Enalapril is a dicarbonyl-containing peptide and angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. As a prodrug, enalapril is converted by de-esterification into its active form enalaprilat. Enalaprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Enalapril also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
Enalapril is a prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is a potent, competitive inhibitor of ACE, the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). It is a medication used to treat high blood pressure, diabetic kidney disease, and heart failure. For heart failure, it is generally used with a diuretic such as furosemide. It is given by mouth or injection into a vein. The onset of effects is typically within an hour when taken by mouth and last for up today.
Mechanism of Action of Enalapril
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 of Enalapril
- 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 of Enalapril
- Low amount of sodium in the blood
- The high amount of potassium in the blood
- An 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
Dosage of Enalapril
Strengths: 2.5 mg; 5 mg; 10 mg; 20 mg; 1.25 mg/mL; 1 mg/mL
Hypertension
- Initial dose (oral tablets or solution): 5 mg orally once a day
- Maintenance dose (oral tablets or solution): 10 to 40 mg orally per day as a single dose or in 2 divided doses
- Maximum dose: 40 mg orally daily as a single dose or in 2 divided doses
In combination with diuretics
- Initial dose: 2.5 mg orally once a day
- If feasible, the diuretic should be discontinued 2 to 3 days prior to initiation of therapy with enalapril. If required, diuretic therapy may be gradually resumed.
- Parenteral: 1.25 to 5 mg IV over a 5 minute period every 6 hours
Congestive Heart Failure
- Initial dose: 2.5 mg orally once a day
- Maintenance dose: 2.5 to 20 mg daily in 2 divided doses
- Maximum dose: 40 mg orally per day in 2 divided doses
Pediatric Hypertension
Oral tablets or solution, Children 1 month to 17 years
- Initial dose: 0.08 mg/kg/day (up to 5 mg) in 1 to 2 divided doses. Adjust dosage based on patient response.
- Maximum dose: Doses greater than 0.58 mg/kg (40 mg) have not been evaluated in pediatric patients.
Side Effects of Enalapril
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 pain when an area is touched or pressed. সহজ বাংলা: চাপ দিলে ব্যথা।" data-rx-term="tenderness" data-rx-definition="Tenderness means pain when an area is touched or pressed. সহজ বাংলা: চাপ দিলে ব্যথা।">tenderness
- chills or fever
- difficulty with moving
- a 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
- a 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 of Enalapril
Enalapril 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 antipsychotics (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
Pregnancy Category of Enalapril
FDA Pregnancy Category D
Pregnancy
ACE inhibitors such as enalapril may cause severe harm or death to the developing fetus if taken by the mother during pregnancy. This medication should not be used during pregnancy. If you become pregnant while taking this medication, contact your doctor immediately.
Lactation
This medication passes into breast milk in small amounts. If you are a breast-feeding mother and are taking enalapril, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding. The safety and effectiveness of this medication have not been established for infants and children with decreased kidney function.
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