Ramipril
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| Systematic (IUPAC) name | |
| (2S,3aS,6aS)-1-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]-octahydrocyclopentabpyrrole-2-carboxylic acid | |
| Identifiers | |
| CAS number | 87333-19-5 |
| ATC code | C09AA05 |
| PubChem | CID 5362129 |
| DrugBank | APRD00009 |
| ChemSpider | 4514937 |
| Chemical data | |
| Formula | C23H32N2O5 |
| Mol. mass | 416.511 g/mol |
| SMILES | eMolecules & PubChem |
| Pharmacokinetic data | |
| Bioavailability | 28% |
| Protein binding | 73% (ramipril) 56% (ramiprilat) |
| Metabolism | Hepatic, to ramiprilat |
| Half-life | 2 to 4 hours |
| Excretion | Renal (60%) and fecal (40%) |
| Therapeutic considerations | |
| Pregnancy cat. | D |
| Legal status | POM (UK) ℞-only (US) |
| Routes | Oral |
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Ramipril (marketed as Ramipro by Westfield Pharma in the Philippines, marketed by Sanofi-Aventis as Tritace and by King Pharmaceuticals as Altace in the United States) is an angiotensin-converting enzyme (ACE) inhibitor, used to treat hypertension and congestive heart failure. ACE inhibitors lower the production of angiotensin II, therefore relaxing arterial muscles while at the same time enlarging the arteries, allowing the heart to pump blood more easily, and increasing blood flow due to more blood being pumped into and through larger passageways.
Ramipril is a prodrug and is converted to the active metabolite ramiprilat by liver esterase enzymes.1 Ramiprilat is mostly excreted by the kidneys. The half-life of ramiprilat is variable (3-16 hours), and is prolonged by heart and liver failure, as well as kidney failure.
It is marketed by King Pharmaceuticals under the brand name Altace. The compound was protected by U.S. Patent 5,061,722 which was assigned to Aventis. The patent was scheduled to expire on 2008-10-29. On 2007-09-11, in an appeal by Lupin Pharmaceuticals the United States Court of Appeals for the Federal Circuit reversed a district court trial verdict, finding that Aventis's patent on Altace was invalid for obviousness - opening the gate of this medicine to generic manufacturers. Ramipril is marketed in India under the brand names of Cardace, Zigpril and Zorem.
Contents
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Indications
Indications for its use include:
- Hypertension;
- Congestive heart failure;2
- Following myocardial infarction in patients with clinical evidence of heart failure;
- Susceptible patients over 55 years: prevention of myocardial infarction, stroke, cardiovascular death or need of revascularization procedures.
- Diabetic nephropathy with microalbuminuria
Cautions
- Do not take potassium supplements without seeking medical advice.
- Do not take during pregnancy
Contraindications
Renovascular disease, severe renal impairment (especially in patients with one kidney or with bilateral renal artery stenosis), volume-depleted patients, history of angioedema while on an ACE inhibitor, pregnancy, hypotension.
Side-effects
- may cause swelling of the mouth, tongue, or throat
- low blood sugar in patients taking other medicine for diabetes which shows as sweating or shakiness
- Dry cough may develop, dizziness, and light-headedness due to low blood pressure. (It is recommended to start treatment with the lowest dose.)
- decreased sex drive
- tiredness and fatigue especially in the early stages
- mouth dryness in the early stages
Dose
Patients are started on the lowest dose and titrated up every 3 - 4 weeks as required.
Dosage comes in the following forms: 1.25 mg, 2.5 mg, 5 mg, 10 mg
Clinical trials
The HOPE trial 3 4 seemed to show that ramipril possessed cardioprotective qualities which extended beyond its qualities as an anti-hypertensive. The HOPE trial and the interpretation of the results have been criticised.5
The AIRE trial 1 6 showed a 27% reduction in mortality.
Ramipril was found to have similar results as telmisartan.7
References
- ^ a b Frampton JE, Peters DH (March 1995). "Ramipril. An updated review of its therapeutic use in essential hypertension and heart failure". Drugs 49 (3): 440–66. PMID 7774515.
- ^ Pilote L, Abrahamowicz M, Eisenberg M, Humphries K, Behlouli H, Tu JV (May 2008). "Effect of different angiotensin-converting-enzyme inhibitors on mortality among elderly patients with congestive heart failure". CMAJ 178 (10): 1303–11. doi:10.1503/cmaj.060068. PMID 18458262.
- ^ http://www.hypertensiononline.org/slides2/slide01.cfm?q=ramipril&dpg=10
- ^ http://ebm.bmj.com/cgi/content/extract/5/2/47
- ^ http://www.medscape.com/viewarticle/430926 "Debate: Do ACE Inhibitors Have Unique Properties, Beyond Their Antihypertensive Effect?"
- ^ "Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators". Lancet 342 (8875): 821–8. October 1993. PMID 8104270.
- ^ Yusuf S, Teo KK, Pogue J, et al (April 2008). "Telmisartan, ramipril, or both in patients at high risk for vascular events". N. Engl. J. Med. 358 (15): 1547–59. doi:10.1056/NEJMoa0801317. PMID 18378520.
See also
- Hypertension
- Hypotension
- Heart failure
- Chest pain
External links
- 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
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