Clinical Pharmacokinetics of Drugs in Patients with Heart Failure

Abstract

Heart failure is one of the leading causes of death in developed countries, and its prevalence is expected to increase further in the coming years. While the pharmacokinetic changes observed in patients with heart failure have been reviewed twice in Clinical Pharmacokinetics, approximately a quarter century has passed since the latest article was published in 1988. Since then, many important classes of agents (e.g. ACE inhibitors, angiotensin receptor antagonists and inotropes) have been introduced for the treatment of heart failure. The aim of the present article is to update the information regarding the pharmacokinetics of these drugs. For this purpose we have made a systematic survey of literature using MEDLINE, EMBASE and Japan Centra Revuo Medicina (in Japanese) and found a total of 111 relevant publications for 58 drugs. Heart failure is a pathophysiological state where the damaged heart, from whatever causes, no longer pumps enough blood for the needs of body tissues at rest or during the normal daily activities. The spectrum of heart failure ranges from acute decompensated heart failure (including circulatory shock) to chronic compensated or decompensated heart failure. Because hypoperfusion of organs may influence drug absorption from the gastrointestinal tract, distribution into tissues and elimination either by the liver or kidneys, it is conceivable that the pharmacokinetics of many drugs may be altered in patients with heart failure. The pharmacokinetic changes of drugs in these patients in the light of a physiologically based pharmacokinetic model are discussed, since this model can interpret altered pharmacokinetics in terms of changes in the binding of drugs in plasma and tissue, blood flow to drug-eliminating organs and intrinsic activity of drug elimination. Pharmacokinetic changes of drugs after intravenous administration are described here in Part 1 and those after oral administration will be discussed in Part 2 in a later issue of the Clinical Pharmacokinetics. Reviewing the retrieved data, it was considered that patients with asymptomatic or compensated chronic heart failure seem to have no or minimal alterations in the pharmacokinetics of parenterally administered drugs as long as there was no concurrent liver and/or kidney dysfunction. In contrast, it was found that the systemic clearance of at least six drugs (i.e. milrinone, carperitide, molsidomine, theophylline, ciclosporin and hydralazine) was reduced after intravenous administration by 50 % or more in patients with acute decompensated heart failure or chronic severe heart failure (New York Heart Association class III or IV) as compared with healthy subjects. Because there is a paucity of information regarding the pharmacokinetics of drugs in patients with severe heart failure, close attention should be paid to monitoring the efficacy of these agents and their associated adverse effects.

Adverse drug reaction-related hospitalisations among patients with heart failure at two hospitals in the United Arab Emirates

“…First, although stabilising HF disease with evidence based medication controls fluid congestion and pharmacokinetic variability, patients with advanced HF and those with decompensated HF have decreased clearance regardless of the pharmacokinetic aspects of the drug [6]. In addition, there is a high rate of renal failure in patients suffering from HF, which is often excluded from pharmacokinetic studies [7].…”

Common Medical Comorbidities Correlated With Poor Outcomes in Hip Periprosthetic Infection

“…From a biologic standpoint, decreased cardiovascular fitness as evidenced by diagnosis of coronary artery disease could be related to poor tissue perfusion, which may lead to impaired wound healing through decreased oxygen and inflammatory cell delivery [19]. Additionally, decreased gut drug absorption and impaired tissue micro-circulation in patients with significant heart disease may reduce drug availability at the intended target site [20, 21]. Alternatively, from the standpoint of operative planning, surgeons may choose to avoid operating on patients with significant CAD due to concerns of perioperative mortality.…”

Silk‐Based Biomaterials for Cardiac Tissue Engineering

“…Prescriptions, such as α / β blockers, nitrates, and anticoagulants, are commonly used to prevent thrombosis and reduce the workload of the heart. [ 19 ] Besides antithrombotic and antiplatelet treatment, catheterization and coronary stents are the main interventions for the treatment of ischemic heart disease, [ 20 ] through enlarging blocked coronary arteries to improving circulation for damaged regions. When the condition becomes more severe and reaches the end stage of HF, coronary artery bypass grafting, heart transplantation, and pacemaker implantation become the options.…”