Hypertension enalapril

Today, captopril (Capoten ) ranks among the most frequently used drugs in the treatment of hypertension. Enalapril (Xanef ) has been commercially available since 1985 as a second ACE inhibitor. The discovery of captopril started an avalanche of research into the synthesis of angiotensin-converting enzyme inhibitors. Some new developments should be mentioned at this point ... 

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. 

Captopril, enalapril Angiotensin converting enzyme Hypertension... 

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,... 

Peptidyl-dipeptidase A (angiotensin-I converting enzyme, ACE, EC 3.4.15.1) plays a pivotal role in the control of blood pressure [80]. It has been established that its active site contains an essential Zn-atom that functions like that of carboxypeptidase A [2], ACE is inhibited by peptides having a proline or aromatic amino acid at the C-terminal position. These observations as well as the similarities with the active site of carboxypeptidase A have allowed a rational design of effective inhibitors of ACE (e.g., captopril (3.4) and enalapril (3.5)) used in the treatment of hypertension [81]. 

Captopril (Capoten ), Enalapril and Lisinopril (Fig. 13) are examples of ACE inhibitors that are rather successful as pharmaceutical drugs against hypertension. In most cases these inhibitors are bound via zinc binding groups (ZBGs) such as thiolates, carboxylates or hydroxamates to the zinc(II) center of the active site. 

Azizi, M., Guyene, T. T., ChateUier, G., Wargon, M., and Menard, J. (1997) Additive effects of losartan and enalapril on blood pressure and plasma active renin. Hypertension. 29, 634-640. 

Q40 A patient with hypertension (male 56 years, weight 55 kg) visits the pharmacy with a new prescription for diclofenac. The patient is already taking enalapril 20 mg daily, atenolol 100 mg daily and... 

Diclofenac is a non-steroidal anti-inflammatory drug. NSAIDs interact with both angiotensin-converting enzyme inhibitors, such as enalapril, and beta-adrenoceptor blockers, such as atenolol, resulting in antagonism to the hypotensive reaction, leading to a hypertensive reaction. NSAIDs interact with... 

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. 

Hyperkaiemia Elevated serum potassium (at least 0.5 mEq/L greater than the upper limit of normal) was observed in 0.4% of hypertensive patients given trandolapril, approximately 1% of hypertensive patients given benazepril, enalapril, ramipril, or moexipril approximately 2% of patients receiving quinapril or lisinopril, approximately 2.6% of hypertensive patients given fosinopril, and approximately 4.8% of CHF patients given lisinopril. Hyperkalemia also occurred with captopril. Vaivuiar stenosis Theoretically, patients with aortic stenosis might be at risk of decreased coronary perfusion when treated with vasodilators, because they do not develop as much afterload reduction as others. 

While essentially all ACE inhibitors have a similar mechanism of action and therefore exhibit similar efficacy in the treatment of hypertension and congestive heart failure, these drugs differ slightly in their pharmacokinetic profiles. Enalapril, lisinopril, and quinapril are excreted primarily by the kidney, with minimal liver metabolism, while the other prodrug compounds are metabolized by the liver and renally excreted. Thus, in patients with renal insufficiency, the half-life of renally excreted ACE inhibitors is prolonged. In addition, patients with impaired liver func-... 

Julie Singer is a 55-year-old white woman who was admitted to the emergency department in acute distress. A previous physical examination showed hypertension and diabetes mellitus type 2. The patient s present medications include enalapril 40 mg, nifedipine 60 mg, and 100 U insulin. A physical examination revealed prominent ankle edema, a palpable spleen, and hepatomegaly. Chest radiography revealed diffuse cardiac enlargement and left ventricular hypertrophy. Based upon the history and clinical hndings, what is your diagnosis and what treatment do you recommend ... 

Although this enzymatic process fills only a niche in the L-lysine market, it is a successful example of a general method for amino acid resolution. It has some superior features compared to the Tanabe L-aminoacylase approach. The L-lysine can be extended to non-protein amino acids such as the use of P. putida aminopeptidase to resolve DL-homophenylalanine to produce precursors for the anti-hypertensive dmg Enalapril. A similar approach has also been used for the production of L-cysteine from DL-2-amino-A2-thiazohne-4-caiboxylate using Sarcina lucea, which is remarkable in that both isomers form L-cysteine. 

Enalapril maleate is an orally active angiotensin converting enzyme (ACE) inhibitor, it lowers peripheral vascular resistance without causing an increase in heart rate. The maleate salt (enalapril) allows better absorption after oral administration. It is an ideal drug for hypertensive patients who are intolerant to beta-blocker therapy. It also shows promise in the treatment of congestive heart failure. Following oral adminishation, enalapril is rapidly absorbed and hydrolysed to... 

Enalapril is an oral prodrug that is converted by hydrolysis to a converting enzyme inhibitor, enalaprilat, with effects similar to those of captopril. Enalaprilat itself is available only for intravenous use, primarily for hypertensive emergencies. Lisinopril is a lysine derivative of enalaprilat. Benazepril, fosinopril, moexipril, perindopril, quinapril, ramipril, and trandolapril are other long-acting members of the class. All are prodrugs, like enalapril, and are converted to the active agents by hydrolysis, primarily in the liver. 

An important class of orally active ACE inhibitors, directed against the active site of ACE, is now extensively used. Captopril and enalapril are examples of the many potent ACE inhibitors that are available. These drugs differ in their structure and pharmacokinetics, but in clinical use, they are interchangeable. ACE inhibitors decrease systemic vascular resistance without increasing heart rate, and they promote natriuresis. As described in Chapters 11 and 13, they are effective in the treatment of hypertension, decrease morbidity and mortality in heart failure and left ventricular dysfunction after myocardial infarction, and delay the progression of diabetic nephropathy. 

Enalapril Inhibits conversion of angiotensin I Arteriolar dilation decreased aldosterone Hypertension heart failure... 

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. 

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. 

Converting enzyme (ACE) inhibitors 176) likewise prevent the formation of angiotensin II and are used in the treatment of renal and essential hypertension. Examples of orally active ACE-inhibitors are (2)-l-[(2S)-3-[N-(S)-mercapto-2-methylpro-panoyl]proline170) (captopril 77), l-[N-(S)-l-carboxy-3-phenylpropyl]-L-alanyl-L-proline-1 -ethyl ester177 (enalapril 78), and 2-[N-[(S)-l-ethoxycarbonyl-3-phenyl-propyl]-L-alanyl]-(lS,3S,5S)-2-azabicyclo[3.3.0]octane-3-carboxylic acid178) (Hoe 498 79). 

There appear to be significant differences between the pioneer drug, captopril, and the enalapril analogues. Differences in these characteristics influence mainly the onset and duration of action. Captopril has a short onset time (1 h) and a relatively short duration of action, and therefore is administered three times daily. Captopril has potential drug-food interactions, and is the only agent that should be spaced from meals. Therefore, captopril is no longer used as a first-choice ACE-inhibitor in clinical practice, except for hypertensive emergencies, acute myocardial ischemia, and acute CHF. 

---