Hypertension can be defined as sustained elevation of systemic blood pressure more than 140/90 mm Hg. Reduced capacitance of the venous system and increased arteriolar resistance due to increased peripheral vascular smooth muscle tone can leading causes for the hypertension. The risk associated with hypertension dependent upon the combination risk factors in the specific individual. They are Age, Gender (males>female), Ethnic group (black>white), diet, smoking, family history, blood cholesterol, diabetes mellitus, & preexisting vascular diseases. Chronic hypertension can lead to strokes (cerebral thrombosis, cerebral hemorrhage), congestive heart failure, and myocardial infarction, and renal failure, malignant hypertension, peripheral vascular disease. If hypertension is diagnosed early and is properly treated the prevalence of morbidity and mortality.

One method of classification blood pressure is,

* Normal blood pressure: < 120/80

* Prehypertension: 120-139/80-89

* Hypertension: > 140/90

* Stage 1 Hypertension: 140-159/90-99

* Stage 2 Hypertension: 160 or greater/100.

Hypertension can be classified as essential hypertension and secondary hypertension. Essential hypertension has no identifiable cause. The majority (80-90%) of patients with hypertension have primary elevation of blood pressure, Essential hypertension has a multifactorial etiology such as Genetic factors, fetal factors(low birth weight),environment factors( obesity, sodium intake,alcohole intake, stress),Humoral mechanism, Insulin resistance.

Secondary hypertension is where blood pressure elevation is the result of a specific and potentially treatable cause. As examples renal diseases, alcohol, pregnancy, endocrine causes, congenital cardiovascular causes and drugs induced, autoimmune diseases.

When considering the complications of hypertension the Cerebrovascular disease and coronary artery disease are the most common causes of death, although hypertensive patients are also prone to renal failure and peripheral vascular disease

Hypertensives have a six fold increase in stroke (both hemorrhagic and atherothrombotic). There is a threefold increase in cardiac death (due either to coronary events or to cardiac failure). Furthermore, peripheral arterial disease is twice as common.

Malignant hypertension

Malignant or accelerated hypertension occurs when blood pressure rises rapidly and is considered with severe hypertension (diastolic blood pressure>120 mmHg). Necrotic arterial lesions, Pappiloedema, Cerebral symptoms, progressive renal failure and retinopathy are some features of malignant hypertension.

Arterial blood pressure mainly depend on the peripheral vascular resistance and cardiac output . These depending factors are controlled mainly by two overlapping control mechanisms: They are baroreflexes, and the renin-angiotensin-aldosterone system .Most antihypertensive drugs lower blood pressure by decreasing peripheral resistance and reducing cardiac output .

• Baroreceptors and the sympathetic nervous system

Baroreceptors are involving the sympathetic nerves system. These are responsible for regulation blood pressure. Baroreceptors are placed on aortic arch and carotid sinus. When blood pressure falls baroreceptors send impulses to cardiovascular centers. Then the CV center prompts reflex responses of decreased parasympathetic and increased sympathetic output.This causes vasoconstriction and increase cardiac output.This causes to compensatory rise in blood pressure.

• Renin-angiotensin-aldosterone system

The kidney arrange for the long-term control of blood pressure. It alters the blood volume. When arterial pressure reduced kidney releases the enzyme called as Renin.mot only that Low sodium intake and greater sodium loss also can increase releasing renin.. This enzyme converts angiotensinogen to angiotensin I,when angiotensin-converting enzyme (ACE) is present, angiotensin I is converted in turn to angiotensin II. Angiotensin II is a vasoconstrictor, it constricts both arterioles and veins,as a result blood pressure is increased. Angiotensin II also, increase glomerular filtration. Additionally, angiotensin II can stimulate aldosterone secretion.Aldosterone increases blood volume due to increase renal sodium reabsorption.. These effects of angiotensin II are mediated by stimulation of angiotensin I(AT1) receptors.

Treatment of Hypertension

The target of hypertension treatment is to lower high blood pressure and protect important organs, like the brain, heart, and kidneys from damage. Treatment for hypertension has been associated with reductions in stroke, heart attack, and heart failure. There is continuous interconnection between blood pressure and the risk of a cardiovascular event. So it is necessary for diminishing blood pressure in the general population by education and implementation of blood pressure lowering manners. Single drug can control mild hypertension. Current references are to initiate therapy with a thiazide diuretic unless there are convincing reasons to employ other drug classes.

Although the choice of first-line drug therapy may exert some effects on different long-term cardiovascular endpoints, randomized clinical trials and meta-analyses demonstrated that blood pressure reduction per se is the primary determinant in primary and secondary prevention. Hypertension is non-curable. But can reduce the consequences of disease or disease progression.so treatments can be mainly identified as pharmacological and non-pharmacological. Pharmacologically antihypertensive drugs can be used. They can be mainly classified as Diuretics, Beta blockers, ACE inhibitors, Angiotensin II receptors antagonists, Renin inhibitors, alpha blockers, Ca2+ channel blockers and others.

Diuretics.

These are called water pills and they are medications that act on the kidneys to help body eliminate sodium and water, reducing blood volume

Examples: – Eplerenone, furosemide, Hydrochlorothiazide, Spironolactone

Thiazide diuretics

Most effective method of the treatment of hypertension is using oral diuretic drugs. Thiazide drug is most commonly used. Thiazide diuretics are often the first – but not the only – choice in high blood pressure medications. Thiazide diuretics, such as hydrochlorothiazide, increase sodium and water defecation. Then they lower blood pressure and decrease in extracellular volume, increasing cardiac output and renal blood flow. With long-term management, plasma volume becomes a normal value, but peripheral resistance declines. These drugs can decrease blood pressure in both the supine and standing positions; these agents respond the sodium and water retention observed with other agents used in the treatment of hypertension. Potassium-sparing diuretics are commonly used joined with thiazides. In combination therapy, Thiazide can be used with a variety of other antihypertensive agents, such as ACE inhibitors, beta-blockers and angiotensin-receptor blockers. In the treatment of black or elderly patients, Thiazide drug especially useful. They are not effective in patients with inadequate kidney function. Loop diuretics may be required in these patients. Absorption and elimination rates vary considerably, although no clear advantage is present for one agent over another. All thiazides are ligands for the organic acid secretory system of the nephron, and as such, they may compete with uric acid for elimination. Thiazide diuretics induce hypokalemia and hyperuricemia in 70 percent of patients and hyperglycemia in 10 percent of patients. Hypomagnesaemia may also occur. Serum potassium levels should be monitored closely in patients who are predisposed to cardiac arrhythmias (particularly individuals with left ventricular hypertrophy, ischemic heart disease, or chronic heart failure) and who are concurrently being treated with both thiazide diuretics and digoxin.

Loop diuretics

The loop diuretics act promptly, even in patients with poor renal function or who have not responded to thiazides or other diuretics. Loop diuretics can decrease renal vascular resistance and increased renal blood flow. Loop diuretics increase the Ca2+ content of urine, When thiazide diuretics decrease the Ca2+ amount of urine, loop diuretics can decrease it.

Potassium-sparing diuretics.

Amiloride and triamterene (inhibitors of epithelial sodium transport at the late distal and collecting ducts) as well as spironolactone and eplerenone (aldosterone-receptor antagonists) reduce potassium loss in the urine. Spironolactone has the additional benefit of diminishing the cardiac remodeling that occurs in heart failure.

Beta blockers.

These medications reduce the workload on the heart and open blood vessels, this cause to heart to beat slower. Here it uses less force. Beta blockers don’t work as well in older adults, the effectiveness of Beta blockers increases when they combine with a thiazide diuretic. These are administered orally. Beta Blockers are considered as first-line drug therapy for hypertension. Primarily Beta blockers decrease cardiac output and as a result blood pressure reduces. Also Beta blockers decrease sympathetic outflow and decrease the formation of angiotensin II due to inhibition the release of renin. And the secretion of aldosterone. It will take few weeks to develop their full effects. The Beta-blockers are more effective for treating hypertension in white than in black patients and in young compared to elderly patients. , severe chronic obstructive lung disease, chronic congestive heart failure, or severe symptomatic occlusive peripheral vascular disease are Conditions that discourage the use of Beta blockers more commonly found in the elderly and in diabetics. The Beta-blockers are useful in treating conditions that may coexist with hypertension, such as supraventricular tachyarrhythmia, previous myocardial infarction, angina pectoris, chronic heart failure, and migraine headache. Bradycardia and CNS side effects such as, lethargy, fatigue hallucinations and insomnia can be occurring due to Beta blockers. Lipid metabolism may be disturbed by Beta blockers because they can increase plasma triacylglycerol and decrease cholesterol, high-density lipoprotein. Abrupt withdrawal of this drug may induce myocardial infarction, sudden death due to ischemic heart disease and angina may be induced by withdrawal of Beta blockers. Hence the doses of these drugs must be carefully managed with hypertension and ischemic heart disease.

Example:-Atenolol, Carvidilol, Nadolol, Timolol

Angiotensin-converting enzyme (ACE) inhibitors.

These medications help relax blood vessels by blocking the formation of a natural chemical that narrows blood vessels.

.The ACE inhibitors reduce blood pressure by decreasing peripheral vascular resistance. It doesn’t increase heart rate, cardiac output, contractility of the heart. ACE is blocked by this drug interfering the cleavage of angiotensin I to form the angiotensin II. Angiotensin II is an effective vasoconstrictor. And also angeotensin converting enzyme is accountable for the breakdown of bradykinin.so due to ACE inhibitors, it increases bradykinin levels and decrease angiotensin II.Bradykinin is a vasodilator. So Vasodilation occurs due to the collective effects of low level of angiotensin II and the increased Brdykinin level. By reducing circulating angiotensin II levels, ACE inhibitors also reduce the level of aldosterone. This kind of drugs is most effective in younger hypertensive patients. However, when used in combination with a diuretic, the effectiveness of ACE inhibitors is similar in white and black patients with hypertension. Management of patients with chronic heart failure is also effectively managed by ACE inhibitors. The dry cough, which occurs in about 10 percent of patients, is thought to be due to increased levels of bradykinin in the pulmonary tree. Potassium levels must be monitored, and potassium supplements (or a high potassium diets) or potassium-sparing diuretics are contraindicated. Because of increased levels of bradykinin, angioedema may occur. It is rare incident. But it may have a life threatening reaction ACE inhibitors should be introduced at first time with the close observation of the physician. Because of the risk of angioedema and first-dose syncope. These are fetotoxic drug. Therefore it shouldn’t be used for the pregnant women.

Example:-Losartan, Valsartan, Olmesartan

Example:-Benazepril, Captopril, Lisinopril, Moexipril

Calcium channel blockers.

These medications help relax the muscles of your blood vessels.Calcium channel blockers may work better for older adults than ACE inhibitors or beta blockers alone. A word of caution for grapefruit lovers, though. Grapefruit juice interacts with some calcium channel blockers, increasing blood levels of the treatment and putting you at higher risk of side effects. When first line agents are ineffective, this method is used. Ca2+ blockers more commonly use in diabetes patients and angina patients. High doses of short-acting calcium-channel blockers should be avoided because of increased risk of myocardial infarction due to excessive vasodilation and marked reflex cardiac stimulation. The calcium-channel blockers are divided into three chemical classes, each with different pharmacokinetic properties and clinical indications.

Diphenylalkylamines:

this class has only one member. It is Verapamil. It has imperative effects on vascular smooth muscles and cardiac muscle cells. Treatments of, supraventricular tachyarrhythmias, angina and migraine headaches Verapamil is used commonly.

Benzodiazepines:

Diltiazem is the only member of this class that is currently approved in the United States. Has verapamil like action. Diltiazam has negative inotropic action. It has a satisfactory side-effect profile also.

Dihydropyridines:

This rapidly expanding class of calcium-channel blockers includes the first-generation nifedipine and it takes only a diminutive time for treating hypertension. Amlodipine, felodipine, isradipine, nicardipine and nisoldipine. These second-generation calcium-channel blockers differ in pharmacokinetics, approved uses, and drug interactions. Vascular calcium channels are often taken the high affinity of the dihydropyradines than calcium channels in the heart. So they are predominantly attractive in treating hypertension.

Example: – Amlodipine, Feladifine, Nicardipine, Nifedifine

Renin inhibition

Renin is a hormone secreted by the juxtaglomerular cells of the kidney and linked with aldosterone in a negative feedback loop.These slow down the manufacture of renin, an enzyme produced by kidneys that starts a chain of chemical steps that increases blood pressure and works by reducing the ability of renin to begin this process. Due to a risk of serious complications. A selective renin inhibitor, aliskiren has been released for the treatment of hypertension. Renin can be directly inhibited by aliskiren. So it, works on the renin-angiotensin-aldosterone system quicker than ACE inhibitors or ARBs. It lowers blood pressure about as effectively as ARBs, ACE inhibitors, and thiazides. It can also be combined other antihypertensive, such diuretics, ACE inhibitors, ARBs, or calcium-channel blocker. During the pregnancy this drug is contraindicated. The combination of maximum doses of aliskiren and valsartan decreased blood pressure more than maximum doses of either agent alone but not more than would be expected with dual therapy consisting of agents of different classes. Calcium concentration of the cell acts an main role in upholding the tone of smooth muscle and in the myocardium contraction. Ca2+ pass in to the muscle cells via special voltage-sensitive calcium channels. This initiates Release of Ca2+ from the sarcoplasmic reticulum and mitochondria are initiated by these drugs, which further upsurges the cytosolic level of calcium. the inward movement of calcium is blocked by Calcium-channel antagonists by binding to L-type calcium channels in the heart. and peripheral vasculature. This causes dilating arterioles.

These drugs have an intrinsic natriuretic effect. So they do not usually require the addition of a diuretic. These agents are very useful when treating the patients with angina,diadetes peripheral vascular disease and asthma. Black hypertension patients respond well to calcium-channel blockers.

Most of these agents have short half-lives following an oral dose. Treatment is required three times a day to maintain good control of hypertension. Sustained-release preparations are available and permit less frequent dosing. Amlodipine does not require a sustained-release preparation and. . has a very long half-life.

.Example:- Aliskiren (Tekturna)

Other drugs

Centrally acting adrenergic drugs.

Clonidine

Clonidine is a drug that acts on Alpha agonist hypotensive agents. This can be used with another Diuretic also.It decreases the adrenergic outflow. But glomerular filteration and renal blood flow are not reduced by Clonidine.So it is very important in complicated hypertensive due to renal diseases. This is administered orally and easily excreted with urine.this drug helps to sodium and water retention of the body.

Vasodilators

The direct-acting smooth muscle relaxants, such as hydralazine and minoxidil, have traditionally not been used as primary drugs to treat hypertension. Vasodilators act by producing relaxation of vascular smooth muscle, which decreases resistance and, therefore, blood pressure. These agents produce reflex stimulation of the heart, resulting in the competing reflexes of increased myocardial contractility, heart rate, and oxygen consumption. These actions may prompt angina pectoris, myocardial infarction, or cardiac failure in predisposed individuals. Vasodilators also increase plasma renin concentration, resulting in sodium and water retention. These undesirable side effects can be blocked by concomitant use of a diuretic and a Beta-blocker.

Hydralazine

This drug acts on arteries and arterioles decreasing vasodialation. It decreases the pheripheral resisrance. Use to control hypertension in pregnancy.

Minoxidil

This drug is orally administered.Severe sodium ,water retention occur. Beta blockers and loop diuretics are used combine with this.

. Hypertensive Emergency

This is a rare condition. But this can create a life threatening situations in which SBP/ DBP is greater than 210/150 mm Hg. Otherwise healthy person with preexisting complications, such as cerebral hemorrhage, encephalopathy aortic stenosis or left ventricular failure. Here it is emergency to reduce blood pressure rapidly by treatments.

Sodium nitroprusside

Nitroprusside can reduce blood pressure of all types of hypertension patients.This is intravenously administered causesing vasodilation. The drug can act on both on arterial and venous smooth muscle. It can diminish cardiac preload. Nitroprusside is metabolized rapidly and requires unremitting infusion to maintain its hypotensive action.

Labetalol

Labetalol can use in hypertensive emergencies and can give intravenously. effects of these drugs are on non-selective Beta blockers. Also it does cause tachycardia.Having the longer half life is the major restriction.

Fenoldopam

This drug is especially useful for patients with renal ineffectuality. Fenoldopam can be administered as an intravenous infusion. Unlike other parenteral antihypertensive agents, fenoldopam sustains or rises renal perfusion while it drops blood pressure. All hypertensive predicaments use this as a safely method. patients with glaucoma contraindicated this drug.

Nicardipine

This drug acts as a calcium-channel blocker. intravenous infusion can be used to administered . The primary dose is 5 mg/h and it can be increased to a maximum of 15 mg/h. The chief restriction of nicardipine in treating is having a long half time.

Use of non-pharmacological therapy in all hypertensive and borderline hypertensive people can be shown as follow

weight reduction

Overweight people have high concentration and activation of renin-angiotensin system. And also activity of sympathetic nerves system is also high.so they maintain a high arterial pressure. So hypertensive patients can decrease their calorie intake and maintain their body’s BMI below 25kg/m2.

low-sodium diet –

Reducing sodium (salt) diet is proven very effective: it decreases blood pressure in about 60% of people..It should maintain less than 6 g sodium chloride per day

limited alcohol consumption -( ≤ 21 units/week for menand ≤ 14 units/week for women)

Discontinuing tobacco smoking and alcohol drinking has been shown to lower blood pressure. The exact mechanisms are not fully understood, but blood pressure (especially systolic) always transiently increases following alcohol and/or nicotine consumption.

dynamic exercise

it decrease the activity of plasma renin. Regular aerobic exercises are recommended.Jogging,swimming and cycling helps to decrease peripheral resistence. Regular mild exercise improves blood flow and helps to reduce resting heart rate and blood pressure.Regular exercise should be done at least 30 minutes brisk walk perday

low-fat and saturated fat diet

increased fruit and vegetable consumption

Additional dietary changes beneficial to reducing blood pressure includes the DASH diet (Dietary Approaches to Stop Hypertension), which is rich in fruits and vegetables and low fat or fat-free dairy foods. In addition, an increase in daily calcium intake has also been shown to be highly effective in reducing blood pressure. Fruits, vegetables, and nuts have the added benefit of increasing dietary potassium, which theoretically can offset the effect of sodium and act on the kidney to decrease blood pressure.

reduce cardiovascular risk by stopping smoking and increasing oily fish consumption.

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Relaxation therapy, such as meditation, that reduces environmental stress, high sound levels and over-illumination can be an additional method of ameliorating hypertension. Biofeedback is also used particularly device guided paced breathing. Obviously, the effectiveness of relaxation therapy relies on the patient’s attitude and compliance.