Drug Information: Enalaprilat
Enalaprilat is an intravenous ACE (angiotensin-converting enzyme) inhibitor used primarily in the management of hypertensive emergencies when oral medication is not feasible. As an ACE inhibitor, Enalaprilat prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to vasodilation, decreased blood pressure, and reduced afterload on the heart. It’s a valuable tool in rapidly lowering blood pressure in critical situations and is often preferred due to its rapid onset of action compared to oral ACE inhibitors. Enalaprilat is the active metabolite of the orally administered prodrug enalapril.
Category
Antihypertensive
Mechanism of Action
Enalaprilat’s mechanism of action centers around its role as an ACE (Angiotensin-Converting Enzyme) inhibitor. ACE is a crucial enzyme in the renin-angiotensin-aldosterone system (RAAS), a hormonal system responsible for regulating blood pressure and fluid balance. Specifically, ACE catalyzes the conversion of angiotensin I to angiotensin II.
Angiotensin II is a potent vasoconstrictor, meaning it narrows blood vessels, increasing blood pressure. It also stimulates the release of aldosterone from the adrenal glands. Aldosterone promotes sodium and water retention by the kidneys, further increasing blood volume and pressure.
Enalaprilat competitively inhibits ACE, preventing the conversion of angiotensin I to angiotensin II. This leads to several key effects:
* **Vasodilation:** Reduced angiotensin II levels cause blood vessels to relax (vasodilation), leading to a decrease in systemic vascular resistance and, consequently, blood pressure.
* **Reduced Aldosterone Secretion:** Decreased angiotensin II also diminishes aldosterone release. This results in reduced sodium and water retention by the kidneys, further contributing to blood pressure reduction and decreased preload.
* **Increased Bradykinin Levels:** ACE also breaks down bradykinin, a vasodilator. By inhibiting ACE, Enalaprilat increases bradykinin levels, contributing to vasodilation and potentially other beneficial effects on cardiovascular function.
The overall effect of Enalaprilat is a reduction in both preload and afterload on the heart, making it effective in managing hypertension and heart failure. Because Enalaprilat is administered intravenously, it bypasses the first-pass metabolism in the liver that occurs with oral Enalapril, allowing for a rapid and predictable therapeutic effect.
Clinical Uses
Enalaprilat is primarily used in the management of hypertensive emergencies, which are situations of severely elevated blood pressure that pose an immediate threat to organ function. These situations often require rapid and controlled blood pressure reduction. Specific clinical uses include:
* **Hypertensive Emergencies:** This is the primary indication. Enalaprilat is used when rapid blood pressure control is crucial to prevent end-organ damage (e.g., stroke, heart attack, kidney failure).
* **Severe Hypertension Unresponsive to Oral Medications:** When oral antihypertensives are ineffective or cannot be administered (e.g., due to vomiting or impaired consciousness), Enalaprilat provides a viable intravenous alternative.
* **Acute Heart Failure:** In some cases, Enalaprilat can be used as an adjunct therapy in acute heart failure, particularly when afterload reduction is desired to improve cardiac output and reduce pulmonary congestion.
* **Postoperative Hypertension:** Enalaprilat can be helpful in controlling blood pressure spikes that sometimes occur after surgical procedures.
* **Hypertension Associated with Renal Disease:** Enalaprilat can be used, with careful monitoring of renal function, in patients with hypertension complicated by kidney disease. However, other ACE inhibitors are preferred and Enalaprilat is reserved for acute situations.
It is important to note that Enalaprilat should be used cautiously and with careful monitoring of blood pressure and renal function due to the risk of hypotension and kidney injury, especially in volume-depleted patients or those with pre-existing renal disease.
Dosage
* **Adults:** The typical initial intravenous dose is 1.25 mg administered over 5 minutes. Blood pressure should be monitored frequently. Additional doses of 1.25 mg may be administered every 6 hours as needed, up to a maximum of 5 mg in 24 hours. Adjustments may be necessary based on individual patient response and renal function.
* **Pediatrics:** Safety and efficacy in pediatric patients have not been definitively established, and its use should be approached with extreme caution. Dosing should be individualized by qualified specialists based on the individual assessment.
* **Renal Impairment:** Dosage adjustments are necessary in patients with renal impairment. The initial dose should be reduced, and blood pressure should be monitored even more closely.
**Route of Administration:** Intravenous (IV) injection.
Indications
* Hypertensive emergencies
* Severe hypertension when oral medication is not feasible
* Adjunctive therapy for acute heart failure
* Postoperative hypertension
Contraindications
* Hypersensitivity to enalapril or other ACE inhibitors
* History of angioedema related to ACE inhibitor therapy
* Bilateral renal artery stenosis or severe renal artery stenosis in a solitary kidney
* Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (CrCl < 60 mL/min)
* Pregnancy (especially the second and third trimesters)
FAQ
**Q: What is Enalaprilat used for?**
A: Enalaprilat is used to rapidly lower blood pressure in hypertensive emergencies when oral medications are not suitable.
**Q: How quickly does Enalaprilat work?**
A: Enalaprilat has a rapid onset of action, typically within 15-30 minutes.
**Q: What are the common side effects of Enalaprilat?**
A: Common side effects include hypotension, dizziness, cough, and renal impairment.
**Q: Can Enalaprilat be used in patients with kidney problems?**
A: Enalaprilat can be used with caution in patients with kidney problems, but dosage adjustments and careful monitoring of renal function are necessary. It’s generally avoided if other options exist.
**Q: Is Enalaprilat safe during pregnancy?**
A: No, Enalaprilat is contraindicated during pregnancy, especially in the second and third trimesters, due to the risk of fetal harm.
**Q: What should I do if my blood pressure drops too low after receiving Enalaprilat?**
A: If blood pressure drops too low, the infusion should be stopped, and the patient should be placed in a supine position with legs elevated. Fluid administration or vasopressors may be necessary.
**Q: How is Enalaprilat administered?**
A: Enalaprilat is administered intravenously by a healthcare professional.
**Q: Can Enalaprilat be given with other blood pressure medications?**
A: Yes, but caution is advised when using Enalaprilat with other antihypertensive medications, as it can increase the risk of hypotension. Careful monitoring of blood pressure is essential.
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