Ropivacaine - How It Works
Clinical pharmacology details from the US FDA-approved label: how Ropivacaine works in your body, how it's absorbed, how long it stays active, and how it's eliminated.
Mechanism of Action
12.1 Mechanism of Action Ropivacaine is a member of the amino amide class of local anesthetics and is supplied as the pure S-(-)-enantiomer. Local anesthetics 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. Clinically, the order of loss of nerve function is as follows: pain, temperature, touch, proprioception, and skeletal muscle tone.
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Ropivacaine is a member of the amino amide class of local anesthetics and is supplied as the pure S-(-)-enantiomer.
Local anesthetics 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.
Clinically, the order of loss of nerve function is as follows: pain, temperature, touch, proprioception, and skeletal muscle tone.
12.2 Pharmacodynamics Studies in humans have demonstrated that, unlike most other local anesthetics, the presence of epinephrine has no major effect on either the time of onset or the duration of action of ropivacaine.
Likewise, addition of epinephrine to ropivacaine has no effect on limiting systemic absorption of ropivacaine.
Systemic absorption of local anesthetics can produce effects on the central nervous and cardiovascular systems.
At blood concentrations achieved with therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance have been reported.
Toxic blood concentrations depress cardiac conduction and excitability, which may lead to atrioventricular block, ventricular arrhythmias and to cardiac arrest, sometimes resulting in fatalities.
In addition, myocardial contractility is depressed and peripheral vasodilation occurs, leading to decreased cardiac output and arterial blood pressure.
Following systemic absorption, local anesthetics can produce central nervous system stimulation, depression or both.
Apparent central stimulation is usually manifested as restlessness, tremors and shivering, progressing to convulsions, followed by depression and coma, progressing ultimately to respiratory arrest.
However, the local anesthetics have a primary depressant effect on the medulla and on higher centers.
The depressed stage may occur without a prior excited stage.
In 2 clinical pharmacology studies (total n=24) ropivacaine and bupivacaine were infused (10 mg/min) in human volunteers until the appearance of CNS symptoms, e.g., visual or hearing disturbances, perioral numbness, tingling and others.
Similar symptoms were seen with both drugs.
In 1 study, the mean ± SD maximum tolerated intravenous dose of ropivacaine infused (124 ± 38 mg) was significantly higher than that of bupivacaine (99 ± 30 mg) while in the other study the doses were not different (115 ± 29 mg of ropivacaine and 103 ± 30 mg of bupivacaine).
In the latter study, the number of subjects reporting each symptom was similar for both drugs with the exception of muscle twitching which was reported by more subjects with bupivacaine than ropivacaine at comparable intravenous doses.
At the end of the infusion, ropivacaine in both studies caused significantly less depression of cardiac conductivity (less QRS widening) than bupivacaine.
Ropivacaine and bupivacaine caused evidence of depression of cardiac contractility, but there were no changes in cardiac output.
Pharmacokinetics
12.3 Pharmacokinetics Absorption The systemic concentration of ropivacaine is dependent on the total dose and concentration of drug administered, the route of administration, the patient's hemodynamic/circulatory condition, and the vascularity of the administration site. From the epidural space, ropivacaine shows complete and biphasic absorption. The half-lives of the 2 phases, (mean ± SD) are 14 ± 7 minutes and 4.2 ± 0.9 h, respectively. The slow absorption is the rate limiting factor in the elimination of ropivacaine that explains why the terminal half-life is longer after epidural than after intravenous administration. Ropivacaine shows dose-proportionality up to the highest intravenous dose studied, 80 mg, corresponding to a mean ± SD peak plasma concentration of 1.9 ± 0.3 mcg/mL. Table 7 Pharmacokinetic (Plasma Concentration-Time) Data From Clinical Trials Route Epidural Infusion* Epidural Infusion* Epidural Block † Epidural Block † Plexus Block ‡ IV Infusion § Dose (mg) 1493 ± 10 2075 ± 206 1217 ± 277 150 187.5 300 40 N 12 12 11 8 8 10 12 C max (mg/L) 2.4 ± 1 ¶ 2.8 ± 0.5 ¶ 2.3 ± 1.1 ¶ 1.1 ± 0.2 1.6 ± 0.6 2.3 ± 0.8 1.2 ± 0.2 # T max (min) n/a ♠ n/a n/a 43 ± 14 34 ± 9 54 ± 22 n/a AUC 0 - (mg.h/L) 135.5 ± 50 145 ± 34 161 ± 90 7.2 ± 2 11.3 ± 4 13 ± 3.3 1.8 ± 0.6 CL (L/h) 11.03 13.7 n/a 5.5 ± 2 5 ± 26 n/a 21.2 ± 7 t 1/2 (hr) ♥ 5 ± 2.5 5.7 ± 3 6 ± 3 5.7 ± 2 7.1 ± 3 6.8 ± 3.2 1.9 ± 0.5 * Continuous 72 hour epidural infusion after an epidural block with 5 or 10 mg/mL. † Epidura