Sodium Nitroprusside Toxicity:
Mechanism of Action:
After parenteral injection, sodium nitroprusside enters red blood cells, where it receives an electron from the iron (Fe⁺²) of oxyhemoglobin. This non-enzymatic electron transfer results in unstable nitroprusside radical and methemoglobin (Hb Fe⁺³). The former moiety spontaneously decomposes into five cyanide ions and the active nitroso (NO) group.
The cyanide ions can be involved in one of three possible reactions:
1) Binding to methemoglobin to form cyan-methemoglobin.
2) Undergoing a reaction in the liver and kidney catalyzed by rhodanase enzyme to form thiocyanate + thiosulfate.
3) Binding to tissue cytochrome oxidase, which interferes with normal oxygen utilization.
N.B. Sodium nitroprusside toxicity is usually related to prolonged administration or occurs in patients with renal or hepatic failure.
Mechanisms of Toxicity:
1) Direct vasodilation: resulting in hypotension and dysrhythmias (most common).
2) Thiocyanate toxicity: (occurs infrequently).
3) Cyanide toxicity: (in rare cases).
4) Methemoglobinemia: (in very rare cases).
Thiocyanate toxicity :
Symptoms:
Anorexia, nausea, abdominal pain, fatigue, and mental status changes, including psychosis, weakness, seizures, tinnitus, and hyperreflexia.
Treatment:
-Toxicity can be minimized by avoiding prolonged administration of nitroprusside and by limiting drug use in patients with renal insufficiency (as thiocyanate is usually excreted in the urine).
-Thiocyanate can be removed by dialysis (if necessary).
Cyanide toxicity:
-An early sign of cyanide toxicity is the acute resistance to the hypotensive effects of increasing doses of sodium nitroprusside (tachyphylaxis). (It should be noted that tachyphylaxis implies acute tolerance to the drug following multiple rapid injections, as opposed to tolerance, which is caused by more chronic exposure).
-Acute cyanide toxicity occurs when the cyanide ions bind to tissue cytochrome oxidase and interfere with normal oxygen utilization. This leads to metabolic acidosis, cardiac arrhythmias, and increased venous oxygen content (as a result of the inability to utilize oxygen).
Symptoms:
-Cyanide toxicity is often associated with the odor of almonds on breath and can result in metabolic acidosis, tachycardia, mental status changes, respiratory arrest, coma, and death.
Treatment:
-Cyanide toxicity can usually be avoided if the cumulative dose of sodium nitroprusside is less than 0.5 mg/kg/h.
-Mechanical ventilation with 100% oxygen to maximize oxygen availability.
-Administering sodium thiosulfate (150 mg/kg over 15 min) or 3% sodium nitrate (5 mg/kg over 5 min), which oxidizes hemoglobin to methemoglobin, or by limiting the administration of nitroprusside.
Methemoglobinemia:
-Methemoglobinemia occurs due to excessive doses of sodium nitroprusside or sodium nitrate, if the level is greater than 15 %, it can result in symptomatic cellular hypoxia.
Treatment:
-Methylene blue (1–2 mg/kg of a 1% solution over 5 min), which reduces methemoglobin to hemoglobin.
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