From keratinocyte to cancer: the pathogenesis and modeling of cutaneous squamous cell carcinoma.

Resistance to diuretic action is frequently encountered in the clinical setting. This is best managed by systematically optimizing the pharmacodynamic-pharmacokinetic factors that may be involved. Important pharmacodynamic measures include improving the underlying disease state, restriction of salt intake, limiting the use of vasodilators which may cause hypotension, lowering protein excretion, and eliminating drugs which may modify the response to the diuretic. Pharmacokinetic measures include using doses which result in diuretic excretion rates which fall on the steep part of the dose-response curve, sustaining diuretic excretion in this range by frequent drug administration, or constant infusion, using more bioavailable drugs and drugs which have less hepatic elimination, and by increasing the diuretic concentration in blood by coadministration with albumin. Using diuretic combinations to systematically inhibit absorption in the proximal tubule, Henle's loop, distal convoluted tubule, and connecting/collecting tubule will usually effect diuresis in all but the most refractory of cases.