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Biomedical subjects

G D Dunham

Publications and source records attributed to G D Dunham.

5 recordsLinked to original sources

Therapeutic range of digoxin's efficacy in heart failure: what is the evidence?

Clinical studies have solidified the utility of digoxin in patients with left ventricular dysfunction and normal sinus rhythm. No definitive data have been published to clarify the range of serum digoxin concentrations associated with clinical benefit. The traditional therapeutic range of 0.8-2.0 ng/ml was developed originally to classify digoxin toxicity, not efficacy. In addition, this reference range was used before publication of the Digitalis Investigators Group trial. Clinical and neurohormonal studies have attempted to characterize serum concentrations that are associated with clinical efficacy.

Cardiotonic Agents↗

Plasma concentrations of diltiazem and desacetyldiltiazem in an overdose situation.

OBJECTIVE: To describe the elimination of diltiazem and desacetyldiltiazem in an overdose situation. CASE SUMMARY: An 18-year-old woman ingested controlled delivery diltiazem 14.94 g in a suicide attempt. After arriving at the hospital unresponsive and hypotensive, her condition progressed to complete heart block, cardiogenic shock, asystole, and acute renal failure. Supportive care consisted of vasopressors, intravenous calcium, intravenous glucagon, charcoal hemoperfusion, temporary transvenous pacing, and an intraaortic balloon pump. After 12 days in the hospital, the patient recovered fully. DISCUSSION: We report a large, documented overdose of diltiazem and detail the pharmacokinetic profiles of both diltiazem and its active metabolite, desacetyldiltiazem. Nonlinear elimination of diltiazem appears to occur at higher concentrations. Although the patient improved clinically following charcoal hemoperfusion, no dramatic effects on diltiazem elimination were apparent. CONCLUSIONS: Survival following massive diltiazem overdose can be achieved with supportive care. Charcoal hemoperfusion had a limited effect on improving the clearance of diltiazem as evidenced by serial plasma concentrations.

Adolescent↗

Clinical and pharmacokinetic profiles of digoxin immune Fab in four patients with renal impairment.

Minimal pharmacokinetic data on digoxin immune Fab are currently available, especially in patients with impaired renal function. The serum concentration-time profiles of total digoxin, free digoxin, and digoxin immune Fab in four patients with moderate to severe renal impairment who received digoxin immune Fab are presented. The calculated elimination half-life of digoxin immune Fab was 25-73 hours. The calculated elimination half-life of total digoxin was 24-72 hours. Free digoxin concentrations rebounded to a peak of 1-2.9 ng/mL 44-97 hours after the administration of digoxin immune Fab. The areas under the curve for digoxin immune Fab were 213-1026 micrograms.h/mL, and total body clearances were 2.3-7.1 mL/min. The total digoxin concentrations peaked at 14-33 times the pre-Fab digoxin concentrations 5-30 hours after digoxin immune Fab administration. In comparing these data with data available from patients with normal renal function, the half-life of digoxin immune Fab and total digoxin was longer, the peak total digoxin concentration occurred later, the ratio of the peak total digoxin concentration to pre-Fab digoxin concentration was larger, and the rebound in free digoxin occurred later in patients with renal impairment. The Fab dose should not be reduced in patients with renal impairment; however, post-Fab monitoring should be extended to compensate for the prolonged half-life of Fab and later rebound of free digoxin.

Adult↗

Treatment of digitalis intoxication with emphasis on the clinical use of digoxin immune Fab.

Many studies and cases of digitalis intoxication have been reported since the time of William Withering's first publication in 1785. Recognition and management of digitalis toxicity is challenging. Before digoxin immune Fab was commercially available, treatment consisted of managing the signs and symptoms of toxicity until the digitalis was eliminated. Digoxin immune Fab offers a safe, effective, and specific method of quickly reversing digitalis toxicity. Factors that must be considered with the clinical use of this agent include the dosage calculation, administration technique, postdose monitoring, pharmacokinetics, mechanism of action, interference with commercially available digoxin assays, partial neutralizing dosing, rebound of free digoxin, and indications for use. For severe, life-threatening toxicity, digoxin immune Fab is the treatment of choice.

Animals↗

Digoxin toxicity: an evaluation in current clinical practice.

BACKGROUND: Serum digoxin concentrations (SDCs) are frequently sampled before completion of drug distribution. If elevated, these concentrations may be misinterpreted, potentially leading to a misdiagnosis of digoxin toxicity. OBJECTIVES: To determine the frequency of elevated SDCs (>2.6 nmol/L [>2.0 ng/mL]) obtained at appropriate postdosing intervals and to evaluate the frequency of clinically defined digoxin toxicity in patients with elevated SDCs. METHODS: The medical records of adult patients with SDCs assayed at 5 general hospitals in North Carolina during a 3-month period (May 1 through July 31, 1996) were prospectively evaluated. Data on SDC, inpatient or outpatient status, and medical or surgical service were collected for all patients. Data on patient demographics, serum chemistry values, indication for digoxin treatment, clinical evidence of digoxin toxicity, and timing of the blood sample relative to administration of the last dose of digoxin were collected for patients with SDCs higher than 2.6 nmol/L (>2.0 ng/mL). RESULTS: Of 3434 SDCs assayed in 2009 patients, 320 (9.3%) were higher than 2.6 nmol/L (>2.0 ng/mL). Fifty-one (15.9%) of the 320 SDCs were drawn at 6 hours or less following a digoxin dose. Sampling time relative to the digoxin dose could not be determined in 70 (21.9%) of the 320 elevated SDCs, leaving 199 (62.2%) of 320 SDCs in 138 patients evaluable for digoxin toxicity. Eighty-three of the 138 patients had clinical evidence of digoxin toxicity for an overall incidence of 4.1%. CONCLUSIONS: Digoxin toxicity occurs less frequently than historically reported. Continued emphasis needs to be placed on obtaining appropriately timed SDCs.

Adult↗