Lidocaine clearance

In patients with heart failure, lidocaine s volume of distribution and total body clearance may both be decreased. Thus, both loading and maintenance doses should be decreased. Since these effects counterbalance each other, the half-life may not be increased as much as predicted from clearance changes alone. In patients with liver disease, plasma clearance is markedly reduced and the volume of distribution is often increased the elimination half-life in such cases may be increased threefold or more. In liver disease, the maintenance dose should be decreased, but usual loading doses can be given. Elimination half-life determines the time to steady state. Thus, although steady-state concentrations may be achieved in 8-10 hours in normal patients and patients with heart failure, 24-36 hours may be required in those with liver disease. Drugs that decrease liver blood flow (eg, propranolol, cimetidine) reduce lidocaine clearance and so increase the risk of toxicity unless infusion rates are decreased. With infusions lasting more than 24 hours, clearance falls and plasma concentrations rise. Renal disease has no major effect on lidocaine disposition. 

Ochs HR, Carstens G, Greenblatt DJ. Reduction in lidocaine clearance dmmg continuous infusion and by coadministration of propranolol. N Engl J Med 1980 303(7) 373-7. 

E Congestive heart failure. Lidocaine is cleared by liver metabolism. Any condition that deaeases liver metabolism or liver blood flow may increase lidocaine levels. If a patient has CHF, advanced age, shock, or liver cirrhosis, a lower infusion rate should be considered. Diabetes, atrial flutter, tachycardia, and sodium levels are unlikely to affect hepatic blood flow or lidocaine clearance. 

Branch, R.A., Shand, D.G., Wilkinson, G.R. Nies, A.S. (1973) The reduction of lidocaine clearance by di-propranolol an example of hemodynamic drug interaction. Journal of Pharmacology and Experimental Therapeutics, 184, 515-519. 

A) The patient s lidocaine volume of distribution is half the average value The patient s lidocaine clearance is twice the average value The patient s lidocaine half-life is four times the average value The patient s infusion rate was accidentally decreased by half The laboratory made a mistake in the assay for lidocaine A patient requires an infusion of procainamide. Its half-life is 2 hours. The infusion is begun at 9 AM. At 1 PM the same day a blood sample is taken the drug concentration is found to be 3 mg/L. What is the probable steady-state drug concentration, eg, after 48 hours of infusion ... 

Schneck DW, Luderer JR, Davis D, Vary J. Effects of nadolol and propranolol on plasma lidocaine clearance. Clin Pharmacol 77ier(1984) 36, 584-7. 

Lidocaine (112), xyloceiine, and dibucaine (113) have been formulated in homo- and copolymers of lactide and glycolide. The goal of these studies has been relatively short-term (24-hr) controlled release of the anesthetic. Injectable microcapsules of lidocaine hydrochloride were produced by an air suspension coating technique and administered i.m. to rabbits (112). Serum levels of Udocaine indicated an initial rise over the first 2 hr and then a gradual decline with clearance after about 8-10 hr. 

The concurrent administration of lidocaine with cimeti-dine but not ranitidine may cause an increase (15%) in the plasma concentration of lidocaine. This effect is a manifestation of cimetidine reducing the clearance and volume of distribution of lidocaine. The myocardial depressant effect of lidocaine is enhanced by phenytoin administration. 

Cardiac failure may also affect metabolism by altering hepatic blood flow. However, even after heart attack without hypotension or cardiac failure, metabolism may be affected. For example, the plasma clearance of lidocaine is reduced in this situation. Other diseases such as those, which affect hormone levels hyper-or hypothyroidism, lack of or excess growth hormone, and diabetes can alter the metabolism of foreign compounds. 

Lidocaine [NE] Decreased clearance of intravenous idocaine increased plasma lidocaine levels. 

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. 

MEXILETINE LIDOCAINE Mexiletine t lidocaine levels (with cases of toxicity when lidocaine is given intravenously) Mexiletine displaces lidocaine from its tissue-binding sites it also seems to l its clearance but the exact mechanism is uncertain at present Watch for the early symptoms and signs of lidocaine toxicity (perioral paraesthesia, T muscle tone)... 

Williams RL, Blaschke TF, Meffin PJ, Melmon KL, Rowland M. Influence of viral hepatitis on the disposition of two compounds with high hepatic clearance Lidocaine and indocyanine green. Clin Pharmacol Ther 1976 20 290-9. 

Patients with liver disease have an increased susceptibility to certain drugs due to decreased hepatic clearance for drugs metabolized by the liver or due to enhanced sensitivity. For example, impaired hepatic metabolism can precipitate central nervous system (CNS) toxicity in patients on theophylline, phenytoin, or lidocaine or ergot poisoning on ergotamine. ... 

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). 

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