Enalapril hypertension treatment

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. 

Figure 4. Weight of the dipped and nondipped kidneys of two-kidney one-dip rats with Goldblatt s hypertension after 12 months of no treatment, enalapril, orminoxidii treatment. p<0.001 compared with no treatment group. Reproduced with permission from [39].

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. 

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]. 

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 ... 

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... 

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. 

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). 

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 ... 

Mr WD was prescribed nifedipine LA 30 mg once daily and enalapril 10 mg twice daily to treat his hypertension. After one week s treatment, his blood pressure was still only 150/85 mmHg, but the patient was complaining of very swollen ankles. He also mentions that he has developed a persistent cough. 

Enalapril is an ACE inhibitor used in the treatment of hypertension and heart failure and prophylactically in patients with asymptomatic left ventricular dysfunction. 

A 52-year-old male renal transplant recipient on stable therapy (4.5 months) with ciclosporin, myco-phenolate mofetil, and co-trimoxazole developed erythrocytosis and hypertension. His leukocyte count fell 19 days after he started to take enalapril. Enalapril was withdrawn, the dose of co-trimoxazole was halved, and the dose of mycophenolate was first reduced and then withdrawn on day 25. On day 28 the leukocyte and neutrophil counts were so low that granulocyte-stimulating factor had to be used. The leukocyte count normalized during continued treatment with ciclosporin and co-trimoxazole. CMV tests were negative. 

Enalapril 5 mg once daily, titrated to BP placebo-controlled trial Hypertensive, GFR of 30-100 mL/min per 1.73 rr 121 Type 2 DM 3 years Clinical albuminuria progression in 7% of enalapril vs. 21 % of placebo group enalapril therapy preserved GFR, while placebo treatment resulted in a loss of 0.33 mL/min per 1.73 m per month Lebovitz et al ... 

Enalapril is an ACE inhibitor that competitively inhibits angiotensin I-converting enzyme, preventing conversion of angiotensin I to angiotensin 11, a potent vasoconstrictor that also stimulates release of aldosterone. It results in deaeases in BP, reduced sodium absorption, and potassium retention. Enalapril is indicated in the treatment of hypertension and symptomatic congestive heart failure (CHE) in combination with diuretics and digitalis and asymptomatic left ventricular dysfunction. 

A good example is the development of the angiotensin converting enzyme (ACE) inhibitors successfully used in the treatment of hypertension. A careful study of the natural substrate and peptide inhibitors of this enzyme led first to captopril followed by enalapril (see above). The former is considered an analogue of a proline dipeptide and the latter a proline tripeptide analogue. 

---