ロピバカイン

3

2.89

Warning

H302 (86.7%): Harmful if swallowed [Warning Acute toxicity, oral]

P261, P264, P264+P265, P270, P271, P273, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P317, P321, P330, P332+P317, P337+P317, P362+P364, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 15 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

Acute Tox. 4 (86.7%)

Acute Tox. 4 (100%)

The first step in the management of systemic toxic reactions consists of immediate attention to the establishment and maintenance of a patent airway and effective assisted or controlled ventilation with 100% oxygen with a delivery system capable of permitting immediate positive airway pressure by mask. Circulation should be assisted as necessary. If necessary, use drugs to control convulsions. Intravenous barbiturates, anticonvulsant agents, or muscle relaxants should only be administered by those familiar with their use. Immediately after the institution of these ventilatory measures, the adequacy of the circulation should be evaluated. Supportive treatment of circulatory depression may require administration of intravenous fluids, and, when appropriate, a vasopressor dictated by the clinical situation (such as ephedrine or epinephrine to enhance myocardial contractile force). (L1712)

Systemic exposure to excessive quantities of lidocaine mainly result in central nervous system (CNS) and cardiovascular effects. CNS effects may include CNS excitation(nervousness, tingling around the mouth) followed by depression. [Wikipedia]

Ropivacaine is generally well-tolerated. A pooled analysis from controlled clinical trials (n=1,661), in which patients received ropivacaine concentrations from 0.125% to 1% for nerve blocks, indicates that the most common adverse reactions are hypotension (32%), nausea (17%), vomiting (7%), bradycardia (6%), and headache (7%). A similar side effect profile occurred in patients who received bupivacaine concentrations of 0.25% to 0.75%. Overall, adverse events with ropivacaine are rare when it is properly administered.

Signs and Symptoms of Overdose

Local anesthetics such as Ropivacaine 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. Specifically, they block the sodium-channel and decrease chances of depolarization and consequent action potentials. In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of affected nerve fibers.

CNS effects may include CNS excitation (nervousness, tingling around the mouth, tinnitus, tremor, dizziness, blurred vision, seizures) followed by depression (drowsiness, loss of consciousness, respiratory depression and apnea). Cardiovascular effects include hypotension, bradycardia, arrhythmias, and/or cardiac arrest - some of which may be due to hypoxemia secondary to respiratory depression.

N01BB09

N - Nervous system

QN - Nervous system

Local anesthetics like ropivacaine block the generation and 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. Specifically, they block the sodium channel and decrease chances of depolarization and consequent action potentials. In general, the progression of anesthesia is related to the diameter, myelination, and conduction velocity of affected nerve fibers.

Ropivacaine undergoes extensive metabolism, primarily via CYP1A2-mediated aromatic hydroxylation to 3-OH-ropivacaine. The main metabolites excreted in the urine are the N-dealkylated metabolite (PPX) and 3-OH-ropivacaine. Other identified metabolites include 4-OH-ropivacaine, the 3-hydroxy-N-dealkylated (3-OH-PPX) and 4-hydroxy-N-dealkylated (4-OH-PPX) metabolites, and 2-hydroxy-methyl-ropivacaine (which has been identified but not quantified). Unbound PPX, 3-hydroxy-, and 4-hydroxy-ropivacaine have demonstrated pharmacological activity in animal models less than that of ropivacaine.

Ropivacaine has known human metabolites that include PPX and 3-hydroxy-ropivacaine.

Hepatic Route of Elimination: Ropivacaine is extensively metabolized in the liver, predominantly by aromatic hydroxylation mediated by cytochrome P4501A to 3-hydroxy ropivacaine. After a single IV dose approximately 37% of the total dose is excreted in the urine as both free and conjugated 3-hydroxy ropivacaine. In total, 86% of the ropivacaine dose is excreted in the urine after intravenous administration of which only 1% relates to unchanged drug. Half Life: Approximately 4.2 hours.

7IO5LYA57N

ROPIVACAINE

Established Pharmacologic Class [EPC] - Amide Local Anesthetic

Chemical Structure [CS] - Amides

Physiologic Effects [PE] - Local Anesthesia

Ropivacaine is an Amide Local Anesthetic. The physiologic effect of ropivacaine is by means of Local Anesthesia.

Drugs that block nerve conduction when applied locally to nerve tissue in appropriate concentrations. They act on any part of the nervous system and on every type of nerve fiber. In contact with a nerve trunk, these anesthetics can cause both sensory and motor paralysis in the innervated area. Their action is completely reversible. (From Gilman AG, et. al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed) Nearly all local anesthetics act by reducing the tendency of voltage-dependent sodium channels to activate.

Ropivacaine pharmacokinetics are highly dependent on the dose, route of administration, and patient condition. Following epidural administration ropivacaine undergoes complete and biphasic absorption.

Following intravenous administration, 86% of the administered dose of ropivacaine is excreted in the urine, 1% of which comprises unchanged parent drug.

Following intravascular infusion, ropivacaine has a steady-state volume of distribution of 41 ± 7 liters. Ropivacaine is able to readily cross the placenta.

Following intravenous administration, ropivacaine has a mean plasma clearance of 387 ± 107 mL/min, an unbound plasma clearance of 7.2 ± 1.6 L/min, and a renal clearance of 1 mL/min.

Use (kg; approx.) in Germany (2009): >500

Used in obstetric anesthesia and regional anesthesia for surgery. Ropivacaine is indicated for local anaesthesia including infiltration, nerve block, epidural and intrathecal anaesthesia in adults and children over 12 years. It is also indicated for peripheral nerve block and caudal epidural in children 1-12 years for surgical pain. It is also sometimes used for infiltration anaesthesia for surgical pain in children.