Local anesthetics (LAs) are used in many clinical scenarios that require the pain practitioner to be intimately familiar with their pharmacokinetic and pharmacodynamic properties. They are used in the prevention of acute, inflammatory, nociceptive, cancer-related, neuropathic, and chronic pain, for diagnostic and prognostic purposes, and in the possible prevention of chronic pain.1
Operating primarily by their interaction with sodium voltage dependent channels (NaVs) to block sodium (Na+) entry into the neuron, LAs interrupt nerve impulse conduction and propagation. However, in recent years, other actions, such as LA interaction with other non-Na+ ion channels and G-protein receptors, which may be important in their ability to prevent and treat pain, have been described.2 These interactions take place in both the central and peripheral nervous system. In a concentration dependent fashion, LAs interrupt autonomic, sensory, and motor impulses, giving rise to autonomic system blockage, sensory analgesia, and muscle paralysis. With a deeper understanding of both the pharmacokinetics and pharmacodynamics of LAs, a higher rate of treatment success can be achieved, with a reduction in side effects. This chapter aims to focus on the newest information regarding LA mechanisms, pharmacodynamics, and toxicity.
LAs, being poorly soluble in water, are mixed with hydrochloride salts. If epinephrine is added to the solution, sodium bisulfate is often added to further lower the pH to about 4 to prevent its oxidative decomposition.
LAs such as lidocaine, tetracaine, and bupivacaine are also manufactured in liposomal vesicles. Such a formulation provides for a prolongation of action and a decrease in toxicity.3 Such a formulation allows for the slow continuous subcutaneous infiltration of the drug providing analgesia for up to 96 hours to decrease toxicity.4
Since the pKa of most LAs is approximately 8, within the acidic carrier medium they are dissolved in, pH 3.9 to 6.5, only approximately 3% of the drug exists in the lipid-soluble form. Because the lipid-soluble form is felt important for LA mechanism of action, alkalinization, via addition of sodium bicarbonate, is used by some practitioners. This process shifts the pH of the medium to become closer to the pKa of the drug, allowing for more of the drug to exist in the lipid-soluble form. The result is a hastening of the onset of LAs in peripheral nerve and neuraxial blocks by 3 to 5 minutes, a deepening of the depth of sensory and motor block, and an increase in the epidural spread of the drug.5 However, prolonged or excessive alkalinization can cause LA molecules to precipitate from suspension. Additionally, the value of adding sodium bicarbonate to solutions to enhance speed of onset also depends on the injection site and the specific physiochemical properties of the individual LA used.6
LAs consist of 4 portions:
Ester or amide linkage
Please Try Again Later
Your institution has exceeded the maximum number of simultaneous users. Please try later.
Want remote access to your institution's subscription?
Sign in to your MyAccess profile while you are actively authenticated on this site via your institution (you will be able to verify this by looking at the top right corner of the screen - if you see your institution's name, you are authenticated). Once logged in to your MyAccess profile, you will be able to access your institution's subscription for 90 days from any location. You must be logged in while authenticated at least once every 90 days to maintain this remote access.
Create a Free MyAccess Profile
Note: If you have registered for a MyAccess profile on any of the Access sites, you can use the same MyAccess login credentials across all sites.
Benefits of a MyAccess Profile:
- Remote access to the site off-campus on any device
- Notification of new content via custom alerts
- Bookmark your favorite content such as chapters, figures, tables, videos, cases and more
- Save and download images to PowerPoint
- Self-Assessment quizzes saved for quick review
- Custom Curriculum access for both instructors and learners
AccessAnesthesiology Full Site: One-Year Subscription
Connect to the full suite of AccessAnesthesiology content and resources including procedural videos, interactive self-assessment, real-life cases, 20+ textbooks, and more
Pay Per View: Timed Access to all of AccessAnesthesiology
24 Hour Subscription $34.95
48 Hour Subscription $54.95
Pop-up div Successfully Displayed
This div only appears when the trigger link is hovered over.
Otherwise it is hidden from view.