Brand Names: Vasotec

Clinical Names: Enalapril

Summary

generic name: Enalapril

trade name: Vasotec®

type of drug: Angiotensin-converting enzyme (ACE) inhibitor.

used to treat: High blood pressure, some forms of heart failure, and, occasionally, early diabetic kidney disease to help prevent progression to frank nephropathy; often in conjunction with a diuretic and/or digoxin.

mechanism: Angiotensin-Converting Enzyme (ACE) is an enzyme in the body which is important for the formation of angiotensin II. The function of angiotensin II is to cause constriction of arteries, thereby elevating blood pressure. ACE inhibitors such lower blood pressure by inhibiting the formation of angiotensin II, thus relaxing the arteries. Relaxing the arteries not only lowers blood pressure, but also improves the pumping efficiency of a failing heart and improves cardiac output in patients with heart failure.

Enalapril is an angiotensin-converting enzyme (ACE) inhibitor. ACE inhibitors are used to treat high blood pressure and, in some cases heart failure. They are also sometimes used in the treatment of early diabetic kidney disease to help prevent progression to frank nephropathy.

overview of interactions:
• nutrient affected by drug: Iron

• nutrient affected by drug: Potassium

• nutrient affected by drug: Sodium Chloride (Salt)



Interactions

nutrient affected by drug: Iron

• research: In several studies of hypertensive patients with renal failure on dialysis mild worsening of anemia has been observed during treatment with enalapril. Gossman et al. have suggested that ACEI-related anemia in renal transplant recipients seems to be due to the erythropoietin-lowering effect of this group of drugs.
(Wong KC, et al. Int J Artif Organs 1995 Dec;18(12):757-762; Incalzi RA, et al. J Am Geriatr Soc. 1998 Jan;46(1):117-118; Ozbek N, et al. Acta Paediatr Jpn. 1997 Oct;39(5):626-627; Gossmann J, et al. Kidney Int. 1996 Sep;50(3):973-978; Albitar S, et al. Nephrol Dial Transplant 1998 May;13(5):1206-1210.)

• nutritional concerns: Supplementation of any minerals by patients with renal failure or on dialysis can be dangerous and should only be done within the context of close medical supervision.

nutrient affected by drug: Potassium

• mechanism: ACE inhibitors enhance potassium levels in the blood. Ohya et al have demonstrated enalapril ability to significantly inhibit plasma aldosterone concentration and urinary aldosterone excretion.
(Ohya Y, et al. Int J Clin Pharmacol Ther 1994 Dec;32(12):655-659.)

• nutritional concerns: Potassium supplements and even high-potassium foods, such as fruit, can lead to problematic interactions and should be avoided. Individuals using ACE Inhibitors are advised to discuss these issues with their prescribing physician, a pharmacist, or both.

nutrient affected by drug: Sodium Chloride (Salt)

• mechanism: Hypertension in obese patients is associated with hyperinsulinemia and salt sensitivity. However, the very low salt diets often prescribed for individuals with high blood pressure may exacerbate hyperinsulinemia, perhaps by activating the renin-angiotensin system.

• nutritional synergy: Preliminary research indicates that under the influence of enalapril, severe salt restriction decreases blood pressure while raising insulin levels in overweight individuals with mild hypertension. Individuals taking enalapril should discuss dietary changes, especially involving restricting salt intake, with their physician and/or a nutritionally-oriented healthcare provider.
(Egan BM, et al. Am J Cardiol 1993 Jul 1;72(1):53-57.)

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References

Albitar S, Genin R, Fen-Chong M, Serveaux MO, Bourgeon B. High dose enalapril impairs the response to erythropoietin treatment in haemodialysis patients. Nephrol Dial Transplant 1998 May;13(5):1206-1210.
Abstract: BACKGROUND: The resistance to recombinant human erythropoietin (rHuEpo) therapy in haemodialysis (HD) patients has multifactorial aetiologies: erythropoietin insufficiency, dialysis insufficiency, iron deficiency, and secondary hyperparathyroidism. Angiotensin-converting enzyme (ACE) inhibitors induce anaemia in patients with essential hypertension, congestive heart failure, chronic renal insufficiency, and renal transplants. Data exist suggesting that ACE inhibitors impair erythropoiesis in HD patients. Therefore the aim of this study was to investigate the impact of enalapril on rHuEpo requirement. METHODS: In the present prospective non-randomized study of 12 months, we compared the effects of enalapril and nifedipine on rHuEpo requirement in 40 hypertensive patients receiving rHuEpo for more than 6 months on maintenance haemodialysis. Twenty normotensive rHuEpo-dependent patients served as a control group. All patients with severe hyperparathyroidism or iron deficiency were excluded. RESULTS: The mean (+/- SD) haemoglobin concentration was > 10 g/dl in all groups. The mean weekly rHuEpo dose increased in the enalapril group (P<0.0001 vs before) and remained constant in the nifedipine and control groups (P=NS vs before). Statistically, there was no differences with regard to iPTH levels, dialysis parameters, iron status, and underlying renal diseases among all groups. CONCLUSION: High-dose enalapril increases rHuEpo requirement and should be reserved for dialysis patients with hypertension uncontrollable with other antihypertensive medications or dialysis patients with cardiac failure.

Egan BM, Stepniakowski K. Effects of enalapril on the hyperinsulinemic response to severe salt restriction in obese young men with mild systemic hypertension. Am J Cardiol 1993 Jul 1;72(1):53-57.
Abstract: Hypertension in obese patients is associated with hyperinsulinemia and salt sensitivity. Very low salt diets may exacerbate hyperinsulinemia, perhaps by activating the renin-angiotensin system. Therefore, the effects of a low salt diet alone and with enalapril on blood pressure and the insulin response to an oral glucose tolerance test were studied in 9 obese (body mass index 35 +/- 2 kg/m2) men with mild hypertension. Measurements were first obtained after a 2-week high-salt (20 mEq/day sodium diet+eleven 1 g salt tablets per day) baseline period. The same measurements were repeated after 2 weeks on a low salt diet (20 mEq/day) and after 2 weeks on low salt diet with enalapril in random sequence. The insulin area under the curve increased from 12.8 +/- 3.0 mU-min/dl during high salt to 16.6 +/- 3.2 mU-min/dl (p < 0.001). Plasma renin activity also increased with salt restriction from 1.4 +/- 0.2 to 3.0 +/- 0.5 ng/ml/hour, p = 0.01. With addition of enalapril to the low sodium chloride diet, the insulin area under the curve (14.5 +/- 2.6 mU-min/dl) was not significantly different from that during the high sodium chloride phase. Mean blood pressure in the laboratory was 105 +/- 1 mm Hg with high salt versus 99 +/- 1 mm Hg with low salt, p < 0.05. Addition of enalapril to the low-salt diet reduced mean blood pressure to 87 +/- 1 mm Hg (p < 0.01 vs low salt), largely by reducing total systemic resistance (p < 0.05). Salt restriction decreases laboratory BP while raising insulin levels in obese men with mild hypertension.

Good, CB, McDermott, L, McCloskey, B. Diet and serum potassium in patients on ACE inhibitors. JAMA 1995 Aug 16;274(7):538. (Letter)

Gossmann J, Thurmann P, Bachmann T, Weller S, Kachel HG, Schoeppe W, Scheuermann EH. Mechanism of angiotensin converting enzyme inhibitor-related anemia in renal transplant recipients. Kidney Int. 1996 Sep;50(3):973-978.

Incalzi RA, Gemma A, Carbonin P. ACE inhibitors: a possible cause of unexplained anemia. J Am Geriatr Soc. 1998 Jan;46(1):117-118. (Letter)

Ohya Y, Ueno M, Takata Y, Tominaga M, Ohmori S, Kobayashi K, Abe I, Fujishima M. Crossover comparison of the effects of enalapril and captopril on potassium homeostasis in patients with mild hypertension. Int J Clin Pharmacol Ther 1994 Dec;32(12):655-659.
Abstract: The effects of two types of angiotensin converting enzyme (ACE) inhibitors, enalapril (long-acting) and captopril (short-acting), on serum electrolytes and circadian rhythm of urinary electrolyte excretions were compared in relation to aldosterone status in patients with essential hypertension and normal renal function. Enalapril (5 mg once daily) and captopril (12.5 mg t.i.d.) were administered to 11 patients for 1 week each in a crossover fashion. Blood sampling in the early morning and 4-hour split urinary sampling for 24 hours were performed on the last day of control and each treatment periods. Enalapril and captopril significantly reduced blood pressure to similar levels. Enalapril but not captopril significantly inhibited plasma aldosterone concentration and urinary aldosterone excretion. Neither drug apparently altered serum or urinary Na levels. Both drugs significantly decreased urinary K excretion (p < 0.05, control: 44 +/- 4 mEq/day, captopril: 39 +/- 2 mEq/day, enalapril: 39 +/- 2 mEq/day; mean +/- SEM), but did not significantly alter serum K level (control: 4.1 +/- 0.1 mEq/l, captopril 4.2 +/- 0.2 mEq/l, enalapril 4.3 +/- 0.1 mEq/l). The circadian rhythm (acrophase) of urinary K excretion was not affected by either drug, while the amplitude was decreased by both, as assessed by the cosinor method. In summary, although enalapril caused more sustained inhibition of aldosterone secretion compared with captopril, both drugs showed similar effects on the K homeostasis in patients with mild essential hypertension.

Ozbek N, Ozen S, Saatci U. Enalapril-induced anemia in a renal transplant patient. Acta Paediatr Jpn. 1997 Oct;39(5):626-627.

Wong KC, Woo KS, Lam WK, Li KT, Lai KN, Nicholls MG, Lui SF. A comparison of the effect of enalapril and metoprolol on renal function, potassium balance, lipid profile, cardiac function, exercise tolerance and quality of life in hypertensive dialysis patients. Int J Artif Organs 1995 Dec;18(12):757-762.
Abstract: 26 patients with hypertension while on hemodialysis or continuous ambulatory peritoneal dialysis for end-stage renal diseases were treated first with enalapril and then changed to metoprolol. Both drugs were shown to be similarly effective in controlling blood pressure. There was no difference between the two drugs in their effects on renal function, potassium balance, lipid profile, cardiac function, exercise tolerance, and quality of life. Mild worsening of anemia was observed during treatment with enalapril. No serious side effects were reported. Use of enalapril is safe in the treatment of hypertension in dialysis patients.