The mechanism of action of sodium nitroprusside (SNP) is similar to NTG. It should be noted that nitric oxide is a potent vasodilator (half-life <10 s) and has its effects throughout the body. Inhaled nitric oxide is often used for treatment of pulmonary hypertension, especially in ICU patients.

Sodium nitroprusside on administration enters red blood cells and results in the formation of 5 cyanide ions and methemoglobin (an electron added to oxyhemoglobin). The cyanide ions exert their toxicity by combing with methemoglobin to form cyanmethemoglobin, combining with thiosulfate in the liver to form thiocyanate, and inhibiting the cytochrome oxidase enzyme system. All these effects can lead to cyanide toxicity (metabolic acidosis, dysrhythmias, tachyphylaxis of its hypotensive effect/acute tolerance). Treatment of cyanide toxicity includes limiting administration of sodium nitroprusside to less than 0.5 mg/kg/h and administration of 100 % oxygen. Methemoglobinemia is treated with intravenous methylene blue (1–2 mg/kg).

Sodium nitroprusside is a potent vasodilator, causing dilation of both the venous and arteriolar beds leading to a decrease in peripheral vascular resistance. It causes a reduction in mainly the preload, but also the afterload. The decrease in preload decreases myocardial oxygen requirements, but this effect is attenuated with an increase in heart rate (reflex tachycardia) and myocardial contractility, which increase oxygen demand. Sodium nitroprusside also dilates cerebral and pulmonary blood vessels, thereby, increasing blood flow. However, this increase in blood flow may be offset by reduction in arterial blood pressure. Therefore, administration of sodium nitroprusside may lead to increased intracranial pressure and ventilation-perfusion mismatch (less blood flow to ischemic areas).

Sodium nitroprusside is an extremely potent vasodilator and leads to a rapid lowering of blood pressure. An arterial line is used to monitor the blood pressure during sodium nitroprusside administration. It is administered via an infusion in a dose of 0.25–10 mcg/kg/min. Its onset of action occurs in 2 min and action lasts briefly after stopping the infusion. The solution is protected from light because of degradation by light.

Hydralazine acts as a direct arteriolar smooth muscle dilator, thus lowering peripheral vascular resistance (afterload) and the blood pressure. The exact mechanism remains unclear, but it may interfere with calcium utilization or activation of guanylyl cyclase.

Hydralazine lowers the blood pressure, which leads to an increase in heart rate and myocardial contractility. To offset these effects in cardiac compromised patients, beta-blockers may be given. Also, hydralazine leads to cerebral and renal vasodilation, and therefore, it is beneficial to use in patients with renal disease as it maintains renal blood flow. Some unwanted side effects include peripheral edema, lupus-like syndrome, pancytopenia, and peripheral neuropathy.

Hydralazine is used to treat hypertension intraoperatively. It is available in a vial, 20 mg/ml, and is diluted to 10 ml (2 mg/ml) prior to use. It is administered in 2–4 mg doses, up to 20 mg. The onset of action is in 10–15 min and lasts long for 2–4 h.

Epinephrine (EPI) is an endogenous adrenergic agonist, which is synthesized, stored, and released from the adrenal medulla. It has a variety of clinical indications including treatment of status asthmaticus, cardiac arrest, shock, anaphylaxis, and also prolongation of regional anesthesia (when mixed with local anesthetics). It has a dose-dependent effect on alpha- and beta-receptors. At low dosages (<0.03 mcg/kg/min), beta effects predominate, which include increases in heart rate, myocardial contractility, and cardiac output. Beta-2 stimulation causes bronchodilation and lowering of diastolic blood pressure due to skeletal muscle vasodilation (Tables 17.2 and 17.3).

At higher dosages (>0.15 mcg/kg/min) of EPI, the alpha effects are pronounced. This leads to increases in blood pressure (systolic) and coronary and cerebral perfusion pressures. Therefore, the physiological response on alpha- and beta-receptors by EPI demonstrates considerable variations (i.e., EPI can stimulate beta-receptors on some beds while stimulating alpha-receptors in others). EPI also possess strong pro-arrhythmogenic properties, especially in times of high sympathetic states (surgery, ischemia, hypoxia, sepsis). Excessive doses can lead to myocardial ischemia, cerebral bleeding, and arrhythmias. Classically described in literature is the administration of halothane with EPI leading to increased sensitization of the myocardium to the arrhythmogenic effects of epinephrine.

Epinephrine is available in vials of 1 mg/ml (1:1,000) or in prefilled syringes of 0.1 mg/ml (1:10,000). It is also commonly added to local anesthetic solutions at a concentration of 1:200,000 (5 mcg/ml). EPI is administered in boluses of 0.05–1 mg depending on the indication. It can also be given via an infusion of 0.01–0.3 mcg/kg/min or 2–20 mcg/min (prepared as 1 mg in 250 ml of D₅W = 4 mcg/ml).

A precursor to EPI, NE serves as an endogenous mediator of the sympathetic nervous system. It has direct alpha-1 stimulation with no beta-2 activity. Stimulation of alpha-1 receptors by NE leads to intense vasoconstriction, an increase in afterload, and reflex bradycardia. Stimulation of beta-1 receptors increases myocardial contractility, which may increase cardiac output. However, this increase in cardiac output is offset by the alpha-1 effects of NE. Therefore, NE is usually reserved for the treatment of refractory shock.

Since NE lacks chronotropic effects, it can improve coronary perfusion pressure without causing ischemia. However, the increase in ventricular filling pressures that NE causes can be attenuated by administrating a vasodilator. While end-organ ischemia is a concern with NE, maintaining MAP greater than 70 mmHg and an adequate cardiac output will minimize this effect. NE is available in 4 ml ampoules (4 mg/4 ml). It is administered as an infusion (4 mg in 250 ml of D₅W = 16 mcg/ml) in a dose of 0.01–1 mcg/kg/min or 2–20 mcg/min.

Ephedrine has both direct and indirect (predominate) actions on alpha- and beta-receptors. Its actions are similar to EPI, but it is less potent than EPI. Ephedrine causes an increase venous return (preload), blood pressure, heart rate, and myocardial contractility, with subsequent increase in cardiac output. Ephedrine is used to treat intraoperative hypotension, though temporarily as the cause is determined. Other effects of ephedrine include its antiemetic properties and treatment of hypotension with spinal anesthesia in obstetrics. Ephedrine does not cause a decrease in uterine blood flow and is, therefore, the vasopressor of choice for obstetrics anesthesia. Administration of ephedrine in patients taking monoamine oxidase inhibitors (for depression) can lead to a hypertensive crisis due to sudden and massive release of adrenergic neurotransmitters. Ephedrine is available as 50 mg/ml 1 ml vials. It is commonly diluted to 5 or 10 mg/ml (with normal saline) and is administered in dosages of 5–10 mg boluses (0.1 mg/kg). Repeated doses of ephedrine may lead to tachyphylaxis (decreased stores of NE).