Local Anesthetics Flashcards
Three chemical elements to be a LA
Benzene ring (lipophilic) Intermediate Chain (ester or amide) Quaternary Amine (hydrophilic)
Metabolism by plasma and tissue cholinesterase via hydrolysis making them shorter acting
Esters
Higher allergy potential and should avoid all if allergy to one
Esters
Metabolized in the liver, significant blood level may develop with rapid absorption (lasts longer)
Amides
Allergy is rare, no cross allergy among or between class
Amides
Longer acting d/t being more lipophilic and protein bound
Amides
Have oxygen
Esters
Have hydrogen
Amides
Which nerves are harder to block
Heavy myelination and large diameter
MOA of LA
LA is injected into tissue around nerve. Equilibrium is reached outside the nerve and non ionized portion (lipid soluble) enters the nerve.
Once inside the axoplasm the drug reequilibrates and the ionized fraction (hydrophilic) attaches to the LA receptor on the inside of the Na channel blocking Na entry and depolarization.
What is LA distribution
Some LA will partake in nonspecific tissue binding in which it diffuses off into tissues (some taken up in bloodstream), is then uptaken and removed.
PKa importance in LA
Lower pKa (closer to 7.4) the faster the onset, larger amount of non-ionized
Protein binding significance with LA
More protein bound, longer duration of action. If it binds strongly to proteins it is probably binding more to tissues, nerves, and the Na channel and takes longer to be removed from system
What do vasoconstrictors do when given with LA
Constrict blood flow to area that you are injecting LA, that way it is not removed as quickly, lasts longer, and causes less bleeding. Decrease rate of vascular absorption
I.e. epinephrine.
Slower onset (stays more local) Higher degree of motor, sensory blockade Longer duration Larger area of blockade Lower peak plasma concentration (unlike with increased dosing which increases ppc)
MOA of vasoconstrictors in LA
Alpha adrenergic receptors in spinal cord are known to activate endogenous analgesic mechanisms
Vasoconstrictive activity
Ion Trapping Causes
LA overdose
Respiratory depression leading to hypoxia and acidosis
Ion Trapping MOA
acidosis increases ionized fraction of LA. Unable to pass out of BBB so stuck in bracing, prolonging CNS toxicity
What is a risk with LA and a fetus
Ion trapping d/t fetal pH being lower than maternal pH. May lead to high levels of LA in fetus
What happens when LA is injected into acidotic or infected tissue
Rendered ineffective d/t loss of lipid solubility from acidotic environment. Unable to penetrate nerve.
Effect of addition of carbonation in LA
Speeds onset and intensity of action. CO2 passes through nerve readily and makes inside of nerve more acidotic, increasing ionized fraction of LA in nerve at Na channel
Effect of addition of bicarbonate to LA
More rapid onset of action by increases pH of solution, increasing non-ionized form of drug, passes through nerve more readily.
Also takes away sting of injection
Potency is correlated with
Lipid solubility.
Increase lipid solubility, increase amount that diffuses through nerve allowing lower dose needed
Time of onset is correlated with…
PKa (dissociation constant). Agents with lower pKa/closer to 7.4 are more non-ionized and thus pass more readily
Metabolism is correlated with…
Chemical linkage
I.e. ester (plasma cholinesterases) or amide (Liver)
