Sodium Nitroprusside Dihydrate
Indications
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. This is also indicated for the treatment of acute congestive heart failure.
Pharmacology
Nitroprusside a powerful vasodilator relaxes the vascular smooth muscle and produce consequent dilatation of peripheral arteries and veins. Other smooth muscle (e.g., uterus, duodenum) is not affected. Sodium nitroprusside is more active on veins than on arteries.
One molecule of sodium nitroprusside is metabolized by combination with hemoglobin to produce one molecule of cyanmethemoglobin and four CN- ions; methemoglobin, obtained from hemoglobin, can sequester cyanide as cyanmethemoglobin; thiosulfate reacts with cyanide to produce thiocyanate; thiocyanate is eliminated in the urine; cyanide not otherwise removed binds to cytochromes. 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. Once activated to NO, it activates guanylate cyclase in vascular smooth muscle and increases intracellular production of cGMP. cGMP stimulates calcium movement from the cytoplasm to the endoplasmic reticulum and reduces calcium available to bind with calmodulin. This eventually leads to vascular smooth muscle relaxation and vessel dilatation.
One molecule of sodium nitroprusside is metabolized by combination with hemoglobin to produce one molecule of cyanmethemoglobin and four CN- ions; methemoglobin, obtained from hemoglobin, can sequester cyanide as cyanmethemoglobin; thiosulfate reacts with cyanide to produce thiocyanate; thiocyanate is eliminated in the urine; cyanide not otherwise removed binds to cytochromes. 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. Once activated to NO, it activates guanylate cyclase in vascular smooth muscle and increases intracellular production of cGMP. cGMP stimulates calcium movement from the cytoplasm to the endoplasmic reticulum and reduces calcium available to bind with calmodulin. This eventually leads to vascular smooth muscle relaxation and vessel dilatation.
Dosage & Administration
Intravenous Hypertensive crisis:
- Adult: For patients not receiving any antihypertensives, initially 0.3-1.5 mcg/kg/ min, adjust gradually according to response. Usual range 0.5-6 mcg/kg/min. Lower doses should be used in patients receiving antihypertensives. Max rate: 8 mcg/kg/min, discontinue infusion if there is no response after 10 min. May continue for a few hr if there is response. Introduce oral antihypertensive as soon as possible.
- Child: Initially, 250-500 nanograms/kg/min, rate may be repeatedly doubled at intervals of 15-20 min until the desired effect is achieved or treatment is judged ineffective. Max rate: 6 mcg/kg/min.
- Elderly: Lower doses may be required.
- Adult: Recommended max dose: 1.5 mcg/kg/min.
- Adult: Intially 10-15 mcg/min, may increase by 10-15 mcg/min every 5-10 min according to response; usual range 10-200 mcg/min. Max: 280 mcg/min.
Interaction
Additive effect when used with other antihypertensives. May prolong the fibrinolytic activity of alteplase. Risk of severe hypotension if used with phosphodiesterase inhibitors. May reduce serum digoxin levels.
Contraindications
Sodium nitroprusside should not be used in the treatment of compensatory hypertension, where the primary hemodynamic lesion is aortic coarctationor 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.
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.
Side Effects
Bradyarrhythmia, hypotension, palpitations, tachyarrhythmia Apprehension, restlessness, confusion, dizziness, headache, somnolence Rash, sweating, Thyroid suppression, Injection site irritation, Muscle twitch, oliguria, renal azotemia, Cardiac dysrhythmia, hemorrhage, decreased platelet aggregation, excessive hypotensive response, Raised intracranial pressure, Metabolic acidosis, Bowel obstruction, Methemoglobinemia, Cyanide poisoning, Thiocyanate toxicity
Pregnancy & Lactation
Pregnancy Category C. There are no adequate, well-controlled studies of Sodium Nitroprusside in either laboratory animals or pregnant women. It is not known whether Sodium Nitroprusside can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Sodium Nitroprusside should be given to a pregnant woman only if clearly needed.
Nursing Mothers: It is not known whether sodium nitroprusside and its metabolites are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from sodium nitroprusside, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Nursing Mothers: It is not known whether sodium nitroprusside and its metabolites are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from sodium nitroprusside, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Precautions & Warnings
Hypothyroidism, renal and hepatic impairment, ischaemic heart disease, impaired cerebral circulation, elderly. Monitor blood thiocyanate concentration if treatment is longer than 3 days and should not exceed 100 mcg/ml. Monitor acid-base balance, venous oxygen concentration and BP. Caution to avoid extravasation. To be diluted with sterile dextrose 5% solution before infusion. Avoid sudden withdrawal. Leber's optic atrophy, low plasma-cobalamin concentrations, impaired pulmonary function. Pregnancy and lactation.
Use in Special Populations
Renal impairment: Dosage adjustments may be necessary
Therapeutic Class
Vasodilator antihypertensive drugs