Even levobupivacaine and ropivacaine (single-enantiomer derivatives), developed to ameliorate cardiovascular side effects, still harbor the potential to disrupt cardiac function. Toxicity from anesthetic combinations is additive. Endocrine
Endocrine and metabolic systems only have slightly adverse effects with most cases being without clinical repercussions. Immunologic allergy
Adverse reactions to local anesthetics (especially the esters) are not uncommon, but legitimate allergies are very rare. Allergic reactions to the esters is usually due to a sensitivity to their metabolite, para-aminobenzoic acid, and does not result in cross-allergy to amides. Therefore, amides can be used as alternatives in those patients. Nonallergic reactions may resemble allergy in their manifestations. In some cases, skin tests and provocative challenge may be necessary to establish a diagnosis of allergy. Also cases of allergy to paraben derivatives occur, which are often added as preservatives to local anesthetic solutions. Methemoglobinemia
Methemoglobinemia is a process where iron in hemoglobin is altered, reducing its oxygen-carrying capability, which produces cyanosis and symptoms of hypoxia. Exposure to aniline group chemicals such as   benzocaine, lidocaine, and prilocaine can produce this effect, especially benzocaine. The systemic toxicity of prilocaine is comparatively low, but its metabolite, o-toluidine, is known to cause methemoglobinemia. Second-generation effects
Application of local anesthetics during oocyte removal during in vitro fertilisation has been up to debate. Pharmacological concentrations of anesthetic agents have been found in follicular fluid. Clinical trials have not concluded any effects on pregnant women.
Long-term therapy may lead to cognitive deficits, especially in the elderly, which may only be partially reversible. The elderly metabolize benzodiazepines more slowly than younger people and are more sensitive to the adverse effects of benzodiazepines compared to younger individuals even at similar plasma levels. Additionally, the elderly tend to take more drugs which may interact or enhance the effects of benzodiazepines. Benzodiazepines, including lorazepam, have been found to increase the risk of falls and fractures in the elderly. As a result, dosage recommendations for the elderly are about half of those used in younger individuals and used for no longer than two weeks. Lorazepam may also be slower to clear in the elderly, leading potentially to accumulation and enhanced effects. Lorazepam, similar to other benzodiazepines and nonbenzodiazepines, causes impairments in body balance and standing steadiness in individuals who wake up at night or the next morning. Falls and hip fractures are frequently reported. The combination with alcohol increases these impairments. Partial, but incomplete, tolerance develops to these impairments. Liver or kidney failure – Lorazepam may be safer than most benzodiazepines in people with impaired liver function. Like oxazepam, it does not require liver oxidation, but only liver glucuronidation into lorazepam-glucuronide. Therefore, impaired liver function is unlikely to result in lorazepam accumulation to an extent causing adverse reactions. Similarly kidney disease has minimal effects on lorazepam levels. Surgical premedication – Informed consent given only after receiving lorazepam premedication could have its validity challenged later. Staff must use chaperones to guard against allegations of abuse during treatment.