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STRUCTURE-ACTIVITY RELATIONSHIPS

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lipophillic group
hydrophilic group
ester linkage
amide linkage
potency
Cm
MLAC
MEAC
onset of action
duration of action

lipophilic group: benzene ring

hydrophilic group: tertiary amine: usually carrys a positive charge at physiologic pH (making it a weak base)

ester linkage intermediate chain

amide linkage intermediate chain

properties of local anesthetics are deteremined by:
-substitutions on the aromatic ring
-intermediate chain linkage (ex. ester vs amide)
-alkyl groups attached to the nitrogen amine

potency is increased by:
-association with lipid solubility
-ability of the local anesthetic to penetrate through a hydrophobic (lipophillic) environment
-greater number of carbon atoms within the molecule
-addition of a halide group to the aromatic ring 2-chloroprocaine more potent than procaine
-ester linkage procaine more potent than procainamide
-large alkyl groups on the tertiary amide nitrogen etidocaine more potent than lidocaine

Cm
-minumun concentration of a local anesthetic that will block nerve impulse conduction
-measure of potency
affected by:
-nerve fiber size
-nerve fiber type
-myelinated vs nonmyelinated fibers
-pH environment of the fiber/tissue
-frequency of stimulation to the nerve
-electrolyte plasma concentration

MLAC
-minimum local analgesic conentration
-median effective local analgesic concentration within a 20 ml volume for epidural analgesia during the 1st stage of labor
-measure of relative potency

MEAC
-minimum effective anesthetic concentration
-concentration which a spinal anesthetic agent produces surgical anesthesia within 20 minutes of administration in 50% of patients

Onset of Action depends on:

pKa:
-relative concentration of the nonionized (lipid soluable) and ionized (water soluable) form of the local anesthetic
-pH when the amount of the nonionized and ionized form of local anesthetic are in equilibrium
-rapid onset when the pKa close to physiologic pH will have more concentration of nonionized (lipid soluable) local anesthetic

Addition of epinephrine
-creates vasocontriction in nearby vessels preventing uptake intravascularly
-less intravascular uptake of local anesthetic creates higher concentration at the site of injection therefore more rapid onset of action

Alkalinization of local anesthetics by theaddition of bicarbonate may:
-speed the onset of action
-improve the quality of anesthetic block
-prolong the anesthetic block
-decrease pain upon injection of local anesthetic

Duration of Action depends on:
-correlation with plasma protein binding (ex. alpha1-acidic glycoprotein bind to local anesthetics)