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INTRODUCTION

The antihypertensive are a class of drugs that are used to treat hypertension (high blood pressure). Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease. There are many classes of antihypertensive, which lower blood pressure by different means; among the most important and most widely used are the thiazide diuretics, the ACE inhibitors, the calcium channel blockers, the beta blockers, and the angiotensin II receptor antagonists or ARBs. Which type of medication to use initially for hypertension has been the subject of several large studies and resulting National Guidelines. The fundamental goal of treatment should be the prevention of the important endpoints of hypertension, such as heart attack, stroke and heart failure. Patient age, associated clinical conditions and end-organ damage also play a part in determining dosage and type of medication administered. The several classes of antihypertensive differ in side effect profiles, ability to prevent endpoints, and cost. The choice of more expensive agents, where cheaper ones would be equally effective, may have negative impacts on national healthcare budget. Antihypertensive therapy has been shown to reduce morbidity and mortality in older patients with elevated systolic or diastolic blood pressures. This benefit appears to persist in patients older than 80 years, but less than one third of older patients have adequate blood pressure control. Systolic blood pressure is the most important predictor of cardiovascular disease. Blood pressure measurement in older persons should include an evaluation for orthostatic hypotension. Low-dose thiazide diuretics remain first-line therapy for older patients. Beta-blockers, angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, and calcium channel blockers are second-line medications that should be selected based on comorbidities and risk factors. Multiple studies have demonstrated that isolated elevated systolic blood pressure is more prevalent in older persons because of increased large-artery stiffness. Systolic blood pressure should be the primary target for the diagnosis and care of older persons with hypertension. Blood pressure should be based on the average of two or more properly measured readings, in the

sitting position, on two or more office visits. Accurate measurement of blood pressure in older persons can be challenging because of cardiovascular changes associated with aging. Age-related may lead to orthostatic hypotension, so blood pressure should be monitored in the sitting and standing positions. Measurements may be inaccurate because of pseudo hypertension, in which the blood pressure cuff fails to compress a calcified artery. This should be considered in patients with resistant hypertension (i.e., patients with inadequate blood pressure control despite treatment with an appropriate three drug regimen), especially if these patients have symptoms of orthostatic hypotension. Resistant hypertension may be caused by white-coat hypertension, and therefore may be transient. Ambulatory blood pressure monitoring may be useful in documenting whitecoat hypertension and verifying hypotensive symptoms in patients receiving antihypertensive agents. One study found that ambulatory blood pressure monitoring was a better predictor of cardiovascular risk than conventional measurements in an older population with isolated systolic hypertension. The goal blood pressure recommended for hypertensive patient is less than 140/90 mm Hg (less than 130/80 mm Hg in patients with diabetes mellitus or chronic kidney disease), because achieving these values has been associated with a decrease in cardiovascular disease complications. Although most data support the treatment of older patients with stage 2 isolated systolic hypertension (systolic blood pressure higher than 160 mm Hg), recommending in treating older patients with stage 1 isolated systolic hypertension (systolic blood pressure 140 to 159 mm Hg) equally aggressively. Observational studies and secondary analyses of randomized controlled trials have documented a relationship between a low diastolic blood pressure.

Measuring blood pressure: mercury sphygmomanometers

Use the correct size cuff. The cuff width should be >40% of the arm circumference. The bladder should be centered over the brachial artery. And the cuff applied snugly. Support the arm in a horizontal position at mid-sternal level. Inflate the cuff while palpating the brachial artery, until the pulse disappears. This provides an estimate of systolic pressure.

Inflates the cuff until 30mmHg above systolic pressure, then place stethoscope over the brachial artery. Deflate the cuff at 2 mmHg/second. Systolic pressure: appearance of sustained repetitive tapping sounds ( Korotkoff I). Diastolic pressure: usually the disappearance of sounds (Korotkoff V). However in some individual example like pregnant women sound are present until zero point. In this case, the muffling of sound, Korotkoff IV, should be used. There are a variety of drugs for antihypertensive treatment but which type of antihypertensive that suitable in elderly for constant and longer period time of use. Some antihypertensive drugs cannot be chose because of several side effects and their inefficacy for elderly. The correct choice of drugs not just can treat older patient but also can prevent any further complication that caused by uncontrolled blood pressure. Perhaps this research can achieve its target in deciding the correct drugs for the treatment which not only can control the blood pressure level but also can give the most comfort to the users especially in the elderly.

Special Considerations When Treating Hypertension

Recommendations for treating hypertension are similar in the general population and older persons. The key points include: (1) Treat isolated systolic blood pressure; (2) Thiazide diuretics should be first line treatment (3) Second-line treatment should be based on comorbidities and risk factors i.e; such as calcium channel blocker or beta blocker. (4) Patients with systolic blood pressure higher than 160 mm Hg or diastolic blood pressure higher than 100 mm Hg usually will require two or more agents to reach goal. (5) Treatment should be initiated with a low dose of the chosen antihypertensive agent, and titrated slowly to minimize side effects such as orthostatic hypotension and weight loss and sodium reduction have been shown to be feasible and effective interventions in older patients with hypertension.

STEPS Comparison of Antihypertensive Agents in Older Persons

Thiazide Diuretics : Contra Indication: Electrolyte disturbance, especially hypokalemia Acute renal insufficiency and dehydration. Drug interaction: digoxin and NSAIDS Side Effect Efficacy : Orthostatis and sexual dysfunction : Hypertension, isolated systolic hypertension, heart failure, diabetes, patients

at high risk for cardiovascular disease, recurrent stroke prevention Simplicity : once daily

Calcium Channel Blocker : Contraindication: Nondihydropyridines: atrioventricular block, bradycardia Dihydropyridines: hypotension, reflex tachycardia,. Drug interactions: cyclosporine and grape fruit juice. Side Effect Efficacy : Peripheral edema, constipation, gingival hyperplasia. : Hypertension, diabetes, patients at high risk for cardiovascular disease.

Symptom control in chronic stable angina, ischemic heart disease, and atrial fibrillation Simplicity : one to two times daily.

Beta Blockers: Contra Indication : Bronchospasm Drug interactions: digoxin, diltiazem verapamil Side Effect Efficacy : Sedation, depression and sexual dysfunction : Hypertension, heart failure, post myocardial infarction, patients at high risk

for cardiovascular disease Simplicity : one to two times daily

Specific Agents

3.1 Thiazide Diuretics. Several issues should be considered when using thiazide diuretics in older patients. Older patients are more prone to thiazide-induced dehydration and orthostatic changes, so physicians should check for orthostatic hypotension and suggest measures for preventing falls. Serum electrolyte levels should be monitored frequently, and hypokalemia should be treated with potassium administration, the addition of a potassium-sparing diuretic like spironolactone or the use of a combination product such as triamterene/hydrochlorothiazide. This is important because in the SHEP trial, older patients with potassium levels less than 3.5 mg per dL (0.9 mmol per L) lost the cardiovascular protective benefit from the thiazide. Although poorly studied, their efficacy may be decreased in patients with chronic kidney disease. Uric acid and thiazides compete for excretion at the level of the renal tubule, so caution is necessary in patients with a history of gout. Although thiazide diuretics have been reported to affect serum glucose and lipid levels adversely, there is a decreased incidence of metabolic abnormalities and associated clinical outcomes with low-dose therapy. Patients taking digoxin and a thiazide diuretic may be at increased risk of digoxin toxicity because of diuretic induced electrolyte disturbances. Non-steroidal anti-inflammatory drugs (NSAID) may reduce diuretic and antihypertensive effects of thiazides. Mechanism of action: Thiazides inhibit NaCl reabsorption from the luminal side of epithelial cells in the DCT by blocking the Na+/Cl- transporter (NCC). Thiazides lowering blood pressure primarily by depleting body sodium stores. Initially, thiazides reduce blood pressure by reducing blood volume and cardiac output; peripheral vascular resistance may increase. After 6-8 weeks, cardiac output return toward normal while peripheral vascular resistance declines. Sodium is believed to contribute to vascular resistance by increasing vessel stiffness and neural reactivity, possibly related to increase sodium-calcium exchange with a resultant increase in intracellular calcium. These effects are reversed by thiazides or sodium restriction.

3.2 Calcium Channel Blockers Calcium channel blockers prevent calcium from entering the cells of the arterial vasculature and cause dilation in the coronary arteries and periphery. There are two classes of calcium channel blockersdihydropyridines and nondihydropyridinesand both are effective treatments for hypertension in older patients. As a group, calcium channel blockers have compelling indications for use in patients at high risk for coronary disease and those with diabetes mellitus .Nondihydropyridines (e.g., diltiazem, verapamil) exhibit negative inotropic and chronotropic effects, making them beneficial in atrial fibrillation and supraventricular tachyarrythmias. Dihydropyridines (i.e., amlodipine) are safe for use in patients with heart failure, hypertension, or chronic stable angina. Short-acting agents are not recommended in clinical practice. In comparison with other antihypertensives, systematic reviews generally have found calcium channel blockers to be equivalent or inferior to other antihypertensive agents. In the Antihypertensive and LipidLowering Treatment to Prevent Heart Attack Trial (ALLHAT), amlodipine was found to be inferior to chlorthalidone in preventing heart failurerelated events. Calcium channel blockers have been found to be effective in salt sensitive hypertensive patients, such as blacks and older persons. Interactions with other drugs and food are reported with some calcium channel blockers. In particular, grapefruit juice may increase the bioavailability of felodipine significantly leading to profound hypotension, and diltiazem can inhibit the metabolism of cyclosporine in transplant patients leading to cyclosporine toxicity. The dihydropyridines, especially nifedipine, can cause orthostatic hypotension, peripheral edema, and gingival hyperplasia. These are particularly problematic in older patients. Verapamil often is a cause of constipation in older persons. Mechanism of action: Calcium channel blocker can reduce peripheral resistance and blood pressure. The mechanism of action in hypertension is inhibition of calcium influx into arterial smooth muscle cells. These drugs like verapamil, diltiazem and dihydropyridine family are equally effective in lowering blood pressure. Doses of calcium channel blocker used in treating hypertension are similar to those used in treating angina. However short acting dihydropyridines not recommended to be used in hypertension because of the cardiac effect that can lead to myocardial infarction.

3.3 Beta Blockers. Beta blockers reduce mortality and morbidity in older patients with hypertension. Additional indications for use of beta blockers in older persons include high risk for coronary disease and prevention of a second myocardial infarction and heart failure. Despite the pharmacokinetic and pharmacodynamics differences among various beta blockers, they have similar clinical antihypertensive efficacy. Beta blockers that are lipophilic (e.g., propranolol) cross the bloodbrain barrier, possibly causing more sedation, depression, and sexual dysfunction in older patients. Beta blockers are contraindicated in patients with severe reactive airway disease, especially the nonselective agents (i.e., propranolol). Particularly in older patients, beta blockers as a class can cause bradycardia, conduction abnormalities, and development of heart failure if started too aggressively in patients with preexisting left ventricular dysfunction. Beta blockers should be tapered before discontinuation to minimize the risk of reflex tachycardia. The effects of beta blockers on lipid profiles are transient and of little clinical significance. Beta blockers should be used with caution in combination with other negative chronotropes, such as diltiazem, verapamil, or digoxin. Mechanism of action: Propranolols efficacy in treating hypertension as well as mast of its toxic effects result from nonselective beta blockade. Propranolol decrease blood pressure primarily as a result of a decrease in cardiac output. Other beta blocker drugs may decrease cardiac output or decrease peripheral vascular resistance to various degrees, depending on cardioselectivity and partial agonist activities. Beta blockade in brain, kidney and peripheral adrenergic neurons has been proposed as contributing to the antihypertensive effect observed with Beta receptor blocker. In spite of confliction, some of the drugs did not cross the blood brain barrier thus give ineffective for the hypertensive treatment. Propranolol inhibits the stimulation of renin production by catecholamine. It is likely that propranolols effect is due in part to depression of the reninangiotensin-aldosterone system. Although more effective in patient with high plasma renin level, propranolol also reduces blood pressure in hypertensive patient with normal or lower renin activity such as in elderly. Beta blocker also might act at the peripheral presynaptic beta adrenoreceptors to reduce sympathetic vasoconstrictor nerve activity. In mild to moderate hypertension, propranolol produces significant reduction in blood pressure without postural hypotension.
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SUMMARY

As being discussed before, thiazide diuretics remain as the first line treatment in treating elderly with hypertension, followed by calcium channel blocker or beta blocker. Most of the time ACE inhibitor did not being chose because of inefficacy in treating elderly that having lower level of renin activities, besides the side effect of ACE inhibitors that can affect the kidney function. However thiazide diuretics, calcium channel blocker and beta blocker can give variety side effect in long period of used. The most common adverse effect of diuretics is potassium depletion except for potassium-sparing diuretics. Although mild degree of hypokalemia are tolerated well by many patients, hypokalemia may be hazardous in person taking digitalis, those who have chronic arrhythmias, or those with acute myocardial infarction or left ventricular dysfunction. Diuretics may also cause magnesium depletion, impair glucose tolerance, and increase serum lipid concentration. Diuretics can increase uric acid concentration and may precipitate gout. The toxicity for calcium channel blocker are direct extension of their therapeutic action. Excessive inhibition of calcium influx can cause serious cardiac depression, including cardiac arrest, bradycardia, atrioventricular block, and heart failure. Minor toxicity includes flushing, dizziness, nausea, constipation, and peripheral edema. The principal toxicities for beta blocker drugs results from blockade of cardiac, vascular, or bronchial beta receptors especially propranolol. The most important of these predictable extensions of the beta blocking action occur in patient with bradycardia or cardiac conduction disease, asthma, peripheral vascular insufficiency, and diabetes. For some beta blocker example like propranolol the discontinuation after prolonged regular used can create a withdrawal syndrome, manifested by nervousness, tachycardia, increased intensity of angina, or increase of blood pressure. Myocardial infarction has been reported in a few patients.

REFERENCES
1) Bertram G. Katzung. Antihypertensive. Basic and Clinical Pharmacology. 10th edition. Mc Graw Hill Inc. 2007. Chapter 11: 159-177. 2) Ujala Verma, Gulsan Bano, Mohan Lal, Kapoor, P. Sharma, Rashmi Sharma. Antihypertensive Efficacy and Amlodipine in Patients of Mild to Moderate Hypertension. Vol. 6 No. 4 Octoberdecember 2004. 193-196 3) T W Auyeung, MB, Geriatri Unit. Tuen Mun Hospital, Tuen Muen, New Territories. Hypertension In Geriatrics. December 1996. Pg 638- 644 4) Marvin Moser, MD; William C. Cushman, MD; Michael G. Ziegler, MD. The Treatment of Hypertension in the Elderly. The Journal of Clinical Hypertension. Vol. 10 no> 1 January 2008. Pg 58-68 5) Murray longmore, Ian B. Wilkinson, Edward H. Davidson, Alexander Foulkes, Ahmad R. Mafi. 8 edition. Oxford University Press. 2010. Pg 132- 135 6) Rene R. Wenzel. Renal Protection in Hypertensive Patients: Selection of Antihypertensive Therapy. 2005. 66 suppl. 2:29-39.