Local anesthetics and nerve blocks Flashcards
Local anesthetic design
-Penetrate peripheral nerve barriers
-interrupt nerve conduction
Conduction of electrical impulses
Na ions flow through ion selective channels cause excitation due to depolarization of nerve cell
Resting membrane potential
Rest: Concentration of Na ions higher outside than inside nerve
Resting membrane potential= -70 mV
Na during depolarization
-Permeability of the membrane to Na increases transiently
-Na ions pass through the membrane through Na selective ion channels that first open and then close in response to depolarization of membrane
K during depolarization
-Membrane permeability to K ions increases
-Normally K is higher inside than outside the nerve, but depolarization causes K efflux and membrane repolarization
How to classify peripheral nerve fibers?
-Fiber size
-physiological function
-Rate of impulse transmission
Myelin
A phospholipid layer that surrounds and insulates the axons of many neurons
-increases speed of impulse propagation along nerve
-increases fiber diameter-insulation barrier to anesthetics
-increases axon diameter- contributes to a delay in onset of motor nerve block by local anesthetics
-Na channels decrease in nuber as internodal distance increases
Myelin and anesthetics
-Serves as a nonspecific binding site for local anesthetics molecules
-relatively impermeable to local anesthetics
Rate of local anesthetic blocks on different fibers
Faster in unmyelinated C fibers than in A fibers
**because there are fewer diffusion barriers around the C fibers than A fibers
A delta fibers
-fast pain and temperature
-myelinated
-second order of blockade; block will give pain relief and loss of temperature sensation
C fibers
-slow pain, autonomic, post ganglionic sympathetic, polymodal nociceptors
-unmyelinated
-second order of block; block will provide pain relief, loss of temperature sensation
Mechanism of action of local anesthetics
1.Diffusion through the nerve cell membrane
2.Enter Na channels
3. Inhibit influx of Na ions
4. Interrupt nerve conduction
Chemical properties that determine local anesthetic effect
-lipid solubility
-dissociation constant
-chemical linkage
-protein binding
Lipid solubility
Positive correlation exists between the degree of lipid solubility and inherent anesthetic potency
Low lipid solubility
-High pKa
-penentrate lipid membranes of large myelinated nerve fibers slowly
-little conduction block develops
High lipid solubility
-low pKa
-penetrate diffusion barriers around alpha A nerves relatively easily
-produce good motor blockade
Dissociation constant
Determines the proportion of an administered dose that exists in the lipid-soluble (uncharged; unionized), tertiary molecular state at a given pH
**most local anesthetics have pKa slightly greater than physiological pH
Lower pKa (dissociation constant)
The greater the proportion of drug that is in the diffusible (lipid-soluble) state
**shorter onset of action
pH equal to drugs at pKa
Means 50% of drug in ionized form and 50% of drug in unionized form
Three essential components of local anesthetic drugs
**BASES
- Lipophilic aromatic ring
- An intermediate ester or amide chain
- A terminal amine
Chemical linkage
Used to classify local anesthetics as it has an effect on their chemical stability and metabolism
Ester linkages
-metabolized rapidly by plasma cholinesterases
-have short half lives when stored in solution without preservatives
Amide linkages
-stable for longer periods of time
-cannot be hydrolyzed by cholinesterase
-enzymatically biotransformed in the liver
Ester drugs
-cocaine
-benzocaine
-procaine
-tetracaine
Amide drugs
-lidocaine
-mepivacaine
-bupivacaine
-ropivacaine
Protein binding
Correlates with duration of action
-high affinity of local anesthetic for plasma proteins (alpha 1-acid glycoprotein)
-increased ability to bind Na channels
-prolonged duration of neural block
Toxicity of local anesthetics
**increased potency=increased toxicity
Produce a dose dependent CNS depression proportional to their inherent local anesthetic potency
Levels of toxicity of local anesthetic drugs
GREATEST
1. Cocaine
2.Bupivacaine
3.Ropivacaine
4. Mepivicaine
5. Lidocaine
LOWEST
Therapeutic concentrations clinical uses
- Treatment of cardiac arrhythmias
- Lower injectable and inhalant anesthetic drug needs
- Produce promotility GI effects
- Treat shock
Negative effects of local anesthetic use
-Potentiate CNS depressant effects of sedatives and opioids causing vasodilation and hypotension
-High concentrations can induce seizure due to inhibition of CNS inhibitory tracts
Lidocaine vs. Bupivacaine toxicity
Lidocaine: first signs are CNS depression, ataxia, seizures
Bupivacaine: first signs of toxicity= arrhythmias
Potentiation of local anesthetics
-Vasoconstrictors
-Hyaluronidase
-pH adjustment
Hyaluronidase
Hyaluronidase depolymerizes hyaluronic acid (which is the tissue cement or ground substance of mesenchyme).
Results in the aiding of local spread of the anesthetic agent
Vasoconstrictors
Local vasoconstriction is obtained by combining vasopressors and local anesthetics
-provides local hemostasis
-delay the absorption of the local anesthetic
pH adjustment
Most local anesthetics are mildly acidic HCl salts to maximize water solubility and improve stability.
Therefore can raise pH (closer to physiological pH) of lidocaine, mepivacaine, bupivacaine by adding NaOH before injection can increase movement across membrane and the onset of epidural analgesia and anesthesia
*likely due to increasing anesthetic base available for diffusion through axonal membranes
Inflammation and local anesthetics
-inflamed tissue is acidic and a greater proportion of molecule is in water soluble form. Means it is unable to cross cell membranes and effectiveness is decreased
Techniques to improve success of nerve blocks
-Nerve stimulator
-Ultrasound guidance
