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Angiotensin converting enzyme inhibitors (ACE inhibitors)

Efective and well tolerated treatment for hypertension.

Less effective in treating African-American patients unless combined with a thiazide diuretic.

Reduce mortality in patients with coronary artery disease, prolongs survival in patients with heart failure or left ventricular dysfunction and preserve renal function in patients with diabetes.

Reduces cardiovascular death, hospitalizations for heart failure, myocardial infarctions in patients with left systolic dysfunction and heart failure.

Renal dysfunction and cough are not absolute contraindications to the use of these agents.

When systolic blood pressure is less than 100 mm Hg or the creatinine is elevated, careful monitoring is warranted during the initiation of therapy.

They slow myocardial remodeling in heart failure and ischemic heart disease, and reduce the recurrence of atrial fibrillation.

Associated with hyperkalemia in as many as 11% of patients on such drugs.

Beneficial in CHF, diabetic nephropathy, nondiabetic renal disease. hypertension, s/p myocardial infarction.

Recommended within first 24 hours of ST-elevation myocardial infarction for anterior infarction, pulmonary congestion, left ventricular ejection fraction of less than 40%, and for any patients with ST-elevation myocardial infarction without contraindications.

Angiotensin-converting enzyme (ACE) inhibitors prevent the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, and lowers aldosterone secretion.

ACE inhibitors attenuate angiotensin I effects onvasoconstriction, sodium retention, and fibrosis.

They are effective and well-tolerated drugs with no adverse effects on plasma lipid levels or glucose tolerance.

Blockade of the renin-angiotensin system decreases the progression of proteinuric kidney disease in patients with diabetes mellitus.

Should not be used in patients with a ST-elevation myocardial infarction within the first 24 hours with risk of hypotension.

Recommended for all patients with type I diabetes and microalbuminuria regardless of blood pressure.

Among patients with DM, ACE inhibitors fared better than placebo in reducing creatinine doubling, and beta-blockers were associated with an increased risk of death.

Hyperkalemia develops in approximately 10% of outpatients within one year of the initiation of treatment.

Risk factors for ACE inhibitors or ARB induced hyperkalemia include renal insufficiency, diabetes, reduce the left ventricle function in advanced age.

Because of the potential for hyperkalemia and renal failure, serum potassium and creatinine levels should be checked 10 to 14 days after initiation of therapy.

The use of trimethoprim-sulfamethoxazole in older patients with ace inhibitors or ARB’s is associated with an increased risk of hyperkalemia relative to other antibiotics.

Elevated levels in 75% of untreated sarcoid patients.

Up to 10% of elevated ACE levels seen in non sarcoid conditions.

Converting enzyme inhibitors (ACE inhibitors)-reduce albumin excretion in both normotensive and hypertensive patients with type 1 or type 2 diabetes.

Converting enzyme inhibitors (ACE inhibitors)-cough occurs in about 15% of patients and in about 8% the cough is bothersome enough to discontinue the drug.

Cough is generally the most common adverse event occurring in 5-35% of patients.

The primary adverse effects of ACE inhibitors include hyperkalemia, dry cough, angioedema, hypotension, dizziness, and renal insufficiency.

 

 

Adverse effects of ACE inhibitors may be more common in patients with renal, autoimmune, or collagen vascular diseases. 

 

In advanced chronic kidney disease, blockade of the RAAS is no longer of renal value and may potentially be detrimental due to reduced  nephron mass and renal ischemia. 

 

Increased age, increase baseline GFR,, heart failure, long-standing diabetes, and macrovascular disease are all associated with increased serum creatinine levels and they represent populations who have limited benefit from RAAS inhibition: Conversely younger individuals with early-stage diabetes and type of filtration of proteinuria may benefit.

Converting enzyme inhibitors (ACE inhibitors)-about 1% have angioedema with the first dose of treatment.

Angioedema induced by angiotensin converting enzyme inhibitors in up to 0.68% of patients who receive ACE inhibitors.

ACE inhibitor related angioedema represents 30 to 40% of all cases seen US EDs..

Most cases of ACE inhibitor related angioedema occur in the first few weeks of treatment.

African-American women have higher incidence of ACE inhibitor angioedema.

ACE inhibitor angioedema have higher incidence in African-American women, older age, tobacco smoking, nonsteroidal anti-inflammatory drug use, seasonal allergies, obesity, a history of transplant, and the history of ACE inhibitor associated cough.

ACE inhibitor induced cough and bronchospasm, as well as angioedema are considered to be related to the elevation in bradykinin levels that occurs when ACE is inhibited.

Angioedema incidence is difficult to estimate as symptoms can take years to appear.

About one third of all cases of angioedema seen in the emergency room are due to ACE inhibitors.

No evidence exists for the use emergency treatment of ACE inhibitor angioedema with cortic steroids, histamine blockers, and intramuscular or subcutaneous epinephrine.

Unacceptable adverse events are more common in patients with allergies and in patients that use anti-histamine and anti-asthma medications.

ACE inhibitors affects almost exclusively the upper aerodigestive tract, but rarely can affect the gut.

Obstruction of the upper airway occurs in 10% of cases and may proceed to laryngeal obstruction and death.

Among patients with ACE inhibitor induced angioedema, time to resolution of symptoms is significantly shorter with Icatibant than with therapy with glucocorticoids and antihistamines.

Slow the progression of chronic kidney disease in the presence or absence of diabetes, particularly in the presence of mild to moderate renal impairment with creatinine levels between 1.5-3.0 mg per dL.

Beneficial in patients with advanced kidney disease.

Can be used in patients with stage risk chronic kidney disease associated defined by creatinine clearance rate of 15-29 cc per minute per 1.73 m2 and serum Creatine 3-5.0 mg per d/L.

Provides renal benefit even with progression of the serum creatinine.

Blockade of the renin-angiotensin-aldosterone system may be incomplete with evidence of continued angiotensin II production.

Use contraindicated during the second and third trimesters associated in utero exposure during this period associated with fetopathy manifested by oligohydramnios, intrauterine growth retardation, hypocalvaria, renal dysplasia, anuria, renal failure and death.

Fetal exposure in the first trimester associated with 2.7 times risk of major congenital malformations compared to fetuses with no exposure to ACE inhibitors.

Significant increased risks of cardiovascular, central nervous system and kidney malformations with first trimester exposure to ACE inhibitors.

Inhibition of the renin-angiotensin system with ACE inhibitors early in pregnancy affects fetal organ development.

Ace inhibitors and angiotensin II receptor blockers reduce hemoglobin levels in several groups of patients at risk for secondary erythrocytosis including patients with heart failure, hemodialysis, or COPD, after cardiac surgery or kidney transplant.

Ace inhibitors and ARB’s are effective treatments for secondary polycythemia related to renal transplant and reactive high-altitude erythrocytosis.

Hemoglobin levels are reduced during the first year of use of ACE inhibitors and to a lesser extent with a ARBs.

Combination therapy with ACE inhibitors and an ARB is associated with an increased risk of adverse events among patients with diabetic neuropathy (Fried LF et al).

In the Ongoing Telmisartan Alone and in the Combination with Ramipril Global Endpoint Trial (ONTARGET) a randomized study of combination therapy was associated with increased cardiovascular risk, no cardiovascular or renal benefits but increased risk of hyperkalemia and acute kidney injury requiring dialysis.

In patients without heart failure ARBs are as efficacious and safe as ACE inhibitors, with better tolerability.

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