Digoxin remains one of the most commonly prescribed of all cardiac medications. The main indications for digoxin usage include atrial fibrillation and heart failure; both these conditions are more prevalent in older patients. Given the aging population and the increasing incidence of heart failure we would expect prescribing of digoxin to remain as frequent or to even increase in older patients. Older patients are also more likely to develop toxicity and diagnosis of digoxin toxicity can be difficult in this group. Numerous components contribute to the development of toxicity in older patients, ranging from aging-related changes in renal function or body mass to polypharmacy and possible interactions with digoxin. It is therefore important to understand how the pharmacokinetics of digoxin may be altered in the older population. Application of basic pharmacological principles may be helpful in anticipating these problems. This review describes the pharmacokinetics of digoxin, the changes in pharmacokinetics with increasing age and how concomitant disease states or drug interactions may affect the pharmacokinetics of digoxin. Greater knowledge about the causes and prevention of digoxin toxicity should further reduce the morbidity and mortality arising from digoxin toxicity, especially in the elderly population.
Background: Ischaemic heart disease (IHD) is a complex disease due to the combination of environmental and genetic factors. Mutations in the MEF2A gene have recently been reported in patients with IHD. In particular, a 21 base pair deletion (Δ7aa) in the MEF2A gene was identified in a family with an autosomal dominant pattern of inheritance of IHD. We investigated this region of the MEF2A gene using an Irish family-based study, where affected individuals had early-onset IHD.
We report the first documented case in the literature of hereditary angioedema presenting after commencement of estrogen replacement therapy for menopausal symptoms. The late presentation of the disease and the precipitation of attacks by physiological doses of estrogen replacement therapy make this a highly unusual case. The pathophysiology of hereditary angioedema and its hormonal links are discussed.
The possible role of the K469E polymorphism in the intercellular adhesion molecule-1 (ICAM-1) gene in the susceptibility to ischaemic heart disease (IHD) was investigated in a well-defined Irish population using two recently described family-based tests of association. One thousand and twelve individuals from 386 families with at least one member prematurely affected with IHD were genotyped for the ICAM-1 K469E polymorphism. Using the combined transmission disequilibrium test (TDT)/sib-TDT and the pedigree disequilibrium test (PDT), no association between the ICAM-1 K469E polymorphism and IHD was found. Our data demonstrate that, in an Irish population, the ICAM-1 K469E polymorphism is not associated with IHD.
A 45-year-old woman with a 5-year history of treated essential hypertension presented with a 2-month history of exertional dyspnea and a 2-week history of intermittent palpitations. Two weeks earlier, she presented to the emergency department of another hospital with palpitations, but these had terminated on arrival. She was told her ECG displayed "low voltages." During the next 2 weeks, she became increasingly dyspneic, feeling short of breath most of the time. She had a sensation of fullness in the chest, frequent palpitations, and ankle edema, so she was referred to a cardiologist. An echocardiogram revealed the presence of a large blood-filled sac markedly compressing the right heart ( Figure 1A through 1C). A CT scan of the thorax confirmed the presence of this sac, which measured 9.6 cm maximum diameter (Figure 2). A differential diagnosis of a sinus of Valsalva aneurysm, a giant right coronary artery aneurysm, or a pseudoaneurysm of the aortic sinus was made. She was referred for surgery because of the severity of her right heart compression and the possibility of rupture of the blood-filled sac. Surgical exploration confirmed that the sac was a true right coronary artery aneurysm, communicating proximally with the right coronary artery ostium and distally with the distal right coronary artery (Figure 3). The right coronary artery was ligated proximally, the aneurysm was excised, and a saphenous vein conduit grafted to the distal vessel. Postoperatively, the patient complained of excessive fatigue and occasional swelling of the ankles. Echocardiography revealed mildly impaired right ventricular function with moderate tricuspid regurgitation. Cardiac catheterization confirmed these findings, but because the right atrial pressure remained low (V wave is 8 mm Hg), we elected to continue with medical management initially.
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