Angiotensin Converting Enzyme (ACE) Inhibitors.

Overview 

  • Help blood vessels to relax and open i.e. to treat hypertension 
  • Improve blood flow and lower blood pressure.

Doctors commonly prescribe ACE inhibitors for heart-related conditions like high blood pressure and heart failure. 

  • Can also help to treat other diseases like diabetes and chronic kidney disease (CKD)
  1. What are ACE inhibitors?

ACE inhibitors are one class of antihypertensives.

Can also help to deal with  conditions like:

    • heart failure 
  • chronic kidney disease(CKD)
  • diabetes
  • proteinuria, extra protein in the urine
  • glomerular diseases, which are ailments that inhibit filtration in the kidney 
  • atherosclerosis, a narrowing of arteries due to accumulation of plaque. 

You’ll typically have an ACE inhibitor only once a day, mostly   in the morning. Doctors may prescribe them in combination with  diuretics or calcium channel blockers, which also help treat high blood pressure.

  • In studies, individuals with hypertension (high blood pressure), heart failure or previous heart attacks that were treated with an ACE inhibitor survived  longer than patients who did not take an ACE inhibitor. 
  • Still, some individuals with hypertension do not react sufficiently to ACE inhibitors alone. 

Types of ACE inhibitors

There are various different medications under the ACE inhibitor classification. The main difference between types is the time. Some types of ACE inhibitors are more beneficial in the short term, while others are more common for long-term treatments.

Common ACE inhibitors comprise:-

Generic name.            Indian   Brand name 

Benazepril                       Benace 

Captopril.                        Aceten, Captopril 

Enalapril                         Envas, Enalap, Epril

Fosinopril                       Monopril, cipla

Lisinopril                         Zestril, Cipril, Lisoril, 

                                         Hipril, Lipril.

Quinapril                         Accupril, Acupil

Ramipril                         Cardace, Zigpril, 

                                        Ramistar, Odipril and 

                                         Zorem

Moexipril                      Univas                                         

Perindopril                Eviper, Perigard,Conape     

Trandolapril                 Mavik, Zetpril. 

Most ACE inhibitors are oral drugs. The exception is enalapril, which physicians will administer intravenously (IV).

  1. How do ACE inhibitors work ?

ACE inhibitors have two main functions.

1st main function 

 Initially , they stop the generation of  angiotensin II. This hormone causes your blood vessels to narrow, decreasing flow. 

As levels of this hormone drop due to ACE inhibitors, vessels will relax and open up, enhancing blood flow around the body.

2nd main function 

  •  Reduce the amount of sodium retained in the kidneys.

The combination of these factors can help to  deal with a range of blood-related conditions, not just hypertension.

  1. Are there any differences among the different types of ACE inhibitors?

ACE inhibitors are relatively similar. Still, they differ in :-

  • how they are excluded from the body and their doses. 
  • Some ACE inhibitors require it to be converted into an active form in the body before they work.
  •  In addition, some ACE inhibitors may struggle more on the ACE (angiotensin converting enzyme) that is existing in tissues than on ACE that is present in the blood.

The significance of this difference or whether one ACE inhibitor is better than another has not been determined. 

  1. How is an ACE inhibitor administered?

ACE inhibitors are pills that you take through the mouth. Try to take your medications at the exact time, or times, each day. 

Do not avoid taking your medicines without speaking to your doctor first.

Caution :-

  • Before taking ibuprofen (Advil, Motrin) or aspirin, speak  to your doctor.
  • Inform  your doctor about what other medicines you are taking. 

Don’t  take  ACE inhibitors if you are pregnant or breastfeeding. Do not take these medicines if you are intending to become pregnant. Speak to your doctor if you become pregnant when you are taking these medicines.

  1. What are the side effects of ACE inhibitors?

Well-tolerated by many  individuals. 

  • Individuals with bilateral (two-sided) renal artery stenosis (narrowing of blood vessels in the kidneys) may suffer worsening of kidney function.
  •  People who have an allergy to ACE inhibitors should avoid them.

The most common side effects are:

  1. Chronic cough
  2. Increased blood potassium levels
  3. Low blood pressure
  4. Dizziness
  5. Headache
  6. Drowsiness
  7. Weakness
  8. Abnormal taste (metallic or salty taste)
  9. Rash

It may take up to a month for coughing to diminish, and if one ACE inhibitor induces cough it is possible that the others will too.

The most severe, but unusual, side effects of ACE inhibitors are:

  • Kidney failure
    1. Allergic reactions
    2. Decrease in white blood cells
  • Significant swelling of tissues (angioedema). 

Dosage 

NORMAL ADULT DOSING

Benazepril: 10 mg (not on a diuretic). 

Captopril: Left ventricular dysfunction after myocardial infarction (LVD after MI): 6.25-12.5 mg 3× times a day (with diuretic) with the purpose of 50 mg three times a day for HFrEF. 

  • Diabetic nephropathy: 25 mg 

Enalapril: 2.5-5 mg once or twice daily, increased up to 40 mg/day every 1-2 weeks in 2.5 mg gap. 

  •  IV : 1.25 mg/dose in  every 6 hours

Fosinopril: 10 mg daily initially, 

  •  Usual dose: 20-40 mg daily.

Lisinopril: 

  • First 10 mg daily (no diuretic) 
  • 5 mg daily (if on diuretic). 

Moexipril: 

Hypertension: 7.5mg (not on a diuretic) 

  •   3.75mg(when combined with a diuretic).
  •  Administer 1 hr before a meal. 
  • Regulation : 7.5-30 mg daily in 1-2 divided doses

Perindopril:

  •  Initial: 4 mg; titrate to required effect every 1-2 weeks to a max dose of 16 mg/day. 
  • Basic dose 4-8 mg/day in 2 divided doses. 

Quinapril: 10-20 mg . Initial dose may be decreased to 5 mg daily (if patient is on a diuretic). 

  • Range: 10-40 mg .

Ramipril: 2.5-5 mg once daily (max. dose of 20 mg/day). 

  • Decreased risk of stroke, MI and death Initial: 2.5 mg for initial  week, then 5 mg  for weeks 2-4, then titrate to 10 mg once daily as withstood

Trandolapril:

  •  CHF/LVD Initial: 1 mg/day, titrated to 4 mg/day as sustained. 

DOSING IN SPECIAL POPULATIONS

RENAL

  • CrCl 10-50 ml/min: decrease initial approved dose by 25%, then titrate to effect.
  • CrCl < 10 ml/min: decrease initial recommended dose by 50%, then titrate to effect.

HEPATIC

  • No dosage adjustment required.

PREGNANCY

  • Avoid pregnancy.
  • Teratogenic and have resulted in neonatal morbidity (cardiovascular and CNS) and mortality.

BREASTFEEDING

    • Concentration in milk is nearly 1% of serum concentration.
  • Neglect ACE inhibitors during breastfeeding.
  1. With which drugs do ACE inhibitors interact?

ACE inhibitors have limited interactions with other drugs.

  • Since ACE inhibitors may raise blood levels of potassium, the use of potassium supplements, salt alternatives (which frequently contain potassium), or other drugs that increase the body’s potassium may result in unreasonable blood potassium levels.
  • There have been statements that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen (Advil, Children’s Advil/Motrin, Medipren, Motrin, Nuprin, PediaCare Fever etc.), indomethacin (Indocin, Indocin-SR), and naproxen (Anaprox, Naprelan, Naprosyn, Aleve) may decrease the effects of ACE inhibitors.
  • ACE inhibitors also may heighten the blood concentration of lithium (Eskalith) and result in a boost in side effects from lithium.
  • Aliskiren enhances the hyperkalemic and nephrotoxic consequence of ACE inhibitors, and use of aliskiren with an ACE inhibitor is contraindicated in patients with diabetes.
  • Sacubitril is contraindicated with ACE inhibitors due to the raised risk of angioedema.
  1. What are ACE inhibitors  and ARBs?
  • Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs)both are first-line treatments for hypertension, or high blood pressure.

ACE inhibitors decrease blood pressure by deterring the production of angiotensin II, a substance that narrows  the blood vessels, while ARBs slow down the action of angiotensin II to deter blood vessel constriction.

ACE inhibitors and ARBs reduce proteinuria. 

  • Proteinuria is correlated with a faster progression of kidney disease.
  • The non-dihydropyridine agents, such as verapamil and diltiazem, have considerable antiproteinuric effects in diabetic—but not in nondiabetic—kidney disease.
  • The dihydropyridine agents, such as amlodipine and nifedipine, normally have no consistent effect on protein excretion.
  •  Other agents, comprising diuretics, ß-blockers and a-blockers have not been indicated to have a consistently significant effect on proteinuria. 
  • Both ACE inhibitors and ARBs decrease the glomerular permeability barrier to proteins and hinder proteinuria and filtered protein-dependent inflammatory signals. 

Why Use STOP ACEi/ARBs in Advanced CKD?

  • Patients with advanced CKD have an increased burden of Cardiovascular disease CVD and potentially stand to progress from the cardio-protective effect of RAAS antagonism. 
  • Other factors outside of RAAS activation such as CKD-mineral bone disease, FGF-23 and alliance with left ventricular hypertrophy, inflammation and oxidative stress may account for the majority of the exponential boost of cardiovascular events associated with advanced CKD.

ACEi and ARBs Medicines and People with Chronic Kidney Disease

Angiotensin-converting enzyme inhibitors (ACE inhibitors) or Angiotensin II Receptor Blockers (ARBs) help protect the kidneys.

  • Having high pressure results in an increase of pressure in the blood vessels of the kidneys. These blood vessels cannot function properly. This induces damage to the kidneys.
  • ACE and ARB medicines lower the pressure inside of the kidneys to a reasonable level.
  • They are particularly helpful for kidneys that are allowing protein to leak into the urine.
    • Kidneys do not release protein into the urine normally.

ACE and ARB medicines can as well decrease the blood pressure in the rest of the body by relaxing the blood vessels.

  • For people with chronic kidney disease, taking ACE and ARB medicines lessens their chance of needing dialysis or a kidney transplant.

People who take these medicines are also less inclined to have a heart attack and stroke.

ACE inhibitors also deal with  several kidney diseases in people who don’t have diabetes, including:-

  • Nephrotic syndrome
  • Proteinuria (extra protein in your urine).
  • Glomerular disease (issues with your kidney’s filtration system).
  • Post-transplant glomerulonephritis (kidney inflammation or filtration problems).

What are the advantages of ACE inhibitors?

ACE inhibitors have numerous advantages that make them first-line medications for treating high blood pressure and other cardiovascular conditions. 

Those include:-

  1. They work. ACE inhibitors have the assistance of extensive scientific research showing they’re beneficial.
  2. They’re preventive. One of the most important consequences of ACE inhibitors is not just that they can deal with existing problems.
  •  They can as well  prevent those problems from happening (either for the first time or again).
  1. They frequently combine well with others. ACE inhibitors are often combined with specific other types of blood pressure-controlling medications into a single drug.
  2. They’re safe. Side effects of ACE inhibitors are usually lesser and rare 

Frequently Asked Questions (FAQs)

  1. What is the most effective ace inhibitor?

When evaluating factors such as increased ejection fraction, stroke volume, and reducing mean arterial pressure, our results indicate that enalapril was the most effective ACE inhibitor. 

  1. What is the safest ace inhibitor?

Ramipril was correlated to the lowest risk of death from any cause. 

Enalapril effectively decreases blood pressure because it simultaneously boosts heart function. Still, it is related with side effects such as increased cough, gastrointestinal distress, and impairment of kidney function in higher doses.

  1. What is the difference between ACEi and beta- blocker?

Beta-blockers treat many of the similar conditions as ACE inhibitors, comprising high blood pressure, chronic heart failure, and stroke. Both kinds of medications also prevent migraines. Unlike ACE inhibitors, yet, beta-blockers can relieve angina (chest pain).

  1. What is better, a beta-blocker or an ACE inhibitor?

If you are symptomless, like several people with high blood pressure are, a doctor will probably attempt an ACE inhibitor first. If your high blood pressure is accompanied by chest pain or anxiety, a beta blocker could be a better choice.

  1. Can you take a beta-blocker and ACE inhibitor at the same time?

 Although there is no apparent pharmacological rationale for the combined use of an ACE inhibitor and a beta-blocker in the treatment of hypertension, this combination has proved to be more beneficial than monotherapy in a number of studies, some of which are reviewed.

  1. What is the most troublesome side effect of ace inhibitors? 

Angioedema. 

Angioedema is the most serious symptom related to ACE inhibitors and occurs in 0.1-0.2% of patients. Airway swelling and obstruction because of  the accumulation of fluid (and bradykinin) are the main features of angioedema.

  1. Should ACE inhibitors be taken at night?

Many doctors advise their patients take heart drugs in the morning with their breakfast, but a new study from Canada suggests that one group of drugs, angiotensin-converting enzyme (ACE) inhibitors, works best when taken at bedtime because they decrease the effect of a hormone that is most active during sleep.

  1. At what GFR do you stop the ACE inhibitor?

ACE inhibitor therapy should not be discontinued unless and until serum creatinine level increases above 30% over baseline during the initial 2 months after initiation of therapy or hyperkalemia (serum potassium level >or=5.6 mmol/L) develops.

  1. Do ACE inhibitors affect GFR?

In general, ACE-inhibition does not impact  normal glomerular filtration rate (GFR) but may boost GFR in patients on a low sodium intake prior to treatment. Since the rise in GFR is minor than the rise in renal blood flow, in most instances a decrease in filtration fraction will occur.

  1. Which is better for kidney ACE or ARB?

ACE inhibitors lessened the incidence of end-stage renal disease (ESRD) by 40 percent, and ARBs reduced this succession by 22 percent.

  1. Are there things I shouldn’t eat or drink while taking an ACE inhibitor?

In general, obey your healthcare provider’s guidance when it comes to what you should or shouldn’t eat or drink. This is very true if your provider tells you to follow a low-sodium diet. Not following that advice could affect your sodium levels. You also should avoid salt alternatives that contain potassium until and unless you talk to your healthcare  provider about whether or not those substitutes are safe.

For instance, capsaicin — the chemical compound that makes food  like peppers spicy — can occasionally worsen an ACE inhibitor-related cough.

Recovery phase questions 

  1. How long can I stay on ACEi?

ACEi are commonly safe for long-term use. In several cases, you can take them indefinitely and for the rest of your life.

  1. Can I ever stop taking these medications?

You should talk to your healthcare provider before you stop receiving these medications. 

  • Stopping them abruptly can cause serious and life-threatening medical events, especially ones like heart attack, stroke or worsening heart failure.

Banking on why you are taking  an ACE inhibitor, it may be feasible to improve your blood pressure to the point where it’s no longer required.

  • Your doctor can assist with tapering off your dose until it’s safe to stop taking it.

In cases where you still have the original health ailment but want to stop taking an ACE inhibitor, your healthcare provider can help you.

  • They can give medication alternatives and assist you in switching to another drug that can also benefit you.

If you forgot a dose 

If it’s been too long, wait and then take only the next dose. Don’t take more than your specified dose to “catch up” because this can result in severe, dangerous lowering of blood pressure.