Products
Most ACE inhibitors are commercially available in the form of tablets and film-coated tablets. The first agent from this group to be approved was captopril, in many countries in 1980. ACE inhibitors are often combined with the thiazide diuretic hydrochlorothiazide (HCT) fix.
Structure and properties
ACE inhibitors are peptidomimetics derived from peptides found in the venom of the South American snake. The first representative captopril were developed in the 1970s. It is an early example of rational drug design. ACE inhibitors, with the exception of captopril and lisinopril, are in the form of prodrugs (usually ester prodrugs) because this increases absorption and bioavailability. The prodrug contains the suffix -pril, and the active ingredient contains the suffix -prilate, for example, enalapril and enalaprilate ( deprotonated). The thiol group of captopril and the one carboxylate group of enalapril interact with the zinc ion in the active site of ACE.
Mechanism of Action
ACE inhibitors (ATC C09AA) interfere with the renin-angiotensin-aldosterone system (RAAS). The effects are based on the inhibition of angiotensin converting enzyme (ACE), which is responsible for the formation of angiotensin II from angiotensin I and also catalyzes the degradation of the vasodilator bradykinin.
Effects
ACE inhibitors:
- Lower blood pressure
- Reduce peripheral resistance and preload and afterload
- Dilate the blood vessels
- Reduce the oxygen consumption of the heart
- Are antihypertrophic
- Decrease aldosterone secretion in the adrenal cortex
- Have a mild diuretic effect
- Increase sodium excretion and potassium reabsorption
- Decrease albumin excretion by the kidney (albuminuria).
Indications
Indications for ACE inhibitors include:
- Essential hypertension (high blood pressure).
- Renovascular hypertension
- Symptomatic heart failure
- Secondary prevention after acute myocardial infarction.
- Recurrence prophylaxis of stroke (with diuretic).
- Stable coronary artery disease
- Renal disease, diabetic nephropathy
Not all agents are approved for the same indications. ACE inhibitors are also used in animals, such as benazepril for the treatment of heart failure in dogs and chronic renal failure in cats.
Active Ingredients
- Captopril (generic, Lopirin is off-label).
- Cilazapril (Inhibace)
- Enalapril (Reniten, generic).
- Fosinopril (generic, Fositen is out of trade).
- Lisinopril (Zestril, generic)
- Perindopril (Coversum, generic).
- Quinapril (Accupro, generics)
- Ramipril (Triatec, generic)
Out of commerce or not on sale in many countries:
- Benazepril (Cibacen)
- Moexipril (Univasc)
- Spirapril (Cardiopril)
- Trandolapril (Gopten)
- Zofenopril (Zofenil)
In many countries exclusively as a veterinary drug:
- Imidapril (Prilium)
Dosage
According to the professional information. The dosage depends on the drug. ACE inhibitors are usually taken once (to twice) daily. However, exceptions exist, such as captopril, which is given up to three times daily.
Contraindications
- Hypersensitivity
- Hereditary or idiopathic angioedema
- Angioedema during previous treatment with an ACE inhibitor or sartan.
- Pregnancy and lactation
- Concurrent use of aliskiren in patients with diabetes mellitus or impaired renal function.
- Children and adolescents: see SmPC.
For complete precautions, see the drug label.
Interactions
Other antihypertensive drugs may potentiate the effects of ACE inhibitors. Drugs that increase potassium levels-such as potassium chloride or potassium-sparing diuretics-may cause hyperkalemia. Other interactions are possible with antidiabetics, lithium, NSAIDs, sartans, aliskiren (contraindicated), gold, mTOR inhibitors, and gliptins (selection). Dual inhibition of the RAAS is not recommended.
Adverse effects
The most common possible adverse effects include a cough, low blood pressure, dizziness, headache, visual disturbances, fatigue, an increase in serum potassium, skin rashes, muscle pain, and digestive disturbances such as nausea and diarrhea. The cough, which can occur with ACE inhibitors, is a nonproductive irritable cough that disappears after discontinuation. Like other side effects, cough is associated with elevation of bradykinin. Occasionally, angioedema may develop with ACE inhibitors. It may occur, for example, on the face, lips, mucous membranes, or larynx.
