Cilazaprilat

{{Infobox drug | name = Cilazaprilat | image = Cilazaprilat_structure.png | width = 200 | alt = | caption = Chemical structure of Cilazaprilat | tradename = | Drugs.com = | MedlinePlus = | pregnancy_AU = | pregnancy_US = | legal_AU = | legal_CA = | legal_UK = | legal_US = | routes_of_administration = Oral | bioavailability = | protein_bound = | metabolism = Hepatic | elimination_half-life = 9 hours | excretion = Renal | CAS_number = 92077-20-6 | ATC_prefix = C09 | ATC_suffix = AA08 | PubChem = 5282130 | DrugBank = DB01340 | ChemSpiderID = 4445530 | UNII = 3G0285N20N | KEGG = D07704 | ChEBI = 3694 | ChEMBL = 1201328 | IUPAC_name = (2S)-1-[(2S)-2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]propanoyl]pyrrolidine-2-carboxylic acid | chemical_formula = C22H31N3O5 | molecular_weight = 417.50 g/mol }}

Cilazaprilat is an angiotensin-converting enzyme inhibitor (ACE inhibitor) used primarily in the treatment of hypertension and congestive heart failure. It is the active metabolite of the prodrug cilazapril.

Pharmacology

Cilazaprilat functions by inhibiting the angiotensin-converting enzyme (ACE), which is responsible for the conversion of angiotensin I to angiotensin II. Angiotensin II is a potent vasoconstrictor and stimulates the secretion of aldosterone from the adrenal cortex, leading to increased blood pressure. By inhibiting ACE, cilazaprilat decreases the production of angiotensin II, resulting in vasodilation and reduced blood pressure.

Mechanism of Action

Cilazaprilat binds to the active site of ACE, preventing the conversion of angiotensin I to angiotensin II. This leads to a decrease in systemic vascular resistance and blood pressure. Additionally, the reduction in angiotensin II levels decreases aldosterone secretion, which reduces sodium and water retention, further lowering blood pressure.

Pharmacokinetics

Cilazaprilat is formed from cilazapril after oral administration. Cilazapril is rapidly absorbed and converted to cilazaprilat in the liver. Cilazaprilat has a half-life of approximately 9 hours and is primarily excreted by the kidneys. Its bioavailability is influenced by hepatic function and renal clearance.

Clinical Use

Cilazaprilat is used in the management of hypertension and heart failure. It is effective in reducing blood pressure and improving cardiac output in patients with heart failure. The drug is typically administered once daily due to its long half-life.

Hypertension

In patients with hypertension, cilazaprilat reduces blood pressure by decreasing peripheral vascular resistance. It is often used in patients who require long-term management of high blood pressure.

Heart Failure

In heart failure, cilazaprilat improves symptoms by reducing afterload and preload on the heart, thereby enhancing cardiac output and reducing the symptoms of heart failure such as dyspnea and fatigue.

Adverse Effects

Common adverse effects of cilazaprilat include cough, dizziness, and hyperkalemia. The cough is thought to be due to the accumulation of bradykinin, which is normally broken down by ACE. Hyperkalemia occurs due to decreased aldosterone levels, leading to reduced potassium excretion.

Contraindications

Cilazaprilat is contraindicated in patients with a history of angioedema related to previous ACE inhibitor therapy. It is also contraindicated in patients with bilateral renal artery stenosis and during pregnancy due to the risk of fetal toxicity.

Interactions

Cilazaprilat may interact with other medications that affect renal function or potassium levels, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and potassium-sparing diuretics. These interactions can increase the risk of renal impairment and hyperkalemia.

See Also

• ACE inhibitors
• Hypertension
• Heart failure

Common ACE inhibitors include the following:

• Benazepril
• Captopril
• Enalapril
• Fosinopril
• Lisinopril
• Moexipril
• Perindopril
• Quinapril
• Ramipril
• Trandolapril