- Ramipril
-
Ramipril 
Systematic (IUPAC) name (2S,3aS,6aS)-1-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]-octahydrocyclopenta[b]pyrrole-2-carboxylic acid Clinical data Trade names Altace AHFS/Drugs.com monograph MedlinePlus a692027 Pregnancy cat. D Legal status POM (UK) ℞-only (US) Routes Oral 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%) Identifiers CAS number 87333-19-5 
ATC code C09AA05 PubChem CID 5362129 DrugBank APRD00009 ChemSpider 4514937 UNII L35JN3I7SJ KEGG D00421 ChEBI CHEBI:8774 ChEMBL CHEMBL1168 Chemical data Formula C23H32N2O5 Mol. mass 416.511 g/mol SMILES eMolecules & PubChem - InChI=1S/C23H32N2O5/c1-3-30-23(29)18(13-12-16-8-5-4-6-9-16)24-15(2)21(26)25-19-11-7-10-17(19)14-20(25)22(27)28/h4-6,8-9,15,17-20,24H,3,7,10-14H2,1-2H3,(H,27,28)/t15-,17-,18-,19-,20-/m0/s1
Key:HDACQVRGBOVJII-JBDAPHQKSA-N
(what is this?) (verify)Ramipril (marketed as Prilace by Arrow Pharmaceuticals in Australia, Ramipro by Westfield Pharma in the Philippines, Tritace by Sanofi-Aventis and Altace by King Pharmaceuticals in the United States) is an angiotensin-converting enzyme (ACE) inhibitor, used to treat high blood pressure and congestive heart failure.
Contents
Mechanism of action
ACE inhibitors lower the production of angiotensin II and also decreasing the breakdown of bradykinin, thereby relaxing arterial muscles and 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. Its effect on bradykinin is also responsible for the dry cough side effect.
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.
Patent
The compound was protected by U.S. Patent 5,061,722 which was assigned to 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 the gate of this medicine to generic manufacturers.
Ramipril is marketed in India under the brand names of Cardace, Zigpril and Zorem.
Indications
Indications for its use include:
- Hypertension;
- Congestive heart failure;[2]
- 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.
- 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
- low blood sugar (in patients taking medication for diabetes), causing sweating or shakiness
- dry cough
- dizziness and light-headedness due to low blood pressure
- tiredness and fatigue, especially in the early stages
- mouth dryness in the early stages
- nausea, vomiting, diarrhea (persistent in rare cases)
- fainting
- change in amount of urine
- signs of infection (e.g., fever, chills, persistent sore throat)
- yellowing of eyes or skin, dark urine
- stomach or abdominal pain
- neutropenia
- impotence (erectile dysfunction or ED)[3]
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:
- rash
- swelling of the face, mouth, tongue, or throat
In extreme cases, Ramipril may lead to potentially fatal liver problems. It is recommended to start treatment with the lowest dose.
Dose
Ramipril 1.25mg Oral Capsule
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[4][5] 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.[6]
The AIRE trial[1][7] showed a 27% reduction in mortality.
Ramipril was found to have similar results as telmisartan.[8]
See also
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. PMC 2335176. PMID 18458262. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2335176.
- ^ Med Tv
- ^ 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. doi:10.1016/0140-6736(93)92693-N. 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.
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
Antihypertensives: agents acting on the renin-angiotensin system (C09) ACE inhibitors
("-pril")Sulfhydryl-containing: Captopril • Zofenopril
Dicarboxylate-containing: Enalapril# • Ramipril • Quinapril • Perindopril • Lisinopril (+HCT) • Benazepril
Phosphonate-containing: Fosinopril
Other/ungrouped: Alacepril • Cilazapril • Delapril • Imidapril • Moexipril • Rentiapril • Spirapril • Temocapril • TrandolaprilAIIRAs/
("-sartan")Azilsartan • Candesartan • Eprosartan • Irbesartan • Losartan • Olmesartan • Tasosartan§ • Telmisartan (+HCT) • Valsartan (+HCT)Renin inhibitors/
("-kiren")Categories:- ACE inhibitors
- Enantiopure drugs
- Prodrugs
- Cyclopentapyrroles
- Carboxylic acids
- Ethyl esters
- Amides
- InChI=1S/C23H32N2O5/c1-3-30-23(29)18(13-12-16-8-5-4-6-9-16)24-15(2)21(26)25-19-11-7-10-17(19)14-20(25)22(27)28/h4-6,8-9,15,17-20,24H,3,7,10-14H2,1-2H3,(H,27,28)/t15-,17-,18-,19-,20-/m0/s1
Wikimedia Foundation. 2010.
