NITROPRUSSIDE SODIUM

Chemistry - A vascular smooth muscle relaxant, nitroprusside sodium occurs as practicallyodorless, reddish-brown crystals or powder. It is freely soluble in water and slightly soluble inalcohol. After reconstitution in D5W, solutions may have a brownish, straw, or light orange colorand have a pH of 3.5 - 6.
Nitroprusside sodium may also be known as sodium nitroprusside or sodium nitroferricyanide.

Storage, Stability, Compatibility

Nitroprusside sodium powder for injection should be storedprotected from light and moisture and kept at room temperature (15-30°C). Nitroprusside solutionsexposed to light will cause a reduction of the ferric ion to the ferrous ion with a resultant loss inpotency and a change from a brownish-color to a blue color. Degradation is enhanced withnitroprusside solutions in Viaflex® (Baxter) plastic bags exposed to fluorescent light. Afterreconstitution, protect immediately by covering vial or infusion bag with aluminum foil or otheropaque material. Discard solutions that turn to a blue, dark red or green color. Solutions protectedfrom light will remain stable for 24 hours after reconstitution. IV infusion tubing need not beprotected from light while the infusion is running. It is not recommended to use IV infusionsolutions other than D5W or to add any other medications to the infusion solution.

Pharmacology - NITROPRUSSIDE SODIUM

Nitroprusside is an immediate acting intravenous hypotensive agent that directlycauses peripheral vasodilation (arterial and venous) independent of autonomic innervation. Itproduces a lowering of blood pressure, an increase in heart rate, mild decrease in cardiac output andsignificant reduction in total peripheral resistance.

Uses, Indications

In human medicine, nitroprusside is indicated for the management of hypertensive crises, acute heart failure secondary to mitral regurgitation, and severe refractory CHF (oftenin combination with dopamine). Its use in veterinary medicine is generally reserved for the treatmentof critically ill patients with one of these conditions only when constant blood pressure monitoringcan be performed.

Pharmacokinetics - NITROPRUSSIDE SODIUM

After starting an IV infusion of nitroprusside, reduction in blood pressure andother pharmacologic effects begin almost immediately. Blood pressure will return to pretreatmentlevels within 1-10 minutes following cessation of therapy.
Nitroprusside is metabolized non-enzymatically in the blood and tissues to cyanogen (cyanideradical). Cyanogen is converted in the liver to thiocyanate where it is eliminated in the urine, feces, and exhaled air. The half-life of cyanogen is 2.7-7 days if renal function is normal, but prolonged inpatients with impaired renal function or with hyponatremia.
Contraindications/Precautions - Nitroprusside is contraindicated in patients with compensatoryhypertension (e.g., AV shunts or coarctation of the aorta), inadequate cerebral circulation, or duringemergency surgery in patients near death.
Nitroprusside must be used with caution in patients with hepatic insufficiency, severe renal impairment, hyponatremia, or hypothyroidism. When nitroprusside is used for controlled hypotensionduring surgery, patients may have less tolerance to hypovolemia, anemia, or blood loss. Geriatricpatients may be more sensitive to the hypotensive effects of nitroprusside.

Adverse Effects, Warnings

Most adverse reactions from nitroprusside are associated with itshypotensive effects, particularly if blood pressure is reduced too rapidly. Symptoms such as nausea, retching, restlessness, apprehension, muscle twitching, dizziness, have been reported in humans.
These effects disappear when the infusion rate is reduced or stopped. Nitroprusside may beirritating at the infusion site; avoid extravasation.
Overdosage - Acute overdosage is manifested by a profound hypotension. Treat by reducing orstopping the infusion and giving fluids. Monitor blood pressure constantly.
Excessive doses, prolonged therapy, a depleted hepatic thiosulfate (sulfur) supply, or severehepatic or renal insufficiency may lead to profound hypotension, cyanogen or thiocyanate toxicity.
Acid/base status should be monitored to evaluate therapy and to detect metabolic acidosis (earlysign of cyanogen toxicity). Tolerance to therapy is also an early sign of nitroprusside toxicity.
Hydroxocobalamin (Vitamin B12a) may prevent cyanogen toxicity. Thiocyanate toxicity may beexhibited as delirium in dogs. Serum thiocyanate levels may need to be monitored in patients onprolonged therapy, especially in those patients with concurrent renal dysfunction. Serum levels>100 micrograms/ml are considered toxic. It is suggested to refer to other references for furtherinformation should cyanogen or thiocyanate toxicity be suspected.

Drug Interactions

The hypotensive effects of nitroprusside may be enhanced by concomitantadministration of ganglionic blocking agents (e.g., trimethaphan, hexamethonium), generalanesthetics (e.g., halothane, enflurane), or other circulatory depressants.
Patients taking other hypotensive agents (e.g beta-blockers, ACE inhibitors, etc.) may bemore sensitive to the hypotensive effects of nitroprusside.
Synergistic effects (increased cardiac output and reduced wedge pressure) may result if dobutamine is used with nitroprusside.