- Metabolism: Levobupivacaine is extensively metabolized with no unchanged levobupivacaine detected in urine or feces. In vitro studies using [14 C] levobupivacaine showed that CYP3A4 isoform and CYP1A2 isoform mediate the metabolism of levobupivacaine to desbutyl levobupivacaine and 3-hydroxy levobupivacaine, respectively. In vivo, the 3-hydroxy levobupivacaine appears to undergo further transformation to glucuronide and sulfate conjugates. Metabolic inversion of levobupivacaine to R(+)-bupivacaine was not evident both in vitro and in vivo. Route of Elimination: Following intravenous administration, recovery of the radiolabelled dose of levobupivacaine was essentially quantitative with a mean total of about 95% being recovered in urine and feces in 48 hours. Of this 95%, about 71% was in urine while 24% was in feces. Half Life: 3.3 hours
- Uses/Sources: For the production of local or regional anesthesia for surgery and obstetrics, and for post-operative pain management
- Health Effects: Acute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.
- Symptoms: nervousness, tingling around the mouth, tinnitus, tremor, dizziness, blurred vision, seizures, depression (drowsiness, loss of consciousness, respiratory depression and apnea). [Wikipedia]
- Treatment: If the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.
- Route of Exposure: The plasma concentration of levobupivacaine following therapeutic administration depends on dose and also on route of administration, because absorption from the site of administration is affected by the vascularity of the tissue. Peak levels in blood were reached approximately 30 minutes after epidural administration, and doses up to 150 mg resulted in mean Cmax levels of up to 1.2 ug/mL.
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: LD50: 5.1mg/kg in rabbit, intravenous; 18mg/kg in rabbit, oral; 207mg/kg in rabbit, parenteral; 63mg/kg in rat, subcutaneous.
Mechanism of Action
|Target Name||Mechanism of Action||References|
|Sodium channel protein type 10 subunit alpha||Local anesthetics such as Levobupivacaine block the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of affected nerve fibers.||