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Vasodilators - Nitroprusside

Mechanism of Action || Pharmacokinetics || Pharmacodynamics || Problems || Things to Consider || Overview || Related Articles || References and Resources Leave a Comment || Search

Mechanism of Action





Nitroprusside is a unique molecule composed of 5 cyanide molecules, 1 nitric oxide (NO) molecule, and 1 iron atom. The nitric oxide molecule is where all the action takes place. When released it acts on venous and arterial smooth muscle cells.

Nitric oxide increases the activity of the enzyme guanylate cyclase, which causes increased cyclic-GMP levels inside cells. Cyclic-GMP binds to receptors on the endoplasmic reticulum of smooth muscle cells, which causes calcium (the main electrolyte responsible for muscle contraction) to get sequestered back into the endoplasmic reticulum (ie: the storage house for calcium in a muscle cell). Less calcium means less smooth muscle contraction, which causes blood vessels to dilate. The end result is a decrease in systemic vascular resistance and blood pressure.

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Pharmacokinetics

The body takes nitroprusside and converts it to thiocyanate in the liver; from there, thiocyanate is excreted back into the blood stream where it is eventually filtered by the kidneys and excreted into the urine.

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Pharmacodynamics

Nitroprusside is given intravenously through a drip. Its blood pressure reducing characteristics can be seen in a matter of minutes. Its effect lasts only about 10 minutes, which is why it is generally given at a constant rate.

Initial drip rates are 0.3 micrograms/kg-body-weight/min with titrations increasing up to 3 micrograms/kg/min to achieve the blood pressure goals specific to the case. Maximum doses are up to 10 micrograms/kg/min, but are seldom needed.

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Problems

Since each molecule of nitroprusside contains 5 cyanide molecules the potential for cyanide toxicity exists; this is especially true at high doses, and if it is used for prolonged periods.

Cyanide toxicity can present with numerous signs and symptoms including confusion, headache, belly pain, and shortness of breath. Lactic acidosis is often present in clinically significant cyanide poisoning, and can be measured via a blood lactate level. An arterial blood gas will also demonstrate a lower than normal pH secondary to the acidosis.

Treatment is with nitrites or thiosulfate. Nitrites work by converting hemoglobin to methemoglobin; methemoglobin enjoys binding irreversibly to cyanide, which reduces its effect on the electron transport chain and cellular respiration. Thiosulfate converts cyanide to thiocyanate, which is pissed out through the kidneys.

Because nitroprusside is initially converted to thiocyanate by the liver, which is then filtered by the kidneys, it should be used with caution in patients with kidney or liver problems.

It has also been shown to increase intracranial pressure, and therefore should not be used in patients with head injury, brain tumors, or hydrocephalus.

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Things to Consider

Before giving nitroprusside the patient should have an arterial line placed so that blood pressure can be measured on a second to second basis.

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Overview

Nitroprusside is a nitric oxide donor that causes dilation of both veins and arteries. The end result is a decrease in systemic vascular resistance and blood pressure. It can cause cyanide and thiocyanate toxicity in liver and renal failure patients. It should also be avoided in patients with elevated intracranial pressure. It should only be administered under controlled settings in a patient with an arterial line.

Related Articles

- Hypertension (high blood pressure)

- Starling's equation

- Systemic vascular resistance

- Approach to hemodynamic instability

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References and Resources

(1) Rhoney D, Peacock WF. Intravenous therapy for hypertensive emergencies, part 1. Am J Health Syst Pharm. 2009 Aug 1;66(15):1343-52.

(2) Rhoney D, Peacock WF. Intravenous therapy for hypertensive emergencies, part 2.Am J Health Syst Pharm. 2009 Aug 15;66(16):1448-57.

(3) Friederich JA, Butterworth JF. Sodium nitroprusside: Twenty years and counting. Anesth Analg 81:152, 1995.

(4) Johanning RJ, Zaske DE, Tschida SJ, et al. A retrospective study of sodium nitroprusside use and assessment of the potential risk of cyanide poisoning. Pharmacotherapy 15:773,1995.

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