NITROPRESS
Clinical safety rating
cautionComprehensive clinical and safety monograph for NITROPRESS (NITROPRESS).
Nitroprusside is a direct-acting vasodilator that releases nitric oxide (NO), which activates guanylyl cyclase in vascular smooth muscle, increasing cGMP levels and causing relaxation of both arterioles and venules.
| Metabolism | Nitroprusside is rapidly broken down in red blood cells and tissues, releasing nitric oxide and cyanide. Cyanide is further metabolized in the liver to thiocyanate via the enzyme rhodanese, which requires thiosulfate. |
| Excretion | Renal: approximately 60% as unchanged drug; hepatic metabolism to inactive metabolites excreted in bile and feces: approximately 40%. |
| Half-life | Terminal elimination half-life: 1–4 minutes (mean 2 minutes) due to rapid metabolism by RBC and tissue esterases; clinical effect dissipates within 10 minutes of infusion cessation. |
| Protein binding | Approximately 60% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | 0.596 L/kg (range 0.5–0.7 L/kg); indicates moderate distribution into total body water and some tissue binding. |
| Bioavailability | Intravenous: 100%; oral: negligible (<1%) due to extensive first-pass metabolism; sublingual/buccal: variable and not clinically reliable. |
| Onset of Action | Intravenous infusion: 30–60 seconds; sublingual: 2–5 minutes (not approved route). |
| Duration of Action | Intravenous infusion: 1–10 minutes after stopping infusion; duration is dose-dependent and titratable for acute hypertensive crises or controlled hypotension. |
| Molecular Weight | 247.20 Da |
Initial dose: 0.3 mcg/kg/min IV continuous infusion; titrate to desired effect. Usual dose: 0.5-10 mcg/kg/min.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment for GFR; use with caution in renal impairment due to potential thiocyanate accumulation. Monitor thiocyanate levels if infusion >3 mcg/kg/min for >24 hours. |
| Liver impairment | No specific Child-Pugh based adjustment; use with caution in severe hepatic impairment due to reduced clearance. |
| Pediatric use | Initial: 0.5-1 mcg/kg/min IV; titrate as needed. Maximum: 10 mcg/kg/min. |
| Geriatric use | Start at low end of dosing range (0.3 mcg/kg/min) due to increased sensitivity and risk of hypotension. |
| 1st trimester | Limited human data; animal studies show fetal toxicity at high doses. Use only if clearly needed. |
| 2nd trimester | May cause fetal hypotension and reduced uteroplacental perfusion. Use with caution. |
| 3rd trimester | May cause fetal hypotension and reduced uteroplacental perfusion. Use with caution. |
Clinical note
Comprehensive clinical and safety monograph for NITROPRESS (NITROPRESS).
| Placental transfer | Crosses the placenta; detected in fetal circulation. |
| Breastfeeding | Excreted in breast milk in small amounts; not expected to cause adverse effects in the infant. Consider benefits vs. risks. |
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | Pregnancy Category C. Animal studies have shown fetal harm (skeletal abnormalities, reduced ossification) at doses below human exposure. No adequate human studies. First trimester: Potential risk of teratogenicity; use only if benefit outweighs risk. Second and third trimesters: May cause fetal cyanide toxicity due to metabolism to thiocyanate; prolonged exposure (≥24 hours) associated with increased fetal mortality and goiter. Avoid use during pregnancy unless no alternative. |
| Fetal Monitoring | Continuous maternal blood pressure monitoring; invasive arterial BP recommended. Monitor fetal heart rate by electronic fetal monitoring during infusion. Monitor maternal thiocyanate levels if infusion >24 hours or in renal impairment (target <10 mg/dL). Assess maternal acid-base status, methemoglobin levels, and oxygen saturation. In prolonged use, monitor fetal growth and thyroid function postpartum. |
| Fertility Effects | No human data on fertility effects. In animal studies, sodium nitroprusside did not impair fertility in rats at doses up to 4 mg/kg/day. Theoretical concern due to cyanide release; however, no specific fertility effects documented. Use with caution in patients attempting conception. |
■ FDA Black Box Warning
Cyanide toxicity: Prolonged infusion or high doses can cause cyanide poisoning, especially in patients with hepatic impairment. Sodium thiosulfate should be co-administered to reduce risk.
| Serious Effects |
Severe hypotensionInadequate cerebral circulationPre-existing increased intracranial pressureAortic coarctationArteriovenous shuntTachycardia or history of angina
| Precautions | Monitor for cyanide toxicity (metabolic acidosis, confusion, seizures) and thiocyanate toxicity (weakness, tinnitus, hypothyroidism). Use caution in renal impairment (thiocyanate accumulation) and hepatic impairment (cyanide accumulation). Avoid in patients with Leber's optic atrophy or tobacco amblyopia due to increased cyanide susceptibility. |
| Food/Dietary | No known food interactions. Avoid excessive intake of foods containing thiocyanate (e.g., cassava, cabbage, broccoli) as they may increase risk of thiocyanate toxicity. |
| Clinical Pearls | Nitroprusside (NITROPRESS) is a potent vasodilator used in hypertensive emergencies. Infusion requires continuous monitoring of blood pressure via arterial line. Must protect from light; wrap infusion bag in aluminum foil. Cyanide toxicity risk: monitor for metabolic acidosis, and co-administer sodium thiosulfate if prolonged use (>24h) or high doses. Do not use in patients with Leber's optic atrophy or tobacco amblyopia due to impaired cyanide metabolism. |
| Patient Advice | This medication is given intravenously to quickly lower very high blood pressure. · You will be in an intensive care unit with continuous blood pressure monitoring. · Report any symptoms of headache, dizziness, nausea, or muscle twitching immediately. · Toxic effects can occur with prolonged use; your doctor may give another drug to prevent toxicity. |
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