Local Anesthetics Flashcards
1
Q
Local anesthetics reversibly block ________ nerve transmission to produce analgesia and anesthesia without loss of consciousness
- Autonomic blockade = Intent vs Side effect
- Increase or decrease in BP due to _________ - Somatic sensory blockade = Intent vs Side effect
- Somatic motor blockade = Intent vs Side effect
A
afferent
- SE, Decrease, Loss of vasotone
- Intent
- SE
2
Q
LAs administered near the site of action:
- _______ around the nerve
- applied ______ to the skin and mucous membranes
- _______ into blood vessels that are first _____________ in order to provide intravenous _________ anesthesia ( _____ block)
- injected into the ____________ and ________ spaces for diffusion to desired levels in the spinal column
A
infiltrated
topically
infiltrated, exsanguinated, regional, Bier
subarachnoid, epidural
3
Q
Myelinated or Unmyelinated Nerve Fiber:
A Schwann-cell wraps itself around the axon several times, enveloping the axon in a myelin sheath
- lipid soluble or insoluble
A
Myelinated, insoluble (barrier)
4
Q
A single Schwann cell surrounds several axons
A
Unmyelinated Nerve Fiber
5
Q
Number of Node of Ranvier needed to be blocked to achieve a nerve block?
A
3
6
Q
Propagation of impulses in myelinated vs unmyelinated?
A
similar in both
7
Q
Unmyelinated fibers: impulses travel along the length of the fiber in a __________ fashion
A
continuous
8
Q
Conduction is “saltatory”so fast (50X) that it appears as if impulses leap from one node of Ranvier (no myelin) to the next
A
Myelinated fibers
9
Q
Ion Channels guarded by a _____________ (opens or closes depending on changing physiologic conditions)
A
gating mechanism
10
Q
The membrane forms a ______ across which there is movement of ions along a concentration gradient between the intracellular and extracellular spaces.
EXTRAcellular contains a high concentration of ________ and low concentration of _________; reverse for intracellular
A
barrier
SODIUM
potassium
11
Q
The velocity an impulse travels is __________ to the diameter of the fiber: the _____ the diameter, the higher the conduction velocity
• Fibers classified according to diameter, three types:
_, _ and _ fibers
A
proportional, larger
A, B and C fibers
12
Q
A-alpha fibers:
A
motor & proprioception
13-22 microns
80-120 m/s
13
Q
A-beta fibers:
A
motor, touch, pressure
6-12 microns
35-45 m/s
14
Q
A- gamma fibers:
A
motor/muscle tone (muscle spindle)
15
Q
A-delta fibers:
A
pain, temperature,touch
1-5 microns
5-35 m/s
16
Q
B-fibers:
A
PREganglionic autonomic (myelinated) 1-3 micrometers
17
Q
C- fibers:
A
dull pain, temperature, touch, POSTganglionic autonomic– NO MYELIN
- 1-2.5 micrometers
- 5-2 m/s
18
Q
Large fibers have the ___est conduction velocity and the ___est threshold for excitability
A
highest, lowest
19
Q
Differential Blockade:
Clinically…. The sensitivity of a peripheral nerve to LA is _______ related to size.
That is why you see _________ blockade first, ________ second and ______ last.
*However…this is not a cause and effect!
A
inversely
autonomic , sensory, motor
20
Q
Differential Blockade:
In a laboratory…larger fibers (A delta and gamma) are actually ______ sensitive to local anesthetics than the C fibers which are unmyelinated and small.
A
more
21
Q
Differential Blockade:
Difference between clinical observation and research theories
A
- anatomic issues/first…..why? larger nerves found deeper in nerve bundles – harder for the LA to reach!
- variable activity in different nerves (pain fibers fire at higher frequency)….i.e. frequency dependent blockade • variable ion channel mechanisms
22
Q
Spread of Local Anesthetic………
A
LOCATION, LOCATION, LOCATION!
23
Q
Outer surface of a peripheral nerve is known as the _____ (usually more ______ structures)
A
mantle, proximal
24
Q
Inner surface known as _____ (these fibers usually serve more _____ structures)
A
core, distal
25
Mixed nerve
Nerve containing both afferent and efferent (sensory and motor) nerves
26
THE SEQUENCE OF ONSET AND RECOVERY FROM A LOCAL ANESTHETIC BLOCK IN A MIXED PERIPHERAL NERVE RELIES HEAVILY ON ?
WHERE IT IS LOCATED
| • This factor is much more important than the inherent sensitivity of the nerve fiber to local anesthetics
27
Clinical sequence of anesthesia:
1st- sympathetic block (vasodilatation, warm skin)
2nd – Loss pain and temperature sensation
3rd – Loss of proprioception
4th - Loss of touch and pressure
5th – Motor blockade (don't need often in most procedures)
28
Nerve Blockade is caused by prevention of voltage dependent increase in ___ Conductance
Na
| -blocks impulse conduction during the depolarization phase of the action potential....not able to reach threshold
29
Voltage gated sodium channels in the inactivated-closed state serve as ________ for local anesthetic molecules
receptors
30
Local anesthetics bind at specific sites on the ___________ of the _________ & physically obstruct the external openings of the channels
internal H gate
| Na channel
31
Local anesthetics prevent passage of sodium ions through these channels by binding and stabilizing them in the ________________ conformational state.
This blocks impulse conduction during the ____________ phase of the action potential.
inactivated-closed
| depolarization
32
LA s easily access nerve cell Na channels in the “activated-open” state
LA’s easily bind to the receptor in the “inactivated-closed” state
The more frequently the nerve is in this state, (i.e. cycled through an action potential) the more rapidly blockade occurs
Resting nerve less sensitive to block than a repetitively stimulated nerve
Lipid solubility determines (i.e. it has to diffuse through the axonal membrane instead of through the Na channel to reach its target)
Frequency or Use Dependent Blockade
33
Distance between Nodes of Ranvier in myelinated fibers contributes to _____________
differential nerve block
34
The internodal distance _______ with fiber diameter
increases
35
An impulse can or cannot make it through two blocked nodes? What about a third?
Blockade of three nodes (1cm) eliminates conduction along a myelinated nerve fiber
36
Differential Nerve Block:
___________ was the first local anesthetic shown to produce a beneficial differential block:
_______ block with incomplete ______ block
• Pain conducting fibers (A delta, C fibers) blocked • A alpha, beta, & gamma fibers not completely blocked • Patients feel pressure but not pain with surgical stimulation
Bupivacaine
| Sensory, motor
37
Differential Nerve Block:
Pain conducting fibers _____ & _____ blocked.
A ____, ____, & _____ fibers not completely blocked. Patients feel _______ but not _____ with surgical stimulation.
A delta, C
alpha, beta, & gamma
pressure, pain
38
Local anesthetics are classified chemically as __________ or _________.
The typical molecule consists of a lipophilic head (___________), an intermediate chain containing either an ________ or an ________ and a hydrophilic tail (______________).
aminoamides, aminoesters
| an aromatic ring, amide (NH), ester (COO-), a tertiary amine
39
How can the name of a LA identify it as an amide?
Amide’s have an i in the drug name before the – caine part
| • Examples – lidocaine, bupivacaine, etidocaine
40
Class of intermediate chain affects biotransformation of the molecule:
Ester linkage readily ___________ by non-specific esterases in the _____ and tissues (mostly ____). Exception being ________.
hydrolyzed (= faster), plasma, liver
| Cocaine - metabolized in liver same as amides, causing reuptake of NorEpi resulting in an increase of available NorEpi?
41
Class of intermediate chain affects biotransformation of the molecule:
Amide linkage ___________ in the _____.
metabolized (= slower), liver
42
Highly lipid-soluble anesthetics are more or less potent and have a longer or shorter duration of action than do water-soluble anesthetics?
more, longer
43
Increase in the length of the intermediate chain (increase number of carbon atoms) increases or decreases potency and toxicity and alters _________ rate and ___.
increases, metabolism rate and DOA
44
Potency and toxicity also increased or decreased with the length of the terminal groups located on the tertiary amine (tail) and aromatic ring.
increased
45
___________ of a chiral drug may vary in terms of the pharmacokinetics, pharmacodynamics, and toxicity.
Enantiomers
| Ex. Bupivacaine (racemic) VS L-Bupivacaine(levo enantiomer)
46
Cm: Minimum Blocking Concentration
* Nerve fiber diameter influence
* Motor nerve higher Cm than sensory
* Tissue pH (ex: add bicarb to increase, do not inject into damaged tissue...more acidic)
* Frequency of nerve stimulation
* Potency of particular LA
47
Drug delivery systems
```
Offer sustained release properties
• Prolonged DOA
• Theoretical decreased toxicity
Liposomes
• Exparel: Bupivacaine extended release liposome injection FDA approved
• Do not mix or inject any other local anesthetic at the same site
• Dose: depends on surgical site
• Max dose: 266mg or 20 ml
Cyclodextrins
Biopolymers
```
48
LA Systemic Absorption:
Absorption is governed by ___________ characteristics and __________ conditions at site of deposit, _______ of solution or vehicle used (Epi?) and ___________ of local anesthetic
physiochemical, physiologic, volume, concentration
49
LA Systemic Absorption:
| Physiochemical factors
pKa, pH, and lipid solubility
50
LA Systemic Absorption:
| Physiologic conditions
tissue pH, pC02, and temperature, patient characteristics
51
Absorption By Type of Block:
```
HIGH ABSORPTION
• Intravenous
• Tracheal
• Intercostal
• Caudal
• Paracervical
• Epidural
• Brachial Plexus
• Subarachnoid
• Subcutaneous
LOW ABSORPTION
```
52
Do ionized or non-ionized drugs cross a lipid membrane?
non-ionized
53
Ionization of Local Anesthetics:
1. ________ form diffuses across the nerve sheath and membrane
2. Once inside the nerve membrane the ionized and non-ionized forms _________
3. _______ form binds a receptor inside the Na channel = blockade
Unionized
re-equilibrate
Ionized
54
Local Anesthetics good example of ionization concepts!
The ionized form is favored when:
• Acidic drug in relatively ____ environment
• Basic drug in relatively ____ environment
basic
| acidic
55
Local Anesthetics good example of ionization concepts!
The non-ionized form is favored when:
• Acidic drug in relatively ____ environment
• Basic drug in a relatively ____ environment
acidic
| basic
56
Local Anesthetics good example of ionization concepts!
All local anesthetics: weak ____ with pka values 7.5-9
• They are packaged in ____ formulations to improve solubility and stability in the vial and often to preserve epinephrine – don’t let this fool you they are ____ upon injection
bases
acidic
basic
57
Local Anesthetics good example of ionization concepts!
pKa = pH at which a drug exists
• __% ionized form
• __% unionized form
50, 50
58
Local Anesthetics good example of ionization concepts!
Good to have equal parts of each form
• ________ penetrates nerve sheath and axon membrane to reach site of action
• ________ form binds and blocks Na channel
Non-ionized
| Ionized
59
LA Onset
• Because the _________ form crosses the lipid-rich nerve cell membrane
• The __ of the local anesthetic solution and the ___ of the drug determine proportion of drug in the non-ionized state
• In areas of high/normal pH values, the rate and amount of absorption is _____; conversely, at lower pH, the rate and amount of absorption are _____
pH, pKa
| higher, lower
60
SLIDE 34
UNDERSTAND!
61
How can the anesthetist influence the pH/pKa relationship to speed onset?
• Adding ______ increases the onset, enhances block depth, and increases the spread of the block
• Infected tissue alterations (____ _____)
• Ion trapping in pregnancy and ______ ________, similar to the _________ concept.
• Temperature: _________ temperature reduces drug absorption across the nerve membrane
bicarb
dont bother
protein binding, re-equilibrate
decreasing
62
Henderson - Hasselbalch
pH-pKa = log non-ion/ion
63
Potency
• Most important factor = ___________
• Highly potent = ______, _______, _______
```
Lipid solubility (increase lip sol = increase potency)
etidocaine, bupivacaine, tetracaine
```
64
Duration of Action is _________ to amount of time LA is in contact with the nerve fiber.
proportional
65
Duration of Action is _________ related to Tissue Blood Flow.
inversely
66
Duration of Action is _________ with the Addition of Vasoconstrictors.
increased
67
Duration of Action is _________ as lipid solubility is increased, but not nearly as much as an increase in ______ _______.
increased
| Protein Binding
68
__________ has less vasodilator activity than __________, providing a slightly ______ duration of action.
Mepivacaine, lidocaine, longer
69
Simultaneous use of a vasoconstrictor and a local anesthetic serves three purposes:
1. _______ of systemic absorption of LA
2. ________ of the LA effect
3. Detection of ___________ _______
Inhibition
Prolongation
intravascular injection
- inject 5cc at a time, assess EKG
70
```
Duration of Action influenced by:
• most important factor?
• More protein bound ________ duration of action (not the same as IV drugs… LAs injected at site of action)
• Uptake by the ____
• __________
```
Protein binding
increased
lungs (Bupiv and Lido and ?)
Metabolism
71
SLIDE 41!
KNOW!!!
72
What determines concentration of LA in the blood?
* Concentration of Local Anesthetic Administered
| * Tissue Blood Flow
73
Metabolism of Local Anesthetics - Esters:
| • Primarily hydrolyzed by _____________ _______ in plasma (and to lesser extent - the liver) (
pseudocholinesterase enzymes, 5
para-aminobenzoic acid (PABA)
cocaine, liver, 10-12
74
Metabolism of Local Anesthetics- Amides:
• Metabolized in the _____ by _________ _____
• More _______ and ______ process than metabolism of Esters
• ________ hydroxylation, ___________ and amide _________
• What does that mean for the possibility of systemic toxicity and cumulative effects??
Liver, Microsomal Enzymes
complex, slower
Aromatic hydroxylation, N-dealkylation and amide hydrolysis
RISK!
75
SLIDE 46 & 47!!!
**Maximum Doses** They are additive( i.e. switching local anesthetics does not increase the max dose!) Also please read section in book (pg 307 in 5th edition) on Tumescent (highly diluted local anesthetic with epi give in large volumes for liposuction).
Example calculation of max dose.....DO PRACTICE AND LEARN GUIDE!!!
76
Local Anesthetic Toxicity CNS S/Sx?
| • What do you do if the patient seizes??
* Circumoral/tongue numbness, tinnitus, vision changes, dizziness, slurred speech, restlessness
* Muscle twitching especially in face and then extremities indicates imminent onset of seizures
* Seizure followed by CNS depression, apnea, hyPOtension
* Cocaine -restlessness, tremors, seizures and euphoria
SEDATE, VENTILATE, 100% FiO2
77
Local Anesthetic Toxicity – Cardiovascular System:
• CVS _____ resistant to toxic effects than CNS (CNS acts as a ______ for CVS toxicity)!
• Hypotension (____ depression), myocardial ________, and __ conduction block
• ________ SVR and C.O, _______ PRi and QRS, arrhythmias including ________ _________, possible CV collapse
• Pregnancy, hypoxia, pH abnormalities and CV modulating drugs ________ the risk
****________ overdose manifests as massive sympathetic outflow, coronary vasospasm, MI, dysrhythmias including V-fib
```
more, warning
SNS, depression, AV
Reduced, widened, ventricular tachycardia
increase
Cocaine
```
78
Most CV toxic = ?
Bupivacaine – cardiac arrest may occur at lower levels of toxic doses (inadvertent IV injection, etc.)
79
Local Anesthetic Toxicity – Treatment of CV Collapse:
• Resuscitation often fails….. __________ ideal
• _________ fractionated dosing
• _________ before every injection (false ________ possible) • Watch ECG for early signs
• Basic ___ immediately
***See figure 10-12 in text American Society of Regional Anesthesia and Pain Medicine Guidelines
• Modified ACLS (limit medications to _________ & ________)
• Intralipid 20% __ ml/kg rapid bolus immediately; follow with infusion __ ml/kg/min X __ minutes
• CPB = ?
Prevention
Incremental
Aspirate, negative
CPR
epinephrine 10-100ug, amiodarone (NO LIDO!)
1.5, 0.25, 10
?
80
Local Anesthetic Toxicity CNS:
• Transient neurologic symptoms (TNS) or Transient radicular irritation – neuro-inflammatory process causes pain in the ________, _______, ________ 6-36 hours after full recovery from SAB – lasts about ______
lower back, buttocks, posterior thighs, 1 week
81
Local Anesthetic Toxicity CNS:
• _____ _____ ________ = diffuse lumbosacral injury, numbness in LE, loss of bowel and bladder control, paraplegia
• Lidocaine _%, ________, and _____________ have been implicated, but probably microcath involved?
Cauda equina syndrome
| Lidocaine 5%, Tetracaine, and Chloroprocaine
82
Local Anesthetic Toxicity CNS:
• ______ _____ _____ __________ = LE paralysis with +/sensory deficit
• Unknown cause, vasoconstrictors?, PVD, advanced age increase the risk
Anterior Spinal Artery Syndrome
83
Allergic Reactions:
| • Incidence
```
1
Plasma
Esters, Amides
Methylparaben
MH
```
84
Local Anesthetic Drug Interactions:
• ______________________ inhibitors may prolong the duration of ester anesthetics
• Cimetidine and propranolol decrease _______ blood flow → decrease clearance of amide local anesthetics and cocaine
• Analgesia promoted by opioids, clonidine, and epinephrine ______ to LA
Pseudocholinesterase
hepatic
added
85
Selection Criteria: How Do I Choose Agents?
* Type of Surgery
* “Spreadability”
* Onset
* Potency
* Duration
* Toxicity Risk
* Site of Metabolism
86
Other Uses of Lidocaine:
• _______ Suppression
• Attenuate ___ elevation during laryngoscopy
• Attenuate __ elevation during laryngoscopy
• Attenuate reflex _____________ that may occur with airway instrumentation
• Suppression of _________ dysrhythmias
```
Cough
ICP
BP
bronchospasm
ventricular
```
87
Dosing main points:
*Concentration, Volume, and Total Dose Administered*
88
Dosing main points:
*Concentration, Volume, and Total Dose Administered*
• Peripheral nerve block
- Volume dictated by ____ of block
- Choose concentration based on limitations of ___ ____ balanced with ______ of blockade desired
type
| max dose
89
Dosing main points:
*Concentration, Volume, and Total Dose Administered*
• Epidural
- Volume dictated to what ____ of block desired
• ____ml/per segment desired
• Choose concentration based on ______ of block desired (i.e. labor VS surgical epidural)
level
1.25-1.6
density
90
Dosing main points:
*Concentration, Volume, and Total Dose Administered*
• Spinal
- These doses you just have to know
Dosing guide?
