A REVIEW ON: HYPERTENSION

ABOUT AUTHORS:
^*1Akanksha baranwal, ²Akanksha Sharma, ³Anamika singh
^1,3Department of pharmacology
²Department of clinical research
Noida Institute of Engineering and Technology
*akankshabaranwal1990@gmail.com

Abstract
The purpose of this review is to provide a basic understanding of the important relationship between microvascular remodelling, angiogenesis and hypertension, that is, provide an overview of recent experimental and clinical evidence from anti-hypertensive and pro- and anti-angiogenic therapy with respect to hypertension and microvascular structure. Microvascular rarefaction, that is, a loss of terminal arterioles and capillaries, is found in most forms of human and experimental arterial hypertension. This further increases peripheral resistance, and aggravates hypertension and hypertension-induced target organ damage. In some cases with a genetic predisposition, hypertension is preceded by a loss of microvessels. Therefore, new therapies aimed at reversing microvascular rarefaction potentially represent candidate treatments of hypertension. The microvasculature is formed by the continuous balance between de novo angiogenesis and microvascular regression. Imbalanced angiogenesis, in addition to functional shut-off of blood flow, contributes to microvascular rarefaction. Numerous clinical trials assessing anti-angiogenic agents in cancer patients show that this therapy leads to microvascular rarefaction and causes or aggravates hypertension. The development of specific pro-angiogenic treatment to correct hypertension or ischaemic disorders, however, it is still in its infancy. On the other hand, long-term treatment by classic anti-hypertensive therapies that present vasodilator activity can correct for hypertension-associated rarefaction in man.

REFERENCE ID: PHARMATUTOR-ART-1845

Introduction of Hypertension
Heart rate variability has long been known to be more of a risk predictor than heart rate, per se, but this month a study evaluates blood pressure variability - and finds that it is and it isn't significant. Plus, inhibition of the renin-angiotensin system with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) has proven efficacy - and now, this month, we have the phase 3 clinical results for a new class of antihypertensive agent (aliskiren) that inhibits renin directly. Plus, what about phosphodiesterase type 5 inhibitors (eg, sildenafil) as antihypertensive agents? Moreover, this month there were reports of a "signal" that diuretics appear to cause breast cancer, at least in some women. Finally, a device to treat hypertension -- and the Chinese begin to deal with their hypertensive population.

Hypertension is classified as either primary (essential) hypertension or secondary hypertension; about 90–95% of cases are categorized as primary hypertension which means high blood pressure with no obvious underlying medical cause. The remaining 5–10% of cases (secondary hypertension) are caused by other conditions that affect the kidneys, arteries, heart or endocrine system.

What is hypertension
When blood exerts too much pressure on the walls of blood vessels, it's called hypertension, or high blood pressure. There usually aren't symptoms until the condition becomes severe.

Methods
Grampian region in Scotland has a population of approximately 500 000 people in an area of 3320 square miles. The local health board has an electronic system which records all prescribing by primary care NHS doctors.

Data on all prescriptions for antihypertensive medicines between November 2001 and October 2002 were obtained from Grampian Health Board and compared with data from November 1998 to October 1999. Antihypertensive medicines were defined as drugs licensed for the management of blood pressure. Data consisted of the total number of prescriptions for each individual antihypertensive drug, and the number of prescriptions per 100 patients for each general practice in Grampian. Information on diagnosis was not available, so all drugs which could be used to treat hypertension were included, although many of these may have been prescribed for other therapeutic indications. The amount of drug usually dispensed by each practice was checked with the Local Health Care Cooperative (LHCC) pharmacist, and standardized for further analysis to a 28 day supply. Location of practice was coded as urban, suburban or rural. Size of practice was measured by number of GP principals (single-handed, 2–6 partners (termed medium size), 7 or more partners (termed large)). Data on the quantity and proportion of generic drug prescribing, defined as drug prescribed using the generic name (even if only branded drug is available), was given for each practice. Information on which surgeries were dispensing practices was also supplied. Drugs supplied in hospital were not included, but drugs recommended by secondary care clinics and subsequently prescribed by general practitioners were.

The Grampian Joint Formulary originally published in 1990 was revised in 1994, 1999 and 2004. New agents which became available between 1999 and 2002 were evaluated by the Grampian Medicines Committee and added to the electronic version of the formulary if appropriate. In this study, each drug was classed as approved or not approved according to whether or not it had been accepted by the Committee by 2002. As the indication for treatment was not known, drugs which the formulary only recommends for certain conditions, e.g. labetalol for pregnancy related hypertension, were scored as approved in all patients.

Sphygmomanometer
The standard instrument used to measure blood pressure is called a mercury sphygmomanometer. Measurements are given as units of mercury, which has filled the central column in standard sphygmomanometers for years. (Of note, many people now view the mercury sphygmomanometer as an environmental health hazard, although modern devices are designed to prevent mercury spillage.)
An inflatable cuff with a meter attached is placed around the patient's arm over the artery, while the patient is seated. The inflated cuff briefly interrupts the flow of blood in the artery, which then resumes as the cuff is slowly deflated.
The person taking the blood pressure listens through a stethoscope for so-called Korotkoff sounds, which first appear as blood begins to flow through the artery and then change in tone and volume as the cuff is deflated.
If a first blood pressure reading is above normal, the health professional may take two or more measurements separated by two minutes with the patient sitting or lying down. Then another measurement may be taken after the patient has been standing for two minutes.

There are two types of sphygmomanometers:

• Manual sphygmomanometers require a stethoscope for auscultation (see below). They are used by trained practitioners. It is possible to obtain a basic reading through palpation alone, but this only yields the systolic pressure.

• Mercury sphygmomanometers are considered to be the gold standard. They measure blood pressure by observing the height of a column of mercury; once made, errors of calibration cannot occur. Due to their accuracy, they are often required in clinical trials of pharmaceuticals and for clinical evaluations of determining blood pressure for high-risk patients including pregnant women.

• Aneroid sphygmomanometers (mechanical types with a dial) are in common use; they require calibration checks, unlike mercury manometers. Aneroid sphygmomanometers are considered safer than mercury based, although inexpensive ones are less accurate. A major cause of departure from calibration is mechanical jarring. Aneroids mounted on walls or stands are not susceptible to this particular problem.

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FDA approves new combination for hypertension
Silver Spring, MD - The US Food and Drug Administration has approved azilsartan medoxomil withchlorthalidone (Edarbyclor, Takeda) for the treatment of hypertension .The new combination is the first fixed-dose therapy in the US to combine an angiotensin-receptor blocker (ARB) with the diuretic chlorthalidone.

Azilsartan medoxomil (Edarbi, Takeda) is already available for the treatment of hypertension in adults. Combining the drug with a diuretic increases its antihypertensive efficacy.

"The approval of Edarbyclor provides an effective treatment option to lower blood pressure for appropriate patients with hypertension who may require a combination of drugs to help achieve blood pressure goals," Dr Domenic Sica (Virginia Commonwealth University Medical Center, Richmond) said in a news release.

The overall clinical program for this new combination with chlorthalidone consisted of five clinical trials involving more than 5000 patients with hypertension. The phase 3 studies evaluating the safety and efficacy of the drug ranged from eight to 52 weeks. The studies showed the new agent lowered systolic blood pressure significantly more than either azilsartan medoxomil or chlorthalidone alone. The levels, as measured by ambulatory blood-pressure monitoring, were similar across races.

New Anti-hypertensive Medications
Because no single medication has proved consistently to lower blood pressure, doctors often prescribe a range of drugs that may include angiotensin receptor blockers, diuretics,angiotensin-converting enzyme inhibitors, beta blockers and calcium-channel blockers.

Research drug companies recognize that there may be difficulty with compliance in patients required to take so many drugs. In response, these companies are developing new combination products. LeadDiscovery, a United Kingdom-based research company, predicts that, in the near future, fixed-dose combinations of antihypertensive drugs will be available, as well as drugs that may treat more than one risk factor at a time.

Leading the way, Pfizer Inc. was the first drug company to offer a combined antihypertensive product. In 2004, Pfizer received approval from the US Food and Drug Administration to market Caduet, a tablet containing Norvasc (amlodipine), for treating high blood pressure, and Lipitor (atorvastatin), for treating high cholesterol.

Other agents that hold promise include oral renin-inhibitors, a novel class of medications that target an enzyme released by the kidneys that can affect blood pressure. Of these new drugs, the first that is expected to be released is Aliskiren, a drug made by Novartis that is currently in phase III testing. LeadDiscovery report that analysts expect Novartis to seek regulatory approval in 2006, and they forecast sales over USD 1 billion by 2008, and over USD 3.6 billion by 2012.

And blood pressure technology research is keeping pace with drug development. For example, in March, University of Rochester Medical Center doctors were first to implant the “Rheos”, a battery-driven generator that activates the body’s natural regulatory systems for blood pressure. The device operates in a fashion similar to a pacemaker, which regulates heart rhythm. The Rheos device stimulates nerves in the carotid arteries to send a message to the brain to reduce blood pressure. Dr. Bisognano is one of the researchers testing the Rheos.

Causes, incidence, and risk factor,pressure, including:

• How much water and salt you have in your body
• The condition of your kidneys, nervous system, or blood vessels
• Your hormone levels

You are more likely to be told your blood pressure is too high as you get older. This is because your blood vessels become stiffer as you age. When that happens, your blood pressure goes up. High blood pressure increases your chance of having a stroke, heart attack, heart failure, kidney disease, or early death.

You have a higher risk of high blood pressure if:

• You are African American
• You are obese
• You are often stressed or anxious
• You drink too much alcohol (more than one drink per day for women and more than two drinks per day for men)
• You eat too much salt in your diet
• You have a family history of high blood pressure
• You have diabetes
• You smoke

hypertension may be due to:

• Chronic kidney disease
• Disorders of the adrenal gland (such as pheochromocytoma or Cushing syndrome)
• Hyperparathyroidism
• Pregnancy or preeclampsia
• Medications such as birth control pills, diet pills, some cold medicines, and migraine medicines
• Narrowed artery that supplies blood to the kidney (renal artery stenosis)

Symptom:-

• Tinnitus, lightheadedness, dizziness and/or vertigo
• Recurrent or worsening distended headache or head heaviness
• Chest oppression, palpitations
• Nose bleeding
• Shortness of breath
• Irritated, and getting anger easily
• Face or eye turns red
• Visual problems or variations
• Trembling, weakness or fatigue
• Disturbed sleep (Insomnia)
• Sore back and/or knees

Reference:-

• Chobanian AV, Bakris GL, Black HR et al. (December 2003). "Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure". Hypertension 42 (6): 1206–52.doi:10.1161/01.HYP.0000107251.49515.c2. PMID 14656957.
• ^ a b c d Carretero OA, Oparil S (January 2000). "Essential hypertension. Part I: definition and etiology". Circulation 101 (3): 329–35. doi:10.1161/01.CIR.101.3.329. PMID 10645931.
• By chris lliades MD medically reviewed by pat F . Bass III MD MPH.
• en.wikipedia.org/wiki/Sphygmomanometer
• ^ Booth, J (1977). "A short history of blood pressure measurement". Proceedings of the Royal Society of Medicine 70 (11): 793–9. PMC 1543468. PMID 341169. Retrieved 2009-10-06.
• ^ Misrin, J. "Aneroid Sphygmomanometer: A Battle for Safer Blood Pressure Apparatus". Retrieved 27 February 2012.
• ^ a b Oscillometry, Explanation of oscillometric detection in Medical Electronics, N Townsend, p48-51
• Adapted from Medscape Medical News—a professional news service of WebMD
• Source: New Hope for Those With High Blood Pressure, HealthDay, July 23, 2005.
• Goldstein LB, Bushnell CD, Adams RJ, et al. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011 Feb;42:517-84. [PubMed]
• Kaplan NM. Systemic hypertension: Treatment. In: Bonow RO, Mann DL, Zipes DP, Libby P, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. 9th ed. Philadelphia, Pa: Saunders Elsevier; 2011:chap 46.

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