18 – Local Anesthetics and Nerve Blocks Flashcards
Local anesthetic drugs are designed to
- Penetrate peripheral nerve barriers
- Interrupt nerve conduction
Conduction of electrical impulses in excitable membranes requires
- Flow of SODIUM ions through ion selective channels
o Occurs in response to depolarization of the nerve cell
Resting membrane potential
- At rest: concentration of Na ions is HIGHER OUTSIDE than inside the nerve
- RMP=-70mV
What is the role of Na during depolarization?
- Permeability of membrane to Na ions increases transiently
- Na ions pass through the membrane by way of Na selective ion channels that first open and then close in response to depolarization of the membrane
What is the role of K during depolarization?
- Membrane permeability to K ions increases
- normally: K is much higher inside than outside
- K efflux and membrane REPOLARIZATION occurs
Action potential is completed in
- Approximately 1-2 msec
How are peripheral nerve fibers classified?
- According to:
o Fiber size
o Physiological function
o Rate of impulse transmission
Myelin
- Phospholipid layer that surrounds and INSULATES axons of many neurons
- INCREASES speed of impulse propagation along the nerve
- Increases the fiber diameter
- *nonspecific binding site for local anesthetic molecules
- Relatively impermeable to local anesthetics
Na channel receptor number and internodal distances
- *less numerous as the internodal distances INCREASES
Myelin: increases axon diameter
- Contribute to a DELAY in onset of motor nerve blockage by local anesthetics
Rate of local anesthetic blockade in C vs A fibers
- FASTER in unmyelinated C fibers than A fibers
- *fewer diffusion barriers around C fibers than A fibers
A delta fibers: function, myelination, order of blockage and signs of blockade
- Fast pain, temperature
- Myelinated
- SECOND
- Pain relief, loss of temperature sensation
C fibers: function, myelination, order of blockage and signs of blockade
- Slow pain, autonomic, postganglionic, sympathetic, polymodal nociceptors
- Unmyelinated
- SECOND
- Pain relief, loss of temperature sensation
Mechanisms of action of local anesthetics
- Diffusion through nerve cell membrane
- Enter Na channels
- Inhibit influx of Na ions
- Interrupt nerve conduction
What are the chemical properties that determine local anesthetic effect? (4)
- Lipid solubility
- Dissociation constant
- Chemical linkage
- Protein binding
Lipid solubility
- POSITIVE correlation exists between degree of lipid solubility and inherent anesthetic POTENCY
Lipid solubility: low
- High pKa
- Penetrate lipid membranes of large myelinated nerve fibers slowly
- Little conduction block develops
- Ex. Procaine
Lipid solubility: high
- Low pKa
- Penetrate diffusion barriers around A-alpha nerves relatively easily
- Produce good motor blockade
- Ex. Mepivicaine
Dissociation constant
- Determines the portion of an administered dose that exists in the lipid-soluble (uncharged), tertiary molecular state at a given pH
- *most local anesthetics have a pKa slightly greater than physiological pH
Low pKa (dissociation constant)
- Greater proportion of drug that is in the diffusible (lipid-soluble) state
- Shorter ONSET OF ACTION
What happens when the pH is equal to the drugs pKa?
- 50% of drug in in ionized form (active)
- 50% of drug is in unionized form
Local anesthetic drugs are BASES that consist of 3 essential components
- Lipophilic aromatic ring
- Intermediate ESTER or AMIDE chain
- Terminal amine
What is the classification of local anesthetics determined by?
- INTERMEDIATE LINKAGE (ester vs. amide)
o *notable effect on chemical stability and METABOLISM
Esters: chemical linkage
- Metabolized rapidly by plasma cholinesterases
- Shorter half-lives when stored in solution w/o preservatives
Amides: chemical linkage
- Stable for LONGER periods of time
- Cannot be hydrolyzed by cholinesterase
- Enzymatically bio transformed in liver
Esters examples
- Cocaine
- Benzocaine
- Procaine
- Tetracaine
Amides examples
- Lidocaine
- Mepivacaine
- Bupivacaine
- Ropivacaine
What does protein binding correlate with?
- DURATION OF ACTION
o High affinity of local anesthetic for plasma proteins
o Increased ability to bind Na channels
o Prolonged duration of neural blockade
Potency and toxicity: order of drugs lowest to highest toxicity
*increased potency=increased risk of toxicity
1. Lidocaine
2. Mepivacaine
3. Ropivacaine
4. Bupivacaine
5. Cocaine
Therapeutic concentrations are clinically useful for
- Treatment of cardiac arrhythmias
- Lowering infectable and inhalant anesthetic drug requirements
- Producing promotility of GI effects
- Treating shock
Negative effects of local anesthetics
- May potentiate CNS depressant effects of sedatives and opioids causing vasodilation and hypotension
- Higher concentrations can induce seizure activity (due to inhibition of CNS inhibitory tracts)
Lidocaine vs. Bupivacaine and first signs of toxicity (+onset and duration)
- Lidocaine: CNS depression, ataxia, seizures
o Onset: 5mins
o Duration: 30-45mins - Bupivacaine: arrhythmias
o Onset: 10-20
o Duration: 2-6hours
Ways to potentiate (increase action/duration) of local anesthetics
- Vasoconstrictors
- Hyaluronidase
- pH adjustment
Vasopressors combined with local anesthetics to produce
- local VASOCONSTRICTION
o provide local hemostasis
o delay the absorption of local anesthetic - Ex. dexmedetomidine
What is hyaluronic acid?
- tissue cement or ground substance of the mesenchyme
What does hyaluronidase do?
- Depolymerizes hyaluronic acid
o Aids in LOCAL spread of the anesthetic agent - Not used as much anymore (more precise where we inject)
What are most local anesthetics marketed as (pH adjustment)?
- Mildly acidic HCL salts to MAXIMIZE water solubility and improve stability
What does raising pH of lidocaine, mepivacaine, and bupivacaine by adding Na-bicarbonate before injection do?
- Accelerate the onset of epidural analgesia and anesthesia
- Alkalinizer=decreases smell
What does adjusting the local anesthetic pH toward physiological range do?
- Increase amount of anesthetic base available for diffusion through axonal membranes
- *should not affect duration of action
Inflammation and local anesthetics
- Inflamed tissue=acidic
- Greater proportion of molecules is in water soluble form
- UNABLE TO CROSS CELL MEMBRANES
- DECREASED EFFECTIVENESS
- Ex. inflammation in dentals
What are some techniques to improve success of nerve blocks?
- Nerve stimulator
- Ultrasound guidance
