Angiotensin II

Angiotensin II is the principal active hormone in the renin–angiotensin system governing blood pressure and fluid balance. Giapreza is a synthetic copy, developed by La Jolla Pharmaceutical, now part of Innoviva. It is delivered continuously into a vein in a hospital, rather than as a self-administered injection.

Supporting references: renin-angiotensin system; Giapreza.

For decades angiotensin II was studied mainly as a hormone or a pathway to inhibit; ACE inhibitors and angiotensin-receptor blockers reduce its effects. Therapeutic infusion came much later.

Supporting references: angiotonin.

The peptide primarily activates AT1 receptors on vascular smooth muscle, causing vessel constriction and a rapid blood-pressure rise. Renin initiates production of angiotensin I, which ACE converts to angiotensin II. Angiotensin II also stimulates adrenal aldosterone release, promoting sodium and water retention, and promotes vasopressin release.

This provides a pathway separate from catecholamine vasopressors such as norepinephrine. In ATHOS-3, patients with vasodilatory shock already receiving high-dose vasopressors reached the blood-pressure target in 69.9% of the angiotensin II group versus 23.4% of placebo recipients. Its approximately one-minute blood clearance allows clinicians to adjust the continuous infusion rapidly to blood pressure.

Supporting references: AT1 receptor; ATHOS-3 trial.

Giapreza received FDA approval in December 2017 to increase blood pressure in adults with septic or other distributive shock. It is generally added when standard vasopressors, such as norepinephrine and vasopressin, are insufficient, rather than used as a first outpatient treatment. This is short-term, closely monitored intensive-care treatment for dangerously low pressure associated with loss of vascular tone.

Thrombotic events, including deep-vein thrombosis, are the central safety concern. The label recommends venous-thromboembolism prophylaxis during treatment. Other reported events include low platelets, rapid heart rate, fungal infection, delirium, acidosis, high blood glucose and reduced blood flow to the extremities. The intensive-care setting provides continuous clinical monitoring.