Calcium channel blockers tacrolimus nephrotox

ACE inhibitors and angiotensin-receptor blockers (ARB) have definite benefits in patients with nephropathy and are believed to have renoprotective effects in most patients. Due to their ability to cause an initial bump in serum creatinine, these agents should be used cautiously when employed in combination with the calcineurin inhibitors. The dihydropyridine calcium channel blockers have demonstrated an ability to reverse the nephrotoxicity associated with cyclosporine and tacrolimus (Table 52-8). In general, antihypertensive therapy should focus on agents with proven benefit in reducing the progression of cardiovascular disease and should be chosen on a patient-specific basis.55 See Chapter 2 for further recommendations for treating HTN. 

Drugs that may affect tacrolimus include nephrotoxic agents (aminoglycosides, amphotericin B, cisplatin, cyclosporine), antifungals, bromocriptine, calcium channel blockers, cimetidine, clarithromycin, danazol, diltiazem, erythromycin, methylprednisolone, metoclopramide, carbamazepine, phenobarbital, phenytoin, rifamycins, cisapride, chloramphenicol, metronidazole, nefazodone, omeprazole, protease inhibitors, macrolide antibiotics, fosphenytoin, and St. John s wort. 

Tacrolimus causes acute reversible renal dysfunction in renal [661-663,667], hver [290,664-666,679,680], heart [681-683] and pulmonary [684, 685] transplant recipients and in patients with immunologically mediated diseases [686]. Tacrolimus-induced GFR and RBF decrease is associated with an important increase in renal vascular resistance, both in humans and rodents [63,679,687-692]. Calcium channel blockers improved renal function in TAC-treated liver transplant recipients [693] and in animal models of TAC nephrotoxicity [689,694-6%]. Tacrohmus acute nephrotoxicity, similar to CSA, shows normal renal histology or non-specific changes such as isometric cytoplasmic vacuolation in tubular epithelial cells, microcalcification, giant mitochondria and lysosomes, and necrosis and early hyahnosis of individual smooth muscle cells in the afferent arterioles, which revert with drug reduction or discontinuation [697-699]. 

Since acute DIN appears to be dose related, pharmacokinetic and pharmacodynamic monitoring is an important means of preventing toxicity. However, the persistent presence of therapeutic or low cyclosporine concentrations cannot preclude nephrotoxicity. Calcium channel blockers may antagonize the vasoconstrictor effect of cyclosporine by dilating glomerular afferent arterioles and preventing acute decreases in renal blood flow and glomerular filtration. Lastly, decreased doses of cyclosporine or tacrolimus, primarily when used in combination with other non-nephrotoxic immunosuppressants, may minimize the risk of toxicity, but this may increase the risk of chronic rejection. 

A renal transplant recipient developed severe nephrotoxicity related to a toxic tacrolimus trough concentration associated with diarrhea and use of a calcium channel blocker. 

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See also in sourсe #XX -- [ ]

See also in sourсe #XX -- [ ]

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