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 Y
ATC code	C09AA05
PubChem	CID 5362129
DrugBank	DB00178
ChemSpider	4514937 Y
UNII	L35JN3I7SJ Y
KEGG	D00421 Y
ChEBI	CHEBI:8774 Y
ChEMBL	CHEMBL1168 Y
Chemical data
Formula	C23H32N2O5
Mol. mass	416.511 g/mol
SMILES O=C(OCC)[C@@H](N[C@H](C(=O)N1[C@H](C(=O)O)C[C@@H]2CCC[C@H]12)C)CCc3ccccc3
InChI 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 Y Key:HDACQVRGBOVJII-JBDAPHQKSA-N Y
Y (what is this?)  (verify)

Ramipril is an angiotensin-converting enzyme (ACE) inhibitor, used to treat high blood pressure and congestive heart failure. It is marketed as Prilace by Arrow Pharmaceuticals in Australia, Ramipro by Westfield Pharma in the Philippines, Tritace by Sanofi-Aventis in Italy and United States and Altace by King Pharmaceuticals in the United States, Ramitens by PharmaSwiss, Ampril by Krka in Slovenia, Corpril by Cemelog-BRS in Hungary, Piramil and Prilinda by Hemofarm in Serbia, by Lek in Poland and by Novartis and Opsonin Pharma Limited as Ramace in Bangladesh, and in Canada as Altace (Sonfi) and Ramipril (Pharmascience).

Medical uses

Indications for its use include:

• Hypertension;
• Congestive heart failure;^[1]
• 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 (kidney damage due to diabetes) with microalbuminuria (protein in the urine)

Contraindications

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, history of angioedema while on an ACE inhibitor, pregnancy, hypotension.

Adverse 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 (low white blood cells)
• impotence (erectile dysfunction)^[2]

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

Ramipril 1.25mg oral capsule.
Letter codes & icons may differ.

ACE inhibitors, as the name suggests, inhibit the actions of angiotensin converting enzyme (ACE), thereby lowering the production of angiotensin II and also 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 (metabolic product) ramiprilat by liver esterase enzymes.^[3] 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 this medicine to generic manufacturers.

Ramipril is marketed in India under the brand names of Cardace, Zigpril, Ramistar and Zorem.

Clinical trials

The HOPE trial^[4][5] seemed to show ramipril possessed cardioprotective qualities which extended beyond its qualities as an antihypertensive. However, the HOPE trial and the interpretation of the results have been criticised.^[6]

The AIRE trial^[3][7] showed a 27% reduction in mortality.

Ramipril was found to have similar results as telmisartan, an angiotensin II receptor blocker (ARB).^[8]

See also

• Angiotensin-converting enzyme (ACE) inhibitor
• Hypertension
• Hypotension
• Heart failure
• Chest pain

References

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