Vasodilators nephrotoxicity

WARNING Renal impair is the major tox foUow administration instructions Uses CMV retinitis w/ HIV Action Selective inhibition of viral DNA synth Dose Rx 5 mg/kg IV over 1 h once/wk for 2 wk w/ probenecid Maint 5 mg/kg IV once/2 wk w/ probenecid (2 g PO 3 h prior to cidofovir, then 1 g PO at 2 h 8 h after cidofovir) X in renal impair Caution [C, -] Contra Probenecid or sulfa allergy Disp Inj SE Renal tox, chills, fever, HA, NA /D, thrombocytopenia, neutropenia Interactions t Nephrotox W/ aminoglycosides, amphot icin B, foscar-net, IV pentamidine, NSAIDs, vancomycin t effects W/zidovudine EMS Monitor ECG for hypocalcemia (t QT int val) and hypokalemia (flattened T waves) OD May cause renal failure hydration may be effective in reducing drug levels/effects Cilostazol (Pletal) TAntiplatelet, Arterial Vasodilator/ Phosphodiesterase Inhibitor] Uses Reduce Sxs of intermittent claudication Action Phosphodiesterase in inhibitor t s cAMP in pits blood vessels, vasodilation inhibit pit aggregation Dose 100 mg PO bid, 1/2 h before or 2 h after breakfast dinner Caution [C, +/-] Contra CHE, hemostatic disorders. 

Nephrotoxicity is caused by drugs that principally affect the renal hemodynamics of the patient depended on vasodilator prostaglandin biosynthesis or angiotensin converting enzyme (ACE) mediated vasoconstriction drugs causing nephrotoxicity include NSAIDs (fenprofen), ACE inhibitors (captopril, and cyclosporin). 

The co-administration of 5-flucytosine with AmB, which is commonly used dinically to obtain a synergistic antifungal effect, protects against acute and chronic nephrotoxicity [107]. The mechanisms by which flucytosine influences the renal response to AmB are not clear but may relate to (i) its administration in 0.9% NaCl, which itself is protective, (ii) a renal vasodilator effect of flucytosine that antagonizes AmB-induced vasoconstriction, and (iii) reduction in renal uptake of AmB [107]. 

Acute CSA-induced nephrotoxicity is a functional abnormality caused by a disproportion of the balance of vasoconstrictor and vasodilator mediators. The main characteristic of this form of nephrotoxicity is an intense intra-renal vasoconstriction, causing RBF decrease and RVR increase, accompanied by variable degree of GFR impairment. The main site for this vasoconstriction is the afferent arteriole but it also occurs in adjacent small arteries, including the glomerular tuft [13,15,16]. 

Hall KA, Wong RW, Hunter GC, Camazine BM, Rappaport WA, Smyth SH, Bull DA, McIntyre KE, Bernhard VM, Misiorowski RE. Contrast-induced nephrotoxicity the effects of vasodilator therapy. J Surg Res 1992 53 317-320. 

Nephrotoxicity. Prostagiandias PGE> and PGi. are powerful vasodilators synthesized in the renal medulla and glomeruli, respectively, and... 

A decrease in prostaglandin synthesis during ARF was shown in early studies . In both haemodynamic (glycerol) and nephrotoxic (mercuric chloride) rabbit models of ARF, whole kidney PGE2 levels were increased. There is also evidence for a protective effect of PGE2 in haemodynamically mediated (norepinephrine-induced) ARF ". Furosemide, which stimulates prostaglandin production has a protective effect on renal function in some models of ARF if administered prophylactically , whereas it is of no benefit in nephrotoxic models . The beneficial effect may depend upon a combination of factors, including increased solute excretion and vasodilation however, furosemide action at other nephron and vascular sites may explain this salutary effect. 

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