Drug Absorption in the Management of Congestive Heart Failure: Loop Diuretics

Abstract

Congestive heart failure is a disease state distinguished by the regular presence of both renal and hepatic abnormalities in drug handling. One such abnormality involves flaws in the process of drug absorption. In most instances, congestive heart failure-related abnormalities in drug absorption are of inconsequential significance. However, this is not the case with loop diuretics. Loop diuretic action ordinarily tracks the rate and extent of absorption if a sufficient amount of diuretic has been given to exceed the threshold for diuretic effect. In congestive heart failure, both the rate and absolute amount of loop diuretic absorbed can be reduced as a function of the heart failure state itself. In this setting, drug dissolution characteristics can assume added significance. Furosemide is the loop diuretic with the widest intra- and interpatient variability of absorption. Alternatively, the loop diuretic torsemide is rapidly and fairly completely absorbed independent of the heart failure state. This pattern of absorption establishes it as the preferred loop diuretic in the otherwise diuretic-resistant heart failure patient. However, the exact role of torsemide in the outpatient management of congestive heart failure remains to be determined.

Predicting Stereoselective Disposition of Carvedilol in Adult and Pediatric Chronic Heart Failure Patients by Incorporating Pathophysiological Changes in Organ Blood Flows–A Physiologically Based Pharmacokinetic Approach

“…These overpredictions in infants may be associated with the knowledge gaps with respect to intestinal permeability and perfusion within CHF patients of this age group, as low drug absorption in comparison with adults has been previously reported in pediatric CHF due to congenital heart defects (Nakamura et al, 1994). Because changes in intestinal morphology, permeability, and absorption are affected in adult CHF patients, the possibility of such changes in pediatric CHF patients cannot be completely ruled out (Sica, 2003;Sandek et al, 2007).…”

“…Predicting Stereoselective PK of Carvedilol-A PBPK Approach 1111 at ASPET Journals on May 11, 2018 dmd.aspetjournals.org CHF (Berkowitz et al, 1963;Sica, 2003). Moreover, in CHF, the absorption of drugs with low solubility is more susceptible to changes in intestinal blood flow; therefore, for drugs like carvedilol (BCS class II)…”

“…In CHF patients there is hepato-splanchic congestion, affecting the passive drug diffusion that results in decreased migration of drug from the intestinal lumen into systemic circulation, which is depicted as decrease in f a of the drug (Sica, 2003). Furthermore, the gastrointestinal absorption of drugs having low solubility like carvedilol (0.01 mg/mL, BCS II) is more sensitive to CHF-associated changes occurring in gut blood flow (Ogawa et al, 2014).…”

“…In CHF, the reduced blood flows to the gastrointestinal tract, the peripheral tissues, as well as the liver and the kidneys can affect the drug absorption, distribution, metabolism, and elimination (ADME) (Berkowitz et al, 1963;Zelis et al, 1975;Sica, 2003;Ogawa et al, 2013). These reductions in the organ blood flows are associated with the severity of disease (Leithe et al, 1984).…”

Approche cognitive de la traduction dans les langues de spécialité : vers une systématisation de la description de la conceptualisation métaphorique

“…Ainsi en est-il du syntagme « drug handling » qui réfère, globalement, aux processus biologiques auxquels sont soumis des substances étrangères introduites dans un organisme vivant, à savoir l'absorption, la distribution, la biotransformation et l'élimination, comme par exemple dans l'exemple suivant : Congestive heart failure is a disease state distinguished by the regular presence of both renal and hepatic abnormalities in drug handling. One such abnormality involves flaws in the process of drug absorption 3 . Le syntagme est relativement fréquent en anglais, et on trouve également le verbe « to handle » dans des contextes du type : One of the most effective ways for the organism to protect itself is to enzymatically transform the xenobiotics into something the body can handle 4 .…”