Vasodilators renal failure

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. 

For severely hypertensive patients, clonidine has been used in combination with a diuretic, a vasodilator, and a -blocker. Some care must be taken, however, because the coadministration of clonidine and a p-blocker may cause excessive sedation. Clonidine is especially useful in patients with renal failure, since its duration of... 

Renal Decreased Na+ and HjO excretion, renal failure, decreased effectiveness of diuretics and antihypertensives PGE2- and PGb-induced vasodilation in juxtamedullary apparatus (increases renal blood flow, antagonizes renin, inhibits reabsorption of Na+ and HjO) cox-1 cox-2... 

Minoxidil is a very efficacious orally active vasodilator. The effect results from the opening of potassium channels in smooth muscle membranes by minoxidil sulfate, the active metabolite. Increased potassium permeability stabilizes the membrane at its resting potential and makes contraction less likely. Like hydralazine, minoxidil dilates arterioles but not veins. Because of its greater potential antihypertensive effect, minoxidil should replace hydralazine when maximal doses of the latter are not effective or in patients with renal failure and severe hypertension, who do not respond well to hydralazine. 

The roles of leukotrienes and cytochrome P450 products in the human kidney are currently speculative. Recently, the 5,6-epoxide has been shown to be a powerful vasodilator in animal experiments. Another recent discovery is that free radicals attack arachidonic acid-containing phospholipids to yield an 8-ep/-PGF2[J that has powerful thromboxane-like properties. Synthesis is not blocked by COX inhibitors but can be blocked by antioxidants. This vasoconstrictor, which is present in humans, is thought to be another important mediator causing renal failure in the hepatorenal syndrome. 

ANTI HYPERTENSIVES AND HEART FAILURE DRUGS NS AIDs 1 hypotensive effect, especially with indometacin. The effect is variable amongst different ACE inhibitors and NSAIDs, but is most notable between captopril and indometacin NSAIDs cause sodium and water retention and raise BP by inhibiting vasodilating renal prostaglandins. ACE inhibitors metabolize tissue kinins (e.g. bradykinin) and this may be the basis for indometacin attenuating hypotensive effect of captopril Monitor BP at least weekly until stable. Avoid co administering indometacin with captopril... 

Prostaglandin synthesis. Nonsteroidal anti-inflammatory drugs (NSAIDs), e.g. indomethacin, attenuate the antihypertensive effect of p-adrenoceptor blockers and of diuretics, perhaps by inhibiting the synthesis of vasodilator renal prostaglandins. This effect can also be important when a diuretic is used for severe left ventricular failure. 

Adverse effects are uncommon, apart from excess of therapeutic effect (electrolyte disturbance and hypotension due to low plasma volume) and those mentioned in the general account for diuretics (below). They include nausea, pancreatitis and, rarely, deafness which is usually transient and associated with rapid i.v. injection in renal failure. NSAIDs, notably indomethacin, reduce frusemide-induced diuresis probably by inhibiting the formation of vasodilator prostaglandins in the kidney. 

The mechanism of the acute kidney injury is thought to be multifactorial and similar to other cases of myoglobinuric renal failure [118, 121-126]. These factors include obstruction of tubules, toxic effects of the pigment or iron on renal tubular cells and altered hemodynamics in association with inhibition of the vasodilator nitric oxide by myoglobin. Experimental animals exposed to heme pigment have increases in the renal synthesis of both heme oxidase and ferritin [125]. This allows for more rapid heme degradation and greater sequestration of potentially toxic iron by the tubular cells [125]. Whether narcotics or the hypotensive, hypoxic environment associated with rhabdomyolysis interfere with these protective effects of the kidney is unknown. 

Hepatorenal syndrome, functional renal failure in the setting of cirrhosis in the absence of intrinsic renal disease, occurs in patients with cirrhosis as a result of intense vasoconstriction within the renal cortical vasculature. It is common and develops in approximately 40% of patients with cirrhosis and ascites within 5 years. The resultant reduction in blood supply to the kidneys causes avid sodium retention and oliguria. The vasoconstriction that occurs in the kidneys is in stark contrast to the state of systemic vasodilation that is characteristic of chronic liver failure. The pathophysiologic mechanism responsible for these effects is unknown, but is linked to the systemic vasodilation, hypovolemia, and hyperkinetic circulation seen in chronic liver failure. ... 

Nephrotoxins or ischemic disorders can initiate acute renal failure. Shock, hemorrhage, septicemia, or vasodilation due to hypertensive medication can precipitate ischemic acute renal failure. Systemic reactions to certain drugs and nephrotoxins such as aminoglycoside antibiotics and heavy metals lead to acute renal failure. The extent of retention of creatinine and urea in blood is directly related to the severity of acute renal failure. This condition is not readily reversible and, as such, should be distinguished from reversible phenomena such as prerenal or postrenal azotemia, in which there is also an increase in levels of plasma urea and creatinine (13). In volume-depleted states, for example, diarrhea, the kidney is hypoprefused. This results in increased back diffusion of urea into the circulation from the tubular fluid because of the reduced urine flow. In addition to an increase in urea levels in circulation, there is also a slow increase in creatinine levels. Plasma urea and creatinine levels can be restored to normal within 24 hours by appropriate fluid and electrolyte replacement in prerenal azotemia. In condi-... 

Zipser RD, Radvan GH, Kronborg IJ, Duke R, Little TE. Urinary thromboxane B2 and prostaglandin E2 in the hepatorenal syndrome evidence for increased vasoconstrictor and decreased vasodilator factors. Gastroenterology 1983 84 697-703. Walshe JJ, Venuto RC. Acute oliguric renal failure induced by indomethacin possible mechanisms. Ann Intern Med 1979 91 47-49. 

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