ACE Inhibitors


Article Author:
Amandeep Goyal
Alberto Goizueta


Article Editor:
Blair Thielemier


Editors In Chief:
Yvonne Carter
Jason Wallen


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Trevor Nezwek
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
7/12/2019 12:32:58 PM

Indications

FDA approved

1. ACE inhibitors can be used as adjunctive therapy in systolic heart failure (HF). HF guidelines recommend ACE inhibitors to help prevent HF in patients with a reduced ejection fraction (EF) who also have a history of myocardial infarction (MI), to prevent HF in any patient with a reduced ejection fraction or to treat patients with HF and reduced EF.

2. ACE inhibitors can be used for the treatment of hypertension (HTN) either alone or in conjunction with other antihypertensives in adults or children greater than 6 years old. Hypertension guidelines recommend initiation of ACE inhibitors for the management of HTN to lower blood pressure (BP) in the following patients:

  • Patients < 60 years of age with SBP = 140 mm Hg or DBP is = 90 mm Hg. The goal of therapy is SBP < 140 mm Hg and DBP < 90 mm Hg.
  • Patients = 18 years of age with diabetes and SBP = 140 mm Hg or DBP = 90 mm Hg. The goal of therapy is SBP < 140 mm Hg and DBP < 90 mm Hg.
  • Patients = 18 years of age with chronic kidney disease (CKD) and SBP = 140 mm Hg or DBP = 90 mm Hg. The goal of therapy is SBP < 140 mm Hg and DBP < 90 mm Hg.

3. Patients with chronic kidney disease (CKD) and HTN:

  • Regardless of race or diabetes status, ACE inhibitors are recommended as initial therapy to improve kidney outcomes.
  • In the non-Black population with diabetes and without CKD, initial antihypertensive therapy should include either thiazide diuretic, calcium channel blocker (CCB), ACE inhibitor, or angiotensin receptor blocker (ARB).
  • In the Black population with diabetes and without CKD, initial antihypertensive therapy should include either a thiazide diuretic or CCB instead of an ACE inhibitor or ARB.

4. Patients with coronary artery disease (CAD) and HTN:

  • ACE inhibitors are recommended as part of a regimen in patients with HTN and chronic stable angina if there is a history of left ventricular dysfunction, diabetes, or CKD.

5. Patients with ST-elevated myocardial infarction (STEMI):

  • ACE inhibitors should be initiated within 24 hours of all STEMI, specifically in patients with anterior MI, heart failure, or left ventricular (LV) ejection fraction (EF) of 40% or less.

Non-FDA approved

May delay the progression of nephropathy and reduce the risks of cardiovascular events in hypertensive patients with diabetes type I and type II.

Mechanism of Action

ACE is involved in the renin-angiotensin system (RAS) and stimulates the conversion of angiotensin I to angiotensin II. ACE inhibitors are competitive inhibitors of ACE, which prevents the conversion of angiotensin I to angiotensin II. Angiotensin II acts as a potent vasoconstrictor that when inhibited can reduce blood pressure by dilating vessels and decreasing aldosterone secretion.[1][2][3]

Administration

ACE inhibitors are most commonly oral agents, but intravenous forms are available.

Adverse Effects

Most Common Adverse Reactions

  • Dizziness (12% to 19%)
  • Hypotension (7% to 11%)
  • Increased BUN and Cr (2% to 11%)
  • Syncope (5% to 7%)
  • Hyperkalemia (2% to 6%)

One percent to 10%: flushing, orthostatic effect, chest pain, altered sense of smell, fatigue, headache, alopecia, diaphoresis, erythema, pruritus, skin photosensitivity, Steven-Johnson Syndrome, toxic epidermal necrolysis, urticaria, diabetes mellitus, gout, SIADH, constipation, diarrhea, dysgeusia, flatulence, pancreatitis, xerostomia, impotence, bone marrow suppression, hemolytic anemia, leukopenia, neutropenia, thrombocytopenia, common cold, weakness, blurred vision, diplopia, photophobia, vision loss, tinnitus, cough.[4][5]

Any Injury

Less than 1%: Acute renal failure, anaphylactoid reactions, angioedema, anuria, arthralgia, arthritis, asthma, ataxia, azotemia, bronchitis, bronchospasm, cardiac arrest, cardiac arrhythmia, cerebrovascular accident, chills, confusion, cutaneous pseudolymphoma, dehydration, drowsiness, dyspepsia, dyspnea, dysuria, eosinophilia, eosinophilic pneumonitis, epistaxis, facial edema, fever, gastritis, hallucination, heartburn, hemoptysis, hepatic necrosis, hepatitis, herpes zoster, hypersomnia, hypervolemia, hypoglycemia, hyponatremia, increased erythrocyte sedimentation rate, insomnia, intestinal angioedema, irritability, laryngitis, leukocytosis, malaise, malignant neoplasm of lung, mastalgia, memory impairment, mood changes, muscle spasm, musculoskeletal pain, myalgia, myocardial infarction, oliguria, orthopnea, orthostatic hypotension, palpitations, paresthesia, paroxysmal nocturnal dyspnea, pemphigus, peripheral edema, peripheral neuropathy, pharyngitis, pleural effusion, pneumonia, positive ANA titer, psoriasis, pulmonary embolism, pulmonary infarct, pulmonary infiltrates, pyelonephritis, rhinitis, rhinorrhea, sinusitis, skin infection, skin lesion, skin rash, sore throat, systemic lupus erythematosus, transient ischemic attacks, tremor, uremia, urinary tract infection, vasculitis, vertigo, viral infection, visual hallucination, weight gain, weight loss, wheezing.

Pregnancy

Use of drugs that inhibit the renin-angiotensin system are associated with teratogenic effects such as oligohydramnios, decreased fetal renal function, anuria, renal failure, skull hypoplasia, and death.

Contraindications

ACE inhibitors are contraindicated in a patient with a history of hypersensitivity to any ACE inhibitor or component of the formulation, angioedema related to previous treatment with ACE inhibitor, idiopathic or hereditary angioedema, or current use of aliskiren in a patient with diabetes mellitus. Also, consider drugs with cross-reactivity with ACE inhibitors.[6][7]

ACE inhibitors are not recommended in pregnant patients and should be discontinued as soon as pregnancy is detected.

Relative ContraindicationsUse with great caution in the following situations:

  • Patients with abnormal renal function. ACE inhibitors can cause elevation of potassium and worsen renal function in patients already on ACE inhibitors. If the patient has abnormal but stable renal function, close monitoring is required while he or she is on an ACE inhibitor. If the renal function starts to decline, the ACE inhibitor should be discontinued immediately.
  • Patients with aortic valve stenosis should not be administered afterload reducers like ACE inhibitors because it can lead to severe hypotension.
  • Similarly, patients who are dehydrated or have hypovolemia should not be treated with ACE inhibitors

Monitoring

Common parameters to monitor are BUN, serum creatinine, renal function, WBC, and potassium. If a patient has collagen vascular disease and/or renal impairment, periodically monitor complete blood count with differential. In patients with hypotensive effects within 1 to 3 hours of initial dose or with increased dosages or preexisting hepatic impairment, consider baseline hepatic function tests.

Toxicity

When used at therapeutic doses, the risk of toxicity is rare. Toxicity is more likely when the drug is used in combination or at supratherapeutic doses.

When ACE inhibitors are combined with other antihypertensive drugs, they have the potential to increase side effects like hyperkalemia, hypotension, and renal failure. One should pay more attention when the patient is prescribed an ACE inhibitor and is already on a potassium-sparing diuretic, NSAIDs, cyclosporine, and anticoagulants.

All the presently available ACE inhibitors have similar antihypertensive effects at equivalent doses. The only ACE inhibitor that is different is captopril. This agent has a short duration of action and is more likely to induce side effects. It is the only ACE inhibitor to penetrate the blood-brain barrier and induce confusion and lethargy.

Enhancing Healthcare Team Outcomes

ACE inhibitors are widely used in medicine for the treatment of hypertension, heart failure and patients with chronic kidney disease. While effective, healthcare workers (nurse practitioners, physicians, and pharmacists) who prescribe these agents should be aware of their side effects and limitations. Patients also need to be monitored for their renal function and electrolyte levels on a regular basis. Finally, the healthcare worker should be aware that these agents can produce a dry chronic cough and another class of antihypertensive should be used.[1][8][9][10]


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ACE Inhibitors - Questions

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Which of the following is a common adverse effect of ACE inhibitors that leads to switching the drug to an angiotensin II receptor blocker?



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You are counseling a patient on eating a healthy diet to maintain his blood pressure, and notice that he is taking lisinopril, an angiotensin-converting enzyme inhibitor. What result will this medication have on his angiotensin I and angiotensin II levels?



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What is the peptide that has been linked to the vasodilatation caused by angiotensin-converting enzyme inhibitors?



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A patient on a thiazide has now become diabetic. Which of the following should now be used to treat the high blood pressure?



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What can be caused by ACE inhibitors when prescribed to patients with congestive heart failure?



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A 53-year-old male has diabetes mellitus. Over the past few visits you have noticed he has become hypertensive, and after a discussion with the patient, lisinopril is started. What effect would this have on the patient's urine sodium and potassium levels?



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Which is a contraindication for use of ACE inhibitors?



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What class of antihypertensive drug is lisinopril?



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Which of the following is not a function of ACE inhibitors?



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Angiotensin-converting-enzyme inhibitors can cause which of the following electrolyte imbalances?



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Which of the following drugs is found to be beneficial in delaying the progression of renal damage in patients with diabetes mellitus?



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Which of the following medications is contraindicated in females who are pregnant?



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Which of the following statements correctly describes the physiological action of ACE inhibitors?



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Select the medication that would be best for decreasing afterload due to a reduction in vascular resistance.



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A 62-year-old female with diabetes mellitus (DM) type 2 on metformin reports that her blood sugar is almost always in the 100's. Her hemoglobin A1c is 5.9 percent and her blood pressure is 145/95 mm Hg. Physical exam was normal including peripheral pulses, peripheral nerves, and the retina. Which of the following would be most appropriate?



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Which of the following medications is contraindicated to treat hypertension in pregnancy?



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What should be done for a female patient with chronic hypertension that is well controlled with her ACE inhibitor in pregnancy?



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What is not a teratogenic effect of ACE inhibitors?



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Which of following medications is the most beneficial to protect against renal failure in patients with diabetes mellitus?



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How do angiotensin converting enzyme (ACE) inhibitors decrease blood pressure?



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A patient was recently started on a new drug and his serum creatinine level started to increase. Which drug most likely caused a rise in serum creatinine levels?



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You have a patient with type 2 diabetes in the clinic and would like to start the patient on an angiotensin-converting enzyme inhibitor (ACE inhibitor). According to the National Diabetes Education Program, which one of the following groups of diabetic patients should receive this drug?



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You have a middle-aged patient with diabetes who has just been diagnosed with hypertension. His BUN is 10 and creatinine is 1.4, and you decide to start him on antihypertensive pharmacotherapy. Based on large epidemiology studies, 20% of patients will develop a dry, non-productive cough on the agent you chose. Which of the following drugs is the most likely antihypertensive agent?



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You have a middle-aged patient with diabetes and recently diagnosed hypertension, who was started on ramipril about a month ago. Which of the following is true about the medication class of which ramipril is a member?



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Which of the following represents a commonly encountered side effect when taking an ACE inhibitor?



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A 56-year-old male presents to the emergency department with crushing substernal chest pain, diaphoresis, and pain in his jaw and left arm. Troponin levels are elevated. After appropriate management, the patient is stabilized and eventually gets discharged from the hospital. He is placed on ACE inhibitors. Which of the following is expected?



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ACE Inhibitors - References

References

Chen YJ,Li LJ,Tang WL,Song JY,Qiu R,Li Q,Xue H,Wright JM, First-line drugs inhibiting the renin angiotensin system versus other first-line antihypertensive drug classes for hypertension. The Cochrane database of systematic reviews. 2018 Nov 14     [PubMed]
Knežević T,Gellineo L,Jelaković A,Premužić V,Dika Ž,Laganović M,Jelaković B, Treatment of hypertension induced albuminuria. Current pharmaceutical design. 2018 Nov 26     [PubMed]
Hradec J, Pharmacological therapy for chronic heart failure. Vnitrni lekarstvi. 2018 Fall     [PubMed]
Leru PM,Anton VF,Bumbea H, Nine year follow-up of a rare case of angioedema due to acquired C1-inhibitor deficiency with late onset and good response to attenuated androgen. Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology. 2018     [PubMed]
Sachs B,Meier T,Nöthen MM,Stieber C,Stingl J, [Drug-induced angioedema : Focus on bradykinin]. Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete. 2018 Apr     [PubMed]
Wilkins B,Hullikunte S,Simmonds M,Sasse A,Larsen PD,Harding SA, Improving the Prescribing Gap For Guideline Recommended Medications Post Myocardial Infarction. Heart, lung     [PubMed]
Shaikh A, A Practical Approach to Hypertension Management in Diabetes. Diabetes therapy : research, treatment and education of diabetes and related disorders. 2017 Oct     [PubMed]
Alzahrani T,Tiu J,Panjrath G,Solomon A, The effect of angiotensin-converting enzyme inhibitors on clinical outcomes in patients with ischemic cardiomyopathy and midrange ejection fraction: a post hoc subgroup analysis from the PEACE trial. Therapeutic advances in cardiovascular disease. 2018 Nov 15     [PubMed]
Brar S,Ye F,James MT,Hemmelgarn B,Klarenbach S,Pannu N, Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With Outcomes After Acute Kidney Injury. JAMA internal medicine. 2018 Oct 27     [PubMed]
Saglimbene V,Palmer SC,Ruospo M,Natale P,Maione A,Nicolucci A,Vecchio M,Tognoni G,Craig JC,Pellegrini F,Lucisano G,Hegbrant J,Ariano R,Lamacchia O,Sasso A,Morano S,Filardi T,De Cosmo S,Pugliese G,Procaccini DA,Gesualdo L,Palasciano G,Johnson DW,Tonelli M,Strippoli GFM, The Long-Term Impact of Renin-Angiotensin System (RAS) Inhibition on Cardiorenal Outcomes (LIRICO): A Randomized, Controlled Trial. Journal of the American Society of Nephrology : JASN. 2018 Nov 12     [PubMed]

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