Antiarrhythmic Effectiveness of Intramuscular Lidocaine: Influence of Different Injection Sites

Schwartz, F.A.C.C. Mortimer L.; Meyer, M.B.; Covino, Benjamín G.; Narang, Ravinder M.; Sethi, Virender; Schwartz, Alison J.; Kamp, Paul

doi:10.1002/j.1552-4604.1974.tb02293.x

Cited by 47 publications

(13 citation statements)

References 8 publications

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“…As a result, antiarrhythmie efficacy has typicaIly been based on nonobjective criteria such as clinical judgementI° or on the basis of PVC rates obtained over short periods of time. 2,17 The limitations of such data are readily apparent, and for this reason no quantitative analysis of the plasma concentration-antiarrhythmic response relationship has been reported.…”

Section: Discussionmentioning

confidence: 98%

Response optimization of drug dosage: Antiarrhythmie studies with tocainide

Meffin

Winkle

Blaschke

et al. 1977

Clin Pharma and Therapeutics

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The benefits of using antiarrhythmic response to optimize dosage regimens of antiarrhythmic drugs in individual patients have been examined. Graded antiarrhythmic response and simultaneously measured plasma drug concentrations have been obtained in 15 patients receiving multiple oral doses of a new antiarrhythmic, tocainide. Plasma drug concentration-antiarrhythmic response data from each of 11 subjects responding to the drug have been fitted by a generalized concentration effect function which is valid over the entire range of response. With the use of experimentally determined pharmacokinetic parameters to define the dose-plasma concentration relationship and plasma drug concentration-response parameters estimated for individual patients, simulations were carried out to show the effect of various dosage regimens on antiarrhythmic response in individual patients. Such simulations provide a means of assessing antiarrhythmic effect in the range of clinical interest (80% to 100% of maximum effect), where the antiarrhythmic effect is a nonlinear function of dose, plasma drug concentration, or their logarithms. The simulations also demonstrate that for identical daily doses and dosing intervals patients show marked variability in antiarrhythmic response.

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Section: Discussionmentioning

confidence: 98%

Response optimization of drug dosage: Antiarrhythmie studies with tocainide

Meffin

Winkle

Blaschke

et al. 1977

Clin Pharma and Therapeutics

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“…For example, considerable interpatient variability in the clearance and protein binding of lignocaine has been reported and infusions of 24 hours or greater are associated with increasing concentrations in both normal volunteers and patients (Bauer et al 1982;LeLorier et al 1977;Prescott et al 1976;Sawyer et al 1981). There are also convincing data which document concentration-dependent protein binding of lignocaine (McNamara et al 1980;Tucker et al 1970), and this drug clearly exhibits a very steep concentration-effect relationship in at least some patient populations (Schwartz et al 1974). Like other basic lipophilic drugs, the free fraction of lignocaine is dependent upon the serum concentration of ai-acid glycoprotein (Routledge et al 1980a(Routledge et al , 1981a.…”

Section: Lignocaine (Lidocaine)mentioning

confidence: 89%

“…The accepted 'normal therapeutic range' of lignocaine (2 to 5 mgjL) is based primarily upon studies using whole blood concentrations (Gianelly et al 1967). Even though plasma concentrations would be expected to be up to 20% greater than whole blood concentrations (Tucker et al 1970), several other reports have confirmed that toxicity is more likely at plasma concentrations of greater than 5 mg/L and an inadequate response is likely at concentrations less than 1.5 to 2 mg/L (Buckman et al 1980;Deglin et al 1980;Schwartz et al 1974). However, there are several reports showing that the antiarrhythmic effect of lignocaine requires plasma concentrations of 6 mg/L or more in some subjects and that little or no toxicity is seen in these select populations (Alderman et al 1974).…”

Section: Lignocaine (Lidocaine)mentioning

confidence: 96%

Free Drug Concentration Monitoring in Clinical Practice

Svensson

Woodruff

Baxter

et al. 1986

Clinical Pharmacokinetics

169

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Recent advances in techniques to determine free drug concentrations have lead to a substantial increase in the monitoring of this parameter in clinical practice. The majority of drug binding to macromolecules in serum can be accounted for by association with albumin and alpha 1-acid glycoprotein. Albumin is the primary binding protein for acidic drugs, while binding to alpha 1-acid glycoprotein is more commonly observed with basic lipophilic agents. Alterations in the concentrations of either of these macromolecules can result in significant changes in free fraction. Diseases such as cirrhosis, nephrotic syndrome and malnourishment can result in hypoalbuminaemia. Burn injury, cancer, chronic pain syndrome, myocardial infarction, inflammatory diseases and trauma are all associated with elevations in the concentration of alpha 1-acid glycoprotein. Treatment with a number of drugs has also been shown to increase alpha 1-acid glycoprotein serum concentrations. A wide variety of biological fluids have been examined for their ability to provide an estimation of free drug concentration at receptor sites. The most useful fluid for estimating free drug concentrations appears to be plasma or serum, with subsequent treatment of the sample to separate free and bound drug by an appropriate technique. The two most widely used methods are equilibrium dialysis and ultrafiltration. Of these two, ultrafiltration has the greatest utility clinically because it is rapid and relatively simple. The major difficulty associated with this method involves the binding of drug to the ultrafilters, but significant progress has been made in solving this problem. Several authors have endorsed the routine use of free drug concentration monitoring. Data examining the clinical usefulness of free drug concentration monitoring for phenytoin, carbamazepine, valproic acid, disopyramide and lignocaine (lidocaine) are reviewed. While available evidence suggests that free concentrations may correlate with clinical effects better than total drug concentrations, there are insufficient data to justify the recommendation of the routine use of free drug concentration monitoring for any of these agents at present.

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“…A larger intramuscular dose of lignocaine (4 to 6 mg/ kg, mean of 450mg) results in therapeutic concentrations within 5 minutes and a longer duration of action, but produces CNS toxicity in the majority of patients (Zener et al 1973). Various sites for intramuscular injection have been studied, and injection into the deltoid muscle results in the most rapid and reliable attainment of therapeutic concentrations (Cohen et al 1972;Schwartz et al 1974).…”

Section: Absorptionmentioning

confidence: 99%

“…Gianelly et al (1967) measured whole blood lignocaine concentrations in patients with acute MI, and quoted a therapeutic range of 2 to 5 mg/L, but provided no reference or data on which this range was based. Reappearance of arrhythmia after intramuscular lignocaine was noted at an average concentration of 2 mg/L in plasma (Bellet et al 1971;Fehmers & Dunning 1972) or whole blood (Schwartz et al 1974). Singh and Kocot (1976) observed recurrence of arrhythmia at a median whole blood lignocaine concentration of 1.3 mg/L, while Sheridan et al (1977) observed arrhythmia return at a plasma concentration of 1.8 mg/L.…”

mentioning

confidence: 94%

The Pharmacokinetics of Lignocaine and β-Adrenoceptor Antagonists in Patients with Acute Myocardial Infarction

Nattel

Gagne

Pineau

1987

Clinical Pharmacokinetics

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Lignocaine (lidocaine) and beta-adrenoceptor antagonists are widely used after acute myocardial infarction. The therapeutic value of these agents depends on the achievement and maintenance of safe and effective plasma concentrations. Lignocaine pharmacokinetics after acute myocardial infarction (MI) are controlled by a number of variables. The single most important is left ventricular function, which affects both volume of distribution and plasma clearance. Other major factors include bodyweight, age, hepatic function, the presence of obesity, and concomitant drug therapy. Lignocaine is extensively bound to alpha 1-acid glycoprotein, a plasma protein which is also an acute phase reactant. Increases in alpha 1-acid glycoprotein concentration occur after an acute MI, decreasing the free fraction of lignocaine in the plasma and consequently decreasing total plasma lignocaine clearance without altering the clearance of non-protein-bound lignocaine. Complex changes in lignocaine disposition occur with long term infusions, and therefore early discontinuation of lignocaine infusions (within 24 hours) should be undertaken whenever possible. Because the risk of ventricular tachyarrhythmia declines rapidly after the onset of an acute MI, lignocaine therapy can be rationally discontinued within 24 hours in most patients. Lignocaine has a narrow toxic/therapeutic index, so that pharmacokinetic factors are critical in dose selection. In contrast, beta-adrenoceptor antagonists' adverse effects are more related to the presence of predisposing conditions (such as asthma, heart failure, bradyarrhythmias, etc.) than to plasma concentration. The pharmacokinetics of beta-adrenoceptor antagonists are important to help assure therapeutic efficacy, to provide information about the anticipated time course of drug action, and to predict the possible role of ancillary drug effects (such as direct membrane action) and loss of cardioselectivity. Lipid solubility is the main determinant of the pharmacokinetic properties of a beta-adrenoceptor antagonist. Lipid-soluble agents like propranolol and metoprolol are well absorbed orally, and undergo rapid hepatic metabolism, with important presystemic clearance and a short plasma half-life. Water-soluble drugs like sotalol, atenolol, and nadolol are less well absorbed, and are eliminated more slowly by renal excretion. Clinical assessment of beta-adrenoceptor antagonism is more valuable than plasma concentration determinations in evaluating the adequacy of the dose of a particular beta-adrenoceptor antagonist.(ABSTRACT TRUNCATED AT 400 WORDS)

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Antiarrhythmic Effectiveness of Intramuscular Lidocaine: Influence of Different Injection Sites

Cited by 47 publications

References 8 publications

Response optimization of drug dosage: Antiarrhythmie studies with tocainide

Response optimization of drug dosage: Antiarrhythmie studies with tocainide

Free Drug Concentration Monitoring in Clinical Practice

The Pharmacokinetics of Lignocaine and β-Adrenoceptor Antagonists in Patients with Acute Myocardial Infarction

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