Articaine has a secondary nitrogen with a pKa of 7.8. It contains an aromatic thiophene ring bioisostere of the phenyl ring found in most other amide anesthetics. The log P of a benzene ring is 2.13 and the thiophene ring log P is 1.81, thus the thiophene ring is more hydrophilic than a phenyl ring. Although the thiophene ring has less lipid solubility than a phenyl ring, articaine is a lipid-soluble compound due to the propylamine, the branched methyl and the substitutions on the thiophene ring. The onset of action of articaine is similar to lidocaine's onset of action. Articaine is available in a 4% solution with epinephrine for use in infiltration and nerve block anesthesia.
Articaine is metabolized rapidly via plasma and tissue carboxyesterase to its primary metabolite, the inactive, water-soluble carboxylic acid. Approximately 40% to 70% of articaine administered epidurally is metabolized to the carboxylic acid, articainic acid. Approximately 4% to 15% of the articainic acid undergoes glucuronide conjugation and only 3% of the dose is recovered unchanged in the urine. The rapid plasma metabolism and reported inactivity of the carboxylic acid metabolite make articaine a potentially safer anesthetic agent when multiple or large doses are necessary.101,102
One of the issues of local anesthetic use is that they are not specific to sensory nociceptors, the "pain neurons." Local anesthetics also block pressure, touch, and motor axons leading to numbness and loss of muscle control. Recent studies in rats have shown that administering the quaternary lidocaine molecule, QX-314, along with capsaicin allows the permanently charged anesthetic access to pain-sensing neurons only. The quaternary charge on QX-314 prevents it from entering all neurons via simple diffusion through the lipophilic membrane. Capsaicin was found to bind to a protein only found on pain-sensing neurons, TRPV1 channels. When capsaicin binds to TRPV1, the channel opens to allow QX-314 to enter the axoplasm and then access the local anesthetic binding site in the sodium channel from the hy-drophilic pathway (Fig. 22.13 hydrophilic pathway C). By specifically blocking the sodium channels of only pain neurons, other nerve function is preserved. This type of pain management would make it possible to have a dental procedure with no pain, yet not leave the entire face numb, or have an epidural during labor and still be able to walk. This is an exciting new opportunity in pain management that is undergoing research presently.103
Another area of research is the formulation of local anesthetic liposomes and microspheres. The principle behind this research is that the local anesthetic molecules are amphi-pathic, with both a hydrophilic and hydrophobic component. The anesthetic molecule can be suspended inside carrier substances made of egg phospholipids and cholesterol liposomes or biodegradable polymers of lactic acid or glycolic acid. The carrier molecule will allow a controlled delivery of the local anesthetic and provide a long duration of action, potentially with less systemic toxicity.91,104 Carrier molecules are also being designed that combine a local anesthetic with an opioid analgesic that may offer alternative analgesic delivery methods.105
1. A nurse anesthetist calls the OR pharmacy to discuss a patient history and get your input on choosing a general anesthetic for an upcoming operation.
ML is a 32-year-old, 5'4", 460-pound woman who is scheduled for an elective gastroplasty (stomach stapling). She has a history of hypertension (150/98 mm Hg), hyper-lipidemia (LDL-cholesterol = 140mg/dL), and a large stage III pressure ulcer on her lower back. The last time that the patient underwent surgery, she could not be roused from the sedation and spent 24 hours in the postanesthetic care unit (PACU). Her prior surgery required 3 hours of general anesthesia maintained with isoflurane. The nurse anesthetist would like to know if one of the other formulary agents offers a shorter recovery time. General anesthetics on the formulary include nitrous oxide, desflurane, sevoflurane, isoflurane, enflurane, and halothane.
2. A medical student was assigned the task of debriding ML's decubitus ulcer and calls the pharmacy to obtain procaine to inject locally before beginning the painful procedure. You review the patient's chart for allergies (no known drug allergies [NKDA]) and notice that the patient is also receiving 1% silver sulfadiazine cream to prevent bacterial colonization of the ulcer. You recommend against using the procaine and suggest a 1% lido-caine with epinephrine instead. Why?
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