||This article may be too technical for most readers to understand. (February 2012)|
|Systematic (IUPAC) name|
|Protein binding||73% (ramipril)
|Metabolism||Hepatic, to ramiprilat|
|Half-life||2 to 4 hours|
|Excretion||Renal (60%) and fecal (40%)|
|Melting point||109 °C (228 °F)|
|(what is this?)|
Ramipril is an angiotensin-converting enzyme (ACE) inhibitor, used to treat high blood pressure (hypertension) and congestive heart failure. By inhibiting an enzyme, ACE inhibitors relax the muscles around small arteries (arterioles). The arterioles expand and allow blood to flow through more easily. This reduces blood pressure.
Indications for its use include:
- High blood pressure
- Congestive heart failure
- Following heart attack in patients with clinical evidence of heart failure
- Susceptible patients over 55 years: prevention of heart attack, stroke, cardiovascular death, or need of revascularization procedures
- kidney damage due to diabetes with protein in the urine (In low doses it is used as a prophylaxis for developing nephropathy and related secondary cardiovascular events.)
Contraindications to its use include renovascular disease (impaired blood flow in the kidneys), severe renal impairment (especially in patients with one kidney or with bilateral renal artery stenosis), volume-depleted patients, a history of angioedema while on an ACE inhibitors, pregnancy, and hypotension.
- Dry cough
- Dizziness and light-headedness due to low blood pressure
- Fatigue, especially in the early stages
- Mouth dryness in the early stages
- Signs of infection (e.g., fever, chills, persistent sore throat)
- Chest pain
- Neutropenia (low white blood cells)
- Impotence (erectile dysfunction)
Serious allergic reactions to this drug are unlikely, but immediate medical attention must be sought if they occur. Symptoms of a serious allergic reaction include, but are not limited to a rash or swelling of the face, mouth, tongue, or throat. In extreme cases, ramipril may lead to potentially fatal liver problems.
Mechanism of action
ACE inhibitors inhibit the actions of angiotensin converting enzyme (ACE), thereby lowering the production of angiotensin II and decreasing the breakdown of bradykinin. The decrease in angiotensin II results in relaxation of arteriole smooth muscle leading to a decrease in total peripheral resistance, reducing blood pressure as the blood is pumped through widened vessels. Its effect on bradykinin is responsible for the dry cough side effect.
Ramipril, a prodrug or precursor drug, is converted to the active metabolite ramiprilat by carboxylesterase 1. Ramiprilat is mostly excreted by the kidneys. Its half-life is variable (3–16 hours), and is prolonged by heart and liver failure, as well as kidney failure.
The compound was protected by U.S. Patent 5,061,722 which was assigned to the German pharmaceutical company Hoechst AG (since merged into Aventis) on 29 October 1991. The patent was scheduled to expire on 29 October 2008. On 11 September 2007, in an appeal by the Indian company Lupin Ltd., the United States Court of Appeals for the Federal Circuit reversed a district court trial verdict and found that Aventis's patent on ramipril was invalid for "obviousness", opening this drug to generic manufacturers.
Ramipril is marketed in India under the brand names of Cardace, Zigpril, Ramistar and Zorem.
The Heart Outcomes and Prevention Evaluation trial seemed to show ramipril possessed cardioprotective qualities which extended beyond its qualities as an antihypertensive. However, the trial and the interpretation of its results have been criticised.
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- Hypertension Online Slides - ramipril, mortality, kidney failure, HOPE
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- http://www.medscape.com/viewarticle/430926 "Debate: Do ACE Inhibitors Have Unique Properties, Beyond Their Antihypertensive Effect?"
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- "The synthesis of Ramipril". Retrieved 2014-07-09.
- "Deprotecting Acetamide: acid vs base.".
- Altace (ramipril), a registered trademark of King Pharmaceuticals, Inc.
- Data Sheet for Ramipril – ChemSpider 18 September 2008
- U.S. National Library of Medicine: Drug Information Portal - Ramipril