Lidocaine, inhibition

The local anaesthetics, tetracaine and lidocaine, inhibited both the release of lysosomal enzymes and the formation of O by PMNs but with variable... 

The sodium-channel inhibitor Amiloride is used for the treatment of chronic bronchitis, and the most frequently used anesthetic drug, lidocain, inhibits voltagegated sodium-channel a subunits, which mediate the pathophysiology of pain. 

Lenfant F, Lahet JJ. Vergely C, et al Lidocaine inhibits potassium efflux and hemolysis in erythrocytes... 

Although in vitro data suggested that lidocaine inhibited oxidative metabolism reactions mediated by the cytochrome P450 isoenzyme CYP2D6, a... 

Martinsson, T. Haegerstrand, A. Dalsgaard, C.J. Ropivacaine and lidocaine inhibit proliferation of non-transformed cultured adult human fibroblasts, endothelial cells and keratinocytes. Agents Actions 1993, 40 (1-2), 78-85. 

Topical anesthetics temporarily inhibit the conduction of impulses from sensory nerve fibers. These drug s may be used to relieve itching and pain due to skin conditions, such as minor bums, fungus infections, insect bites, rashes, sunburn, and plant poisoning, such as poison ivy. Some are applied to mucous membranes as local anesthetics. Examples of local anesthetics include benzocaine (Lanacane), dibucadne (Nupereainal), and lidocaine (Xylocadne). 

The existence of nitric oxide synthase (NOS) in phagocytes (see below) provides a different kind of stimulation and the inhibition of NADPH oxidase. It has been found [72] that the low physiological concentrations of peroxynitrite formed from NO and superoxide stimulated superoxide production by PMA-activated human PMNs through the ERK MAPK pathway, while higher peroxynitrite concentrations inhibited it. Moreover, NADPH oxidase was inhibited by lidocaine, a sodium-blocker, in OZ-activated neutrophils through the suppression of p47phox translocation [73]. 

Mechanism - Structurally like lidocaine, mexiletine inhibits the inward sodium current, thus reducing the rate of rise of the action potential. Phase 0. Mexiletine decreases the effective refractory period (ERP) in Purkinje fibers. The decrease in ERP is of lesser magnitude than the decrease in action potential duration (APD), with a resulting increase in ERP/APD ratio. 

Omeprazole can inhibit the metabolism of drugs metabolised mainly by the cytochrome P-450 enzyme subfamily 2C (diazepam, phenytoin), but not of those metabolished by subfamilies lA (caffeine, theophylline), 2D (metoprolol, propranolol), and 3A (ciclosporin, lidocaine (lignocaine), quinidine). Since relatively few drugs are metabolised mainly by 2C compared with 2D and 3A, the potential for omeprazole to interfere with the metabolism of other drugs appears to be limited, but the half lives of diazepam and phenytoin are prolonged as much as by cimetidine. 

Modified and reproduced, with permission, from Courtney KR Mechanism of frequency-dependent inhibition of sodium currents in frog myelinated nerve by the lidocaine derivative GEA. J Pharmacol Exp Ther 1975 195 225.)... 

Illyin, V.I. Comparative study of inhibition ofhSkMI sodium channels by Co102862, lidocaine and bupivacaine, Biophysical. J. 1999, 76, A82. 

The only other anesthetic to cause serious toxicity for which a metabolic drug interaction has been reasonably well characterized is the local anesthetic and antiarrhythmic agent lidocaine. Amiodarone decreased lidocaine systemic clearance in a patient (primarily by inhibition of CYP3A4 N-dealkylation of lidocaine) and yielded concentrations of lidocaine that led to seizures (78,79). 

Drugs metabolized by CYP that interact with cimetidine include, but are not limited to, the following lidocaine, quinidine, midazolam, triazolam, nifedipine, verapamil, and fentanyl (4). In each instance, inhibition of CYP by cimetidine results in reduced metabolic clearance and increases in serum concentrations of the other drug, which can lead to the expected toxicity and adverse experiences characteristic of the other drug. 

Recently, specific binding to sodium channels was demonstrated for the state-dependent sodium channel blocker [3H]BPBTS [105]. BPBTS is a potent blocker of all sodium channel subtypes tested, including native TTX-resistant channels expressed in mouse sensory neurons. Binding of [3H]BPBTS is inhibited by the local anesthetics tetracaine and lidocaine at concentrations known to interact with channels in the open and/or inactivated state. 

ADRENERGIC NEURONE BLOCKERS-GUANETHIDINE LOCAL ANAESTHETICS l clinical efficacy of guanethidine when used in the treatment of complex regional pain syndrome-type 1 The local anaesthetic i the reuptake of guanethidine Be aware. Consider use of a local anaesthetic that minimally inhibits reuptake, e.g. lidocaine when possible... 

BETA-BLOCKERS LIDOCAINE 1. Risk of bradycardia (occasionally severe), 1 BP and heart failure with intravenous lidocaine 2. Risk of lidocaine toxicity due to t plasma concentrations of lidocaine, particularly with propranolol and nadolol 3. t plasma concentrations of propranolol and possibly some other beta-blockers 1. Additive negative inotropic and chronotropic effects 2. Uncertain, but possibly a combination of beta-blocker-induced reduction in hepatic blood flow (due to 1 cardiac output) and inhibition of metabolism of lidocaine 3. Attributed to inhibition of metabolism by lidocaine 1. Monitor PR, BP and ECG closely watch for development of heart failure when intravenous lidocaine is administered to patients on beta-blockers 2. Watch for lidocaine toxicity 3. Be aware. Regional anaesthetics should be used cautiously in patients with bradycardia. Beta-blockers could cause dangerous hypertension due to stimulation of alpha-receptors if epinephrine is used with focal anaesthetic... 

CANNABIS ANAESTHETICS-LOCAL-LIDOCAINE Unpredictable changes in plasma concentrations. Risk of toxicity or therapeutic failure with intravenous lidocaine Induction or inhibition of CYP3A4-mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption Be aware. Watch for signs of toxicity, especially when cannabis use abruptly changes... 

Pharmacokinetic. Agents metabolised in the liver provide higher plasma concentrations when another drug that inhibits hepatic metabolism, e.g. cimetidine, is added. Enzyme inducers enhance the metabolism of this class of P-blockers. P-adrenoceptor blockers themselves reduce hepatic blood flow (fall in cardiac output) and reduce the metabolism of p-blockers and other drugs whose metabolic elimination is dependent on the rate of delivery to the liver, e.g. lignocaine (lidocaine), chlorpromazine. 

The many drug interactions described with cimetidine are largely attributable to inhibition of CYP isozymes or renal clearance of other drugs. Cimetidine also reduces hepatic blood flow and so can, for example, reduce the clearance of lidocaine. In the kidneys cimetidine interferes with the tubular excretion of procainamide and quinidine. Both effects are small, and the long list of drugs for which interference is demonstrable (Table 1) is out of all proportion to the number for which interference is of chnical significance. 

Some beta-blockers reduce hepatic blood flow and inhibit microsomal enzymes, reducing the clearance of lidocaine there is a clinically significant increase in the plasma concentration of lidocaine during concomitant propranolol therapy (75). 

Cimetidine inhibits the metabolism of lidocaine (76,77) and reduces protein binding, increasing toxicity. 

Various types of immunodepressant effects of local anesthetics can be detected by laboratory testing, although they may have no clinical significance. Lidocaine dose-dependently inhibits EA rosetting by human lymphocytes. In vitro depression of human leukocyte random motility and phagocytosis has also been reported (SED-11, 220) (41). 

Miller RD, Way WL. Inhibition of snccinylchoUne-induced increased intragastric pressnre by nondepolarizing muscle relaxants and lidocaine. Anesthesiology 1971 34(2) 185-8. 

The antiarrhythmic of choice for SuVT is lidocaine because of its fast onset and ease of administration. Lidocaine is a class IB antiarrhythmic that inhibits sodium ion channels, decreasing the action potential duration and effective... 

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