Drug Absorption

PHARMACOTHERAPY IN CHF

CHF SEPTEMBER/OCTOBER 2003

287

Pharmacotherapy in Congestive Heart Failure
Domenic A. Sica, MD Editor

Drug Absorption in the Management of Congestive Heart Failure: Loop Diuretics
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 theprocess 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 ofthe 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. (CHF. 2003;9:287–292) ©2003 CHF, Inc. The effects of congestive heart failure (CHF) on drug disposition are multifaceted,with distinct influences on pharmacokinetic parameters such as rate and extent of drug absorption and systemic drug elimination. 1–9 Reduced gastric emptying leads to a lag in drug absorption and decreased peak plasma concentrations of a number of medications. Moreover, drugs with a high hepatic extraction ratio achieve higher-than-expected plasma concentrations in patients with CHF. Alternatively,drugs requiring biotransformation to active forms— like angiotensin-converting enzyme (ACE) inhibitors—generally are marked by a delay in the conversion process. Nonetheless, the pharmacotherapy of CHF is such that ACE inhibitors and angiotensin-receptor blockers are often administered. These drugs often reduce the glomerular filtration rate, which slows drug elimination and offsets circumstancesof reduced absorption.

Systemic Absorption
It would be a logical assumption that the pathophysiologic circumstances of CHF might modify the rate and/or extent of drug absorption. For example, muscle blood flow is normally reduced in CHF. This occurs due to both the regional shunting of blood flow away from muscle as well sympathetically mediated vasoconstriction in muscle beds. However, thelatter may be a modifiable factor through exercise training.10 These processes slow the rate of drug absorption from intramuscular sites and thereby delay the onset and/or prolong drug action by a depot effect.11 Most drug absorption within the gastrointestinal tract takes place in the upper jejunum. The rate and extent of a drug’s absorption are linked to the physicochemical properties of the drug,intestinal blood flow, surface area available for absorption, gastric emptying time, and exposure time as it relates to

Domenic A. Sica, MD From the Departments of Medicine and Pharmacology, Section of Clinical Pharmacology and Hypertension, Division of Nephrology, Medical College of Virginia of Virginia Commonwealth University, Richmond, VA Address for correspondence: Domenic A. Sica, MD,Professor of Medicine and Pharmacology, Chairman, Clinical Pharmacology and Hypertension, Division of Nephrology, Medical College of Virginia of Virginia Commonwealth University, MCV Station Box 980160, Richmond, VA 23298-0160 E-mail: dsica@hsc.vcu.edu

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PHARMACOTHERAPY IN CHF

CHF SEPTEMBER/OCTOBER 2003

intestinal motility. Changes in the rate of gastric...