Chloroprocaine

log Kow= 2.86

2.5

2.86

VERY SOL IN CHLOROFORM; INSOL IN ETHER /HYDROCHLORIDE/

1.30e+00 g/L

STABLE IN AIR /HYDROCHLORIDE/

AQ SOLN ... TURN YELLOW ON STANDING /HCL/

9

9.1

Crystals; mp: 176-178 °C (microstage); bitter taste; aq soln are just acid to litmus and turn yellow on standing; about 1 g sol in: 22 ml water @ 20 °C, 100 ml 95% ethanol /Hydrochloride/

WHITE /HCL/

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

The first step in the management of convulsions, as well as underventilation or apnea due to unintentional subarachnoid injection of drug solution, consists of immediate attention to the maintenance of a patent airway and assisted or controlled ventilation with oxygen and a delivery system capable of permitting immediate positive airway pressure by mask. Immediately after the institution of these ventilatory measures, the adequacy of the circulation should be evaluated, keeping in mind that drugs used to treat convulsions sometimes depress the circulation when administered intravenously. Should convulsions persist despite adequate respiratory support, and if the status of the circulation permits, small increments of an ultra-short acting barbiturate (such as thiopental or thiamylal) or a benzodiazepine (such as diazepam) may be administered intravenously; the clinician should be familiar, prior to the use of anesthetics, with these anti-convulsant drugs. Supportive treatment of circulatory depression may require administration of intravenous fluids and, when appropriate, a vasopressor dictated by the clinical situation (such as ephedrine to enhance myocardial contractile force). If cardiac arrest should occur, standard cardiopulmonary resuscitative measures should be instituted. (L1712)

NERVE BLOCKS LAST AN AVG OF 1 HR. THE ADDITION OF EPINEPHRINE 1:200,000 PROLONGS THE DURATION TO AS MUCH AS 1.5 HR. /HYDROCHLORIDE/

EFFECTS OF PROCAINE & PHYSOSTIGMINE ARE ANTAGONISTIC, & THOSE OF PROCAINE & CURARE ADDITIVE. /PROCAINE/

... /Procaine/ is hydrolyzed in vivo to produce paraaminobenzoic acid, which inhibits the action of sulfonamides. /Procaine/

BUPIVACAINE & OTHER AMIDE LOCAL ANESTHETICS INHIBIT HYDROLYSIS OF CHLOROPROCAINE BY HUMAN SERUM.

For more Interactions (Complete) data for CHLOROPROCAINE (19 total), please visit the HSDB record page.

Central Nervous System Effects: These are characterized by excitation and/or depression. Restlessness, anxiety, dizziness, tinnitus, blurred vision or tremors may occur, possibly proceeding to convulsions. High doses, or unintended intravascular injection, may lead to high plasma levels and related depression of the myocardium, hypotension, bradycardia, ventricular arrhythmias and, possibly, cardiac arrest. Neurologic side effects These observations may include spinal block of varying magnitude (including total spinal block), hypotension secondary to spinal block, loss of bladder and bowel control, and loss of perineal sensation and sexual function. Arachnoiditis, persistent motor, sensory and/or autonomic (sphincter control) deficit of some lower spinal segments with slow recovery (several months) or incomplete recovery have been reported in rare instances. [Wikipedia]

Parenteral (intravenous injection). The rate of systemic absorption of local anesthetic drugs is dependent upon the total dose and concentration of drug administered, the route of administration, the vascularity of the administration site, and the presence or absence of epinephrine in the anesthetic injection.

Local anesthetic systemic toxicity (LAST) refers to local anesthetics reaching toxic plasma levels. Initial signs of LAST are tinnitus, perioral numbness, and metallic taste. Classically, LAST progresses from central nervous system excitation (anxiety, muscle twitching, seizures) to depression (sleepiness, loss of consciousness, and respiratory depression) followed by cardiac excitation (tachycardia, hypertension) and finally depression (bradycardia, hypotension, arrhythmias, asystole). However, the classic presentation is not always seen, and initial symptoms can be quite delayed.

Chloroprocaine acts mainly by inhibiting sodium influx through voltage gated sodium channels in the neuronal cell membrane of peripheral nerves. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is thus inhibited. The receptor site is thought to be located at the cytoplasmic (inner) portion of the sodium channel. It is hypothesized that Chloroprocaine binds or antagonizes the function of N-methyl-D-aspartate (NMDA) receptors as well as nicotinic acetylcholine receptors and the serotonin receptor-ion channel complex.

CHLOROPROCAINE (15 MG/KG TOTAL DOSE) IV INFUSION IN PREGNANT SHEEP DECR UTERINE BLOOD FLOW & OXYGEN CONSUMPTION WITHOUT AFFECTING ARTERIAL OR UTERINE VENOUS BLOOD.

Quantative measurements of endoneural edema, cytoplasmic lipid droplets, nerve fiber injury and Schwann cell damage were used to elucidate the pathogenesis of local anesthetic induced injury to the sciatic nerve in the rat. ... Histopathologic measurements were conducted on rat sciatic nerves removed 48 hr after the extraneural injection of one of three concn of the local anesthetic 2-chloroprocaine, procaine, etidocane or lidocaine. All four drugs produced a concn dependent incr in every measure of injury assessed by light microscopy with computer assisted morphometry of transverse 1 mu thick sections. Edema, lipid inclusions and fiber injury were /observed/ predominantly in the subperineural region and to a lesser degree in the central of nerve fascicles. ... Electron microscopic evaluation of Schwann cell injury indicated that the Schwann cells of unmyleiated fibers were more likely to undergo lysis after exposure to local anesthetics, whereas those myleinated fibers were morelikely to accumulate cytoplasmic lipid droplets.

LD50 Mouse ip 266 mg/kg

LD50 Mouse sc 1069 mg/kg

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

N - Nervous system

S - Sensory organs

QN - Nervous system

QS - Sensory organs

Chloroprocaine is an ester local anesthetic agent indicated for the production of local or regional anesthesia with effects on the cardiovascular and central nervous systems. Compared with lidocaine and bupivacaine, chloroprocaine has shorter ambulation and discharge times. Chloroprocaine has minimal effects on cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance at therapeutic doses. However, at toxic blood concentrations, chloroprocaine may cause atrioventricular block and cardiac arrest, as well as decreased cardiac output and arterial blood pressure. A high concentration of chloroprocaine in plasma can also lead to central nervous system stimulation, depression, or both. Some signs of central stimulation include restlessness, tremors and shivering, which may progress to convulsions. Depression, coma and respiratory arrest may also occur. As with other local anesthetics, patients may experience depression of the central nervous system without a prior stage of stimulation.

Chloroprocaine acts mainly by binding to the alpha subunit on the cytoplasmic region of voltage-gated sodium channels and inhibiting sodium influx in neuronal cell membranes. This lowers the nerve membrane permeability to sodium and decreases the rate of rise of the action potential. Therefore, chloroprocaine inhibits signal conduction and leads to a reversible nerve conduction blockade. The progression of anesthesia depends on the diameter, myelination and conduction velocity of nerve fibers, and the order of loss of nerve function is the following: 1) pain, 2) temperature, 3) touch, 4) proprioception, and 5) skeletal muscle tone.

Local anesthetics prevent the generation and the conduction of the nerve impulse. Their primary site of action is the cell membrane. ... Local anesthetics block conduction by decreasing or preventing the large transient increase in the permeability of excitable membranes to Na+ that normally is produced by a slight depolarization of the membrane. ... As the anesthetic action progressively develops in a nerve, the threshold for electrical excitability gradually increases, the rate of rise of the action potential declines, impulse conduction slows, and the safety factor for conduction decreases; these factors decrease the probability of propagation of the action potential, and nerve conduction fails. ... /Local anesthetics/ can block K+ channels. ... blockade of conduction is not accompanied by any large or consistent change in resting membrane potential due to block of K+ channels. /Local anesthetics/

... SITE AT WHICH LOCAL ANESTHETICS ACT, AT LEAST IN ... CHARGED FORM, IS ACCESSIBLE ONLY FROM THE INNER SURFACE OF THE MEMBRANE. ... LOCAL ANESTHETICS APPLIED EXTERNALLY FIRST MUST CROSS THE MEMBRANE BEFORE THEY CAN EXERT A BLOCKING ACTION. /LOCAL ANESTHETICS/

... /TWO POSSIBILITIES:/ ACHIEVE BLOCK BY INCR SURFACE PRESSURE OF LIPID LAYER THAT CONSTITUTES NERVE MEMBRANE ... CLOSING PORES THROUGH WHICH IONS MOVE. ... /OR:/ AFFECT PERMEABILITY BY INCR DEGREE OF DISORDER OF MEMBRANE. /LOCAL ANESTHETICS/

... ACID SALT MUST BE NEUTRALIZED IN TISSUE & FREE AMINE LIBERATED BEFORE DRUG CAN PENETRATE TISSUES & PRODUCE ANESTHETIC ACTION. ... FORM OF MOLECULE ACTIVE IN NERVE FIBERS IS CATION. ... CATION ... COMBINES WITH SOME RECEPTOR IN MEMBRANE TO PREVENT GENERATION OF ACTION POTENTIAL. /LOCAL ANESTHETICS/

... /SUGGESTED/ THAT PROCAINE ... DIMINISHES RELEASE OF ACETYLCHOLINE BY MOTOR-NERVE ENDINGS. /PROCAINE/

In adults, the average _in vitro_ plasma half-life of chloroprocaine is 21 seconds for males and 25 seconds for females. In neonates, the average _in vitro_ plasma half-life is 43 seconds. Following intrapartum epidural anesthesia, the apparent _in vivo_ half-life of chloroprocaine detected in maternal plasma was 3.1 minutes (range from 1.5 to 6.4 minutes).

... Plasma half-life /is/ approximately 25 seconds.

In plasma, chloroprocaine is quickly metabolized by pseudocholinesterases, a group of enzymes that perform the hydrolysis of the ester linkage. In ocular tissues, chloroprocaine is metabolized by nonspecific esterases. The hydrolysis of chloroprocaine leads to the production of ß-diethylaminoethanol and 2-chloro-4-aminobenzoic acid, which inhibits the action of the sulfonamides.

2-DIETHYLAMINOETHYL 4-AMINO-2-CHLOROBENZOATE YIELDS 4-AMINO-2-CHLOROBENZOIC ACID IN GUINEA PIGS. LIVETT, BH & RM LEE, BIOCHEM PHARMAC 17, 385 (1968). /FROM TABLE/

HYDROLYZED /CHIEFLY/ BY PLASMA PSEUDOCHOLINESTERASES /& ALSO BY ESTERASES IN LIVER/ AS DIETHYLAMINOETHANOL & 2-CHLORO-4-AMINOBENZOIC ACID /HUMAN, PARENTERAL. ANIMAL STUDIES SUGGEST THAT SOME LOCAL ANESTHETICS MAY UNDERGO BILIARY RECYCLING/ /CHLOROPROCAINE HCL/

Chloroprocaine is rapidly metabolized in plasma by hydrolysis of the ester linkage by pseudocholinesterase. Route of Elimination: Chloroprocaine is rapidly metabolized in plasma by hydrolysis of the ester linkage by pseudocholinesterase. Urinary excretion is affected by urinary perfusion and factors affecting urinary pH. Half Life: 21 +/- 2 seconds

5YVB0POT2H

CHLOROPROCAINE

Established Pharmacologic Class [EPC] - Ester Local Anesthetic

Chemical Structure [CS] - Esters

Physiologic Effects [PE] - Local Anesthesia

Chloroprocaine is an Ester Local Anesthetic. The physiologic effect of chloroprocaine 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.

Thanks to its low risk for systemic toxicity, chloroprocaine has a rapid onset of action that usually ranges between 6 to 12 minutes. The duration of chloroprocaine-induced anesthesia may be up to 60 minutes. The absorption rate of local anesthetics depends on the total dose and concentration of chloroprocaine, as well as the route of administration, the vascularity of the administration site, and the presence or absence of epinephrine in the anesthetic injection. The presence of epinephrine reduces the rate of absorption and plasma concentration of local anesthetics. The systemic exposure to chloroprocaine following its topical ocular administration has not been evaluated.

Like most local anesthetics and their metabolites, chloroprocaine is mainly excreted by the kidneys. The urinary excretion of chloroprocaine may be affected by urinary perfusion and factors that have an effect on urinary pH.

PROCAINE IS READILY ABSORBED FOLLOWING PARENTERAL ADMIN ... DOES NOT LONG REMAIN @ SITE OF INJECTION. ... FOLLOWING ABSORPTION, PROCAINE IS RAPIDLY HYDROLYZED ... /PROCAINE/

... Binding of the anesthetic to proteins in the serum and to tissues reduces the concentration of free drug in the systemic circulation and, consequently, reduces toxicity. ... /Ester local anesthetics/ are hydrolyzed and inactivated primarily by a plasma esterase, probably plasma cholinesterase. The liver also participates in hydrolysis of local anesthetics. /Local anesthetics/

THE SYSTEMIC TOXICITY OF CHLOROPROCAINE IS LESS THAN THAT OF ALL OTHER LOCAL ANESTHETICS BECAUSE OF ITS RAPID HYDROLYSIS BY PLASMA CHOLINESTERASE ... WHICH SHORTENS THE PLASMA HALF-LIFE.

... ENZYMATIC HYDROLYSIS OF PROCAINE /GIVES/ ... PARA-AMINOBENZOIC ACID & DIETHYLAMINOETHANOL. FORMER IS EXCRETED IN URINE TO EXTENT OF ABOUT 80%, EITHER UNCHANGED OR IN CONJUGATED FORM. ONLY 30% OF DIETHYLAMINOETHANOL CAN BE RECOVERED IN URINE; REMAINDER UNDERGOES METABOLIC DEGRADATION ... /PROCAINE/

MEDICATION

For the production of local anesthesia by infiltration and peripheral nerve block. They are not to be used for lumbar or caudal epidural anesthesia.

2-CHLORO-4-NITROBENZOIC ACID IS REACTED WITH THIONYL CHLORIDE & RESULTING ACID CHLORIDE CONDENSED WITH 2-(DIETHYLAMINO)ETHANOL. REDN OF NITRO ESTER WITH IRON & ACIDULATED WATER YIELDS CHLOROPROCAINE BASE...CONVERTED INTO THE HYDROCHLORIDE BY DISSOLVING IN SUITABLE SOLVENT & INTRODUCING HCL.

...synthesized by esterification of 4-amino-2-chlorobenzoic acid with 2-diethylaminoethanol and subsequent transformation to the hydrochloride form. /Hydrochloride/

NESACAINE (ASTRA): SOLUTION 1% AND 2% IN 30 ML CONTAINERS (2% NOT FOR CAUDAL OR EPIDURAL ANESTHESIA); NESACAINE MPF: SOLUTION 2% AND 3% IN 30 ML CONTAINERS FOR CAUDAL OR EPIDURAL ANESTHESIA (CONTAINS NO PRESERVATIVE) /CHLOROPROCAINE HCL/

NESACAINE (PENNWALT). SOLN 1% & 2% IN 30 ML MULTIPLE-DOSE CONTAINERS (NOT FOR CAUDAL OR EPIDURAL ANESTHESIA. NESACAINE-CE (PENNWALT). SOLN 2% & 3% IN 30 ML SINGLE-DOSE CONTAINERS (FOR CAUDAL OR EPIDURAL ANESTHESIA; CONTAINS NO PRESERVATIVE). /CHLOROPROCAINE HYDROCHLORIDE/