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Biomedical subjects

D W Holt

Publications and source records attributed to D W Holt.

At least 163 records · Page 9Linked to original sources
PubMed1984

Management of cardiac drug overdose.

Although overdoses from cardiac drugs are uncommon, these are compounds with narrow therapeutic indices and they may give rise to serious acute toxicity from accidental, deliberate or even iatrogenic overdosage. Through the National Poisons Information Service for England and the Poisons Unit laboratory, we monitor reports of serious toxicity from this group of drugs and use the information gained to assess our recommendations for treatment. This article reviews the toxicity and the management of overdosage with digoxin and representative drugs from each class of anti-arrhythmic drugs. From these observations, a general plan of management applicable to all cardiac drugs is proposed and its is suggested that this form of monitoring should be continued.

Adrenergic beta-Antagonists↗
PubMed1984

A study to compare the efficacy, plasma concentration profile and tolerability of conventional mexiletine and slow-release mexiletine.

In order to evaluate and compare slow-release mexiletine 360 mg 12 hourly and conventional mexiletine 200 mg 8 hourly, twelve patients with symptomatic ventricular arrhythmias have been studied. Ambulatory electrocardiographic monitoring was performed before treatment and at the end of two, two week long treatment periods during which slow-release mexiletine and conventional mexiletine were administered in random order. On the last day of each treatment period frequent blood samples for drug assay were collected during a dosage interval. Each formulation produced greater than 70% suppression of ventricular ectopic beats in 55% of patients. The variation between pre-dose and observed peak plasma concentration was 29.6% with slow-release mexiletine and 71.6% with mexiletine (P less than 0.01). The time from pre-dose to observed peak concentration was 4.0 h (+/- 1.6 SD) with slow-release mexiletine and 2.0 h (+/- 1.8 SD) with conventional mexiletine (P less than 0.05). Three patients were withdrawn from the study in the first treatment period because of central nervous system or gastric adverse effects. Overall, side-effects were marginally fewer on therapy with slow-release mexiletine. We conclude that, in the nearest equivalent dosage, the slow-release formulation is as effective as conventional mexiletine and at least as well tolerated. The fluctuations in plasma mexiletine concentration are less marked on the slow-release preparation despite the longer dosage interval, which allows effective oral therapy with a twice daily dosage.

Administration, Oral↗
PubMed1984

The pathogenesis of amiodarone-induced pigmentation and photosensitivity.

A new method has been used to measure tissue levels of amiodarone and its major metabolite desethylamiodarone. Amiodarone-pigmented skin has a drug and metabolite concentration ten times that of non-pigmented skin. Iodine-rich amiodarone and its metabolite have been detected in secondary lysosomes by energy dispersive analysis of X-rays. Amiodarone induces a phototoxic reaction with an action spectrum in both the UV-B and UV-A wavelengths.

Adult↗
PubMed1983

Amiodarone pharmacokinetics.

The single-dose pharmacokinetics of amiodarone have been studied in volunteer subjects given 400 mg doses by the intravenous and oral routes. The data show the compound to have a very large volume of distribution, a low total clearance, and a long and variable terminal elimination half-life. In patients the terminal elimination half-life was on the order of 40 days, with a more rapid phase of elimination in the first few days following the withdrawal of therapy. The terminal elimination half-life of desethylamiodarone was longer than that of the parent compound. High concentrations of amiodarone and its desethyl metabolite were found in tissue samples, with fat forming a potentially large tissue reservoir of the drug.

Adipose Tissue↗
PubMed1983

High-performance liquid chromatographic measurement of atenolol: methodology and clinical applications.

A simple high-performance liquid chromatographic method has been developed for the measurement of atenolol in plasma, breast milk, and urine. The sample (250 microliters) is Vortex-mixed for 30 s with approximately 50 mg sodium chloride, 10 mol/L sodium hydroxide solution (50 microliters), internal standard solution (aqueous benzimidazole, 1.69 mumol/L) (50 microliters) and methyl-tert-butyl ether containing 10% (vol/vol) heptafluorobutanol (200 microliters). After centrifugation (9950 X g, 2 min), a portion (100 microliters) of the resulting extract is analysed on a microparticulate (5 micron) silica column using methanol containing 1 mmol/L d-10-camphorsulphonic acid monohydrate as the mobile phase, and the column effluent is monitored by fluorescence detection using an excitation wavelength of 195 nm. A specimen, together with a quality control sample, can be analysed in duplicate within 30 min. The limit of accurate measurement of the assay is 20 micrograms/L, no endogenous sources of interference have been observed and interference from other drugs is minimal.

Adult↗
PubMed1983

Evaluation of fetal arrhythmias by echocardiography.

The normal fetal heart shows variation in rate and rhythm. Twenty three cases that fell outside the normal patterns of variation of heart rate and rhythm were evaluated by echocardiography. Ten showed atrial or ventricular extrasystoles and these were not associated with perinatal morbidity or mortality. Seven cases showed complete heart block, two in association with structural cardiac abnormality. Six cases were of supraventricular tachycardia, five of which were successfully treated and one was delivered prematurely. It was possible to diagnose accurately the type of arrhythmia using the M-mode echocardiogram to compare the relation between atrial and ventricular contraction. Cross-sectional echocardiography allowed identification of associated structural abnormalities. Recognition that an arrhythmia is present and appropriate prenatal treatment if this is indicated will avoid unnecessary operative or premature deliveries.

Arrhythmias, Cardiac↗
PubMed1983

High-performance liquid chromatographic measurement of amiodarone and desethylamiodarone in small tissue samples after enzymatic digestion.

A method is described for the measurement of amiodarone and desethylamiodarone in small tissue samples. With the exception of fat, for which lipase is used, the tissues are digested with a proteolytic enzyme. After the addition of an internal standard the analytes are extracted from the homogeneous digest into an organic solvent and measured by high-performance liquid chromatography (HPLC) with UV detection at 240 nm. The method shows good reproducibility using tissue samples as small as 20 mg and suggests extensive accumulation of both compounds in some tissues, with particularly high concentrations in tissues associated with adverse effects of the drug.

Adipose Tissue↗
PubMed1983

Renal elimination of amiodarone and its desethyl metabolite.

Two patients in chronic renal failure receiving amiodarone for the treatment of refractory arrhythmias were commenced on dialysis, in one case, intermittent peritoneal dialysis, in the other, haemodialysis. Plasma concentrations of amiodarone and its desethyl metabolite were consistent with the dose received, whilst neither compound was recovered in the dialysate. In these patients and in 10 additional patients with normal renal function taking amiodarone, only negligible amounts of either compound were detected in urine. These findings suggest that amiodarone may be a suitable antiarrhythmic agent for use in patients with chronic renal failure.

Amiodarone↗
PubMed1983

Absorption and antiarrhythmic efficacy of sustained-release mexiletine.

Absorption of the antiarrhythmic agent mexiletine from conventional capsules (200 mg) and two sustained-release formulations (360 and 432 mg) was studied in four healthy volunteer subjects, and use of the 360-mg preparation was studied in nine patients who had been using conventional capsules. In the four volunteers, acute dosage with the 432-mg preparation produced a markedly lower peak mexiletine concentration and fewer side effects than did two 200-mg capsules. Chronic dosing in two volunteers, which indicated that the 360-mg preparation produced fewer side effects and lower predose and peak plasma mexiletine concentrations than did the 432-mg preparation, suggested the use of equivalent doses of the 360-mg preparation in the nine patients who had been using 100-, 200-, or 250-mg preparations. The arrhythmia control produced by the slow-release preparation, as measured by 24-hour ECGs, was comparable to that produced by the conventional forms of mexiletine; gastrointestinal side effects were less marked when patients took the slow-release preparation, despite higher mean predose plasma mexiletine concentrations associated with use of the 360-mg preparation. Reduced frequency of daily dosage as well as patient acceptance are clinical advantages of the slow-release preparation.

Absorption↗