Excretion pumps inhibition

Bile salt export pump (BSEP gene symbol ABCB11) mediates the biliary excretion of nonconjugated bile salts, such as taurocholic acid, glycocholic acid and cholic acid, and therefore is responsible for the formation of the bile acid-dependent bile flow [97, 98]. Its hereditary defect results in the acquisition of PFIC2, a potentially lethal disease which requires liver transplantation [17, 81, 82, 99]. As discussed in Section 12.5.2, the inhibition of BSEP following drug administration may result in cholestasis. 

PRAMIPEXOLE, ROPINIROLE H2-RECEPTOR BLOCKER-CIMETIDINE T efficacy and adverse effects of pramipexole 1 renal excretion of pramipexole by inhibition of cation transport system. Inhibition of CYP1A2-mediated metabolism of ropinirole Monitor closely i dose of pramipexole may be required. Adjust dose of ropinirole as necessaiy or use alternative acid suppression, e.g. H2 antagonist proton pump inhibitor (not omeprazole or lansoprazole)... 

Chloride ions in food are almost completely absorbed from the intestinal tract. They are filtered from plasma at the glomeruh and passively reabsorbed, along with Nap in the proximal tubules. In the thick ascending limb of the loop of Henle, Cl is actively reabsorbed by the chloride pump, whose action promotes passive reabsorption of Nah Loop diuretics such as furosemide and ethacrynic acid inhibit the chloride pump. Surplus CP is excreted in the urine and is also lost in the sweat, especially in hot environments. 

Troglitazone sulfate (Ml, the main metabolite) undergoes biliary excretion and accounts for up to 85% of the dose in humans (Loi et al. 1999). In patients with hepatic impairment, troglitazone sulfate was found to accumulate about fourfold in plasma with a threefold increased half-life (Ott et al. 1998 Loi et al. 1999). This metabolite also inhibited the canalicular bile salt export pump (Bsep), organic anion transporting polypeptide (OATP) transporters as well as drug transporters, suggesting it contributes to the hepatotoxicity. 

Another ABC transporter is sister P-glycoprotein, otherwise called the bile salt export pump (BSEP or ABCBl 1). It has been suggested that inhibition of this pump may increase the risk of cholestasis, see Drug transporters under Drug excretion interactions , (p.7). 

Proton pump inhibitors may affect renal, and possibly hepatic, clearance of methotrexate by inhibition of methotrexate transporter proteins. It has been suggested that omeprazole may inhibit the activity of a hydrogen-ion dependent mechanism in the kidney, on which methotrexate depends for its excretion, so that its loss is diminished. It has also been suggested that the situation with lansoprazole may be similar, but that pantoprazole may differ since at about the pH found in the renal tubules (pH 5), pantoprazole is more slowly activated than omeprazole. However, a case of an interaction with pantoprazole has also been reported. ... 

Amiloride a drug which inhibits the influx of Na into cells. It was discovered as a natriuretic agent which increases Na excretion but does not affect K excretion (Baer et al. J. Pharmacol. Exp. Ther. 157 (1967) 472). Animal cells have 2 systems for Na transport. The Na /K ATPase (inhibited by ouabain) exports Na and imports K, each against its concentration gradient. In addition, there is a pump which imports Na and exports H, and this is inhibited by A., hence the designation amiloride-sensitive Na pump . A. has subsequently been found to be relatively unspecific, e.g. it also inhibits protein synthesis Its derivative, dimethylamiloride, is a more spedfic... 

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