Local Anesthetics Flashcards
Chemistry of local anesthetics
Local anesthetics are drugs that transiently block nerve conduction when applied to nerve tissue in appropriate concentrations
pKa of the drug and pH of tissue determine amount of drug that exists in solution as lipid soluble (free base) or water soluble (cation) when injected
Amphipathic molecules
Two types of local anesthetics
Esters and amides
Metabolism of esters
Metabolized by plasma pseudocholinesterases
except for cocaine (hepatic)
prolonged in patients with atypical cholinesterase
Para-aminobenzoic acid (PABA) degradation product
known allergen
majority of allergies to local anesthetics are associated with ester agents
Metabolism of amides
Hepatic metabolism via cytochrome p-450 pathway
prolonged in patients with liver disease
Rarely allergenic - if reaction due to Multi-dose vials use methylparaben as a preservative
metabolized to PABA
utilize preservative free amide in patient with allergy to esters
Classification (naming) trick for esters vs amides
MOA of local anesthetics
Impairing propagation of the action potential in axons
Directly interacting with sodium channels in the nerve membranes thereby inhibiting the passage of sodium
Does NOT alter the resting membrane potential but it slows the rate of depolarization —— threshold potential is not met ——action potential is not propagated
Properties and determinants of blockade
Potency
Onset
Duration of action
What is potency
Definition: amount of a drug required to produce a given effect
Lipid solubility appears to be the most significant property of local anesthetic molecules in determining potency
Lipophilic local anesthetics more easily cross nerve membranes
How to increase potency of a drug
In general, lengthening the connecting hydrocarbon chain or increasing the number of carbon atoms on the tertiary amine or aromatic ring results in a more potent drug
What is onset of action
Definition: time it takes following administration for a drug’s effect to come to prominence
Factors Affecting Onset of action
Addition of sodium bicarbonate to the local anesthetic solution may speed onset - increases amount of nonionized form
Infected tissues (lower pH) results in a delayed onset of action because of decreased proportion of nonionized form (pKa)
What is duration of action
Definition: length of time the drug has a pharmacological effect
Plasma binding appears to be the most significant property of local anesthetic molecules in determining duration of action
High degree of protein binding results in prolonged duration of effect
Factors Affecting Protein Binding
Addition of vasoconstrictors (epinephrine) prolongs duration of action – Decreases local blood flow and thereby reduces drug absorption ——enhanced neuronal uptake resulting in greater and longer blockade
How are nerve fibers classified
fiber diameter (small v large)
myelinated vs. unmyelinated
function (autonomic, sensory, motor)
Differences in blockades in nerve fiber types
Differential block = clinical phenomenon that nerve fibers with different functions have different sensitivities to local anesthetic blockade.
- Sympathetic nerve fibers (2 segments above pain)
- Pain/touch nerve fibers (2 segments above motor)
- Motor nerve fibers
Blood concentration of local anesthetics reliant on
amount injected
rate of absorption from injection site
rate of tissue distribution
rate of biotransformation and excretion
Levels of absorption from highest to lowest
Intravenous
Intercostal
Lumbar epidural
Brachial plexus
Subcutaneous
Factors Influencing Local Anesthetic Blockade
- Dose of local anesthetic
- Addition of vasocontricter: epinephrine, NE impair blood flow and uptake so more stays in nerve
- Addition of sodium bicarb: decrease onset time
- Local mixture: toxic effects are additive
- Pregnany: increased sensitivity bc engorged epidural veins
What is methemoglobinemia
Methemoglobinemia: oxidation of the ferrous form of hemoglobin to the ferric from = unable to bind and transport oxygen
Side effect unique to prilocaine and benzocaine
Treated with methylene blue
SX of CNS toxicity
Initial excitation
Tinnitus, Dizziness, Circumoral numbness, Blurred vision, Agitation, Tonic clonic seizures
Progress to CNS depression
Slurred speech, Drowsiness, Unconsciousness
SX of cardiovascular toxicity
Bupivacaine highest tendency for cardiac toxicity
Block fast cardiac sodium channels Purkinje fibers and ventricles
Decreases rate of depolarization
Decreases conduction times
P-R interval prolongation and QRS widening
Severe bradycardia
Ventricular dysrhythmias
Arrest
Profound hypotension - ateriolar vascular smooth muscle relaxation
cocaine is a vasoconstrictor
ropivacaine is a mild vasoconstrictor
Potentiated by hypoxia, hypercarbia, and acidosis
TX for systemic toxicity to local anesthetic
Stop anesthetic
Lipid emulsion (20%) therapy
Bolus 1.5 mL/kg, continuous infusion 0.25 mL/kg/min
Continue for 10 min after attaining circulatory stability
