Angiotensin-converting-enzyme inhibitor (ACE inhibitor) is a pharmaceutical drug used primarily for the treatment of hypertension (elevated blood pressure) and congestive heart failure. This group of drugs causes relaxation of blood vessels as well as a decrease in blood volume, which leads to lower blood pressure and decreased oxygen demand from the heart. They inhibit the angiotensin-converting enzyme, an important component of the renin-angiotensin system.
Types
ACE inhibitors are easily identifiable by their common suffix, ‘-pril’. ACE inhibitors can be divided into three groups based on their molecular structure:
Sulfhydryl-containing agents
- Captopril
- Zofenopril
Dicarboxylate-containing agents
This is the largest group, including:
- Enalapril
- Ramipril
- Quinapril
- Perindopril
- Lisinopril
- Benazepril
- Imidapril
- Trandolapril
- Cilazapril
Phosphonate-containing agents
- Fosinopril is the only member of this group
Naturally occurring
- A comprehensive resource on anti-hypertensive peptides is available in form of a database. It contains around 1700 unique antihypertensive peptides
- Arfalasin (HOE 409) is an angiotensin antagonist.
Dairy products
- Casokinins and lactokinins, breakdown products of casein and whey, occur naturally after ingestion of milk products, especially cultured milk. Their role in blood pressure control is uncertain.
- The lactotripeptides Val-Pro-Pro and Ile-Pro-Pro produced by the probiotic Lactobacillus helveticus or derived from casein have been shown to have ACE-inhibiting and antihypertensive functions. In one study, L. helveticus PR4 was isolated from Italian cheeses.
Types overall………………………………………………………………….
| ACEinhibitors (“-pril”) |
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|---|
Mechanism of action
Normally, angiotensin I is converted to angiotensin II by an angiotensin-converting enzyme (ACE). Angiotensin II constricts blood vessels, increasing blood pressure. Enalaprilat, the active metabolite of enalapril, inhibits ACE. Inhibition of ACE decreases levels of angiotensin II leading to less vasoconstriction and decreased blood pressure.
There are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of 1277; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have the much greater affinity for an inhibitory activity against the C-domain. Enalaprilat, the principal active metabolite of enalapril, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Enalapril also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors. Enalaprilat’s affinity for ACE is approximately 200,000 times greater than that of ATI and 300-1000 times greater than that enalapril.
Indications
- Diabetic Nephropathies
- High blood pressure (Hypertension)
- Diabetic kidney disease
- High blood pressure
- Left ventricular dysfunction
- Heart failure
- Hypertensive emergency
- Alport syndrome
- Symptomatic congestive heart failure
- Asymptomatic left ventricular dysfunction
- Also for the treatment of essential or renovascular hypertension and symptomatic congestive heart failure. It may be used alone or in combination with thiazide diuretics.
Contra-Indications
- Low amount of sodium in the blood
- The high amount of potassium in the blood
- The inherited disorder of continuing episodes of swelling
- Reduction in the body’s resistance to infection
- Decreased function of bone marrow
- Decreased neutrophils a type of white blood cell
- Narrowing of the aortic heart valve
- Hypertrophic cardiomyopathy
- Renal artery stenosis
- Abnormally low blood pressure
- Liver problems
- Pregnancy
- Brain blood flow problem
- Hemodialysis with high-flux membrane
Side Effects
The most common
- a severe headache, rapid heartbeat, stiffness in your neck,
- chest pain, fast or slow heart rate;
- swelling, rapid weight gain;
- Xerostomia (dry mouth)
- A headache
- Fatigue
- Skin reactions
- Hypotension
- Anxiety
- Constipation
- Nausea/vomiting
- Weight gain/loss
- Erectile dysfunction
More common
- Abdominal or stomach pain, discomfort, or tenderness
- chills or fever
- difficulty with moving
- headache, severe and throbbing
- joint or back pain
- muscle aching or cramping
- muscle pains or stiffness
- chest pressure or squeezing pain in the chest
- discomfort in arms, shoulders, neck or upper back
- excessive sweating
- feeling of heaviness, pain, warmth and/or swelling in a leg or in the pelvis
- sudden tingling or coldness in an arm or leg
- sudden slow or difficult speech
- sudden drowsiness or need to sleep
- fast breathing
- sharp pain when taking a deep breath
- fast or slow heartbeat
- coughing up blood
- rust colored urine
- decreased amount of urine
Rare
- Anxiety
- change in vision
- chest pain or tightness
- confusion
- cough
- Agitation
- arm, back, or jaw pain
- blurred vision
- chest pain or discomfort
- convulsions
- extra heartbeats
- fainting
- hallucinations
- a headache
- irritability
- lightheadedness
- mood or mental changes
- muscle pain or cramps
- muscle spasm or jerking of all extremities
- nervousness
Drug Interactions
ACEIs may interact with the following drugs, supplements, & may change the efficacy of drugs
- allopurinol
- alpha blockers (e.g., alfuzosin, doxazosin, tamsulosin)
- alpha agonists (e.g., clonidine, methyldopa)
- amphetamines (e.g., dextroamphetamine, lisdexamphetamine)
- angiotensin II receptor blockers (ARBs; e.g., candesartan, losartan)
- antidiabetes medications (e.g., insulin, metformin, glyburide)
- atypical anti-psychotics (e.g., clozapine, olanzapine, quetiapine, risperidone)
- azathioprine
- barbiturates (e.g., butalbital, pentobarbital phenobarbital)
- beta-adrenergic blockers (e.g., atenolol, propranolol, sotalol)
- calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
- canagliflozin
- ciprofloxacin
- conivaptan
- diuretics (water pills; e.g., furosemide, hydrochlorothiazide, triamterene)
- duloxetine
- “gliptin” diabetes medications (e.g., linagliptin, saxagliptin, sitagliptin)
- heparin
- iron dextran complex
- iron gluconate
- levodopa
- medications that increase potassium levels (e.g., potassium supplements, spironolactone, amiloride, and salt substitutes containing potassium)
- metformin
- nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., ibuprofen, indomethacin, naproxen)
- other angiotensin-converting-enzyme inhibitors (ACEIs; e.g., captopril, ramipril)
- pentoxifylline
- phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil, vardenafil)
- pregabalin
- sodium phosphates
- temsirolimus
- tizanidine
- tolvaptan
- trimethoprim
References
-
PubChem
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