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PHARMACOKINETICS

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absorption
distribution
metabolism and excretion

absorption

Transdermal
EMLA cream ( eutectic mixture of local anesthetic)
-requires contact time under an occlusive dressing for at least 1-hour for sufficient analgesia for starting an intravenous line
-1:1 mixture of 5% lidocaine and 5% prilocaine within an oil in water emulsion
depth of penetration, duration of action, and amount of drug absorbed depends on:
-application time
-dermal blood flow
-drug dose

Site of Injection:
systemic absorption is greatest for intravenous>tracheal>intercostal>caudal>paracervical>epidural>brachial plexus>sciatic>subcut.

Prescence of vasoconstrictors: (ex. epinephrine, phenylephrine, norepinephrine)
-decreases systemic absorption therefore increases uptake from neuron
-enhanced quality of analgesia
-prolonged duration
-limits side effects
-shorter acting local anesthetics more effected by addition of vasoconstrictors opposed to longer acting local anesthetics

Local Anesthetic Agent
-highly tissue bound anesthetics are more slowly absorbed (ex. etomidate)

Distribution
primarily dependant on organ uptake
factors that influence organ uptake are:
-tissue perfusion
-tissue/blood partition coefficient
-tissue mass

Metabolism and excretion
-depends on structure of local anesthetic (ester vs amide)

Ester local anesthetics
-mainly metabolized by pseudocholinesterase (plasma esterase)
-rapid ester hydrolysis
-water soluable metabolites excreted by the kindey in the urine
-PABA metabolite of ester often associated with allergic reaction
-esters injected intrathecally are metabolized once absorbed back into the systemic circulation

Amide local anesthetics
-metabolized by the hepatic microsomal enzymes
-generally the rate of metabolism is slower than esters but depends on the specific local anesthetic agent
-dependant on hepatic function and hepatic blood flow
ex. hepatic dysfunction may reduce the rate of metabolism of local anesthetics and may results in systemic toxicity
-accumulation of o-toluidine derivative a metabolite of prilocaine in large doses may cause methemoglobin
-benzocaine may also cause methemoglobin
-treatment of methemoglobin is intravenous methylene blue (1-2 mg/kg given over 5 minutes)