Enalapril in hypertension

The phase I clinical testing of enalapril began in 1980 in a study in which its efficacy to inhibit intravenously administered angiotensin I was determined. Oral doses as low as 2.5 mg produced a substantial decrease in ACE, activity and lowering was evident even 21-24 hours after the drug was given (129). Phase II and phase III trials began in 1981, and the first approval to use enalapril in hypertension came in 1984 and in heart failure in 1986. 

Oparil S. Eprosartan versus enalapril in hypertensive patients with angiotensin-converting enzyme inhibitor-induced cough. Curr Ther Res Clin Exp 1999 60 1-4. 

Keane WF, Polls A, Wolf D, Faison E, Shahinfar S. The long-term tolerability of enalapril in hypertensive patients with renal impairment. Nephrol Dial Transplant 1997 12(Suppl 2) 75-81. 

Lebovitz HE, Wiegmann TB, Cnaan A, et al. Renal protective effects of enalapril in hypertensive NIDDM role of baseline albuminuria. Kidney IntSuppl 1994 45 S 150-155. 

Captopril, l-[(2S)-3-mercapto-2-methyl-propionyl]-L-proline, the first orally active inhibitor of the angiotensin-converting enzyme (ACE) on the market. The positive effects of captopril and other ACE inhibitors like enalapril in hypertension and heart failure result primarily from suppression of the renin-angiotensin-aldosterone system. Captopril causes a fall in blood pressure in hypertensive patients [M. A. Ondetti et al.. Science 1977,196,441 ... 

Bain, S.C., Le Guen, C.A., Lunec, J. and Barnett, A.H. (1991). Comparison of the free radical scavenging activity of captopril versus enalapril a three-month trial in vivo study in hypertensive diabetic patients. J. Human Hypertens. 5, 511-515. 

Moreover, whether or not hypertension is caused by an elevated level of renin or other reasons, angiotensin-converting enzyme inhibitors lower both systolic and diastolic arterial pressure in hypertensive patients, and their effects are enhanced by diuretics. Angiotensin-converting drugs of this series (captopril, enalapril) are effective antihypertensive drugs used both independently and in combination with other drugs to treat all types of hypertension as well as to treat cardiac insufficiency. 

Rizzoni, D., Ported, E., Piccoli, A., et al. 1998. Effects of losartan and enalapril on small artery structure in hypertensive rats. Hypertension 32 305-310. 

Cocco G, Ettlin T, Baumeler HR. The effect of amlodipine and enalapril on blood pressure and neurohumoral activation in hypertensive patients with Ribbing s disease (multiple epiphysal dystrophy). Clin Cardiol 2000 23(2) 109-14. 

The long-term safety of enalapril in patients with severe renal insufficiency and hypertension has been evaluated in a pooled analysis of three similar, randomized, placebo-controlled clinical trials in 317 patients with renal insufficiency (101). Only patients without diabetes were included. Follow-up was for 2 and 3 years. One protocol used a fixed dose (5 mg/day) and the other two allowed titration up to 40 mg/day. Cough occurred in 18% of the patients taking enalapril and in 6.1% of those taking placebo. Hypotension (5.9 versus 1.2%) and paresthesia (7.8 versus 2.4%) were more frequent with enalapril Angioedema (1.3 versus 0.6%) and first-dose hypotension (1.3 versus 0%) tended to occur more often with enalapril. Hyperkalemia, defined as any increase from baseline and left to the judgement of the investigators, was excessive in the enalapril-treated patients (28 versus 8.8%). Finally, the hematocrit fell more often with enalapril (7.1 versus 2.0%). 

The LIVE (Left ventricular regression, Indapamide Versus Enalapril) study was a 1-year, prospective, randomized, double-blind comparison of modified-release indapamide 1.5 mg and enalapril 20 mg in reducing left ventricular mass in 411 hypertensive patients with left ventricular hypertrophy (9). For equivalent reductions in blood pressure, indapamide was significantly more effective than enalapril in reducing left ventricular mass index. 

Even low dosages of angiotensin-converting enzyme (ACE) inhibitors, such as enalapril, can cause profound first-dose hypotension in hypertensive patients treated with a thiazide (37). This is rare if volume depletion and sodium depletion are avoided. 

Webster J, Robb OJ, Witte K, Petrie JC. Single doses of enalapril and atenolol in hypertensive patients treated with bendrofluazide. J Hypertens 1987 5(4) 457-60. 

Reams GP, Bauer JH, Gaddy P. Use ofthe converting enzyme inhibitor enalapril in renovascular hypertension. Hypertension 1986 8 290-297. 

Hodsman GP, Brown JJ, Gumming AMM, Davies DE, East BW, Lever AF, Morton JJ, Murray GD, Robertson JIS. Enalapril in treatment of hypertension with renal artery stenosis. Am J Med 1984 77 (2A) 52-59. 

Reams GP, Bauer JH. Effect of enalapril in subjects with hypertension associated with moderate to severe renai dysfunction. Arch intern Med 1986 146 2145-2148. 

Lacourciere, Y, Belanger, A, Godin, C, Halle, JP, Ross, S, Wright, N, Marion, J Long-term comparison of losartan and enalapril on kidney function in hypertensive type 2 diabetics with early nephropathy. Kidney Int. 58 762-769, 2000. 

Nawarskas JJ, TownsendRR, CiriglianoMD, Spinier SA. Effect of aspirin on blood pressure in hypertensive patients taking enalapril or losartan. AmJHypertens(l999) 12, 784-9. 

Polonia J, Boaventura I, Gama G, Camoes I, Bernardo F, Andrade P, Nunes JP, Brand o F, Cerqueira-Gomes M. Influence of non-steroidal anti-inflammatory drugs on renal function and 24 h ambulatory blood pressure-reducii effects of enalapril and nifedipine gastrointestinal therapeutic system in hypertensive patients. JHypertens (1995) 13, 925-31. 

In a double-blind, crossover study in hypertensive subjects, the combination of atenolol 50 mg once daily and enalapril 20 mg once daily increased the hypotensive effect of either drug alone, but the effect was 30 to 50% less than additive. ... 

In one study, sulindac 200 mg twice daily given to patients taking capto-pril 100 to 200 mg twice daily caused only a small rise in blood pressure (from 132/92 to 137/95 mmHg). Sulindac 150 mg twice daily did not attenuate the blood pressure response to captopril when it was substituted for ibuprofen in an elderly woman. Similarly, sulindac 200 mg twice daily did not blunt the antihypertensive effect of enalapril in 9 patients with hypertension. Two studies in black women also found that sulindac 200 mg twice daily for one month did not alter the antihypertensive effect of fosinopril 10 to 40 mg daily or lisinopril 10 to 40 mg daily (given with hydrochlorothiazide 25 mg daily). - ... 

Noveck RJ, McMahon FG, Bocanegra T, Karem A, Sugimoto D, Smith M. Effects of oxa-prozin on enalapril and enalaprilat pharmacokinetics, pharmacodynamics blood pressure, heart rate, plasma renin activity, aldosterone and creatinine clearances, in hypertensive patients. Clin Pharmacol Ther ( 997), 61,208. 

Preston RA, Alonso A, Panzitta D, Zhang P, Kaiara AH. Additive effect of drospirenone/17-fl-estradiol in hypertensive postmenopausal women receiving enalapril. AmJHypertens(2(Xl2)... 

For example, characterization of enalapril and pCD complex was performed by combining C CP/MAS with several sofid-state techniques [15]. These experiments leaded to the conclusion that the complex was a new solid amorphous form that was difierent from its precursors. Enalapril is used in hypertension treatment and sufiers d radation in the sohd state as a consequence of its interaction with the difierent excipients commonly used in tablet formulation, such as microcrystaUine cellulose, magnesium stearate and eudragit E. 

Urinary tract Bilateral renal artery stenosis was unmasked by enalapril in a 9-year-old girl with severe hypertension [50 ]. 

Kostis, O.B., Packer, M., Black, H.R., Schmieder, R., Henry, D., and Levy, E. (2004) Omapatrilat and enalapril in patients with hypertension the omapatrilat cardiovascular treatment vs. enalapril (OCTAVE) trial. Am.J. Hypertens., 17, 103-111. 

All 10 ACE inhibitors available in the United States can be dosed once daily for hypertension except captopril, which is usually dosed two or three times daily. The absorption of captopril (but not enalapril or lisinopril) is reduced by 30% to 40% when given with food. 

Some optically active compounds have been studied [54], The benzazepinone diacid (CGS 12831, 27) was found to have the best in vitro inhibitor potency in a series of lactam compounds, but it showed only marginal biological activity following oral administration, presumably because of poor absorption. The corresponding monoethyl ester (CGS 14824A, 28) was much more potent in vivo [54, 56]. This compound (28) was found to produce dose-dependent antihypertensive effects in conscious normotensive and spontaneous hypertensive rats, generally similar to those produced by enalapril. Evaluation of (28) in healthy volunteers [57, 58] shows that it is an effective,... 

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