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ramipril (Altace)

Tradename: Altace. C23H32N2O5 Indications: - hypertension - chronic heart failure - LV systolic dysfunction - left ventricular diastolic dysfunction - diabetic nephropathy - nephroprotective agent in patients with diabetes mellitus - nondiabetic proteinuric nephropathy - atherosclerosis - recovery from myocardial infarction - reduces risk of fatal stroke* by 60% [4] - scleroderma renal crisis [7] * even in patients without high blood pressure Dosage: HTN. Start 2.5 mg PO QD, max 20 mg/day. Tabs: 1.25, 2.5, 5, 10 mg. Pharmacokinetics: 1) 28% oral bioavailability, not significantly affected by food 2) peak plasma levels reached 1 hour after oral dose 3) metabolized in the liver by ester hydrolysis to diacid ramiprilat (active metabolite) 4) two other inactive metabolites 5) peak ramiprilat obtained 2-4 hours after oral dose of ramipril 6) ramiprilat has 6 times ACE inhibitory activity as ramipril 7) protein binding of ramipril is 73%; that of ramiprilat is 56% 8) 60% of drug eliminated in the urine, 40% in the feces 9) < 2% of drug recovered unchanged in the urine 10) elimination is triphasic a) initial phase 1/2life of 2-4 hours (ramipril) b) clearance of free ramiprilat 9-18 hours, 13-17 hours after multiple doses c) terminal elimination phase > 50 hours (ramiprilat) Adverse effects: 1) cough 2) increased risk of angioedema 3) hypotension 4) dizziness 5) syncope 6) vertigo 7) hepatic failure (rare) 8) neutropenia/agranulocytosis (rare) 9) hyperkalemia 10) worsening renal function 11) nausea/vomiting 12) diarrhea 13) chest pain Drug interactions: 1) NSAIDs may interfere with action of ACE inhibitors a) prostaglandins act on afferent glomerular arterioles b) increased risk of hyperkalemia 2) phenothiazines may increase effect of ACE inhibitors 3) K+ & K+ sparing diuretics increase the risk of hyperkalemia Mechanism of action: 1) see ACE inhibitor 2) may prevent progression of atherosclerosis (10 mg/day) [4,5] a) treating 50 patients for 4 years seems to prevent 1 major cardiovascular event [5] b) see HOPE trial

Interactions

drug interactions drug adverse effects (more general classes) monitor with ACE inhibitors

Related

African American Study of Kidney Disease & Hypertension (AASK) HOPE & HOPE Too trials

General

angiotensin-converting enzyme (ACE) inhibitor

Properties

INHIBITS: angiotensin converting enzyme SIZE: MW = 415 kD MISC-INFO: elimination route LIVER KIDNEY protein-binding 73% pregnancy-category D safety in lactation ? 1/2life 13-17 HOURS

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Prescriber's Letter 7(11):62 2000
  3. Physician's Desk Reference (PDR), 56th ed, Medical Economics, 2002
  4. Prescriber's Letter 9(4):19 2002
  5. Prescriber's Letter 10(10):59 2003
  6. Journal Watch 24(8):62, 2004 Marre M et al, BMJ 328:495,2004 PMID: 14960504 http://bmj.bmjjournals.com/cgi/content/full/328/7438/495
  7. Deprecated Reference