Therapeutic Drug Monitoring of Antiarrhythmic Agents

Brown, James E.; Shand, David G.

doi:10.2165/00003088-198207020-00003

Cited by 28 publications

(9 citation statements)

References 117 publications

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“…From the above data, the therapeutic range of lignocaine serum concentrations has been accepted as 2.0 to 5 mg/L (Brown and Shand, 1982;Follath 11 et aI., 1983). Although it is clear that most patients n~ed concentrations > 2.0 mg/L for a salutary response, one should remember that efficacy may require concentrations higher than the usual upper limit if toxicity can be avoided.…”

Section: Correlation Of Serum Concentrations With Clinical Responsementioning

confidence: 99%

Comparison of Drug Dosing Methods

Burton

Vasko

Brater

1985

Clinical Pharmacokinetics

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The literature reviewed herein clearly demonstrates the poor correlation between drug dosing and the ability to achieve a specific serum drug concentration and between drug dosing and clinical response, especially for drugs with a narrow therapeutic index. There is, however, a better correlation between serum drug concentration and observed clinical response. Thus, clinicians use serum drug concentrations to more accurately dose drugs. Numerous dosing methods have been developed in an attempt to improve the relationship between dosing, serum drug concentration, and response. The major hypothesis is that if dosing methods can be developed that will accurately predict serum drug concentrations, these methods would be useful in improving clinical care. Several dosing methods have been developed including use of 'standard' doses, population-based predictive algorithms and nomograms, pharmacokinetic equations, and Bayesian feedback. Some of these methods are accurate and useful, whereas others are not. This review evaluates the commonly used dosing methods (some of which utilise serum drug concentration feedback for dosage estimation) for 5 drugs: gentamicin, digoxin, phenytoin, theophylline, and lignocaine (lidocaine). These drugs were selected since they exhibit a representative cross section of pharmacokinetic parameters and since they exhibit a representative cross section of pharmacokinetic parameters and since they have narrow therapeutic ranges. An individualised method and a Bayesian method, both using serum drug concentration feedback, appear most accurate and precise in dosing to achieve desired serum drug concentrations and, hence, response. Our bias from personal experience with this method and from published use by others is that the Bayesian method is more flexible in that any number of serum drug concentrations may be used to determine dose, instead of the 3 or more required for the individualised method. Although use of these methods would appear to be cost-effective in timely provision of health care by reduction of toxicity and hospital stay, only sparse data have been generated to support this conclusion. Thus, further examination of the cost-effectiveness of drug dosing methods is necessary to establish their place in routine patient care.

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Section: Correlation Of Serum Concentrations With Clinical Responsementioning

confidence: 99%

Comparison of Drug Dosing Methods

Burton

Vasko

Brater

1985

Clinical Pharmacokinetics

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“…The commonly accepted therapeutic plasma concentration range for procainamide is 4 to 10 J.Lg/ ml (Brown and Shand, 1982). However, one study has shown that plasma procainamide concentrations as high as 33 J.Lgjml may be required to suppress recurrent ventricular tachycardia in some patients and can be tolerated well (Greenspan et aI., 1980).…”

Section: J Pharrnacokinetic Propertiesmentioning

confidence: 99%

“…Rapid acetylators achieve plasma concentrations that may be therapeutic within 24 hours, but these patients also have lower plasma concentrations of procainamide (Crawford et a\., 1982;Lima et a\., 1978). The contribution of NAPA to the therapeutic effect of a given dose of procainamide is therefore varied and difficult to quantitate (Brown and Shand, 1982). There are currently no data demonstrating that a change in procainamide dose during the first 24 hours of therapy is required based on a patient's acetylator status.…”

Section: J Pharrnacokinetic Propertiesmentioning

confidence: 99%

Pharmacokinetic and Pharmacodynamic Considerations in Drug Therapy of Cardiac Emergencies

Pentel

Benowitz

1984

Clinical Pharmacokinetics

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In the drug therapy of cardiac emergencies, it is necessary to rapidly achieve therapeutic drug concentrations and adjust drug dose as the patient's clinical status changes. Cardiac dysfunction is often present and may alter drug pharmacokinetics. Circulatory failure causes sympathetically mediated vasoconstriction in most tissues, with relative sparing of the brain and heart due to autoregulation. Blood flow to vasoconstricted tissues is reduced, and the available cardiac output is redistributed so that the heart and brain receive a greater fraction. Drug distribution to tissues is therefore slowed, and the initial concentration of drug in blood is higher when circulatory failure is present than when it is absent. This higher blood concentration is reflected by higher concentrations of drug in the brain and heart, which are relatively well perfused. Initial doses of many drugs need to be reduced in patients with circulatory failure to prevent cardiac or central nervous system toxicity. Cardiac output is markedly diminished during cardiopulmonary resuscitation (CPR), but blood flow distribution is qualitatively similar to that of circulatory failure with spontaneous circulation. Pneumatic trousers increase lower extremity vascular resistance and may produce a similar redistribution of blood flow. Drug distribution during the use of CPR or pneumatic trousers should be similar to that of circulatory failure with spontaneous circulation, but few data are available to guide drug dosing during the use of these interventions. Animal data suggest that the central volume of distribution of some drugs during CPR may be as small as one-tenth of normal. Drug metabolism in circulatory failure may be impaired by reduced hepatic blood flow resulting in decreased clearance of highly extracted drugs, or by hepatocellular dysfunction resulting in decreased clearance of poorly extracted drugs. Drug excretion may be impaired by reduced renal blood flow resulting in decreased filtration or secretion and increased reabsorption. The maintenance dose of many drugs must therefore be reduced in the presence of circulatory failure. Intravenous drug administration is preferred in patients with circulatory failure. The central intravenous route is often convenient but must be used cautiously when administering potentially cardiotoxic drugs. Intratracheal administration appears to be a promising alternative for some drugs, such as adrenaline (epinephrine). Intracardiac injections are hazardous and offer no demonstrated advantage over other routes.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…The therapeutic plasma concentration range has not been definitely established, but recent reviews of the literature point to lower and upper limits of approximately 2-3 mg/l (6-9 umol 1) and 5-6 mg,l (15-18 ,Amol l), respec-tively (Brown & Shand, 1982;Garfein, 1982;Kates, 1980). Intravenous dosing schedules for the treatment of ventricular arrhythmias associated with acute myocardial infarction are designed with the aim of rapidly attaining therapeutic plasma concentrations.…”

Section: Introductionmentioning

confidence: 99%

Sustained release disopyramide compared to plain capsules after change‐ over from intravenous infusion.

Lien¹,

Om²

1983

Brit J Clinical Pharma

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I The plasma concentration profile of disopyramide was examined in 13 patients with arrhythmias following acute myocardial infarction.2 Intravenous loading doses of 1.5 mg/kg followed by 0.7 mg/kg and then infusion of 0.3 mg kg-lh-1 resulted in final concentrations between 2.4 and 4.9 mgA1.3 Change-over to oral therapy with disopyramide sustained release (SR) tablets was smooth, and therapeutic plasma concentrations were maintained throughout. 4 Comparison of the plasma concentrations in a subsequent cross-over study with disopyramide plain capsules 150 mg every 6 h and SR tablets 250 mg every 12 h, each being administered for 3 days to attain a steady state, showed that the bioavailability and the variation of the plasma concentration were similar with both regimens. 5 In patients with body weight between 62 and 92 kg disopyramide SR tablets 250 mg every 12 h matched the preceding infusion rate of 0.3 mg kg-'h-I resulting in plasma concentrations close to steady state already on the first day of oral therapy. 6 The absorption of disopyramide SR tablets is only moderately delayed, and the preparation can be used twice daily in direct succession of intravenous infusion.

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Therapeutic Drug Monitoring of Antiarrhythmic Agents

Cited by 28 publications

References 117 publications

Comparison of Drug Dosing Methods

Comparison of Drug Dosing Methods

Pharmacokinetic and Pharmacodynamic Considerations in Drug Therapy of Cardiac Emergencies

Sustained release disopyramide compared to plain capsules after change‐ over from intravenous infusion.

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