El Uses, Dosage, Side Effects, Food Interaction and all others data.
El, after hydrolysis to enalaprilate, inhibits Angiotensin Converting Enzyme (ACE). ACE is a peptidyl dipeptidase that catalyses the conversion of angiotensin I to the vasoconstrictor substance angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. The beneficial effects of enalapril in hypertension and heart failure appear to result primarily from suppression of the renin-angiotensin aldosterone system
El is an antihypertensive agent that exhibits natriuretic and uricosuric properties. El lowers blood pressure in all grades of essential and renovascular hypertension, and peripheral vascular resistance without causing an increase in heart rate. Individuals with low-renin hypertensive population were still responsive to enalapril. The duration of hypertensive effect in the systolic and diastolic blood pressure persists for at least 24 hours following initial administration of a single oral dose, and repeated daily administration of enalapril confers an additional reduction in blood pressure and a steady-state antihypertensive response may take several weeks. In patients with severe congestive heart failure and inadequate clinical response to conventional antihypertensive therapies, treatment with enalapril resulted in improvements in cardiac performance as observed by a reduction in both preload and afterload, and improved clinical status long-term. Furthermore, enalapril was shown to increase cardiac output and stroke volume while decreasing pulmonary capillary wedge pressure in patients with congestive heart failure refractory to conventional treatment with digitalis and diuretics. In clinical studies, enalapril reduced left ventricular mass, and did not affect cardiac function or myocardial perfusion during exercise. El is not highly associated with the risk of bradycardia unlike most diuretics and beta-blockers and it does not produce rebound hypertension upon discontinuation of therapy.
El is not reported to produce hypokalaemia, hyperglycaemia, hyperuricaemia or hypercholesterolaemia. In the kidneys, enalapril was shown to increase renal blood flow and decrease renal vascular resistance. It also augmented the glomerular filtration rate in patients with a glomerular filtration rate less than 80 mL/min. When used in combination, enalapril was shown to attenuate the extent of drug-induced hypokalemia caused by hydrochlorothiazide and the antihypertensive effects of both drugs were potentiated.
|Enalapril Other Names
|ánalapril, Enalapril, Enalaprila, Enalaprilum
|amlodipine, lisinopril, metoprolol, losartan, furosemide, carvedilol, hydrochlorothiazide, spironolactone, hydralazine, nifedipine
It is reported that less than 50% of enalaprilat is bound to human plasma proteins, based on limited data from binding studies of enalaprilat in human plasma both by equilibrium dialysis and by ultrafiltration.
|Approved, Vet approved
|Angiotensin-converting enzyme (ACE) inhibitors
|Sunij Pharma Pvt Ltd
|September 19, 2023 at 7:00 am
El is used for-
- All grades of essential hypertension and renovascular hypertension either alone or in combination with other antihypertensive agents especially thiazide diuretics.
- Prevention of symptomatic heart failure.
- Treatment of congestive heart failure (adjunct), usually in combination with diuretics and digitalis.
- Prevention of coronary ischaemic events in patients with left ventricular dysfunction.
El is also used either alone or as an adjunct in the treatment of angina, diabetic nephropathy and Raynaud's disease.
How El works
The renin-angiotensin-aldosterone system (RAAS) is a signaling pathway that works in synergism with the sympathetic system to regulate blood pressure and fluid and electrolyte homeostasis. Activation of this system upon stimulation by different factors, such as low blood pressure and nerve impulses, leads to increased release of norepinephrine (NE) from sympathetic nerve terminals and effects on the vascular growth, vasoconstriction, and salt retention in the kidneys. Renin is released from Renin acts on the precursor prottein angiotensinogen, which is a plasma globulin synthesized from the liver, to produce cleaved peptide hormone angiotensin I. Angiotensin I then can be further cleaved by ACE to produce angiotensin II, a vasoconstrictive peptide hormone. Present in different isoforms, angiotensin converting enzyme (ACE) is peptidyl dipeptidase enzyme expressed in various tissues, including the vascular tissues, such as the heart, brain, and kidneys. ACE also plays a role in inactivation of bradykinin, a potent vasodepressor peptide. Angiotensin II mediates various actions on the body by working on its G-protein coupled receptors, AT1 and AT2. It causes direct vasoconstriction of precapillary arterioles and postcapillary venules, inhibits the reuptake of NE thereby increasing available levels, stimulates the release of catecholamines from the adrenal medulla, reduces urinary excretion of sodium ions and water by promoting proximal tubular reabsorption, stimulates synthesis and release of aldosterone from the adrenal cortex, and stimulates hypertrophy of both vascular smooth muscle cells and cardiac myocytes.
El is a pharmacologically inactive prodrug that requires hepatic biotransformation to form enalaprilat, its active metabolite that works on the RAAS to inhibit ACE. Biotransformation is critial for the therapeutic actions of the drug, as enalapril itself is only a weak inhibitor of ACE. ACE inhibition results in reduced production and plasma levels of angiotensin II, increased plasma renin activity due to the loss of feedback inhibition by angiotensin II, and decreased aldosterone secretion. However, plasma aldosterone levels usually return to normal during long-term administration of enalapril. Decreased levels of angiotensin II subsequently leads to the dilatation of peripheral vessles and reduced vascular resistance which in turn lower blood pressure. While inhibition of ACE leading to suppression of RAAS is thought to be the primary mechanism of action of enalapril, the drug was shown to still exert antihypertensive effects on individuals with low-renin hypertension. It is suggested that enalapril may mediate its pharmacological actions via other modes of action that are not fully understood. As ACE is structurally similar to kininase I, which is a carboxypeptidase that degrades bradykinin, whether increased levels of bradykinin play a role in the therapeutic effects of enalapril remains to be elucidated.
Hypertension: Initially 5 mg once daily if used alone or 2.5 mg daily if used in addition to diuretic, in elderly patients or in patients with renal impairment. Usual maintenance dose is 10-20 mg once daily. However, in severe hypertension it may be increased to a maximum of 40 mg once daily.
Heart failure (adjunct) and asymptomatic left ventricular dysfunction: Initially 2.5 mg under close medical supervision. Usual maintenance dose is 20 mg daily in 1-2 divided doses
Dizziness and headache are more commonly reported side effects. Fatigue and asthenia were reported in 2-3% of patients. Other side effects occurred in less than 2% of patients and included hypotension, orthostatic hypotension, syncope, nausea, diarrhoea, muscle cramps, rash and cough.
Less frequently renal dysfunction, renal failure and oliguria have been reported. Angioedema, hyperkalemia and hyponatremia have also been reported rarely
LD50 and Overdose
Oral LD50 in rats is 2973 mg/kg. Lethality was observed with single oral doses of enalapril above 1000 mg/kg in mice and greater than or equal to 1775 mg/kg in rats. Serum enalaprilat levels 100- and 200-fold higher than usually seen after therapeutic doses have been reported after ingestion of 300 mg and 440 mg of enalapril, respectively. While there is limited data about enalapril overdose in humans, overdosage may result in marked hypotension and stupor based on the pharmacological properties of the drug. Most common adverse effects of enalapril include cough, hypotension, stupor, headache, dizziness and fatigue. If hypotension is seen, usual treatment of intravenous infusion of normal saline solution is recommended. Elat may be removed from systemic circulation with the use of hemodialysis. It has been removed from neonatal circulation by peritoneal dialysis.
Maternal and fetal toxicity occudred in some rabbits treated with enalapril at doses of 1 mg/kg/day or more. There was no fetotoxicity, expressed as a decrease in average fetal weight, or teratogenicity in rats treated with enalapril at doses up to 200 mg/kg/day, which is about 333 times the maximum human dose. In mice and rats receiving enalapril at doses ranging from 90 to 180 mg/kg/day, there was no evidence of a tumorigenic effect. Neither enalapril or its active metabolite were shown to be mutagenic or genotoxic in in vitro and in vivo studies. There were no adverse effects on reproductive performance of male and female rats treated with up to 90 mg/kg/day of enalapril.
Use in special populations
Caution is warranted in patients who are concurrently using another ACE inhibitors with enalapril, as there have been incidences of agranulocytosis with the use of captopril, which is another ACE inhibitor. This adverse event may be particularly significant in patients with renal impairment or collagen vascular disease. As enalapril and enalaprilat were shown to be secreted in human milk in trace amounts, the use of enalaprilat in nursing women is not recommended. Significant fetal transfer occurs with enalapril and enalaprilat thus the use of the drug in pregnant women should be strongly avoided. Caution is advised when enalapril is used in patients who are elderly or with renal impairment, as dosage adjustments may be appropriate. The antihypertensive effect of angiotensin converting enzyme inhibitors is generally lower in individuals of African descent, usually a low-renin hypertensive population.
Assess renal function; regular WBC counts in patient w/ collagen vascular disease eg SLE & scleroderma. Patient receiving immunosuppressive therapy; those prone to salt or water depletion. Pregnancy.
Combination with other antihypertensive agents such as b blockers, Methyldopa, calcium antagonists and diuretics may increase the antihypertensive efficacy. Adrenergic blocking drugs should only be combined with El under careful supervision. Concomitant Propranolol may reduce the bioavailability of El, but this does not appear to be of any clinical significance. Concomitant therapy with Lithium may increase the serum Lithium concentration.
- Avoid hypertensive herbs (e.g. bayberry, blue cohosh, cayenne, ephedra, and licorice). Additive hypertensive effects may occur.
- Avoid potassium-containing products. Potassium products increase the risk of hyperkalemia.
- Take with or without food. The absorption is unaffected by food.
[Moderate] GENERALLY AVOID: Moderate-to-high dietary intake of potassium can cause hyperkalemia in some patients who are using angiotensin converting enzyme (ACE) inhibitors.
In some cases, affected patients were using a potassium-rich salt substitute.
ACE inhibitors can promote hyperkalemia through inhibition of the renin-aldosterone-angiotensin (RAA) system.
MANAGEMENT: It is recommended that patients who are taking ACE inhibitors be advised to avoid moderately high or high potassium dietary intake.
Particular attention should be paid to the potassium content of salt substitutes.
El Drug Interaction
Moderate: aspirin, aspirin, aspirin, aspirin, furosemide, furosemideUnknown: omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, atorvastatin, atorvastatin, metoprolol, metoprolol, clopidogrel, clopidogrel, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol
Volume of Distribution
The volume of distribution of enalapril has not been established. Elat is shown to penetrate into most tissuesm, in particular the kidneys and vascular tissuem, although penetration of the blood-brain barrier has not been demonstrated after administration at therapeutic doses. In dog studies, enalapril and enalaprilat cross the blood-brain barrier poorly. Minimal penetration occurs into breast milk but significant fetal transfer occurs. The drug crosses the placental barrier in rats and hamsters.
Following oral administration, the peak plasma concentrations (Cmax) of enalapril is achieved within 1 hour post dosing while the Cmax of enalaprilat occurs at three to four hours post dosing. The steady-state is achieved by the fourth daily dose and there is no accumulation with repeated dosing. However, accumulation of enalaprilat may occur in patients with creatinine clearance less than 30 mL/min. Food intake is reported to have a minimal effect on drug absorption. Following oral administration, about 60% of enalapril was absorbed. Bioavailability of enalapril averaged about 40% when intravenous enalaprilat was used as a reference standard.
The average terminal half life of enalaprilat is 35-38 hours. The effective half life following multiple doses is 11-14 hours. The prolonged terminal half-life is due to the binding of enalaprilat to ACE.
Following oral administration in healthy male volunteers, the renal clearance was approximately 158 ± 47 mL/min. It is reported that enalapril and enalaprilat are undetectable in the plasma by 4 hours post-dosing.
El is mainly eliminated through renal excretion, where approximately 94% of the total dose is excreted via urine or feces as either enalaprilat or unchanged parent compound. About 61% and 33% of the total dose can be recovered in the urine and feces, respectively. In the urine, about 40% of the recovered dose is in the form of enalaprilat.
Pregnancy & Breastfeeding use
Category D: Contraindicated in pregnancy. The drug is excreted in trace amount in human milk and caution should be exercised if given to nursing mothers.
Aortic stenosis or outflow tract obstruction. Renovascular disease. Severe resistant HTN. Peripheral vascular disease or generalized atherosclerosis.
Use in the elderly (over 65 years): The starting dose should be 2.5 mg. Enaril is effective in the treatment of hypertension in the elderly. The dose should be titrated according to need for the control of blood pressure.
- Lightheadedness, dizziness, or fainting
- Decrease in urine output
- Drowsiness, headache, or back pain
- Slow or irregular heartbeat.
- Fluids through an intravenous line (IV)
- Medications to increase blood pressure
- Other treatments based on complications that occur
- Closely monitoring the heart and lungs.
What is El used for?
El used to reduce high blood pressure and to prevent or treat heart failure. If you have high blood pressure, taking enalapril will help prevent a future heart attack or stroke. This medicine is only available on prescription.
How safe is El?
El is generally safe to take for a long time.El works best when you take it for a long time. Taking El for a long time can sometimes cause your kidneys to not work as well as they should. Your doctor will check how well your kidneys are working with regular blood tests.
How does El work?
El relaxes and widens your blood vessels. This lowers your blood pressure and makes it easier for your heart to pump blood around your body.
What are the common side effects of El?
Common side effects of El are include:
- dry, tickly cough that does not go away.
- feeling dizzy or lightheaded, especially when you stand up or sit up quickly. This is more likely to happen when you start taking enalapril or move on to a higher dose.
- mild skin rash.
- blurred vision.
Is El safe during pregnancy?
El is considered contraindicated during pregnancy. Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity and death when administered during pregnancy. A committee of the National Institutes of Health has recommended that these drugs be avoided during pregnancy.
Is El safe during breastfeeding?
Small amounts of El may get into breast milk. This can cause low blood pressure in the baby. If your baby was born full term and healthy, it's generally safe to take El while you're breastfeeding.
Can I drink alcohol with El?
El lowers your blood pressure and drinking alcohol can increase its effects. This can make you feel dizzy or lightheaded. During the first few days of taking El or after a dose increase, it's best to stop drinking alcohol until you see how the medicine affects you.
When is the best time to take El?
Your first dose El may make you feel dizzy, so it's best to take it at bedtime. After that, if you don't feel dizzy, you can take it at any time of day.
When should you not take El?
Do not take El within 36 hours before or after taking medicine that contains sacubitril.If you have diabetes, do not use El together with any medication that contains aliskiren .
What foods to avoid while taking El?
Increased level of potassium can lead to irregular heartbeat. It is better to avoid potassium rich foods like bananas, oranges, green leafy vegetables and potassium containing salt when you are on El.
Can I take El at night?
El is best to take it at bedtime.
Does El make me pee?
This effect may increase the amount of urine you make when you first start the medication.El also helps to relax the blood vessels so that blood can flow through the body more easily.
How quickly does El work?
El usually starts to work within an hour, and the effect lasts for at least 24 hours.
Can El cause hair loss?
El can also lead to thinning hair.
What happens if I miss a dose of El?
If you miss a dose of El leave out that dose and take your next dose at the usual time. Do not take a double dose to make up for the forgotten dose.
Who should not take El?
Do not use El if you are pregnant. If you become pregnant, stop taking this medicine and tell your doctor right away.Also you should not use El if you have ever had angioedema. Do not take El within 36 hours before or after taking any medicine that contains sacubatril .
What happen if I stop El suddenly?
Stopping El may cause your blood pressure to rise and this may increase your risk of heart attack and stroke. If you're bothered by side effects, your doctor may be able to prescribe you a different medicine.
Will El affect my fertility?
There's no firm evidence to suggest that taking El will reduce fertility in either men or women. However, speak to a pharmacist or your doctor before taking it if you're trying to get pregnant.
How long does it take El to work?
El usually starts to work within an hour, and the effect lasts for at least 24 hours. Some people will require several weeks of treatment until the best effect on their blood pressure is seen.
Can El cause erectile dysfunction?
El do not typically cause erectile dysfunction.