Local Anesthetics Flashcards
Local Anesthetic effect on neural electrophysiology
Increases excitation threshold
Slows impulse conduction
Decreases action potential rate of rise
Decreases action potential amplitude
LA Site of Action
Voltage-gated Na+ channels
*Characteristics of Nerve Fiber sensitivity to LA blockade
- Nerve fibers differ greatly in their sensitivity to LA blockade based on the fibers: D.E.P.F
1. Diameter-small fibers are first to be blocked
2. Effects on other excitable membrane- weak NMB, antiarrythmic properties (lidocaine), potential for lethal arrhythmias (Bupivacaine)
3. Position in nerve bundle- peripheral nerves of bundle are blocked first
4. Firing frequency- blockade more pronounced at higher frequencies
*Classification of Nerve Fibers based on sensitivity to LA blockade
Autonomic Sympathetic B-fiber nerves-Most senstitive to blockade
Autonomic Sensory C fibers-Highly sensitive to blockade
Somatic sensory/motor nerve fibers Aa Ab-least sensitive
Clinically, LA produce sequential loss of:
Autonomic fx»>Sensory fx»>Motor fx
Structurally, All LA have a similar structure that consists of:
Lipophilic, Hydrocarbon, Hydrophilic portions
The hydrocarbon portion of LAs vary and can be classified as either:
Esters or Amides
Amide LA include:
Mepivacaine, Etidocaine, Prilocaine, Lidocaine, Bupivacaine, and Ropivacaine
Rapid acting Amide LAs include
Mepivacaine
Etidocaine
Lidocaine
Prilocaine
Ester LA include:
Chloroprocaine-Rapid
Procaine-Slow
Tetracaine-Slow
LA acid/base properties
Local anesthetics, all of which have a pKa > 7.4, become more charged at neutral or acidic pH (i.e. they accept protons when the pH is ~ 7.4), and are less charged at more basic pH (able to cross cell membrane)
Why is the acid/base properties of LA important?
This is important because the uncharged base forms are more soluble in lipid environments, and lipid solubility is correlated with potency
Because LAs are prepared in acidic HCL salts (pH 4-7), they tend to be
highly ionized & water soluble
this means a vial contains equal mixtures fo nonionized, lipid-soluble (free base) & ionized water-soluble (cationic) molecules
the uncharged base in LA is the most important molecule because
It readily crosses the lipid bilayer, and is the reactive species.
What does the uncharge base in LA react to once inside the cell
Intracellular Hydrogen Ions to form an ammonium ion complex
What does the newly formed LA ammonium complex react
Sodium channels
LA’s exert it’s effect on neurons by binding to Na channels and prolonging entry of sodium ions which ——-
repolorization, and therefore subquent depolorization of the cell
Increased Lipid Solubility (Pka >7.4) of LA correlates to
Increased potency
the solubility/potency relationship of LA is similar to what anesthetic
Inhalation agents
Cm is defined as:
the lowest drug concentration required for conduction blockade
Cm is influenced by
nerve fiber: Size Type pH Frequency of Action Potential
Larger nerves have lower or higher Cm
Higher
Increased pH ——Cm
lowers
Increased Action Potential frequency—Cm
lowers
pKa of LA determines
Onset of action
Protein binding determines
Duration of action
the greater the protein binding, the longer the duration of action
Predict the following LAs DOA based on their protein binding % Chlorprocaine 0% Lidocaine 65% Mepivacaine 78% Bupivacaine 96% Ropivacaine 93%
Clor.. (< 30 min-Short) Lido.. (1hr-Medium) Mepiv...(1 hr-Medium) Bupiv...(>2 hr-Long) Ropiv...(>2 hr-Long)
**LA systemic absorption varies by site of injection, name the order from greatest to least absorptive sites
ITIC.PEB.SFS
Intravenous>Tracheal>Intercostal>Caudal>
Paracervical>Epidural>Brachial Plexus>Sciatic/Femoral>Subcutaneous
Common additives used to Increase LA activity include:
Sodium Bicarbinate
Opioids
Alpha-adrenergic agonist (Clonidi/Dexmed)
Epinephrine
Epinephrine added to LA
useful for local and epidural analgesia where epinephrine can reduce the peak local anesthetic concentrations in blood and also serve as part of a test dose to detect acccidental intravenous injection of local anesthetic.
It can also prolong the duration of regional blocks
Sodium Bicarbonate added to LA
Raises the pH of the mileau, thus less of the LA is charged, and more of it is lipid soluble. DO NOT ADD TO BUPIVACAINE (as precipitation may occur).
Ester LA metabolism
Rapid hydrolysis by plasma cholinesterase
Chloroprocaine>Procaine>Tetracaine
Amides LA metabolism
Undergoe pulmonary extraction (Lidocaine, Bupivacaine, Prilocaine)
Hepatic metabolism
*Caution with sever liver dx
Systemic toxicity and LA
Systemic toxicity (CNS and/or CVS)
Local Toxicity- nervous tissue injury
CNS toxicity and LA
(tinnitus, paresthesias, agitation, lethargy, seizures, and coma)
- Neurologic manifestations precede cardiovascular manifestations
- Hypoxia, Acidosis, Hypercapnea potentiate LA toxicity
CVS toxicity and LA
A-V block, arrhythmias, myocardial depression, cardiac arrest
- bupivacaine being the most cardiotoxic
- Hypoxia, Acidosis, Pregnacny, HyperKalemia can exacerbate both cardiac toxicities
LA toxicity: Maximum Safe Doses (mg/kg)
Lidocaine (3-5) x2 w/ epi
Bupivacaine (1-2.5) 3 w/ epi
Ropivacaine (3) 3.5 w/ epi
Chloroprocaine (20-22)
LA (local) toxic effects
Transient Neurologic Symptoms (M-S lower back pain, buttocks, & post. thighs) begin within 36 hours after recovery from spinal anesthesia, but self-limiting
Cauda Equina Syndrome
- diffuse lumbar sacral injury with bowel/bladder sphincter dysf., & paraplegia.
- Assoc. with hyperbaric 5% lidocaine via continuous spinal microcatheters
- increased risk w/ lidocaine and the lithotomy position.
LA and Allergic rxns
Occurs with esters>amides
*cross -sensitivities do not exist between classes of LA
LA and Adverse Effects
Methemoglobinemia-seen w/ Prilocaine use
- avoid in OB use
- Tx w/ Methylene Blue IV
- Amide- can cross the placental barrier and can cause Ion-trapping in fetus.
- Esters don’t cross PB
Lidocaine
- Most widely used
- Rapid onset
- Immediated action and toxicity
- Lidocaine toxicity (and all local anesthetic toxicity) can cause circumoral numbness, facial tingling, restlessness, vertigo, tinnitus, slurred speech, and tonic-clonic seizures. Local anesthetics are actually CNS depressants, thus tonic-clonic seizures are thought to be caused by depression of inhibitory pathways.
- Used in liposuctions, and ETT to blunt sympathetic response
*Lidocane’s dose-dependent (mcg/mL) systemic effects
1-5 mcg/mL>>> Analgesia 5-10 mcg/mL>>>light headed,tinnitus, circum. numbness, muscle twithing, hypoten, myocardial depress. 10-15 mcg/mL>>> Seizures,unconscious. 15-25 mcg/mL>>> Coma, Resp. arrest >25 mcg/mL>>> CV depression
Mepivacaine
- Rapid onset
- In contrast to lidocaine, no Vasodilator properties
Bupivacaine
- Slow onset (need to work)
- Long DOA
- Highly Toxic
Ropivacaine
- (S)- enatiomer of bupivacaine
- Less Cardiotoxic than Bupivacaine
- Less potent & DOA than Bup..
- Less Moter blockade than Bup..
LevoBupivacaine
- (S)- enatiomer of Bupivacaine
- Identical physio-chemical properties of Bu.
- Less systemic/cardiotoxicity than Bu.
Etidocaine
- similar to bupivicane
- More potent motor block than sensory block
Cocaine
- ONSET slow
- DOA short
- Significant SNS stimulation-blocks presynaptic reuptake of NE & Dopamine
- *Avoid in HTN, CAD, patients receiving catecholamines
- TOPICAL use ONLY
Cocaine Toxicity
Nitroglycerin
Beta-adrenergic blockers
Alpha-adrenergic blockers
Benzodiazeines
Procaine
- DOA short
- ONSET slow
- Hydrolyzed to PABA by cholinesterase
Chloroprocaine
- ONSET rapid
- DOA short
- Metabolized rapidly by plasma cholinesterase- reason for low toxicity profile
- Preservatives»neurotoxicity
Of the Esters Tetracaine
has highest potency, but onset slow
Of the Amides, Lidocaine
has the lowest potency, but onset most Rapid
