Angiotensin Converting Enzyme Inhibitor

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Contents 1 More Specific Terms 2 Pharmacology 3 Indications 4 Contraindications 5 Monitor 6 Adverse-effects 7 Drug-interactions 8 Mechanism-of-action 9 Notes 10 More General Terms 11 Additional Terms 12 References

More Specific Terms

• benazepril (Lotensin)
• captopril (Capoten)
• enalapril (Vasotec)
• enalaprilat (Vasotec IV)
• fosinopril (Monopril)
• lisinopril (Prinivil, Zestril)
• moexipril (Univasc)
• perindopril (Aceon, Coversyl)
• quinapril (Accupril)
• ramipril (Altace)
• trandolapril (Mavik, indolapril)

Pharmacology

• renin-angiotensin deactivation
• vasodilation
• enhanced vital organ perfusion
• attenuation of hyponatremia
• attenuation of hypokalemia
• decreased fluid retention
• decreased ventricular filling pressure
• decreased systemic vascular resistance
• increased cardiac output
• little or no change in blood pressure* or heart rate
• lower intraglomerular pressure

• diminished transglomerular capillary hydrostatic pressure
• inhibition of angiotensin II-mediated constriction of efferent glomerular arterioles
• diminished proteinuria, especially in diabetics

• * a small amount of diuretic is often synergistic with an ACE inhibitor for lowering blood pressure

Indications

• heart failure
• diabetes mellitus (renal protective)
• stroke prevention [5]; atherosclerosis# in general [8,18]
• coronary artery disease (see PEACE trial, EUROPA trial)
• hypertension
• migraine prophylaxis* [7]
• chronic renal failure [13]

• up to stage 4 kidney disease [15] ( GFR 15-29 mL/min/1.73 m2 & serum creatinine 3-5 mg/dL)

• * only lisinopril shown to have beneficial effects [7]
• # only ramipril ( Altace) & perindopril ( Aceon) shown to be of benefit [8]

Contraindications

• pregnancy: fetal growth retardation, congenital malformation, neonatal renal failure, fetal demise, all trimesters [17]
• renal artery stenosis
  

• inappropriate uses

• ACE inhibitors as a class do not diminish risk of dementia [19]
  

Monitor

• serum potassium every 6 months*
• serum creatinine every 6 months*
• urinalysis
• CBC

• * Serum creatinine & K+ should be checked within 1-2 weeks of starting an ACE inhibitor. [4]
  

• monitor with ACE inhibitors

Adverse-effects

• cough

• may occur after several weeks to 1 year
• dose reduction may alleviate cough
• switching ACE inhibitor is generally of little benefit
• risk 2.7 fold higher southeast Asians than others [16]

• hyperkalemia & hyponatremia via inhibition of aldosterone secretion*
• hypotension & renal insufficiency with reduced preload
• acute renal insufficiency may develop in patients with bilateral renal artery stenosis*
• rash
• angioedema (1%) [6,9]

• generally occurs within 1st week
• may occur years later
• more common in blacks than whites
• probably via inhibiting breakdown of bradykinin [9]
• incidence in blacks 3-fold greater than whites [16]
• small intestine angioedema presenting as acute abdominal pain [20]

• dysgeusia
• increased serum creatinine

• 15-20% initial increase is acceptable [4]
• decline in creatinine within 1 month, otherwise discontinue

• proteinuria may or may not [2] be present
• leukopenia
• vasomotor rhinitis, rhinopharyngeal inflammation
• obstructive sleep apnea [12]
• may exacerbate psoriasis [4]
  
• 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
• ACE inhibitors potientiate effect of diuretics via hypertrophy of loop of Henle
  
• 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 angiotensin II receptor antagonists
• 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

• ACE inhibitors block conversion of angiotensin 1 to angiotensin 2 by inhibiting angiotensin converting enzyme
• angiotensin 2 is a potent vasoconstrictor & stimulates aldosterone secretion from the adrenal cortex, resulting in increased sodium & water retention
• ACE inhibitors also inhibit degradation of bradykinin

• may account for adverse effects of cough & angioedema [6,9]
• increase in nitric oxide release & vasodilation

• reduced antihypertensive effect in African Americans
• ACE inhibitors decrease resistance of postglomerular efferent aterioles, decreasing glomerular filtration pressure
• may slow progression to end-stage-renal-disease [14]
• may slow progression of atherosclerosis [5,8]
• may improve insulin sensitivity [11]
• centrally-active ACE inhibitors ( captopril, fosinopril, lisinopril, perindopril, ramipril, & trandolapril) cross the blood-brain barrier while benazepril, enalapril, moexipril, & quinapril do not

Notes

• more effective when combined with sodium restriction

More General Terms

• vasodilator agent
• protease inhibitor

Additional Terms

• ACE inhibitors & dementia
• ACE inhibitors vs angiotensin receptor blockers (ARB)
• angiotensin
• angiotensin converting enzyme (ACE)
• angiotensin II receptor antagonist (ARB)

References

1. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 117
2. contribution from Peter Baylor, M.D. VAMC, UCSF Fresno
3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
4. Medical Knowledge Self Assessment Program (MKSAP) 11, 15, American College of Physicians, Philadelphia 1998, 2009
5. Prescriber's Letter 9(4):19 2002
6. Prescriber's Letter 9(11):62 2002
7. Journal Watch 23(4):34, 2003 BMJ 322:19, 2001
8. Prescriber's Letter 10(10):59 2003
9. Prescriber's Letter 11(7):31 2004
10. Prescriber's Letter 9(10):41 2002 Comparison of Oral ACE Inhibitors Detail-Document#: [1] (subscription needed) [2]
11. Prescriber's Letter 12(6): 2005 Comparison of Outcomes Between Angiotensin-Converting Enzyme Inhibitors and Angiotensin-Receptor Blockers Detail-Document#: [3] (subscription needed) [4]
12. Prescriber's Letter 12(7): 2005 Evidence for Preventing Type 2 Diabetes Detail-Document#: [5] (subscription needed) [6]
13. Cicolin A et al Angiotensin-coverting enzyme inhibitors and obstructive sleep apnea Mayo Clin Proc 2006; 81:53
14. Hou FF, Zhang X, Zhang GH, Xie D, Chen PY, Zhang WR, Jiang JP, Liang M, Wang GB, Liu ZR, Geng RW. Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med. 2006 Jan 12;354(2):131-40. PMID: [7]
    - Hebert LA. Optimizing ACE-inhibitor therapy for chronic kidney disease. N Engl J Med. 2006 Jan 12;354(2):189-91. No abstract available. PMID: [8]
15. Casas JP, Chua W, Loukogeorgakis S, Vallance P, Smeeth L, Hingorani AD, MacAllister RJ. Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis. Lancet. 2005 Dec 10;366(9502):2026-33. Review. PMID: [9]
16. Prescriber's Letter 13(3): 2006 Angiotensin-Converting-Enzyme Inhibitors in Severe Kidney Disease Detail-Document#: [10] (subscription needed) [11]
17. McDowell SE et al, Systemic review and meta-analysis of ethnic differences in risks of adverse reactions to drugs used in cardiovascular medicine. BMJ 2006; 332:1177 PMID: [12]
    - Eliasson E, Ethnicity and adverse drug reactions: Personalized drug treatment is getting closer but will not replace good clinical judgment. BMJ 2006; 332:1163 PMID: [13]
18. Prescriber's Letter 13(7): 2006 ACE Inhibitors and the Risk of Birth Defects Detail-Document#: [14] (subscription needed) [15]
19. Dagenais GR et al, Angiotensin-converting enzyme inhibitors in stable vascular disease without left ventricular systolice dysfunction or heart failure: A combined analysis of three trials. Lancet 2006, 368:581 PMID: [16]
    - Remuzzi G and Ruggenenti P Overview of randomized trials of ACE inhibitors. Lancet 2006, 368:555 PMID: [17]
20. Sink KM et al Angiotensin-Converting Enzyme Inhibitors and Cognitive Decline in Older Adults With Hypertension: Results From the Cardiovascular Health Study Arch Intern Med. 2009;169(13):1195-1202 PMID: [18]
21. Scheirey CD et al. Angiotensin-converting enzyme inhibitor-induced small-bowel angioedema: Clinical and imaging findings in 20 patients. AJR Am J Roentgenol 2011 Aug; 197:393. PMID: [19]
22. Slagman MCJ et al. Moderate dietary sodium restriction added to angiotensin converting enzyme inhibition compared with dual blockade in lowering proteinuria and blood pressure: Randomised controlled trial. BMJ 2011 Jul 26; 343:d4366. PMID: [20]
23. National Guideline Clearinghouse Expert consensus document on angiotensin converting enzyme inhibitors in cardiovascular disease. ngc-guideline: [21]
    - Annual monitoring for patients on persistent medications: percentage of health plan members 18 years of age and older who received at least a 180-days supply of ambulatory medication therapy for angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) during the measurement year and at least one serum potassium and either a serum creatinine or a blood urea nitrogen therapeutic monitoring test in the measurement year. National Committee for Quality Assurance ngc-guideline: [22]

angiotensin-converting enzyme [ACE] inhibitor