Sodium Nitroprusside

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Overview

What is Sodium Nitroprusside?

Sodium nitroprusside is disodium pentacyanonitrosylferrate(2-) dihydrate, a hypotensive agent whose structural formula is:

Sodium Nitroprusside, whose molecular formula is Na[Fe(CN)NO] • 2HO, and whose molecular weight is 297.95. Dry sodium nitroprusside is a reddish-brown powder, soluble in water. In an aqueous solution infused intravenously, sodium nitroprusside is a rapid-acting vasodilator, active on both arteries and veins.

Sodium nitroprusside solution is rapidly degraded by trace contaminants, often with resulting color changes. (See section.) The solution is also sensitive to certain wavelengths of light, and it must be protected from light in clinical use.

Sodium Nitroprusside Injection is available as:

50 mg Fliptop Vial – Each 2 mL vial contains the equivalent of 50 mg sodium nitroprusside dihydrate in sterile water for injection.

What does Sodium Nitroprusside look like?

What are the available doses of Sodium Nitroprusside?

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What should I talk to my health care provider before I take Sodium Nitroprusside?

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How should I use Sodium Nitroprusside?

Sodium nitroprusside is indicated for the immediate reduction of blood pressure of adult and pediatric patients in hypertensive crises. Concomitant longer-acting antihypertensive medication should be administered so that the duration of treatment with sodium nitroprusside can be minimized.

Sodium nitroprusside is also indicated for producing controlled hypotension in order to reduce bleeding during surgery.

Sodium nitroprusside is also indicated for the treatment of acute congestive heart failure.

Depending on the desired concentration, the solution containing 50 mg of sodium nitroprusside must be further diluted in 250 to 1,000 mL of sterile 5% dextrose injection. The diluted solution should be protected from light, using the supplied opaque sleeve, aluminum foil, or other opaque material. It is not necessary to cover the infusion drip chamber or the tubing.

What interacts with Sodium Nitroprusside?

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What are the warnings of Sodium Nitroprusside?

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What are the precautions of Sodium Nitroprusside?

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What are the side effects of Sodium Nitroprusside?

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What should I look out for while using Sodium Nitroprusside?

Sodium nitroprusside should not be used in the treatment of compensatory hypertension, where the primary hemodynamic lesion is aortic coarctation or arteriovenous shunting.

Sodium nitroprusside should not be used to produce hypotension during surgery in patients with known inadequate cerebral circulation, or in moribund patients (A.S.A. Class 5E) coming to emergency surgery.

Patients with congenital (Leber's) optic atrophy or with tobacco amblyopia have unusually high cyanide/thiocyanate ratios. These rare conditions are probably associated with defective or absent rhodanase, and sodium nitroprusside should be avoided in these patients.

Sodium nitroprusside should not be used for the treatment of acute congestive heart failure associated with reduced peripheral vascular resistance such as high-output heart failure that may be seen in endotoxic sepsis.

(See also the at the beginning of this insert.)

The principal hazards of Sodium Nitroprusside administration are excessive hypotension and excessive accumulation of cyanide (see also and ).

What might happen if I take too much Sodium Nitroprusside?

Overdosage of nitroprusside can be manifested as excessive hypotension or cyanide toxicity (see ) or as thiocyanate toxicity (see ).

The acute intravenous mean lethal doses (LD) of nitroprusside in rabbits, dogs, mice, and rats are 2.8, 5.0, 8.4, and 11.2 mg/kg, respectively.

How should I store and handle Sodium Nitroprusside?

Store at 20° to 25°C (68° to 77°F).[See USP Controlled Room Temperature]DISPENSE IN TIGHT, LIGHT-RESISTANT CONTAINER.Keep out of the reach of children.Store at 20° to 25°C (68° to 77°F).[See USP Controlled Room Temperature]DISPENSE IN TIGHT, LIGHT-RESISTANT CONTAINER.Keep out of the reach of children.Store at 20° to 25°C (68° to 77°F).[See USP Controlled Room Temperature]DISPENSE IN TIGHT, LIGHT-RESISTANT CONTAINER.Keep out of the reach of children.Store at 20° to 25°C (68° to 77°F).[See USP Controlled Room Temperature]DISPENSE IN TIGHT, LIGHT-RESISTANT CONTAINER.Keep out of the reach of children.Sodium Nitroprusside Injection is supplied in an amber-colored vial as follows:

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Clinical Information

Chemical Structure

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Clinical Pharmacology

Infused sodium nitroprusside is rapidly distributed to a volume that is approximately coextensive with the extracellular space. The drug is cleared from this volume by intraerythrocytic reaction with hemoglobin (Hgb), and sodium nitroprusside's resulting circulatory half-life is about 2 minutes.

The products of the nitroprusside/hemoglobin reaction are cyanmethemoglobin (cyanmetHgb) and cyanide ion (CN¯). Safe use of sodium nitroprusside injection must be guided by knowledge of the further metabolism of these products.

As shown in the diagram below, the essential features of nitroprusside metabolism are:

Cyanide ion is normally found in serum; it is derived from dietary substrates and from tobacco smoke.

Cyanide binds avidly (but reversibly) to ferric ion (Fe+++), most body stores of which are found in erythrocyte methemoglobin (metHgb) and in mitochondrial cytochromes. When CN¯ is infused or generated within the bloodstream, essentially all of it is bound to methemoglobin until intraerythrocytic methemoglobin has been saturated.

When the Fe+++ of cytochromes is bound to cyanide, the cytochromes are unable to participate in oxidative metabolism. In this situation, cells may be able to provide for their energy needs by utilizing anaerobic pathways, but they thereby generate an increasing body burden of lactic acid. Other cells may be unable to utilize these alternative pathways, and they may die hypoxic deaths.

CN¯ levels in packed erythrocytes are typically less than 1 μmol/L (less than 25 mcg/L); levels are roughly doubled in heavy smokers.

At healthy steady state, most people have less than 1% of their hemoglobin in the form of methemoglobin. Nitroprusside metabolism can lead to methemoglobin formation (a) through dissociation of cyanmethemoglobin formed in the original reaction of sodium nitroprusside with Hgb and (b) by direct oxidation of Hgb by the released nitroso group. Relatively large quantities of sodium nitroprusside, however, are required to produce significant methemoglobinemia.

At physiologic methemoglobin levels, the CN¯ binding capacity of packed red cells is a little less than 200 μmol/L (5 mg/L). Cytochrome toxicity is seen at levels only slightly higher, and death has been reported at levels from 300 to 3,000 μmol/L (8 to 80 mg/L). Put another way, a patient with a normal red-cell mass (35 mL/kg) and normal methemoglobin levels can buffer about 175 mcg/kg of CN¯, corresponding to a little less than 500 mcg/kg of infused sodium nitroprusside.

Some cyanide is eliminated from the body as expired hydrogen cyanide, but most is enzymatically converted to thiocyanate (SCN¯) by thiosulfate-cyanide sulfur transferase (rhodanase, EC 2.8.1.1), a mitochondrial enzyme. The enzyme is normally present in great excess, so the reaction is rate-limited by the availability of sulfur donors, especially thiosulfate, cystine, and cysteine.

Thiosulfate is a normal constituent of serum, produced from cysteine by way of β-mercaptopyruvate. Physiological levels of thiosulfate are typically about 0.1 mmol/L (11 mg/L), but they are approximately twice this level in pediatric and adult patients who are not eating. Infused thiosulfate is cleared from the body (primarily by the kidneys) with a half-life of about 20 minutes.

When thiosulfate is being supplied only by normal physiologic mechanisms, conversion of CN¯ to SCN¯ generally proceeds at about 1 mcg/kg/min. This rate of CN¯ clearance corresponds to steady-state processing of a sodium nitroprusside infusion of slightly more than 2 mcg/kg/min. CN¯ begins to accumulate when sodium nitroprusside infusions exceed this rate.

Thiocyanate (SCN¯) is also a normal physiological constituent of serum, with normal levels typically in the range of 50 to 250 μmol/L (3 to 15 mg/L). Clearance of SCN¯ is primarily renal, with a half-life of about 3 days. In renal failure, the half-life can be doubled or tripled.

Non-Clinical Toxicology

Sodium nitroprusside should not be used in the treatment of compensatory hypertension, where the primary hemodynamic lesion is aortic coarctation or arteriovenous shunting.

Sodium nitroprusside should not be used to produce hypotension during surgery in patients with known inadequate cerebral circulation, or in moribund patients (A.S.A. Class 5E) coming to emergency surgery.

Patients with congenital (Leber's) optic atrophy or with tobacco amblyopia have unusually high cyanide/thiocyanate ratios. These rare conditions are probably associated with defective or absent rhodanase, and sodium nitroprusside should be avoided in these patients.

Sodium nitroprusside should not be used for the treatment of acute congestive heart failure associated with reduced peripheral vascular resistance such as high-output heart failure that may be seen in endotoxic sepsis.

(See also the at the beginning of this insert.)

The principal hazards of Sodium Nitroprusside administration are excessive hypotension and excessive accumulation of cyanide (see also and ).

The hypotensive effect of sodium nitroprusside is augmented by that of most other hypotensive drugs, including ganglionic blocking agents, negative inotropic agents, and inhaled anesthetics.

Like other vasodilators, sodium nitroprusside can cause increases in intracranial pressure. In patients whose intracranial pressure is already elevated, sodium nitroprusside should be used only with extreme caution.

The most important adverse reactions to sodium nitroprusside are the avoidable ones of excessive hypotension and cyanide toxicity, described above under . The adverse reactions described in this section develop less rapidly and, as it happens, less commonly.

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Reference

This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
"https://dailymed.nlm.nih.gov/dailymed/"

While we update our database periodically, we cannot guarantee it is always updated to the latest version.

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Professional

Clonazepam Description Each single-scored tablet, for oral administration, contains 0.5 mg, 1 mg, or 2 mg Clonazepam, USP, a benzodiazepine. Each tablet also contains corn starch, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and povidone. Clonazepam tablets USP 0.5 mg contain Yellow D&C No. 10 Aluminum Lake. Clonazepam tablets USP 1 mg contain Yellow D&C No. 10 Aluminum Lake, as well as FD&C Blue No. 1 Aluminum Lake. Chemically, Clonazepam, USP is 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one. It is a light yellow crystalline powder. It has the following structural formula: C15H10ClN3O3 M.W. 315.72

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Interactions

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