1 сем / DIURETICS

APPENDIX 5.

Mechanism of hyperuricemia induced by furosemide and some other acidic drugs that undergo renal tubular secretion

OAT4

Furosemide Furosemide

OAT1

a-KG2- Hyperuricaemic drugs:

• Loop diuretics

• Thiazides

• Aspirin – LOW dose

•Pyrazinamide

pyrazinic acid

This figure demonstrates that tubular secretion of furosemide (and some other acidic drugs – see listed in the figure) is coupled to the reabsorption of urate.

Furosemide is taken up from the blood into the renal proximal tubular cell by the tertiary-active transporter OAT1 (an organic acid -ketoglutarate exchanger) located in the basolateral membrane of these cells. Then, furosemide is transported across the apical (luminal) membrane of the tubular cells partly by OAT4 in exchange for urate. Subsequently urate is exported from the cell into the blood via GLUT9 (a glucose transporter) across the basolateral membrane by facilitated diffusion (see also Pharmacokinetics, Part 2).

Note: The bulk of urate is reabsorbed by the urate transporter (URAT1) which, like OAT4, is localized in the luminal membrane of tubular cells (not shown). Urate reabsorption by URAT1 is inhibited by the uricosuric drugs that are used to treat hyperuricemia, such as probenecid, benzbromarone and sulfinpyrazone, as well as aspirin in high dose.

APPENDIX 6. How to answer an exam question?

Exam question:

Basic mechanisms of drug action (examples of drug effects on receptors, ion channels, enzymes, carrier systems, and effects mediated by physicochemical interactions).

One possible answer: DIURETICS