Sunday, October 4, 2015

Hypertension : An overview

Hypertension (HTN or HT), also known as high blood pressure or arterial hypertension, chronic abnormal increase in arterial blood pressure. Blood pressure (BP) is expressed by two measurements, the systolic and diastolic pressures, which are the maximum and minimum pressures, respectively, in the arterial system. The systolic pressure occurs when the left ventricle is most contracted; the diastolic pressure occurs when the left ventricle is most relaxed prior to the next contraction. Normal blood pressure at rest is within the range of 100–140 millimeters mercury (mmHg) systolic and 60–90 mmHg diastolic. Hypertension is present if the blood pressure is persistently at or above 140/90 mmHg for most adults; different numbers apply to children.

Increase in blood pressure can be seen during exercise, during endurance work or during heavy labored work but it gets normalized with time and is not harmful. But long term increase in BP can lead to  hypertensive heart disease, coronary artery disease, stroke, aortic aneurysm, peripheral artery disease, and chronic kidney disease. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischaemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease.

Hypertension can be mainly of two types – primary hypertension (or essential) maximum cases are of such types of hypertension and in this no underlying cause of the disease is known. And the rest of the other causes are of secondary hypertension which is caused due to an identifiable cause such as renal disease or adrenal hyperfunction, or an endocrine disorder such as excess aldosterone, cortisol, or catecholamines.
                                                Systolic BP (mm hg)                Diastolic BP (mm hg)
                        Normal                     130-139                                          85-89
                        Mild                           140-159                                          90-99
                        Moderate                 160-179                                          100-110
                        Severe                       180-209                                          110-119
                        Very severe                >210                                               >120

Reno-vascular hypertension is mainly caused due to improper functioning of RAS (rennin-angiotensin system), which when functioning normally can regulate blood pressure and fluid balance. Angiotensinogen (in liver) is the starting inactive peptide which is converted to angiotensin-I (A-I) in presence of renin (kidney), which is then converted to angiotensin-II (A-II) by angiotensin converting enzyme (ACE) (thought to be found in lung capillary).

A-II is 100 times more biologically potent than A-I but has a very short t1/2 (1 min) and its first degradation product is termed as angiotensin-III (A-III) which is 3-9times less potent that A-II, except when secreting aldosterone it is equipotent. Angiotensin-I may have some minor activity, but angiotensin-II is the major bio-active product. So, whenever there is problem in the RAS cycle there is abnormality in blood pressure and fluid balance in our body.

Angiotensin-II increases sympathetic activity causes tubular Na+ Cl-, K+ excretion and water retention, arteriolar vasoconstriction and increase in BP, ADH (antidiuretic hormone secretion) secretion which causes water absorption in collecting duct, enhancing adrenaline/nor-adrenaline release from adrenal medulla/adrenergic nerve endings and by increasing central sympathetic outflow. In addition to secreting aldosterone, A-III promotes Na+/H+ exchange in proximal tubule causing increased Na+ Cl- and bicarb reabsorption. Vasodilators and diuretics stimulate rennin release by lowering BP.

Classification of antihypertensive drugs
1.Adrenergic receptor antagonists
a.Beta blockers
      b.Alpha blockers:
          c.Mixed Alpha + Beta blockers:
Diuretics help the kidneys eliminate excess salt and water from the body's tissues and blood.
          a.Loop diuretics:
                                 ethacrynic acid
           b.Thiazide diuretics:
                                 hydrochlorothiazide and chlorothiazide
            c.Thiazide-like diuretics:
             d.Potassium-sparing diuretics:

3.Calcium channel blockers
Calcium channel blockers block the entry of calcium into muscle cells in artery walls.

4.ACE inhibitors
ACE inhibitors inhibit the activity of Angiotensin-converting enzyme (ACE), an enzyme responsible for the conversion of angiotensin I into angiotensin II, a potent vasoconstrictor.
      Indomethacin (and other NSAIDs) attenuates the hypotensive action of captopril.
5.Angiotensin II receptor antagonists
Angiotensin II receptor antagonists work by antagonizing the activation of angiotensin receptors.
      Losartan is 10,000 times more selective for A-I than A-II still is its competitive antagonist but has partial activity. It causes fall in BP in hypertensives which lasts for 24hours.

6.Aldosterone antagonists
Aldosterone receptor antagonists:
Aldosterone antagonists are not recommended as first-line agents for blood pressure, but spironolactone and eplerenone are both used in the treatment of heart failure.
7.Centrally acting adrenergic drugs
Central alpha agonists lower blood pressure by stimulating alpha-receptors in the brain which open peripheral arteries easing blood flow. Central alpha agonists, such as clonidine, are usually prescribed when all other anti-hypertensive medications have failed. For treating hypertension, these drugs are usually administered in combination with a diuretic.
Adverse effects of this class of drugs include sedation, drying of the nasal mucosa and rebound hypertension.
Some adrenergic neuron blockers are used for the most resistant forms of hypertension:
Vasodilators act directly on the smooth muscle of arteries to relax their walls so blood can move more easily through them; they are only used in hypertensive emergencies or when other drugs have failed, and even so are rarely given alone.
Sodium nitroprusside, a very potent, short-acting vasodilator, is most commonly used for the quick, temporary reduction of blood pressure in emergencies (such as malignant hypertension or aortic dissection). Hydralazine and its derivatives are also used in the treatment of severe hypertension, although they should be avoided in emergencies. They are no longer indicated as first-line therapy for high blood pressure due to side effects and safety concerns, but hydralazine remains a drug of choice in gestational hypertension.
9.Adrenergic receptor agonists
              Alpha-2 agonists:

Referred from: