spinal) injection of Local Anesthetic
A.Sympathetic block is 2-6 dermatomes higher than sensory block
B.Motor block is 2 dermatomes lower than sensory block
What pH are agents with lower pKa are more un-ionized?
A.Agents with lower pKa are more un-ionized at pH=7.4
A.Un-ionized form is lipid soluble and can easily penetrate axon cell membrane –> faster conduction block
Look at slide 28 on Regional ANesthesia Neuroanatomy (couldnot copy and paste table)
What blocks sodium channels which will inturn block nerve conduction?
A.LA blocks sodium channels –> block nerve conduction
More lipid solubility means what?
B.More lipid solubility –> more easier to cross cell membrane
When local anesthetics are highly protein bound they will have what kind of duration?
C.LA that are highly protein bound will have prolong duration of action
What does pKa of a local anesthetic determine?
D.pKa of a LA determines the speed of onset
1.Lower pKa = faster onset
In regards to potency of local anesthetics, the greater the oil: water coeffcient __________________
A.Greater the oil : water coefficient, the greater the lipid solubility
The more lipid solubility of the LA; the greater its _______
B.The more lipid solubility of the LA; the greater its potency
Potency depends on what 5 things?
C.Potency also depends on
- Fiber size
- Myelination
- pH (acidic pH antagonizes block)
- Frequency of nerve stimulation
- Electrolyte balance ( hypokalemia and hypercalcemia antagonize block)
Potency of LA
look at slide 31 in Regional Anesthesia under Neuroanatomy (unable to paste chart)
What is the duration of action determined by (two properties)?
A.Duration of action of a LA is determined by two properties
- The degree of protein binding
a. Most important factor
b. Mainly alpha-1 acid glycoprotein (AAG)
c. Greater the protein binding, the longer the duration of action
d. Protein bound LA acts as reservoir of LA; maintaining slow release
ProtLAH D Prot - + LAH+ D LA + H+
●
- Lipid solubility
a. Greater the lipid solubility, longer the duration of action
b. Lipids act as reservoir of LA; maintaining the nerve block
Duration of Action of Local Anesthetics
Agents that are most ________ and have the greatest protein binding are ________
Agents that are most lipid soluble and have the greatest protein binding are longest acting
Look at slide 33 in NeuroAnatomy
What 5 things determine blood concentration of LA?
A.Blood concentration of LA is determined by
- Presence or absence of a vasoconstrictor
a. Epinephrine INCREASES duration of action of spinal anesthesia by 75-100% by alpha adrenergic action (vasoconstriction DECREASES the rate of absorption) - Alpha-2 agonist INCREASES blocks
- Tissue Blood Flow
- .Concentration injected
a. Greater the concentration of injected LA, longer the duration of action - Number and frequency of injections
What is the blood flow ranking?
REMEMBER:
In Time I Can Please Everyone But Susie & Sally.
Tissue blood flow
a. Higher the blood flow, faster the absorption and wash away from injection site –> decrease the duration of action
b. Blood flow ranking :
1) Intravenous
2) Tracheal
3) Intercostal
4) Caudal
5) Paracervical
6) Epidural
7) Brachial Plexus
8) Subarachnoid , Sciatic, Femoral
9) Subcutaneous
Esters are LA that are metabolized by what?
A.Ester local anesthetics are metabolized by plasma pseudocholinesterase (or plasma cholinesterase)
- That’s why do not accumulate in blood
- Esters are derived from benzoic acid
What are amides metabolized by?
A.Amides are metabolized by liver P-450 enzyme system
- Abnormal liver function –> toxicity
- Very little excretes by kidneys
What can benzocaine cause?
A.Benzocaine can cause methemoglobinemia
What is the agent of choice for obstetrics and why?
A.Chloroprocaine is agent of choice for obstetrics because it is rapidly metabolized. This prevents toxic effects to fetus. (Remember LA cross the placental barrier)
________ is slowly metabolized, increases likelihood of toxicity
A.Tetracaine is slowly metabolized, increases likelihood of toxicity
What is system toxicity determine by in local anesthetics?
A.Systemic toxicity is determined by the concentration of LA achieved in the blood
Toxic manifestations of lidocaine (2-4 mg/ml is therapeutic concentration) are:
Plasma Conc. of Lidocaine
Toxic Manifestations for any Local Anesthetic
3 mg/ml Circumoral and tongue numbness
4 mg/ml Lightheadedness and tinnitus
6 mg/m Visual disturbance
8 mg/ml Muscular twitching
10 mg/ml Unconsciousness
12 mg/ml Convulsions
15 mg/ml Coma
20 mg/ml Respiratory arrest
26 mg/ml Cardiovascular collapse
Esters how have many i’s while amides have how many i’s?
1.Esters have one ‘i’ (procaine, chloroprocaine) while amides have two ‘i’ (prilocaine, lidocaine, etidocaine)
What patients may have a prolong duration of LA?
2.Patient with atypical pseudocholinesterase have prolong duration of action
Chronic therapy with what prolongs the action of ester LA?
1.Chronic therapy with acetylcholinesterase inhibitors ( edrophonium, physostigmine, echothiophate) prolongs the action of ester LA
___________ is a metabolic end-product of ester metabolism may cause hypersensitivity reaction
2.Para-aminobenzoic acid (PABA) is a metabolic end-product of ester metabolism may cause hypersensitivity reaction
What depresses the activity of pseudocholinesterase by 80% ?
3.Dibucaine depresses the activity of pseudocholinesterase by 80% (Dibucaine number)
_________ may cause methemoglobinemia.
Prilocaine may cause methemoglobinemia
Toxic dose of lidocaine with epinehrine?
5.With epinephrine toxic dose of lidocaine is 6 mg/kg
What is responsible for hypotension in LA?
6.Sympathetic blockade is responsible for hypotension
−Vasodilatation –> decrease preload –> hypotension
If beta adrenergic effects are not required what med would you add?
7.Add phenylephrine instead of epinephrine if beta adrenergic affects are not required
