Angiotensin

Uses

Angiotensin is a peptide hormone of the RAAS system used to raise blood pressure in septic or other forms of shock.

Angiotensin is a vasoconstrictor indicated for increasing blood pressure in adults with septic or other distributive shock .

Angiotensin is also used to associated treatment for these conditions: Hypotension

How Angiotensin works

As part of the renin-angiotensin-aldosterone-system (RAAS), angiotensin II raises blood pressure by vasoconstriction, increased aldosterone release by the adrenal zona glomerulosa, sodium and water reabsorption in the proximal tubular cells, and vasopressin secretion

The direct action of angiotensin II on surrounding vessel walls is facilitated by binding to the G-protein-coupled angiotensin II receptor type 1 (AT-1) on vascular smooth muscle cells, which stimulates Ca2+/calmodulin-dependent phosphorylation of myosin and causes smooth muscle contraction that results in vasoconstriction .

The RAAS is ultimately regulated by a negative feedback effect of angiotensin II on renin production by the juxtaglomerular cells of the renal afferent arteriole. Unresuscitated septic shock associated with marked hypovolemia, extracellular fluid volume depletion, decreased cardiac output, low arterial blood pressure and decreased systemic vascular resistance causes an increase in renin secretion by the juxtaglomerular cells, resulting in elevated angiotensin II plasma levels and an increased secretion of aldosterone from the adrenal cortex. Angiotensin binding to AT-1 receptors causes dose-dependent vasoconstriction of both afferent and efferent glomerular arterioles. The most pronounced effect of angiotensin II results on efferent arterioles, resulting in reduced renal blood flow and increased glomerular filtration pressure.

Toxicity

Overdose with angiotensin II would be expected to result in hypertension, necessitating close monitoring and supportive care . Effects are also expected to be brief as the half-life of angiotensin II is less than one minute .

In the ATHOS-3 clinical study there was a higher incidence of arterial and venous thrombotic and thromboembolic events in patients who received angiotensin II compared to placebo treated patients. The major imbalance was in deep venous thromboses - which prompts the potential need to use concurrent venous thromboembolism (VTE) prohphylaxis .

Adverse effects of noticeable potential (>= 10%) include thromboembolic events (ie. like deep vein thrombosis) including arterial and venous thrombotic events, thrombocytopenia, tachycardia, and fungal infection. Effects whose potential are < 10% include delirium, acidosis, hyperglycemia, peripheral ischemia .

Concomitant use of angiotensin converting enzymes (ACE) inhibitors may increase the response of angiotensin II .

Concomitant use of angiotensin II blockers (ARBs) may decrease the response to angiotensin II .

There are no formal data regarding the safe use of angiotensin II in pregnant women. However, septic or other distributive shock is a medical emergency that can be fatal if left untreated. Delaying treatment in pregnant women with hypotension associated with septic or otherdistributive shock is likely to increase the risk of maternal and fetal morbidity and mortality .

There is no formal data regarding whether or not angiotensin II may become present in human milk and there is no data available on the effects of angiotensin II on the breastfed child or the effects on milk production .

The safety and efficacy of angiotensin II in pediatric patients has not yet been established .

There is no difference in the safety or efficacy between patients less than 65 years old and those 65 years or older when treated with angiotensin II .

There is no difference in pharmacokinetics between male and female patients .

The pharmacokinetics of angiotensin II are not expected to be influenced by renal impairment or hepatic impairment .

Food Interaction

Volume of Distribution

The official prescribing information for angiotensin II notes that no specific studies have yet been conducted that examine the distribution of angiotensin II .

Elimination Route

Following the intravenous infusion of angiotensin II in adult patients with septic or other distributive shock, the serum levels of angiotensin II observed were similar at baseline and hour 3 after the intravenous infusion. After 3 hours of treatment, the serum level of angiotensin I (the angiotensin II precursos peptide) is however, reduced by about 40% .

Half Life

The plasma half-life of intravenously administered angiotensin II is less than one minute .

Clearance

The official prescribing information notes that the clearnace of angiotensin II is not dependent on hepatic function or renal function .

Elimination Route

The official prescribing information notes that no specific studies have been conducted that examine the elimination of angiotensin II.

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