Nitroprusside

Drug Information: Nitroprusside

Nitroprusside is a potent vasodilator primarily used in hypertensive emergencies. It is a fast-acting medication that works by relaxing smooth muscle in blood vessels, leading to a rapid decrease in blood pressure. Due to its rapid onset and offset of action, it requires continuous blood pressure monitoring during administration. Nitroprusside is metabolized to cyanide, which can lead to toxicity if not managed properly, particularly with prolonged infusions or in patients with impaired renal function.

Category

Vasodilator (including nitrates)

Mechanism of Action

Nitroprusside’s primary mechanism of action involves the release of nitric oxide (NO). Within the vascular smooth muscle cells, nitroprusside is metabolized, leading to the liberation of NO. Nitric oxide then activates guanylate cyclase, an enzyme responsible for converting guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP). Increased levels of cGMP cause vasodilation by dephosphorylating myosin light chains, inhibiting their interaction with actin, and consequently relaxing the smooth muscle cells. This vasodilation affects both arterial and venous vessels, reducing both preload and afterload on the heart. This balanced vasodilation makes nitroprusside particularly useful in rapidly reducing blood pressure in hypertensive emergencies. The short half-life of nitroprusside is due to its rapid metabolism and the degradation of cGMP, allowing for precise blood pressure control. However, the breakdown of nitroprusside releases cyanide ions, which are normally converted to thiocyanate by the enzyme rhodanase in the presence of a sulfur donor. In patients with impaired renal function or those receiving prolonged infusions, cyanide can accumulate, leading to toxicity.

Clinical Uses

Nitroprusside is primarily used in the management of hypertensive emergencies, including malignant hypertension and hypertensive encephalopathy. It is also employed to control blood pressure during and after certain surgical procedures, especially those involving the heart. Additionally, it can be used to reduce afterload in patients with severe heart failure, thereby improving cardiac output. Controlled hypotension during surgery, particularly vascular or neurosurgical procedures, is another application of nitroprusside. Because of the risk of cyanide toxicity, nitroprusside is typically reserved for short-term use and is not a first-line agent for chronic hypertension management.

Dosage

Nitroprusside is administered intravenously via continuous infusion.

Adult Dosage: The typical starting dose is 0.3 mcg/kg/min, which can be titrated upwards to a maximum of 10 mcg/kg/min. The dosage is carefully adjusted based on the patient’s blood pressure response, aiming for a controlled reduction.
Pediatric Dosage: The dosage in pediatric patients is similar to adults, with an initial dose of 0.3 mcg/kg/min, titrated up to a maximum of 8-10 mcg/kg/min, carefully monitored and adjusted based on blood pressure response. Blood pressure must be continuously monitored during administration to prevent hypotension.

Indications

Common indications for Nitroprusside include:
* Hypertensive emergencies
* Malignant hypertension
* Controlled hypotension during surgery
* Acute heart failure (afterload reduction)

Contraindications

Contraindications for Nitroprusside include:
* Compensatory hypertension (e.g., arteriovenous shunt or coarctation of the aorta)
* Inadequate cerebral circulation
* Patients with acute heart failure associated with reduced systemic vascular resistance
* Congenital (Leber’s) optic atrophy or tobacco amblyopia
* Severe renal or hepatic impairment (due to risk of cyanide toxicity)
* Hypersensitivity to nitroprusside

FAQ

Q: What is Nitroprusside used for?
A: Nitroprusside is primarily used to rapidly lower blood pressure in hypertensive emergencies and to control blood pressure during surgery.

Q: How does Nitroprusside work?
A: It works by releasing nitric oxide, which relaxes the smooth muscles in blood vessels, causing them to widen and reduce blood pressure.

Q: What are the common side effects of Nitroprusside?
A: Common side effects include hypotension, nausea, vomiting, and muscle twitching. More serious side effects include cyanide toxicity and thiocyanate toxicity.

Q: How is Nitroprusside administered?
A: Nitroprusside is administered intravenously via a continuous infusion.

Q: How is cyanide toxicity treated?
A: Cyanide toxicity can be treated with sodium nitrite and sodium thiosulfate, which help convert cyanide to less toxic forms.

Q: What monitoring is required during Nitroprusside infusion?
A: Continuous blood pressure monitoring is essential, as well as monitoring for signs of cyanide and thiocyanate toxicity. Arterial blood gases and electrolyte levels may also be checked.

Q: Who should not take Nitroprusside?
A: Nitroprusside is contraindicated in patients with compensatory hypertension, inadequate cerebral circulation, Leber’s optic atrophy, and severe renal or hepatic impairment.

Q: Is Nitroprusside safe for pregnant women?
A: Nitroprusside should be used with caution in pregnant women, and only if the potential benefit justifies the potential risk to the fetus.