The interaction of calcium and local anesthetics was investigated with the lipid extracted human RBC membrane fragments treated with carbodiimide in order to titrate carboxyl groups. A water soluble carbodiimide [1-cyclohexyl-3-(2-morpholinoethyl) carbodiimide methotoluene-p-sulfonate], referred to as a carbodiimide reagent, and glycine methylester were used for this purpose. About 76% of carboxyl groups of the fragments were modified at a concentration of 0.05M carbodiimide reagent. The interaction of calcium and local anesthetics such as procaine and lidocaine with these fragments still showed typical competition. However, when the calcium binding was decreased to 8% at a higher concentration of carbodiimide reagent (0.08M), the local anesthetics still inhibited the calcium binding, but were not competitive in nature. In other words, if concentrations of the carbodiimide reagent were raised, the degree of inhibition by the local anesthetics was gradually decreased and was not competitive in nature. Finally, no inhibition was demonstrated when the concentration of the reagent was 0.1 to 0.4M. The above findings, seem to suggest that local anesthetics such as procaine and lidocaine interact with carboxyl groups, in addition to phosphodiester groups of phospholipids as previously reported, and inhibited competitively calcium binding to carboxyl groups of the membrane fragments.
Anesthetics, Local/pharmacology* ; Calcium/metabolism* ; Carbodiimides/pharmacology* ; Cell Membrane/metabolism ; Erythrocytes/metabolism* ; Human ; In Vitro ; Protein Binding

The interaction of calcium and local anesthetics was investigated with the lipid extracted human RBC membrane fragments treated with carbodiimide in order to titrate carboxyl groups. A water soluble carbodiimide [1-cyclohexyl-3-(2-morpholinoethyl) carbodiimide methotoluene-p-sulfonate], referred to as a carbodiimide reagent, and glycine methylester were used for this purpose. About 76% of carboxyl groups of the fragments were modified at a concentration of 0.05M carbodiimide reagent. The interaction of calcium and local anesthetics such as procaine and lidocaine with these fragments still showed typical competition. However, when the calcium binding was decreased to 8% at a higher concentration of carbodiimide reagent (0.08M), the local anesthetics still inhibited the calcium binding, but were not competitive in nature. In other words, if concentrations of the carbodiimide reagent were raised, the degree of inhibition by the local anesthetics was gradually decreased and was not competitive in nature. Finally, no inhibition was demonstrated when the concentration of the reagent was 0.1 to 0.4M. The above findings, seem to suggest that local anesthetics such as procaine and lidocaine interact with carboxyl groups, in addition to phosphodiester groups of phospholipids as previously reported, and inhibited competitively calcium binding to carboxyl groups of the membrane fragments.
Anesthetics, Local/pharmacology* ; Calcium/metabolism* ; Carbodiimides/pharmacology* ; Cell Membrane/metabolism ; Erythrocytes/metabolism* ; Human ; In Vitro ; Protein Binding

The effect of drugs on calcium-binding to cardiac muscle membrane fragments and its turnover rate was studied. Ouabian, acetylcholine, isoproterenol and norepinephrine did not have any effect either on calcium-binding to membrane fragments or an washout ahnd release curves of previously bound calcium. Local anesthetics inhibited the calcium-binding. Tetracaine at concentrations of 1 and 10 mM inhibited the calcium-binding by 30% and 54%, respectively, while 10 mM lidocaine inhibited it by 17%. Propranolol, a well-known adrenergic beta-blocker, also inhibited calcium-binding at the external calcium concentration of 10(-3) M. This effect of propranolol may be attributed to its local anesthetic-like action, rather than to the adrenergic blocking effect.
Anesthetics, Local/pharmacology* ; Animal ; Calcium/metabolism* ; Cardiotonic Agents/pharmacology* ; Cell Membrane/metabolism ; In Vitro ; Myocardium/metabolism*

The effect of drugs on calcium-binding to cardiac muscle membrane fragments and its turnover rate was studied. Ouabian, acetylcholine, isoproterenol and norepinephrine did not have any effect either on calcium-binding to membrane fragments or an washout ahnd release curves of previously bound calcium. Local anesthetics inhibited the calcium-binding. Tetracaine at concentrations of 1 and 10 mM inhibited the calcium-binding by 30% and 54%, respectively, while 10 mM lidocaine inhibited it by 17%. Propranolol, a well-known adrenergic beta-blocker, also inhibited calcium-binding at the external calcium concentration of 10(-3) M. This effect of propranolol may be attributed to its local anesthetic-like action, rather than to the adrenergic blocking effect.
Anesthetics, Local/pharmacology* ; Animal ; Calcium/metabolism* ; Cardiotonic Agents/pharmacology* ; Cell Membrane/metabolism ; In Vitro ; Myocardium/metabolism*

BACKGROUND: Epidural clonidine reduces pain after surgery. The aim of this study was to evaluate the effect of adding low-dose clonidine to continuous epidural local anesthetics and fentanyl on pam relief. METHODS: 100 patients scheduled for gynecologic low abdominal surgery were investigated. All patients were given 10cc of 0.25% bupivacaine with fentanyl 100 ug through epidural catheter. Group I was infused with combined 0.15% bupivacaine and fentanyl 5 ug/ml at a rate of 2cc/hr. Group II was infused with combined 0.15% bupivacaine and fentanyl 5 ug/ml and 150 ug of clonidine at a rate of 2cc/hr. Pain was assessed on a visual analogue pain scale for 2 postoperative days. Changes in blood pressure, heart rate, and incidence of side effects were observed. RESULTS: VAS observed 20min, 1hr, 1day, 2days after operation were significantly lower in Group II than Group I . Blood pressure and heart rates were significantly changed in Group II but not in Group I for 2 hours after epidural injection. The incidence of side effects was similar between Group I and Group II. CONCLUSIONS: Continuous low-dose epidural clonidine infusion reduces blood pressure and heatt rates significantly but enhances postoperative analgesic effect of combined epidural bupivacaine and fentanyl without increased side effects.
Anesthetics ; Anesthetics, Local ; Blood Pressure ; Bupivacaine* ; Catheters ; Clonidine* ; Fentanyl* ; Heart Rate ; Humans ; Incidence ; Injections, Epidural ; Pain Measurement ; Pharmacology

The incidence of life-threatening anaphylactoid reactions during anesthesia has been increasing. Specific allergic reactions during anesthesia are usually due to muscle relaxants, barbiturates, local anesthetics, narcotics, radiocontrast media, antibiotics, and colloids. Thrombokinase, a hemostatic agent, has been used widely in clinical practice and severe anaphylactoid reactions to thrombokinase can occur rarely. We experienced two cases of anaphylactoid reactions after thrombokinase administration.
Anesthesia ; Anesthetics, Local ; Anti-Bacterial Agents ; Barbiturates ; Colloids ; Contrast Media ; Factor Xa* ; Hypersensitivity ; Incidence ; Narcotics ; Pharmacology

Local anesthetics at a concentration of 10 mM(procaine and lidocaine) were found to inhibit competitively Ca++ binding to lipidextracted RBC membrane, and also to egg albumin film fixed on cover glasses or impregnated into Whatman filter paper (No. 1). A competitive inhibition by local anesthetics was also found in Ca++ binding to Whatman filter paper which had been pretreated with organic solvents to extract possible contaminated lipids. Therefore, it is suggested that the local anesthetics inhibit Ca++ binding not only to phospholipids but to some macromolecules such as membrane proteins, egg albumin film and filter paper.
Anesthetics, Local/pharmacology* ; Calcium/metabolism* ; Cell Membrane Permeability/drug effects ; Erythrocytes/cytology* ; Filtration ; Human ; Lidocaine/pharmacology ; Ovalbumin/metabolism* ; Procaine/pharmacology

AIMTo study the cutaneous permeation kinetics and pharmacodynamics of lidocaine gel.

METHODSThe concentration of lidocaine in dermis following topical application in rats was determined by the cutaneous microdialysis technique and related parameters were calculated; the pharmacodynamics of the gel was evaluated by electric stimulation method with EMLA (eutectic mixture of local anesthetics) cream as a control.

RESULTSThe peak of percutaneous absorption kinetic profile of lidocaine gel across rat skin occurred at 1.25 h; the onset time of local anesthetic action of lidociane gel was similar to that of EMLA, but both the duration and depth of anesthetic effect were superior to EMLA cream.

CONCLUSIONLidocaine gel showed good anesthetic effect. The minimum effective concentration of lidocaine in dermis is 12 mg.L-1.

Anesthesia, Local ; Anesthetics, Local ; pharmacokinetics ; pharmacology ; Animals ; Gels ; Lidocaine ; pharmacokinetics ; pharmacology ; Male ; Pain Threshold ; drug effects ; Prilocaine ; pharmacokinetics ; pharmacology ; Random Allocation ; Rats ; Rats, Wistar ; Skin Absorption

OBJECTIVETo examine the effects of procaine and lidocaine on intracellular Ca(2+) release from sarcoplasmic reticulum ryanodine-sensitive Ca(2+) stores.

METHODSThe experiment was performed on hippocampal slices from 60-80 g male Mongolian gerbils. Levels of intracellular Ca(2+) concentration in the slices were measured by microfluorometry. The slices were perfused with 50 mmol/L KCl containing medium for 30 seconds. Then, the medium was switched to physiological medium. After 5 min of incubation, the slice was perfused with 20 mmol/L caffeine containing physiology medium for 2 min. Following incubation, the slice was superfused with physiological medium until the end of the experiment. The effects of procaine and lidocanin (100 micro mol/L) on caffeine-evoked Ca(2+) release were evaluated by adding them to the medium after high K(+) medium perfusion.

RESULTSCaffeine induced a marked increase in intracellular Ca(2+) concentration which was then decreased 12% upon the addition of procaine (P < 0.05); however, lidocaine, did not induce a similar inhibitory reaction.

CONCLUSIONProcaine inhibits ryanodine-receptor mediated Ca(2+) release from intracellular Ca(2+) stores, while lidocaine may inhibit Ca(2+) release through other mechanisms.

Anesthetics, Local ; pharmacology ; Animals ; Calcium ; metabolism ; Gerbillinae ; Hippocampus ; drug effects ; metabolism ; Lidocaine ; pharmacology ; Male ; Procaine ; pharmacology ; Ryanodine ; pharmacology ; Ryanodine Receptor Calcium Release Channel ; physiology

OBJECTIVETo study the effect of levobupivacaine and bupivacaine on the contractility of isolated uterine muscle strips from pregnant and non-pregnant female rats.

METHODSFull-thick myometrial strips were prepared from 18- to 21-day pregnant (n=8) and non-pregnant rats (n=7). After contractions became regular, strips were exposed to cumulative concentrations of the two drugs from 10(-8) to 10(-4) mol/L, amplitude and frequency of the uterine contraction was recorded.

RESULTSTwo local anesthetics caused a concentration dependent inhibition on contractility of myometrial strips from pregnant and non-pregnant rats. In the myometrium from non-pregnant rats, -logIC(50) of levobupivacaine and bupivacaine were 4.85 and 4.25 respectively. In the myometrium from pregnant rats, similar concentrations of levobupivacaine and bupivacaine were observed, -logIC(50) were 2.7 and 2.9 respectively. Levobupivacaine produced an increase in amplitude of contractions, while bupivacaine showed an increased trend in frequency.

CONCLUSIONThese results demonstrate that levobupivacaine and bupivacaine may inhibit myometrium contractility. The inhibitory effect of levobupivacaine or bupivacaine is not enhanced by gestation in rat. Levobupivacaine may have more positive influence than bupivacaine in pregnant myometrium.

Anesthetics, Local ; pharmacology ; Animals ; Bupivacaine ; analogs & derivatives ; blood ; pharmacology ; Dose-Response Relationship, Drug ; Female ; In Vitro Techniques ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Uterine Contraction ; drug effects