Sodium nitroprusside (SNP), sold under the brand name Nitropress among others, is a medication used to lower blood pressure. This may be done if the blood pressure is very high and resulting in symptoms, in certain types of heart failure, and during surgery to decrease bleeding. It is used by continuous injection into a vein. Onset is nearly immediate and effects last for up to ten minutes. Common side effects include low blood pressure and cyanide toxicity. Other serious side effects include methemoglobinemia. It is not generally recommended during pregnancy due to concerns of side effects. High doses are not recommended for more than ten minutes. It works by increasing nitric oxide levels in the blood, which increases cGMP levels in cells, and causes dilation of blood vessels. Sodium nitroprusside was discovered as early as 1850 and found to be useful in medicine in 1928. It is on the World Health Organization's List of Essential Medicines. Sodium nitroprusside is light sensitive, so it needs to be shielded from light to prevent degradation. It is available as a generic medication.
Medical uses Sodium nitroprusside is intravenously infused in cases of acute hypertensive crises. Its effects are usually seen within a few minutes. Nitric oxide reduces both total peripheral resistance and venous return, thus decreasing both preload and afterload. So, it can be used in severe congestive heart failure where this combination of effects can act to increase cardiac output. In situations where cardiac output is normal, the effect is to reduce blood pressure. It is sometimes also used to induce hypotension (to reduce bleeding) for surgical procedures (for which it is also FDA, TGA, and MHRA labelled). The medication is extremely beneficial for use in medical patients because the effects of the medication will directly stop the second that it stops being infused. This is due to the metabolism of the drug, and the rapid inactivation to thiocyanate once conversion of the drug stops. This compound has also been used as a treatment for aortic valve stenosis, oesophageal varices, myocardial infarction, pulmonary hypertension, respiratory distress syndrome in the newborn, shock, and ergot toxicity.
Contraindications Sodium nitroprusside should not be used for compensatory hypertension (e.g. due to an arteriovenous stent or coarctation of the aorta). It should not be used in patients with inadequate cerebral circulation or in patients who are near death. It should not be used in patients with vitamin B12 deficiency, anaemia, severe renal disease, or hypovolaemia. Patients with conditions associated with a higher cyanide/thiocyanate ratio (e.g. congenital (Leber's) optic atrophy, tobacco amblyopia) should only be treated with sodium nitroprusside with great caution. Its use in patients with acute congestive heart failure associated with reduced peripheral resistance is also not recommended. Its use in hepatically impaired individuals is also not recommended, as is its use in cases of pre-existing hypothyroidism. Its use in pregnant women is advised against, although the available evidence suggests it may be safe, provided maternal pH and cyanide levels are closely monitored. Some evidence suggests sodium nitroprusside use in critically ill children may be safe, even without monitoring of cyanide level.
Adverse effects Adverse effects by incidence and severity Common
Unknown frequency
Serious
Ileus Reduced platelet aggregation Haemorrhage Increased intracranial pressure Metabolic acidosis Methaemoglobinaemia Cyanide poisoning Thiocyanate toxicity
Overdose Due to its cyanogenic nature, overdose may be particularly dangerous. Treatment of sodium nitroprusside overdose includes the following:
Discontinuing sodium nitroprusside administration Buffering the cyanide by using sodium nitrite to convert haemoglobin to methaemoglobin as much as the patient can safely tolerate Infusing sodium thiosulfate to convert the cyanide to thiocyanate. Haemodialysis is ineffective for removing cyanide from the body but it can be used to remove most of the thiocyanate produced from the above procedure.
Toxicology The cyanide can be detoxified by reaction with a sulfur-donor such as thiosulfate, catalysed by the enzyme rhodanese. In the absence of sufficient thiosulfate, cyanide ions can quickly reach toxic levels. Hydroxocobalamin can be administered to reduce the risk of thiocyanate toxicity induced by nitroprusside.
Interactions The only known drug interactions are pharmacodynamic in nature, that is it is possible for other antihypertensive drugs to reduce the threshold for dangerous hypotensive effects to be seen.
Mechanism of action As a result of its breakdown to nitric oxide (NO), sodium nitroprusside has potent vasodilating effects on arterioles and venules (arterial more than venous), whereas other nitrates exhibit more selectivity for veins (e.g., nitroglycerin). Sodium nitroprusside breaks down in circulation to release nitric oxide (NO). It does this by binding to oxyhaemoglobin to release cyanide, methaemoglobin and nitric oxide. NO activates guanylate cyclase in vascular smooth muscle and increases intracellular production of cGMP. cGMP activates protein kinase G which activates phosphatases which inactivate myosin light chains. Myosin light chains are involved in smooth muscle contraction. The result is vascular smooth muscle relaxation, which allow vessels to dilate. This mechanism is similar to that of phosphodiesterase 5 (PDE5) inhibitors such as sildenafil (Viagra) and tadalafil (Cialis), which elevate cGMP concentration by inhibiting its degradation by PDE5. A role for NO in various common psychiatric disorders including schizophrenia, bipolar disorder and major depressive disorder has been proposed and supported by several clinical findings. These findings may also implicate the potential of drugs that alter NO signalling such as SNP in their treatment. Such a role is also supported by the findings of the recent SNP clinical trial.
Structure and properties
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