ACE Inhibitors: Congestive Heart Failure: Difference between revisions

(Update the introduction. Added a new section on contraindications. Provided other minor additional information.)
(Added Lisinopril as a common ACE inhibitor)
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* Captropil<ref name=":0">Ciccone CD. Renin Angiotensin System Inhibitors. ''Pharmacology in rehabilitation.'' 5th ed. Philadelphia: F.A. Davis Company; 2016</ref>: given 25 mg 3 times daily and has a shorter half-life of 3.3 hours requiring the patient to take it more frequently<ref>U.S. Food and Drug Administration (FDA). CAPOTEN® (Captopril Tablets, USP). Available online at: <nowiki>https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/018343s084lbl.pdf</nowiki>.  Last accessed 11/29/18.</ref>.  
* Captropil<ref name=":0">Ciccone CD. Renin Angiotensin System Inhibitors. ''Pharmacology in rehabilitation.'' 5th ed. Philadelphia: F.A. Davis Company; 2016</ref>: given 25 mg 3 times daily and has a shorter half-life of 3.3 hours requiring the patient to take it more frequently<ref>U.S. Food and Drug Administration (FDA). CAPOTEN® (Captopril Tablets, USP). Available online at: <nowiki>https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/018343s084lbl.pdf</nowiki>.  Last accessed 11/29/18.</ref>.  
* Lisinopril<ref>Simpson K, Jarvis B. Lisinopril: a review of its use in congestive heart failure. Drugs. 2000 May;59(5):1149-67. doi: 10.2165/00003495-200059050-00012. PMID: 10852646.</ref>: Initial dose 2.5 to 5 mg orally once a day. Maintenance dose is increased as tolerated. Maximum dose is 40 mg orally once a day.<ref>Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013 Oct 15;128(16):1810-52.</ref>


== Adverse Effects ==
== Adverse Effects ==
* Cough: Dry, non-productive paroxysmal cough is reported in about 1 to 10% of people who use ACE inhibitors.<ref>Pinargote P, Guillen D, Guarderas JC. ACE inhibitors: upper respiratory symptoms. BMJ Case Rep. 2014 Jul 17;2014</ref> <ref>Israili ZH, Hall WD. Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy. A review of the literature and pathophysiology. Ann Intern Med. 1992 Aug 01;117(3):234-42</ref>This adverse reaction is more commonly reported among women than men.<ref>Os I, Bratland B, Dahlöf B, Gisholt K, Syvertsen JO, Tretli S. Female sex as an important determinant of lisinopril-induced cough. Lancet. 1992 Feb 08;339(8789):372. </ref> Often, cessation of therapy leads to stoppage of cough.<ref>Herman LL, Padala SA, Ahmed I, et al. Angiotensin Converting Enzyme Inhibitors (ACEI) [Updated 2021 Aug 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: <nowiki>https://www.ncbi.nlm.nih.gov/books/NBK431051/</nowiki></ref> Experimental studies also suggest the use if non-steroidal anti-inflammatory agents and intermediate low-dose Aspirin to be helpful with ACE inhibitors-induced cough.<ref>Tenenbaum A, Grossman E, Shemesh J, Fisman EZ, Nosrati I, Motro M. Intermediate but not low doses of aspirin can suppress angiotensin-converting enzyme inhibitor-induced cough. Am J Hypertens. 2000 Jul;13(7):776-82</ref>  
* Cough: Dry, non-productive paroxysmal cough is reported in about 1 to 10% of people who use ACE inhibitors.<ref>Pinargote P, Guillen D, Guarderas JC. ACE inhibitors: upper respiratory symptoms. BMJ Case Rep. 2014 Jul 17;2014</ref> <ref>Israili ZH, Hall WD. Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy. A review of the literature and pathophysiology. Ann Intern Med. 1992 Aug 01;117(3):234-42</ref>This adverse reaction is more commonly reported among women than men.<ref>Os I, Bratland B, Dahlöf B, Gisholt K, Syvertsen JO, Tretli S. Female sex as an important determinant of lisinopril-induced cough. Lancet. 1992 Feb 08;339(8789):372. </ref> Often, cessation of therapy leads to stoppage of cough.<ref>Herman LL, Padala SA, Ahmed I, et al. Angiotensin Converting Enzyme Inhibitors (ACEI) [Updated 2021 Aug 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: <nowiki>https://www.ncbi.nlm.nih.gov/books/NBK431051/</nowiki></ref> Experimental studies also suggest the use if non-steroidal anti-inflammatory agents and intermediate low-dose Aspirin to be helpful with ACE inhibitors-induced cough.<ref>Tenenbaum A, Grossman E, Shemesh J, Fisman EZ, Nosrati I, Motro M. Intermediate but not low doses of aspirin can suppress angiotensin-converting enzyme inhibitor-induced cough. Am J Hypertens. 2000 Jul;13(7):776-82</ref>
* Rare: Hypotension and Renal Failure because ACE inhibitors are primarily excreted through the kidneys.
* Rare: Hypotension and Renal Failure because ACE inhibitors are primarily excreted through the kidneys.
* Minor side effects, normally resolved with adjusting the dosage<ref name=":0" />, include:  
* Minor side effects, normally resolved with adjusting the dosage<ref name=":0" />, include:  

Revision as of 20:29, 19 November 2021

Introduction[edit | edit source]

Angiotensin Converting Enzyme (ACE) Inhibitors are a important class of drugs used in the management of Congestive Heart Failure (CHF). They have been shown to decrease mortality in patients with left ventricular systolic dysfunction or exhibit congestive heart failure after an infarction.[1] In addition, there have been increasing evidences that support their effectiveness in reducing all-cause mortality and cardiovascular deaths.[2]   

Mode of Action[edit | edit source]

ACE inhibitors prevent vasoconstriction by suppressing the angiotensin converting enzyme, preventing angiotensin I from converting into angiotensin II. Angiotensin converting enzyme is responsible for converting angiotensin I to angiotensin II which is responsible for vasoconstriction[3]. In addition to being a powerful vasoconstrictor, Angiotensin II is also responsible for hypertrophy of vascular tissues and aldosterone secretion.  Hypertrophy of vascular tissues causes vessels to become narrow resulting in increased workload on the heart.  Aldosterone secretion is primarily responsible for water retention which can increase vascular fluid volume also increasing the workload on the heart. Therefore, the inhibition of angiotensin II decreases the amount of pressure in the heart which decreases workload on the heart[4].  Another beneficial effect of ACE inhibitors is that they increase bradykinin levels in the blood by decreasing their breakdown.  Bradykinin is responsible for vasodilation[5].  

[6]

Common Ace Inhibitors[edit | edit source]

In general, these medications help decrease cardiac output by limiting vasoconstriction and inhibiting aldosterone secretion promoting vasodilation. Common ACE inhibitors for patients with CHF are:  

  • Benazepril: given 10 mg once daily and gradually increased to 20-40 mg per day with a half-life of 10-11 hours and 12 hours respectively.  If given with a diuretic the initial dose should be 5mg[7][8]
  • Fosinopril: given 10 mg once daily and gradually increased to 20-40 mg per day with a half-life of 10-11 hours and 12 hours respectively.  If given with a diuretic the initial dose should be 5mg[7][8]
  • Captropil[9]: given 25 mg 3 times daily and has a shorter half-life of 3.3 hours requiring the patient to take it more frequently[10].  
  • Lisinopril[11]: Initial dose 2.5 to 5 mg orally once a day. Maintenance dose is increased as tolerated. Maximum dose is 40 mg orally once a day.[12]

Adverse Effects[edit | edit source]

  • Cough: Dry, non-productive paroxysmal cough is reported in about 1 to 10% of people who use ACE inhibitors.[13] [14]This adverse reaction is more commonly reported among women than men.[15] Often, cessation of therapy leads to stoppage of cough.[16] Experimental studies also suggest the use if non-steroidal anti-inflammatory agents and intermediate low-dose Aspirin to be helpful with ACE inhibitors-induced cough.[17]
  • Rare: Hypotension and Renal Failure because ACE inhibitors are primarily excreted through the kidneys.
  • Minor side effects, normally resolved with adjusting the dosage[9], include:
    • Angioedema (an area of swelling of the lower layer of skin and tissue just under the skin or mucous membranes skin)[18]
    • Rashes
    • GI discomfort
    • Dizziness
    • Hypotension

Contraindications[edit | edit source]

ACE inhibitors are generally contraindicated with patients who have a history of angioedema, either hereditary or idiopathic.[19] In addition, ACE inhibitors are also contraindicated in patients with hypersensitivity related to the drugs.[19] Furthermore, ACE inhibitors should not be administered to patients already on a direct renin inhibitor such as Aliskiren. Also, ACE inhibitors have been known to be associated with cause complications in pregnancy, hence should not be administered during pregnancy.[20]

Implications for Physiotherapy[edit | edit source]

ACE inhibitors cause a reduction in BP this coupled with the naturally occurring post-exercise hypotension can result in excessive reductions in blood pressure. This can lead to dizziness and, in rare instances, syncope. Post-exercising clients on ACE inhibitors may need education in adhering to a gradual cool-down after each and every exercise session to prevent these symptoms and benefit the body by enhancing venous return and the prevention of blood pooling in the skeletal muscle. A gradual cool-down of five to 10 minutes of light aerobic activity allows the body to return to homeostasis and prevents excessive reductions in blood pressure.[21]

References[edit | edit source]

  1. Pitt B. ACE inhibitors in heart failure: prospects and limitations. Cardiovascular drugs and therapy. 1997 May;11(1):285-90.
  2. Tai C, Gan T, Zou L, Sun Y, Zhang Y, Chen W, Li J, Zhang J, Xu Y, Lu H, Xu D. Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on cardiovascular events in patients with heart failure: a meta-analysis of randomized controlled trials. BMC cardiovascular disorders. 2017 Dec;17(1):1-2.
  3. Montezano AC, Nguyen Dinh Cat A, Rios FJ, Touyz RM. Angiotensin II and vascular injury. Current Hypertension Reports. 2014;16(6):431
  4. Katragadda S, Arora RR. Role of angiotensin-converting enzyme inhibitors in vascular modulation: beyond the hypertensive effects. American Journal of Therapeutics. 2010;17(1):e11-23
  5. Regoli D, Plante GE, Gobeil F Jr. Impact of kinins in the treatment of cardiovascular diseases. Pharmacology & Therapeutics. 2012;135(1):94-111.
  6. British Heart Foundation How do ACE inhibitors work? Available from: https://www.youtube.com/watch?v=xIlaQuRaZmk (last accessed 17.6.2019)
  7. 7.0 7.1 U.S. Food and Drug Administration (FDA). Lotensin (benazepril hydrochloride). Available online at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019851s042lbl.pdf. Last accessed 11/29/18.
  8. 8.0 8.1 U.S. Food and Drug Administration (FDA). MONOPRIL (fosinopril sodium tablets). Available online at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/19915se5-037_monopril_lbl.pdf. Last accessed 11/29/18.
  9. 9.0 9.1 Ciccone CD. Renin Angiotensin System Inhibitors. Pharmacology in rehabilitation. 5th ed. Philadelphia: F.A. Davis Company; 2016
  10. U.S. Food and Drug Administration (FDA). CAPOTEN® (Captopril Tablets, USP). Available online at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/018343s084lbl.pdf.  Last accessed 11/29/18.
  11. Simpson K, Jarvis B. Lisinopril: a review of its use in congestive heart failure. Drugs. 2000 May;59(5):1149-67. doi: 10.2165/00003495-200059050-00012. PMID: 10852646.
  12. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013 Oct 15;128(16):1810-52.
  13. Pinargote P, Guillen D, Guarderas JC. ACE inhibitors: upper respiratory symptoms. BMJ Case Rep. 2014 Jul 17;2014
  14. Israili ZH, Hall WD. Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy. A review of the literature and pathophysiology. Ann Intern Med. 1992 Aug 01;117(3):234-42
  15. Os I, Bratland B, Dahlöf B, Gisholt K, Syvertsen JO, Tretli S. Female sex as an important determinant of lisinopril-induced cough. Lancet. 1992 Feb 08;339(8789):372.
  16. Herman LL, Padala SA, Ahmed I, et al. Angiotensin Converting Enzyme Inhibitors (ACEI) [Updated 2021 Aug 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK431051/
  17. Tenenbaum A, Grossman E, Shemesh J, Fisman EZ, Nosrati I, Motro M. Intermediate but not low doses of aspirin can suppress angiotensin-converting enzyme inhibitor-induced cough. Am J Hypertens. 2000 Jul;13(7):776-82
  18. Wikipedia Angioedema Available from: https://en.wikipedia.org/wiki/Angioedema (last accessed 17.6.2019)
  19. 19.0 19.1 Brown NJ, Ray WA, Snowden M, Griffin MR. Black Americans have an increased rate of angiotensin converting enzyme inhibitor-associated angioedema. Clin Pharmacol Ther. 1996 Jul;60(1):8-13.
  20. Quan A. Fetopathy associated with exposure to angiotensin converting enzyme inhibitors and angiotensin receptor antagonists. Early Hum Dev. 2006 Jan;82(1):23-8.
  21. American Council of Exercise How Common Medications May Affect Your Clients’ Exercise Programs Available from: https://www.acefitness.org/certifiednewsarticle/3296/how-common-medications-may-affect-your-clients/ (last accessed 17.6.2019)