Ramipril

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Contents 1 Introduction 2 Indications 3 Dosage 4 Pharmacokinetics 5 Adverse-effects 6 Drug-interactions 7 Mechanism-of-action 8 More General Terms 9 Additional Terms 10 Internet Database 11 References

Introduction

• Tradename: Altace. C23H32N2O5

Indications

• hypertension
• LV systolic dysfunction
• nephroprotective agent in patients with diabetes mellitus
• recovery from myocardial infarction
• atherosclerosis
• reduces risk of fatal stroke* by 60% [4]

• * 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

• 28% oral bioavailability, not significantly affected by food
• peak plasma levels reached 1 hour after oral dose
• metabolized in the liver by ester hydrolysis to diacid ramiprilat (active metabolite)
• two other inactive metabolites
• peak ramiprilat obtained 2-4 hours after oral dose of ramipril
• ramiprilat has 6 times ACE inhibitory activity as ramipril
• protein binding of ramipril is 73%; that of ramiprilat is 56%
• 60% of drug eliminated in the urine, 40% in the feces
• < 2% of drug recovered unchanged in the urine
• elimination is triphasic

• initial phase 1/2life of 2-4 hours (ramipril)
• clearance of free ramiprilat 9-18 hours, 13-17 hours after multiple doses
• terminal elimination phase > 50 hours (ramiprilat)
  

• elimination via liver
• elimination via kidney
• protein binding = 73 %
• 1/2life = 13-17 hours ramiprilat

Adverse-effects

• cough
• increased risk of angioedema
• hypotension
• dizziness
• syncope
• vertigo
• hepatic failure (rare)
• neutropenia/ agranulocytosis (rare)
• hyperkalemia
• worsening renal function
• nausea/vomiting
• diarrhea
• chest pain
  
• drug adverse effects of ACE inhibitors

Drug-interactions

• NSAIDs may interfere with action of ACE inhibitors

• prostaglandins act on afferent glomerular arterioles
• increased risk of hyperkalemia

• phenothiazines may increase effect of ACE inhibitors
• K+ & K+ sparing diuretics increase the risk of hyperkalemia
  
• drug interaction(s) of renin-angiotensin inhibitors with trimethoprim-sulfamethoxazole
• drug interaction(s) of lithium carbonate with ACE inhibitors
• drug interaction(s) of ACE inhibitors with aliskiren
• drug interaction(s) of ACE inhibitors with angiotensin II receptor antagonists
• drug interaction(s) of potassium chloride with ACE inhibitors
• drug interaction(s) of spironolactone with ACE inhibitors
• drug interaction(s) of diuretics with ACE inhibitors
• drug interaction(s) of beta blockers with ACE inhibitors
• drug interaction(s) of NSAIDs with ACE inhibitors
• drug interaction(s) of ACE inhibitors, angiotensin II receptor antagonists & beta-blockers
• drug interaction(s) of NSAIDs, diuretics & ACE inhibitors

Mechanism-of-action

• see ACE inhibitor
• may prevent progression of atherosclerosis (10 mg/day) [4,5]

• treating 50 patients for 4 years seems to prevent 1 major cardiovascular event [5]
• see HOPE trial

More General Terms

• angiotensin-converting enzyme [ACE] inhibitor

Additional Terms

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

Internet Database

PubChem: 55688
PubChem: 5038

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 <PubMed> PMID: [1] <Internet> [2]

ramipril (Altace)