Loop diuretics Nonsteroidal anti-inflammatory drugs

Prostaglandins are important in maintaining glomerular filtration and substrate for diuretic action. When synthesis of prostaglandins is inhibited, as with nonsteroidal anti-inflammatory drugs (Chapter 36), the efficacy of diuretics—especially loop diuretics—decreases. 

Cyclodextrin-based drug delivery systems The hydrophilic cyclodextrins have been extensively )plied to enhance the oral bioavailabilily of steroids, cardiac glycosides, nonsteroidal anti-inflammatory drugs, barbiturates, antiepileptics, benzodiazepines, antidiabetics, vasodilators, etc. Delayed and prolonged release of diltiazem and molsidormine was achieved by their complexation with CD derivatives, modified release of nifedipine can be achieved by its complexation with 2-HP-P-CD fiirosemide and piretanide (loop diuretics) release can be modified after complexation with DM-P-CD. Prednisolone dosage forms can be optimized also by complex-formation with 2-HP-P-CD. 

Interactions. Several types of drug interfere with lithium excretion by the renal tubules, causing the plasma concentration to rise. These include diuretics (thiazides more than loop type), ACE inhibitors and angiotensin-11 antagonists, and nonsteroidal anti-inflammatory analgesics. Theophylline and sodium-containing antacids reduce plasma lithium concentration. The effects can be important because lithium has such a low therapeutic ratio. Diltiazem, verapamil, carbamazepine and pheny-toin may cause neurotoxicity without affecting the plasma lithium. Concomitant use of thioridazine should be avoided as ventricular arrhythmias may result. 

The most important susceptibility factors are pre-existing chronic kidney disease (CKD eGFR below 60 mVmin) and chronic kidney disease associated with diabetes [15]. Other factors include age over 70 years, the presence of congestive heart failure, nephrotoxic drugs (loop diuretics, metformin, nonsteroidal anti-inflammatory agents), volume depletion, and repeated exposure within short periods of time (under 72 hours). 

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