Local Anesthetics Flashcards
Local anesthetics are used to treat
chronic and acute pain; major component of clinical anesthesia
Local anesthetics are drugs that
reversibly block conduction of electrical impulses along nerve fibers
Schwann cells act to
support and insulate each axon
In unmyelinated nerves,
single Schwann cells cover several axons
In myelinated nerves,
the Schwann cell covers only one axon and has several concentric layers of myelin
To block impulses in myelinated fibers
it is necessary for local anesthetic to inhibit channels in three successive nodes
Fasciculi are
bundles of axons
The three connective tissues of fasciculi include
endoneurium, perineurium, and epineurium
The endoneurium is
a thin, delicate collage that embeds the axon in the fascicule
The perineurium consists of
layers of flattened cells that binds groups of fascicules together
The epineurium surrounds
the perineurium and is composed of connective tissue that holds fascicles together to form a peripheral nerve
The intracellular ratio of potassium is
30:1
The Nernst equation is
the potential to cause a reaction
expresses the charged created by K+ concentration gradient
The local anesthetic site of action is
specific sites on the Na+ channel
preferential to open and inactive states
to a lesser extent it also blocks K+ channels, Ca2+ channels and GPCRs
The mechanism of action of local anesthetics is to
block transmission of nerve impulses
LAs do not alter the resting transmembrane potential or threshold potential
The frequency-dependent blockade is
the use of a “use-dependent” or “phasic block”
the resting nerve is less sensitive to LA than one repeatedly stimulated
The modulated receptor hypothesis of LA action is
preference to attach during active or inactive states
Describe the mechanism of action of local anesthetics
diffusion of an unionized base across the nerve membrane
re-equilibrium between the base and cationic forms
binding of the cation to a receptor inside the sodium channel resulting in its blockade and inhibition of Na_ conduction
All local anesthetics are considered to be
weak bases
Nerves have different sensitivity to LAs based on
small diameter and lack of myelin (both enhance sensitivity)
larger nerves conduct impulses faster and are harder to block
Describe which nerve fibers are blocked first
preganglionic are blocked with low concentrations followed by small C fiber and small A fibers resulting in a loss of pain and temperature
The first thing that will be seen if a block is working is
vasodilation; an engorged arm
Type B fibers are
small in diameter <3
lightly myelinated
preganglionic autonomic vasomotor
have early block onset
Type C fibers are
found in the sympathetic and dorsal root
function as postganglionic vasomotor and pain, warm and cold temperatures, and touch
have no myelination
moderate diameter and early block onset
Type A fibers are
blocked last
heavily myelinated
large diameter
The chemical structure of local anesthetics includes
an aromatic ring system
tertiary amine
either an ester or amide linkage
Local anesthetics that are esters include
procaine, chloroprocaine, tetracaine, cocaine, benzocaine
Local anesthetics that are amides include
lidocaine, mepivacaine, prilocaine, bupivacaine, ropivacaine, articaine
The ester or amide linkage is relevant clinically because
it has implications for metabolism, duration, and allergic potential
affects drug potency, speed of onset, duration of action, and differential block potential
Key differences about esters include
ester metabolism is through plasma, occurs throughout the body and is rapid
esters have a higher potential for allergy- cross reactivity among esters
tend to have shorter acting due to ready metabolism
Key differences about amides include
allergy is extremely rare- no cross allergy among the class or between ester and amide agents metabolized in the liver longer acting because they are more liphophilic and protein bound
The minimum effective concentration of LA is
necessary to produce conduction blockade of a nerve impulse
min. concentration of motor fibers approx. twice that of sensory fibers
less LA is needed for intrathecal vs. epidural anesthesia
An important distinction between LA and other medications is
agents are meant to remain localized in the area of injection- the higher the concentration injected, the faster the onset
systemic absorption results in termination of the drug
Absorption influences
drug termination and toxicity- the slower a LA is absorbed, the less likely toxicity
Lipid solubility correlates with
protein binding, increased potency, longer duration of action, tendency for severe cardiac toxicity
A strong relationship exists between potency and
lipid solubility
larger lipid-soluble LA are water insoluble and highly protein bound
LAs bind to
alpha 1 acid glycoprotein
These factors affect duration of action:
injection site
relationship between protein binding and lipid solubility- drug tends to remain in vicinity of Na+ channel
lidocaine, bupivacaine, and tetracaine onset and duration of action
lidocaine: fast, duration is 90-120 minutes
bupivacaine: slow, duration of action 180-600 minutes
tetracaine: slow; duration 180-600 minutes
Local anesthetic is absorbed the quickest via
intravenous, tracheal, caudal, paracervical, epidural, brachial, sciatic, subcutaneous
The speed of absorption has implications to
toxicity
LA cause relaxation of
smooth muscle (lidocaine, ropivacaine, and cocaine are exceptions) relaxation causes vasodilation that decreases duration of action, increases plasma concentration and potential toxicity
Additives include
clonidine, dexmedetomidine, epinephrine, opioids, sodium bicarbonate, ketorolac, dexamethasone, hyaluronidase
Epinephrine is a
vasoconstrictor that reduces the rate of vascular absorption- increased duration and potency of block while decreasing risk of systemic toxicity
Epinephrine is unique in that it does not
prolong the block for all LA to same extent
lidocaine, mepivacaine, and procaine- local infiltration, peripheral nerve block and epidural
prilocaine and bupivacaine- prolonged with peripheral but not epidural
Sodium bicarbonate is used as an additive because
it raises the pH of the LA solution resulting in more drug in the nonionized state
commonly used in epidurals
may result in less pain on injection
major limitation is the precipitation that can occur
The absorption or injection of LA into systemic circulation results in
rapid redistribution
with esters broken down in blood and amides free floating
Which organs receive the most local anesthetic first?
brain, heart, and lungs receive most initially because they are highly perfused- can be concerning because of toxic levels to brain and heart
Renal dysfunction affects clearance
far less than hepatic failure
hepatic failure affects protein binding to both A1AG and albumin
Pregnancy causes
mechanical changes that result in reduction in epidural space
hormonal changes that progesterone levels affect sensitivity to LA
LAST is
local anesthetic systemic toxicity and is a serious but rare event during regional anesthesia
LAST most commonly occurs from
an inadvertent intravascular injection- initial blocking of inhibitory neurons thought to cause seizures
blocking of cardiac ion channels results in bradycardia- Vfib is most serious complication
Shorter acting drugs are thought to be
less cardiotoxic
more potent agents have higher lipid solubility and protein binding
LAST is most common in
epidurals, axillary, and interscalene
very uncommon
The classic clinical presentation of LAST:
rapid onset and includes agitation tinnitus, circumoral numbness, blurred vision, and metallic taste
followed by muscle twitching, unconsciousness, and seizures
very high levels can result in cardiac and respiratory arrest
Prevention strategies for LAST include
test dosing, incremental injection with aspiration, use of pharmacologic markers, and ultrasound
Treatment for LAST includes
prompt recognition and diagnosis
airway management priority followed by seizure suppression, prevent hypoxia and acidosis
lipid emulsion therapy
Vasopressors (no vasopressin)
The lipid emulsion therapy mechanism of action is
- capture local anesthetic in blood (lipid sink)
- increased fatty acid uptake by mitochondria
- interference of Na+ channel binding
- Promotion of calcium entry
- accelerated shunting
Max dose of lidocaine is
4 mg/kg; 7 mg/kg with epi
Max dose of mepivacaine is
4 mg/kg; 7 mg/kg with epi
max dose of bupivacaine is
3 mg/kg
Max dose of ropivacaine is
3 mg/kg
Max dose of procaine is
12 mg/kg
Max dose of chloroprocaine is
11 mg/kg, 14 mg/kg with epi
Max dose of prilocaine is
7 mg/kg; 8.5 mg/kg with epi
Max dose of tetracaine is
3 mg/kg
Esters are metabolized to and derivates of
para aminobenzoic acid (PABA)
Side effects of local anesthetics include
methemoglobinemia- Fe2+ converted to ferric hemoglobin Fe3+ causing reduced oxygen carrying capability and tissue hypoxia
presents as decreasing oxygen saturation not responsive to therapy
Prilocaine can cause methemoglobinemia because
one of its metabolites is ortho-toluidine
dosing should not exceed 2.5 mg/kg
should be avoided in children under 6, pregnant women, patients taking other oxidizing drugs
Treatment of methemoglobinemia includes
methylene blue, transfusion, or dialysis
Cauda equina syndrome
manifests as bowel and bladder dysfunction with lower extremity weakness and sensory impairment related to cord ischemia
risk factors include supernormal doses of LA or maldistribution of LA within intrathecal space
Transient neurologic symptoms are associated with
intrathecal lidocaine and can present as burning, aching, cramp like pain in the low back and radiating down the thighs
other risk factors include lithotomy position and outpatient surgery
Lidocaine is used for
antiarrhythmic, topical, induction, nebulized, multimodal pain management, regional anesthetic
lidocaine is used in the ACLS algorithm to
depress myocardial automaticity
EMLA or Eutetic mixture of local anesthetic is
1:1 lidocaine: prilocaine mixture used to numb skin
EMLA is contraindicated in
mucous membranes, broken skin, infants <1 month, history of methemoglobinemia
Lidocaine can be used on induction to
decrease pain of Propofol, attenuate CV response to intubation, attenuate increase in ICP in patients with decreased compliance
may also attenuate cough
Topical lidocaine can be used to
Decrease “emergence phenomenon”- coughing, sore throat, and dysphonia
LTA administered at induction has little effect on
prevention of coughing during extubation; surgeries <2 hr., reduced coughing by 26%
30 minutes prior to extubation caused significant decrease in coughing
The most effective technique to prevent emergence phenomenon is
using alkalozied lidocaine in the cuff
needs approximately 60 minutes required to achieve desired effect, low does alkalized lidocaine (40 mg) shown to be more effective
The technique used in the alkalized lidocaine cuff is:
achieve correct pressure using air remove and record amount of air required add 2 mLs of lidocaine add 1-2 mLs of sodium bicarbonate add saline to match cuff volume
An airway block is achieved by
4% lidocaine applied directly to oropharynx or a transtracheal block of 4% lidocaine injected through the cricothyroid membrane
Infusions of lidocaine have been used
as part of a multimodal management plan to supplement general anesthesia
the mechanism of action of lidocaine infusions
relatively unknown
may involve sodium channels
block priming of polymorphonuclear granulocytes
Lidocaine infusions are used for
reduction of postoperative pain and speed up return of bowel function in open and laparoscopic procedures
decrease pain and improve functional outcomes in prostatectomy, thoracic, and spine procedures
Concerns with lidocaine infusion
accumulation
Lidocaine infusions are considered to be
uncertain to the benefits in pain score, GI recovery, PONV, and opioid consumption
Peripheral nerve blocks include
Bier block
Neuraxial anesthesia includes
spinal and epidural
A bier block is
an intravenous regional anesthesia
indicated for short procedures
25-50 mL of 0.5% lidocaine–> onset time 5-10 minutes
tourniquet pain at 20 minutes
With epidural anesthesia, we should always
aspirate and test dose
can always convert labor epidural to a surgical epidural
Effects of lidocaine on organs include:
CNS, respiratory, cardiovascular, immunological, musculoskeletal, hematological
1-5 mcg/mL of lidocaine in plasma causes
analgesia
5-10 mcg/mL of lidocaine in plasma causes
circumoral numbness, tinnitus, skeletal muscle twitching, systemic hypotension, myocardial depression
10-15 mcg/mL of lidocaine in plasma causes
seizures, unconsciousness
15-25 mcg/mL of lidocaine in plasma causes
apnea & coma
> 25 mcg/mL of lidocaine in plasma causes
cardiovascular depression
Treatment for LAST includes:
benzodiazepines and hyperventilation- raises seizure threshold
propofol reliably terminates seizure activity
maintain a clear airway
adequate ventilation and oxygenation
The administration of 1.5 mg/kg of lidocaine can
decrease cerebral blood flow and ICP, block reflex bronchoconstriction on intubation, blunt sympathetic response to intubation
Exparel is
bupivacaine combined with liposomal agent
Exparel is used as
part of a multimodal treatment regimen to provide non-opioid pain control
-dose is based on surgical site and volume required to cover the area
Exparel should only be administered with
bupivacaine, never lidocaine
Exparel should be used cautiously in patients with
hepatic disease
Contraindications to exparel include
obstetrical paracervical blockade
Patients <18 years of age
epidural or intrathecal anesthesia
certain peripheral nerve blocks
Adverse effects of exparel include
> 10% nausea and vomiting
<10% dizziness, tachycardia, headache, somnolence, bradycardia, hypoesthesia, lethargy
Cocaine is used primarily
topical anesthesia of the nose and throat
Cocaine has the ability to
block the monoamine transporter in the adrenergic system
blocking reuptake of catecholamines resulting in significant vasoconstriction
Cocaine should be used with caution with
other epinephrine containing solutions, MOA inhibitors, tricyclics
