Local Anesthetics Flashcards
(141 cards)
1
Q
1884 Local anesthetics
A
cocaine introduced and used in ophthalmology and dentistry
2
Q
Lidocaine synthesized in
A
• 1943- Lidocaine synthesized (amide)
3
Q
First local anesthetic-
A
• Cocaine-
4
Q
Gold standard of local anesthetics
A
Lidocaine
5
Q
The fraction of drugs bound to proteins in plasma correlates with the
A
duration of local anesthetic activity:
6
Q
Protein Binding from more to less
BERMeLPC
A
Bupivacaine> Etidocaine> Ropivicaine> Mepivacaine> Lidocaine> Procaine and 2-chloroprocaine
7
Q
NO DIRECT relationship exists between
A
LA plasma protein-binding and binding to specific membrane-bound Na+ channels.
8
Q
There is a direct correlation between
A
protein binding and lipid solubility, as there is for all drugs.
9
Q
The MORE LIPID SOLUBLE THE DRUG, THE MORE LIKELY IT WILL
A
REMAIN IN THE LIPID-RICH ENVIRONMENT OF THE AXONAL MEMBRANE WHERE THE Na+
CHANNELS RESIDE!
10
Q
Local anesthetics ; Water solublity
• Bases
A
• Poorly water soluble
11
Q
LA are weak
A
Bases
12
Q
When mixed with hydrochloric acid they
A
ionize and become water soluble (Hydrochloride)
13
Q
Slows onset of action- LA must become
A
unionized to penetrate tissue
14
Q
How does adding bicarbonate help LA
A
Alkalization of local anesthetic solution
• Shortens onset time
• Decreases pain on injection
• May cause precipitation of local anesthetic
15
Q
Add NaHCO3. Will speed onset by how many minutes?
A
onset of peripheral nerve blocks & epidural blockade by 3- 5 minutes
16
Q
Functional unit of peripheral nerves
A
Axons
17
Q
• Extension of a centrally located neuron
A
Axon
18
Q
cells surround each axon and function as support and insulation
A
Schwann cell-
19
Q
•In unmyelinated nerves, single Schwann cells
cover
A
several axons
20
Q
•In larger nerves the Schwann cell sheath covers ______and has several layers of lipid substance known as ________
A
covers only one axon and has several layers of a lipoid
substance known as myelin
21
Q
• Small segments of nerve that do not contain any myelin
A
Nodes of Ranvier
22
Q
Primary area where local anesthetics exert their action
A
Nodes of Ranvier
23
Q
• Myelinated nerves
small vs large, impulse conduction
A
- Larger
- Conduct impulses faster
- More difficult to block with local anesthetics than unmyelinated
24
Q
How many nodes of Ranvier must be blocked to prevent nerve conduction?
A
2-3 nodes of Ranvie
25
Structures found in peripheral nerves that contain bundles of axons
Fasciculi
26
Components of the peripheral nerve contain 3 layers of connective tissue
* Endoneurium
* Perineurium
* Epineurium
27
Act as barriers that local anesthetics must
| penetrate in order to work
Layers (epineurium)
28
Resting peripheral nerves have a negative membrane potential of
-70 to -90 mV
29
Movement of K+ out of the cell leaves an
excess of negatively charged organic ions inside
30
Two opposing forces are at play(2)
• Net result is a modest movement of K+ out of the cell
Concentration gradient pushes K+
out of the cell while the negative charge
| keeps K+ in the cell
31
This process is expressed by the
Nernst equation
32
• Sodium channels have 3 functional states
• Closed (resting)
• Open- nerve is stimulated and results in a conformational change in the proteins of the sodium channel
• Conformational change results in reversal of the membrane potential
Inactive
33
How does LA work?
Local anesthetics produce their effects by blocking the
| sodium channels
34
Local anesthetics have a greater affinity for Na+
| channels that are in the
open or inactive state
35
For LA to exert their actions they must
First penetrate the cell membrane before they produce these effects
36
For LA to exert their actions they must First penetrate the cell membrane before they produce these effects
This interaction is most likely the mechanism of
action of the drug _______which can only exist
in the uncharged form
benzocaine
37
What is the CM
* Lowest concentration of a drug that is needed for blocking impulse propagation
* Analogous to MAC
38
Variables that affect Cm: Increase Cm
Increased nerve fiber diameter
Increased myelination
Greater distance between nodes of Ranvier
39
Variables that affect Cm: DEcrease Cm
Increased tissue pH
High frequency of nerve stimulator
Pregnancy
Elevated temperature
40
• Three groups of nerve fibers
```
• A
• Alpha
• Beta
• Gamma
• Delta
B
C
```
41
• Most myelinated
• A-alpha
42
Fastest conduction velocity (60-120 m/s)
A-ALPHA
43
Responsible for skeletal muscle tone, reflexes
A-GAMMA
44
Responsible for pain, temperature & touch
A-Delta
45
Last blocked by local anesthetics
A-Alpha
46
Slowest conduction (0.5-2.3 m/s)
C-Fibers
47
Second fibers to be blocked along with A-delta fiber
C fibers
48
First then second blocked
B fibers
| A-delta and C fibers
49
Conducts pain, temperature, touch, postganglionic sympathetic neurons
C fibers
50
Only UNMYELINATED fibers
C fibers
51
• Constitute preganglionic autonomic nerves
B Fibers
52
Proprioception, touch, pressure
A-Beta
53
• Largest 15-20 microns
A-alpha
54
• Motor and proprioception are the last to be blocked
(A-alpha, beta andGamma)
55
is currently the best example of a differential block
Bupivicaine
56
Epidural Bupivicaine 0.125%
blocks autonomics, partial pain, temperature but not touch, proprioception or motor function
57
Epidural Bupivicaine 0.25% blocks
autonomics, pain and temperature but not touch, proprioception and moto
58
Epidural Bupivicaine 0.5% blocks
autonomics, pain, temperature, touch
| and proprioception & motor
59
Blocking order
| B-DcGBA
Blocking order
• First-- B, Autonomics
• Second-- A- delta, fast pain temp; C, slow pain autonomics
• Third– A-gamma, muscle tone, motor
• Fourth– A-beta, Sensory- touch, pressure
• Fifth– A-alpha, Motor, skeletal muscle
60
Fast pain and temp
A-delta
61
muscle tone, motor
A-gamma,
62
Sensory- touch, pressure
A-beta,
63
Motor, skeletal muscle
A-alpha,
64
slow pain autonomics
C
65
throbbing pain & temperature
• C fibers-
66
Sympathetic and parasympathetic preganglionic neurons are B fibers
C fibers
67
Myelinated nerves conduct action potentials ____________than unmyelinated nerves
faster than
68
Larger diameter nerves conduct______than smaller diameter nerves
faster than
69
• Local anesthetics have 3 characteristic segments
* Aromatic ring (lipophilic portion)
* Intermediate carbon group ( ester or amide)
* Tertiary amine (hydrophilic group)
70
Either an ester or an amide linkage bind the
aromatic ring to the tertiary amine
71
Linkage characterizes the drug as either an
Ester
| Amide
72
• Esters are hydrolyzed by
plasma cholinesterase and to a lesser extent in the liver
73
• Paraaminobenzoic acid (PABA) is a metabolite
hydrolysis
74
Is a metabolite of hydrolysis responsible for the
| higher incidence of allergic reactions in esters
Paraaminobenzoic acid (PABA)
75
• Amides are metabolized in the
liver
76
Greater chance to accumulate and cause systemic toxicity
Amide
77
• Allergic reactions are rare-
Allergic are rade with AMIDE< due
| to preservative methylparaben-structure similar to PABA
78
ph of esters range
8.5-8.9
79
pH of amide range
Close to pH(7.4) 7.6-8.1
80
Distribution of local anesthetics
* Dependent on blood flow
| * High initial uptake by lung
81
Distriubution of LA: _________is a major factor
Redistribution
82
LA Ultimately eliminated via
* Metabolism
| * Excretion
83
Amide vs esters: which tend to be more widely distributed
Amides
84
• Determined by Lipid solubility
Potency
85
Duration of Action
| •Determined by
Protein binding –more important
86
Potency vs protein binding which is more important
Protein binding
87
Most important determinant of onset of action of LA
Ionization
88
Drugs with lower pKa (Amides)
Less ionized at physiological pH
| Shorter onset of action
89
Decreased tissue pH=
more ionized local
90
Patients at high risk of poor quality anesthetic effect
Renal failure
| Septic pt with metabolic acidosis
91
*Chloroprocaine is the exception to the rule. The fast onsetof chloroprocaine may be due to the
high concentration that
| is injected .
92
* Interventions to affect onset and duration
| * Carbonation
- theoretically improve the onset & intensity
| of block
93
• Sodium bicarbonate may reduce the
latency of onset and increase the duration of action
94
• Results in more of the drug in the unionized state
Adding sodium bicarbonate
95
Major limitation of bicarbonate
MAY FORM PRECIPITATE
96
Dextran may
increase the duration of action
97
All local anesthetics except 2 produce relaxation of vascular smooth muscle
except Mepivacaine & Cocaine
98
LA injection•Results in an______ in blood flow to the area where drug is applied and causes (2)
increase
• Decrease in duration of action
• Increased potential of systemic toxicity
99
Degree of VASODILATION From more to least
Lidocaine > procaine > Mepivacaine (none)
| Bupivacaine = Etidocaine
100
No vasodilation with this LA
Mepivacaine
101
• Effects on systemic toxicity is dependent on
* Total dose given
* Concentration
* Volume administered
102
Area where the local anesthetic is applied also determines
the speed and
| extent of systemic absorption/ toxicity
103
Most to least absorption
IvTIcCauPac
EpiBraSubaSciFemSub
Intravenous > Tracheal > Intercostal > Caudal > Paracervical > Epidural >
Brachial Plexus > Subarachnoid/Sciatic/Femoral > Subcutaneous
104
Addition of a vasoconstrictor, such as epinephrine, to the local anesthetic can
reduce the rate of systemic absorption
105
Action of Epinephrine
Helps increase the concentration of drug at the site
| of action, which results in a longer, more intense block and less systemic toxicity
106
Epinephrine prolongs the duration of action for local infiltration, peripheral nerve block and epidural administration of
Procaine
Mepivacaine
lidocaine
107
Epinephrine prolongs the duration of action for local infiltration & peripheral nerve blocks, but no significant effects with epidural
Prilocaine
Bupivicaine
Etidocaine
108
Epinephrine has been proven to be the most effective agent usual concentration is
1:200,000 or 5 mcg/ml
109
Esters are Hydrolyzed by in
pseudocholinesterase
• Plasma- primary route
• Red blood cells
• Liver
110
Metabolite of hydrolysis responsible for allergic reactions associated with esters
PABA- para amino benzoic acid
111
_____________ is the most toxic ester
Tetracaine
112
leading to prolonged spinal action To terminate must diffuse out of the CS
No spinal cholinesterase's
113
Rate of Hydrolysis
• Chloroprocaine > Procaine > Tetracaine
114
Plasma T ½ of both Procaine & Chloroprocaine is less
than
| 1 minute
115
Factors that effect plasma cholinesterase
| • Saturated
• Drugs that are inhibited or metabolized by plasma cholinesterase, like succinylcholine,
could reduce the metabolism of ester LA’s
116
Liver disease severe enough to reduce the amount of
cholinesterase
More prone to toxicity
Exception-
Procaine, Chloroprocaine toxicity unlikely in pt
| with liver disease
117
Amide Metabolism primarily ______, affected by
•
•
Liver disease and CHF can affect the metabolism of amide LA’s
Greater chance to accumulate & cause systemic toxicity
Allergic reaction is
If occurs, most likely due to
in liver
Hepatic enzyme activity
• Hepatic blood flow
Rare
preservatives in preparation
118
Rate of metabolism Greatest to slowest
| PELMeB
Prilocaine > Etidocaine > Lidocaine > Mepivacaine > Bupivacaine
119
Primary factors affecting rate of clearance of amide local anesthetics
Hepatic enzyme activity & hepatic blood flow
120
Clearance is independent of
potency, lipid solubility, protein binding
| & chemical structure
121
• Sequence of LA CNS toxicity •
1. Circumoral numbness •
2. lightheadedness •
3. Tinnitus •
4. Visual Disturbances •
5. Slurring of Speech •
6. Muscle twitching •
7. Unconsciousness •
8. Grand mal seizures •
9. Coma •
10. Apnea
122
LidocaineToxic Manifestations
• Plasma concentration Effect
• 1-5 mcg/ml
•
Analgesia
123
LidocaineToxic Manifestations
| • Plasma concentration Effect• 5-10 mcg/ml
```
Circumoral/tongue numbness
Tinnitus
Systemic hypotension
Muscle twitching
Myocardial depression
```
124
LidocaineToxic Manifestations
| • Plasma concentration Effect• 10-15 mcg/ml
Seizures
| Unconsciousness
125
LidocaineToxic Manifestations
| • Plasma concentration Effect 15-20 mcg/ml
•Apnea, Coma
126
LidocaineToxic Manifestations
| • Plasma concentration Effect >25 mcg/ml
Cardiovascular collapse
127
Midazolam 5-10 minutes prior to local anesthetic injection can help prevent
Vigilance! Monitor EKG, BP, SPO2 continuously
Communicate with the patient to observe for S/S of
toxicity
he CNS toxicity of LA’s
128
• Use agents less likely to cause toxicity (3)
produce limited systemic toxicity due
to short distribution & elimination ½ time
• Lidocaine, Prilocaine & chloroprocaine
129
• Aspirate syringe before injection- watch for
blood or CSF
130
syringe before injection
• Aspirate
131
• Acid- Base status of patient
Respiratory & metabolic acidosis= increased risk for toxicity- causes less
protein binding and more free drug available
• Alkalosis = decreased risk
132
Elevation of carbon dioxide tension causes
cerebral dilation which leads to more drug being delivered to the brain
133
At 1st sign of toxicity have pt
voluntarily hyperventilate- will
| decrease transfer of agent into cells
134
Acute lowering of the CO2 tension may also
lower the seizure threshold
135
CNS Toxicity Treatment
| are the primary concern
• Seizures
136
Seizure First intervention- maintain
patent airway and oxygenate pt
137
* If hypotension occurs and is unresponsive to conservative treatment
* Vasopressor may be necessary
* Ephedrine 15-30 mg is usually drug of choice
| * Atropine 0.4 mg can be used to treat bradycardia
138
CNS toxicity and seizures
| Succ
Use of ultra short muscle relaxant such as succinylcholine can help control the convulsive state
Will not stop seizures
Will stop muscle contractions
May need immediate intubation
139
Cardiovascular Toxicity
| •Related to the
potency of the drug
140
Cardiovascular Toxicity •Related to the
potency of the drug
141
Peripheral effects of the local anesthetics are biphasic
• At lower concentrations LA’s
• Increased doses cause
•
* vasoconstrict
* increase SVR
Vasodilation
• Possible hypotension
