pharmacokinetics local |

pharmacokinetics local

Sun, 12/02/2007 - 12:41 — oxygen

PHARMACOKINETICS Listen to Audio 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)

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