Local Anesthetics Flashcards
LAs MOA
Reversibly block conduction/transmission along nerve fibers
Preferentially bind to open & inactive VGNa+ channels
- Binds internally to VGNa+
Also block K+, Ca2+, & GPCRs
Do not alter the resting transmembrane or threshold potential
What surrounds each nerve axon?
Schwann cells
Support & insulate each axon
What are the Nodes of Ranvier?
Periodic segments b/w Schwann cells along the axon that do not contain myelin
High VGNa+ channels concentration here
Saltatory Conduction
APs jump from node to node to increase the transmission speed
How many nodes must be block for LAs to inhibit channels in myelinated fibers?
3 successive nodes
Axon bundles are called ______
Fasciculi
Fasciculi are covered with 3 connective tissue layers
- Endoneurium - thin, delicate collagen that embeds the axon in the fascicle (innermost layer)
- Perineurium - flattened cells layers that bind fascicle groups together (middle layer)
- Epineurium - surrounds the perineurium; composed from connective tissue that holds the fascicles together to form a peripheral nerve
What must occur for LAs to exert effects?
Diffuse through all 3 connective tissue layers (endoneurium, perineurium, & epineurium)
What restores the RMP?
Na+/K+ pump
3 Na+ ions exit
2 K+ ions enter
Which nerve fibers are most difficult to block?
Larger nerves - conduct impulses faster & are harder to block
Smaller nerve lacking myelin enhance the sensitivity to LAs
LAs preferentially bind to smaller & unmyelinated fibers
What indicates a successful LA blockade?
Vasodilation ↓BP indicates pre-ganglionic fibers (SNS tone)
Type B light myelination 1st blocked
Nerve Fiber Blockade Onset
Type B pre-ganglionic (autonomic vasomotor) →
Type C fibers (sympathetic post-ganglionic vasomotor & dorsal root - pain, warm/cold, & touch) →
Type A β (touch & pressure) λ (muscle tone) Δ (pain, cold, & touch) →
Type A α (proprioception & motor)
LA Chemical Structure
Ester -COOCH or amide -N binds the aromatic ring to the Carbon group
Ester LAs
Shorter acting LA (Tetracaine longest-acting ester < 90min)
Plasma & tissue cholinesterase metabolism via hydrolysis
Para aminobenzoic acid (PABA)
LA allergies uncommon, but higher potential w/ esters
Ester allergy avoid ALL ester LAs d/t cross-reactivity
Amide LAs
Longer acting (more lipophilic & protein bound)
Require transport to the liver for metabolism
Hepatic CYP1A2 & CYP3A4
Amide allergies are extremely rare
No cross-allergy b/w ester & amide LAs
What increases LA onset?
Higher concentration injected → faster onset
What terminates LA effects?
Systemic absorption results in drug termination
What does lipid solubility correlate with?
- Protein binding
- ↑potency
- Longer DOA
- ↑severe cardiac toxicity
Amides are more lipid soluble
LAs are _____ _____
Weak bases
Basic drugs become more ionized when placed in a solution w/ pH < pKa
Drugs w/ pKa closer to physiologic pH → faster onset
Weak bases bind to α acid glycoprotein (lesser extent to albumin)
LA impact on smooth muscle:
RELAXATION
Vasodilation ↓DOA ↑plasma concentration & potential toxicity
Exceptions: Lidocaine, ropivacaine, & cocaine
Highest → lowest blood concentrations
IV → tracheal → caudal → paracervical → epidural → brachial → sciatic → SQ
Drugs to add to LAs spinal/epidural:
- Clonidine
- Dexmedetomidine
- Epinephrine
- Opioids
- Na+ bicarb
- Ketorolac
- Dexamethasone
- Hyaluronidase
Epinephrine
Vasoconstriction ↓vascular absorption rate
↑duration & block potency
↓systemic toxicity risk
Sodium Bicarbonate
Commonly used in epidural anesthesia
Theoretically ↑LA solution pH → more drug in the non-ionized state
↓pain on injection
Limitation = precipitation
What receives the highest LA plasma concentration initially?
Highly perfused tissues - brain, heart, & lungs
Risk → toxic levels
What receives the most secondary LA after re-distribution?
Muscles receive the most after 2° distribution
What LAs are impacted with severe hepatic disease?
Amide LAs
Hepatic metabolism CYP450
How does renal dysfunction affect LA clearance?
Impacts protein binding to α1 glycoprotein & albumin
Renal dysfunction affects clearance far less than hepatic failure
Pregnancy Physiological Changes
Engorged epidural veins ↓epidural space
Hormonal changes → progesterone levels affect LA sensitivity
Local Anesthetics
SEs & Complications
LAST
Cauda equina syndrome
Transient neurologic symptoms
LAST
Local anesthetic systemic toxicity
Rare, but serious
ALWAYS ASPIRATE
What most commonly causes LAST?
Inadvertent IV injection
- Blocks inhibitory neurons thought to cause seizures
- Blocks cardiac ion channels → bradycardia
What the most serious LAST complication?
Ventricular fibrillation
What LAs are thought to be less cardiotoxic?
Shorter acting LAs
- More potent agents higher lipid solubility & protein binding
LAST Clinical Presentation
Rapid onset usually w/in one minute
S/S: Tinnitus, metallic taste, agitation, blurred vision, & circumoral numbness
Muscle twitching, unconsciousness, & seizures
TOXIC LEVELS → cardiac & respiratory arrest
LAST Incident Rate
0.4 per 10,000
LAST most common following what procedures?
- Epidural - veins & dura
- Interscalene - carotid artery & IJ vein
- Axillary less common
How to prevent LAST
Test dose to ensure in the right spot NOT in the vein or dura
Incremental injection w/ aspiration
Use pharmacologic markers
Ultrasound
LAST Treatment
Prompt recognition & diagnosis
1° airway management - adequate ventilation & oxygenation
Seizure suppression - benzodiazepines & Succinylcholine
Hyperventilation ↑seizure threshold
Prevent hypoxia & acidosis
Lipid emulsion 20% 1.5mL/kg rapid infusion over 2-3min → 0.25mL/kg/min IBW
NOT propofol
Vasopressors - Epi < 1mg/kg NOT vasopressin
Lipid Emulsion Therapy MOA
- Captures LA in blood → lipid sink
- ↑fatty acid uptake by mitochondria
- Interferes w/ Na+ channel binding
- Promotes Ca2+ entry
- Accelerated shunting
Methemoglobinemia
Ferris (Fe2+) Hgb → Ferric (Fe3+) Hgb
↓oxygen-carrying capacity → tissue hypoxia
↓SpO2 not responsive to therapy
Benzocaine-induced methemoglobinemia
Methemoglobinemia Treatment
Methylene blue 1-2 mg/kg over 3-10 minutes
High levels may require transfusion or dialysis
Cauda Equina Syndrome
Cause - LA or nerve compression
Manifests as bowel & bladder dysfunction w/ LE weakness & sensory impairment r/t cord ischemia
Transient Neurologic Symptoms
Associated w/ intrathecal lidocaine
Presentation - burning, aching, cramping pain in the lower back that radiates down the thighs up to 5 days postop
Risk factors include lithotomy position & outpatient surgery
Lidocaine HCl (Xylocaine)
Weak base amide LA
Rapid onset
Protein binding 64-70%
↓DOA
Lidocaine Uses
- Antiarrhythmic
- Topical
- Induction to blunt SNS
- Nebulized
- Multimodal pain management
- Regional anesthetic
Lidocaine
Antiarrhythmic
ACLS algorithm Class IB Depress myocardial automaticity Vtach or Vfib 1-1.5 mg/kg IV Refractory 0.5-0.75 mg/kg Total dose 3 mg/kg Maintenance infusion 1-4 mg/min (30-50 mcg/kg/min)
Lidocaine
Topical
Eutectic mixture of LA (EMLA)
Lidocaine:Prilocaine 1:1 mixture
Contraindicated use on mucous membranes, broken skin, infants < 1mos old, methemoglobinemia history
Lidocaine
Induction
1-1.5 mg/kg IBW
↓pain associated w/ Propofol
Admin 1-3 min prior to laryngoscopy attenuate HTN
Blunt CV sympathetic response to intubation
↓CBF → attenuates ↑ICP in patients w/ ↓compliance
Block reflex bronchoconstriction
What causes the pain associated with Propofol on injection?
Phenol
How best to prevent the pain associated with Propofol?
Large bore IV
AC vein
Tourniquet 60 second veno occlusion
Opioid dose
Lidocaine LTA
Laryngotracheal topicalization anesthesia
Decrease emergence phenomenon - coughing, sore throat, & dysphonia
Lidocaine 4% pre-filled 4mL syringe (remove excess → easier to inject exact dose)
DL then insert LTA holding the catheter at the end near the syringe
Place LTA w/ black marking at the vocal cord level then inject
Lidocaine
Airway Block
Nebulized lidocaine 4% direct to the oropharynx
Swish & spit or swallow lidocaine
Tongue depressor w/ lidocaine gel
Spray as you go
Transtracheal block inject 4% through the cricothyroid membrane
Lidocaine
Multimodal
Pain management
Infusion 2 mg/kg/hr
↓narcotic requirements
MOA unknown
Reduces postop pain w/ open & laparoscopic GI surgeries
↓pain associated w/ improved functional outcomes in prostatectomy, thoracic, & spine procedures
Lidocaine
Regional
Peripheral nerve blocks
- Bier block
Neuraxial anesthesia - spinal & epidural
Bier Block
Short procedures
Lidocaine 0.5% 25-50mL
Onset 5-10 minutes
Tourniquet pain at 20 minutes
Lidocaine Dose-Dependent Effects
Plasma Concentration 1-5 μ/mL
Analgesia
Lidocaine Dose-Dependent Effects
Plasma Concentration 5-10 μ/mL
Tinnitus, circumoral numbness, skeletal muscle twitching, systemic HoTN, & myocardial depression
Lidocaine Dose-Dependent Effects
Plasma Concentration 10-15 μ/mL
Seizures
Unconsciousness
Lidocaine Dose-Dependent Effects
Plasma Concentration 15-25 μ/mL
Apnea & coma
Lidocaine Dose-Dependent Effects
Plasma Concentration > 25 μ/mL
Cardiovascular depression
Exparel
Liposomal bupivacaine
*Only mix w/ NS 0.9% or bupivacaine
Lidocaine breaks down the capsule → bupivacaine bolus ↑toxicity risk
Caution in patients w/ hepatic disease
Exparel SEs
N/V
Dizziness, headache, bradycardia, tachycardia, somnolence, hypoesthesia, & lethargy
Cocaine
Original LA derived from the cocoa plant
Only naturally occurring
Blocks the monoamine transporter in the adrenergic system
Unable to reuptake catecholamines → vasoconstriction
1° topical nose & throat
Max dose 5mL 5%
Caution w/ other epi containing solutions, MAOIs, & tricyclics
