TO STUDY THE EFFICACY AND EFFECTS ON LIPID METABOLISM, ANTHROPOMETRY AND BLOOD PRESSURE OF COMBINATION TREATMENT WITH ARB+HCTZ AND ACES+HCTZ IN HYPERTENSIVE PATIENT

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About Authors:
Rajak Sandeep1, Kothiyal Preeti2, Mathur Prashant1
1Department of clinical pharmacy,
2Department of pharmacology,
Division of Pharmaceutical sciences,
Shri Guru Ram Rai Institute of Technology And Sciences, Patel Nagar, Dehradun-248001, Uttarakhand, India
sandeep.rajak1886@gmail.com

Abstract
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are widely prescribed for the treatment of hypertension and heart failure, as well as for kidney disease prevention in patients with diabetes mellitus and the management of patients after myocardial infarction.Both combination therapies of an Angiotensin II receptor blocker (ARB) with the thiazide hydrochlorothiazide (HCTZ) and an Angiotensin converting enzymes (ACEs) with HCTZ are recommended to achieve blood pressure (BP) goals in antihypertensive treatment. However, although HCTZ is known to have unfavorable effects on lipid metabolism, the effects of HCTZ in the ARB+HCTZ and ACEs+HCTZ combination on lipid metabolism have not been fully elucidated. The objective of present study was “To study the Efficacy and Effects on Lipid Metabolism, anthropometry and blood pressure of Combination Treatment With ARB+HCTZ and ACEs+HCTZ in hypertensive patient.”

All prescription of hypertensive patients coming to the medicine OPD and IPD would be screened and those prescribed with  ACE-inhibitors+HCTZ and ARBs+HCTZ combination of  drugs will be selected for this study.

REFERENCE ID: PHARMATUTOR-ART-2084

PharmaTutor (ISSN: 2347 - 7881)

Volume 2, Issue 1

Received On: 02/012/2014; Accepted On: 17/12/2014; Published On: 15/01/2014

How to cite this article: S Rajak, P Kothiyal, P Mathur, To study the Efficacy and Effects on Lipid Metabolism, anthropometry and blood pressure of Combination Treatment with ARB+HCTZ and ACEs+HCTZ in hypertensive patient, PharmaTutor, 2014, 2(1), 112-128

Inclusion criteria

  • Patient at the age above 18 years or below 80 years.
  • Patient suffering from BP and who are prescribed with ACE-inhibitor+HCTZ and ARBs+HCTZ combination of drugs.

Exclusion criteria

  • Patient below 18 years or above 80 years.
  • Patient co-prescribed with other antihypertensive drug.

On follow up a significant changes observed in systolic and diastolic blood pressure (p=0.0001) where as no significant changes was observed in lipid level as well as BMI or waist to hip ratio. Thus it concluded that ARBs+HCTZ was more efficacious in decreasing SBP than was ACEs+HCTZ combination in the management of hypertension. The unfavorable effect on lipid metabolism and BMI were observed with either combination.

INTRODUCTION

Hypertension
Hypertension (HTN) is the term used to denote elevated blood pressure (BP). It is defined as the condition in which BP remains consistent to systolic blood pressure (SBP) >140 mmHg and diastolic blood pressure (DBP) >90 mmHg. HTN can lead to heart disease, kidney disease or blindness and stroke. High BP is called “The Silent Killer” because it usually has no symptoms. It is one of the most common cardiovascular diseases in America and Worldwide [1].

Systolic Blood Pressure. The systolic pressure (the first and higher number) is the force that blood exerts on the artery walls as the heart contracts to pump out the blood. High systolic pressure is now known to be a greater risk factor than diastolic pressure for heart, kidney, and circulatory complications and for death, particularly in middle−aged and elderly adults. The wider the spread between the systolic and diastolic measurements, the greater the danger [2].

In fact, elevated systolic pressure may pose a significant danger for heart events and stroke events even when diastolic is normal −− a condition called isolated systolic hypertension. Isolated systolic hypertension is the most common form of hypertension in people older than fifty. In one study it comprised 87% of hypertension cases in people between ages 50 and 59.

Diastolic Blood Pressure. The diastolic pressure (the lower and second number) is the measurement of force as the heart relaxes to allow the blood to flow into the heart. High diastolic pressure (the second and lower number) is a strong predictor of heart attack and stroke in young adults[2].

Pulse Pressure. Pulse pressure is the difference between the systolic and the diastolic readings. It appears to be an indicator of stiffness and inflammation in the blood−vessel walls. The greater the difference between systolic and diastolic numbers, the stiffer and more injured the vessels are thought to be. Although not yet used by physicians to determine treatment, evidence is suggesting that it may prove to be a strong predictor of heart problems, particularly in older adults. Some studies suggest that in people over 45 years old, every 10−mm Hg increase in pulse pressure increases the risk for stroke increases by 11%, cardiovascular disease by 10%, and overall mortality by 16%. (In younger adults the risks are even higher.)[3].

  • The heart pumps blood with excessive force.
  • The body's smaller blood vessels (known as the arterioles) narrow, so that blood flow exerts more pressure against the vessels' walls.

Although the body can tolerate increased blood pressure for months and even years, eventually the heart may enlarge (a condition called hypertrophy), which is a major factor in heart failure. Such pressure can also injure blood vessels in the heart, kidneys, the brain, and the eyes.

Blood pressure is measured in millimeters of mercury (mm Hg). For example, excellent blood pressure would be less than 120/80 mm Hg (systolic/diastolic). Blood pressure is now categorized as optimal, normal, high normal, and hypertensive. The hypertensive category is further divided, according to severity [2].

Drug classification
Angiotensin converting enzyme. [ACE-Inhibitor]

Angiotensin converting enzyme (ACE-inhibitors) inhibitors block an enzyme that narrows blood vessels. This makes blood vessels relax and widen, reducing blood  pressure. ACE -inhibitors inhibitAngiotensin-converting enzyme (a component of the blood pressure-regulating renin-angiotensin system), thereby decreasing the tension of blood vessels and blood volume, thus lowering blood pressure. ACE inhibitors are used primarily to treat hypertension, although they may also be prescribed for cardiac failure, diabetic nephropathy, chronic renal failure, renal involvement in systemic sclerosis.        

The ability to reduce levels of angiotensin II with orally effective inhibitors of angiotensin converting enzyme (ACE) represents an important advance in the treatment of hypertension. Captopril (CAPOTEN) was the first such agent to be developed for the treatment of hypertension. Since then, enalapril (VASOTEC), lisinopril (PRINIVIL), quinapril (ACCUPRIL), ramipril (ALTACE), benazepril (LOTENSIN), moexipril (UNIVASC), fosinopril (MONOPRIL), trandolapril (MAVIK), and perindopril (ACEON) also have become available. These drugs have proven to be very useful for the treatment of hypertension because of their efficacy and their very favorable profile of adverse effects, which enhances patient adherence [4].

The ACE inhibitors appear to confer a special advantage in the treatment of patients with diabetes, slowing the development and progression of diabetic glomerulopathy. They also are effective in slowing the progression of other forms of chronic renal disease, such as glomerulosclerosis, and many of these patients also have hypertension. An ACE inhibitor is the preferred initial agent in these patients [4].

The endocrine consequences of inhibiting the biosynthesis of angiotensin II are of importance in a number of facets of hypertension treatment. Because ACE inhibitors blunt the rise in aldosterone concentrations in response to Na+ loss, the normal role of aldosterone to oppose diuretic-induced natriuresis is diminished. Consequently, ACE inhibitors tend to enhance the efficacy of diuretic drugs. This means that even very small doses of diuretics may substantially improve the antihypertensive efficacy of ACE inhibitors; conversely, the use of high doses of diuretics together with ACE inhibitors may lead to excessive reduction in blood pressure and to Na+ loss in some patients [4].

Common adversedrugreactions include: 
hypotension, cough, hyperkalemia, headache, dizziness, fatigue, nausea, and renal impairment.

Angiotensin II Receptor Blocker. [ARBs]
Angiotensin II is a very potent chemical that causes muscles surrounding blood vessels to contract, thereby narrowing blood vessels. This narrowing increases the pressure within the vessels and can cause high blood pressure (hypertension).Angiotensin II receptor blockers (ARBs) are medications that block the action of angiotensin II by preventing angiotensin II from binding to angiotensin II receptors on blood vessels.ARBs are used for controlling high blood pressure, treating heart failure, and preventing kidney failure in people with diabetes or high blood pressure. 

There are two distinct subtypes of angiotensin II receptors, designated as type 1 (AT1) and type 2 (AT2). The AT1 angiotensin II-receptor subtype is located predominantly in vascular and myocardial tissue and also in brain, kidney, and adrenal glomerulosa cells, which secrete aldosterone . The AT2 subtype of angiotensin II receptor is found in the adrenal medulla, kidney, and in the CNS, and may play a role in vascular development. Because the AT1 receptor mediates feedback inhibition of renin release, renin and angiotensin II concentrations are increased during AT1-receptor antagonism. The clinical consequences of increased angiotensin II effects on an uninhibited AT2 receptor are unknown; however, emerging data suggest that the AT2 receptor may elicit antigrowth and antiproliferative responses.

Therapeutic Uses:
When given in adequate doses, the AT1 receptor antagonists appear to be as effective as ACE inhibitors in the treatment of hypertension. As with ACE inhibitors, these drugs may be less effective in African-American and low-renin patients.

The full effect of AT1 receptor antagonists on blood pressure typically is not observed until about 4 weeks after the initiation of therapy. If blood pressure is not controlled by an AT1 receptor antagonist alone, a low dose of a hydrochlorothiazide or other diuretic may be added. In several randomized, double-blind studies of patients with mild-to-severe hypertension, the addition of hydrochlorothiazide to an AT1 receptor antagonist produced significant additional reductions in blood pressure in patients who demonstrated an insufficient response to hydrochlorothiazide alone. A smaller initial dosage is preferred for patients who have already received diuretics and therefore have an intravascular volume depletion, and for other patients whose blood pressure is highly dependent on angiotensin II. Given the different mechanisms by which they act, there is no assurance that the effects of ACE inhibitors and antagonists of the AT1 receptor will be equivalent in preventing target organ damage in patients with hypertension.

The most common side effects are cough, elevated potassium levels in the blood (hyperkalemia), low blood pressure, dizziness, headache, drowsiness, diarrhea, abnormal taste sensation (metallic or salty taste), and rash.Compared to ACE inhibitors, cough occurs less often with ARBs.

Thiazide hydrochlorothizide.[HCTZ]
Thiazide diuretics were the first tolerated efficient antihypertensive drugs that significantly reduced cardiovascular morbidity and mortality in placebo-controlled clinical studies. Although these drugs today still are considered a fundamental therapeutic tool for the treatment of hypertensive patient

Hydrochlorothiazide belongs to thiazide class of diuretics. It reduces blood volume by acting on the kidneys to reduce sodium (Na) reabsorption in the distal convoluted tubule. The major site of action in the nephron appears on an electroneutral Na+-Cl- co-transporter by competing for the chloride site on the transporter. By impairing Na transport in the distal convoluted tubule, hydrochlorothiazide induces a natriuresis and concomitant water loss. Thiazides increase the reabsorption of calcium in this segment in a manner unrelated to sodium transport [5]. Additionally, by other mechanisms, HCTZ is believed to lower peripheral vascular resistance[6].

Common Side Effects.Common side effects of diuretics are fatigue, depression, irritability, urinary incontinence, loss of sexual drive, breast swelling in men, and allergic reactions. Diuretics can trigger attacks of gout. They may also increase the risk of gastrointestinal (GI) bleeding. Diuretics may raise cholesterol level and, used alone, they have no effect on enlarged heart size (hypertrophy). Arrhythmias can also occur as an interaction between diuretics and certain drugs, including some antidepressants, anti−arrhythmic drugs themselves, and digitalis [5][6].

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