Local Anesthetics: Pharmacology and Toxicity

Local anesthesia is essential for pain control in dentistry. The authors assessed the comparative effect of local anesthetics on acute dental pain after tooth extraction and in patients with symptomatic irreversible pulpitis.

The authors searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and the US Clinical Trials registry through November 21, 2020. The authors included randomized controlled trials (RCTs) comparing long- vs short-acting injectable anesthetics to reduce pain after tooth extraction (systematic review 1) and evaluated the effect of topical anesthetics in patients with symptomatic pulpitis (systematic review 2). Pairs of reviewers screened articles, abstracted data, and assessed risk of bias using a modified version of the Cochrane risk of bias 2.0 tool. The authors assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach.

Fourteen RCTs comparing long- vs short-acting local anesthetics suggest that bupivacaine may decrease the use of rescue analgesia and may not result in additional adverse effects (low certainty evidence). Bupivacaine probably reduces the amount of analgesic consumption compared with lidocaine with epinephrine (mean difference, –1.91 doses; 95% CI, –3.35 to –0.46; moderate certainty) and mepivacaine (mean difference, –1.58 doses; 95% CI, –2.21 to –0.95; moderate certainty). Five RCTs suggest that both benzocaine 10% and 20% may increase the number of people experiencing pain reduction compared with placebo when managing acute irreversible pulpitis (low certainty).

Bupivacaine may be superior to lidocaine with epinephrine and mepivacaine with regard to time to and amount of analgesic consumption. Benzocaine may be superior to placebo in reducing pain for 20 through 30 minutes after application.

Levobupivacaine is a long-acting local anesthetic that is both safe and non-toxic. However, few researchers have examined the efficacy and safety of peritonsillar injections of levobupivacaine for postoperative pain relief. The goal of this study was to assess current randomized controlled trials that employed this strategy. A literature review was conducted using databases such as DELPHIS, PUBMED, COCHRANE, and SCOPUS. A total of fifteen randomized controlled trials were found and thoroughly reviewed. There were no fatalities reported. One study reported a case of nausea and vomiting. In most of the studies, levobupivacaine with magnesium, epinephrine, dexamethasone hydrochloride, tramadol, or levobupivacaine alone were compared to a placebo. Four trials employed different combinations of levobupivacaine and other medicines to recruit adults. Most of the studies had a modest sample size. As a result, larger research with more representative populations should be conducted. Despite certain flaws in the trial design, our findings suggest that levobupivacaine is safe and effective at reducing postoperative pain.

Evaluating patient comfort during full awake local anesthesia in carpal tunnel release surgery, without tourniquet use, by using epinephrine to obtain a completely dry surgical field.

We included into the study 41 patients who underwent carpal tunnel syndrome surgery under full awake combined anesthesia, using a 9-point questionnaire. Pain and anxiety in all patients were evaluated through a Wang-Baker 0–5 scale. The injection solution consisted of 0.1cc of epinephrine and 10cc of 1% lidocaine (1:100.000); 5cc were used for local cutaneous anesthesia, and 5cc were used for distal median nerve block. All patients underwent a classic, open carpal tunnel release.

Anxiety scores during anesthesia and the post-operative period did not show a statistically significant difference (p > 0.01), with keeping their levels at low perception scores (average score of 1.68 ± 0.38 CI 95%, with a modal value of 2, compared to an average of 0.78 ± 0.29 CI 95% with a modal value of 0). Similar results were obtained for pain scores during anesthesia (1.73 ± 0.48 CI 95% with a most frequent modal score of 1). Our results also showed that the effects of combined anesthesia in carpal tunnel release surgery persisted well into the 6-hour post-operative moment, pain scores remaining low, statistically significant similar to recorded values during the anesthesia moment (p > 0.01), at an average of 2.29 ± 0.5 CI 95% with a modal value of 1. No serious complications were recorded.

Combined distal median nerve block and local anesthesia with epinephrine:lidocaine provides a comfortable option for patients, with minimal risks of complications.

The Na_v1.7 sodium channel are expressed in dental pulp, so identifying analogous molecules of local anesthetics with high affinity for this channel under inflammatory conditions would be very useful in dental anesthesia. The aim of this study was to evaluate local anesthetics analogues against Na_v1.7 channel through molecular docking and dynamics. 3267 ligands were selected for virtual screening: 1 control ligand (Flecainide), 10 local anesthetics and 3256 structural analogues with human Na_v1.7 (PDB 5EK0). Molecular protocol validation was performed with Flecainide-Na_vAb complex (PDB 6MVX). Molecular docking through AutoDock-Vina by binding energy between ligand-receptor and molecular dynamics simulation through AMBER16 software was developed. A predictive search of the ADME and toxicological properties were performed. The molecule-1 ligand presented the best binding energy (−6.4 kcal/mol), followed by the molecule-2 ligand with −6.3 kcal/mol. On molecular dynamics, molecule-1 analogue had the best behavior with the lowest RMSD, RMSF, SASA and Rg scores. In ADME and toxicological properties, all molecules had no violations of Lipinski's rules and had oral toxicity class III. Molecule-1 analogue can act as a potential drug for local anesthetics under inflammatory conditions by blocking pain pathways through Na_v1.7 channel.