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
