Pharmacotherapy/Treatment Of Hypertension (High Blood Pressure)

Blood pressure is the force exerted on the walls of the arteries by circulating blood. High blood pressure is when the pressure exceeds what is termed normal. This is also called hypertension.

There are two types of pressure exerted by the blood on the arteries. They are systolic and diastolic blood pressure. Systolic blood pressure (SBP) is the pressure exerted on the arteries by circulating blood when the heart pumps blood around the arteries.

Diastolic blood pressure (DBP) on the other hand is the pressure the circulating blood exert on the walls of the arteries when the heart is at rest. When the heart is at rest, blood from the veins flows inside. SBP is always higher than DBP.

To put it in simple terms, hypertension is high mean arterial pressure. This can happen when the volume of blood in the arteries is too high or heart rate is too fast and strong or blood vessels too tight or blood vessels too thick.

Read Also: Meaning of blood pressure measurement

Hypertension is a disease affecting people of all ages and ethnic groups. It is more common in the elderly. About 972 million people (26 percent) are battling with hypertension and it is expected to increase to 29 percent by 2025. In Africa, about 27 percent of people have been diagnosed with hypertension and 18 percent in America. Risk and complication are higher in brown skin people, low to middle income countries.

Types Of Hypertension

1. Primary (essential) hypertension: there is no known or likely cause but can be attributed to genetics. Occur in majority of cases (90-95 percent)

2. Secondary hypertension: some conditions have been pin to it although these are subject to change as the main cause is not yet confirmed. They are more drug resistant and occur in about 5-10 percent of cases. Causes are polycystic kidney disease, chronic kidney disease, urinary tract obstruction, renin-producing tumors, etc.

Stages Of Hypertension

Elevated blood pressure: 120-129 mmHg systolic and less than 80 mmHg diastolic

Stage 1 hypertension is a systolic pressure ranging from 130 to 139 mm Hg or a diastolic pressure ranging from 80 to 89 mm Hg. Stage 2 hypertension is a systolic pressure of 140 mm Hg or higher or a diastolic pressure of 90 mm Hg or higher.

Hypertension crisis is an umbrella word for hypertension urgency and emergency. A hypertensive urgency is a clinical situation in which blood pressure is very high with minimal or no symptoms, and no signs or symptoms indicating acute organ damage. This contrasts with a hypertensive emergency where severe blood pressure is accompanied by evidence of progressive organ or system damage. Some groups put the figure at systolic BP >220 mm Hg or diastolic BP >120 mm Hg.

Please note that some classified pre-hypertension as 120-139 mmHg systolic and 80-89 mmHg diastolic. They went on to classify stage one as 140-159 mmHg systolic and 90-99 mmHg diastolic. Stage two is systolic above 160 mmHg and diastolic above 100 mmHg. As for hypertension, some groups put it at systolic above 180 mmHg and diastolic above 110 mmHg.

Symptoms

Most cases of hypertension don't show symptoms. That is why it is called a silent killer. However, when symptoms occur probably when the pressure is very high, it comes with;

1. Morning headache

2. Irregular heartbeat rhythms

3. Nosebleed

4. Vision changes

5. Buzzing in the ear

Severe Hypertension Symptoms

1. Fatigue

2. Nausea and Vomiting

3. Confusion

4. Anxiety

5. Chest pain and muscle tremor

Complications

1. Hard arteries

2. Burst or block arteries to brain or heart

3. Angina

4. Heart attack

5. Heart failure

6. Stroke

7. Kidney failure due to damage

Diagnosis

Blood pressure can be high at any point in time. Hypertension is diagnosed with two different days blood pressure measurement. Normal blood pressure reading of less than 120 mmHg systolic and diastolic less than 80 mmHg. But hypertension is diagnosed when the reading is above systolic 140 mmHg and diastolic 90.

Sphygmomanometer

Measurements of hypertension can be done in the office of a pharmacist or medical doctor using a sphygmomanometer and stethoscope. A sphygmomanometer consists of an inflatable cuff wound round the arm just one cm above the elbow with the top right above the carotid artery. The cuff consists of two tubes. One is connected to a bulb for inflation and the other to mercury scale. Others use dial compass readers. There are also automatic blood pressure machines that can be used at home. To avoid white coat blood pressure, patients are advised to use this machine at home. White coat blood pressure is that blood pressure taken at the office of a pharmacist or medical which is usually high because of fear of the office.

Risk Factors

1. Excess salt consumption

2. Saturated fat

3. Trans fat

4. Inactivity

5. Tobacco smoking

6. Alcohol

7. Caffeine

8. Obesity

9. Diabetes

10. Kidney disease

11. Family history

12. Age above 65 years

Pathophysiology Of Hypertension

There is still much uncertainty about the pathophysiology of hypertension. A small number of patients (between 2% and 5%) have an underlying renal or adrenal disease as the cause for their raised blood pressure. In the remainder, however, no clear single identifiable cause is found and their condition is labelled “essential hypertension”.

It is probable that a great many interrelated factors contribute to the raised blood pressure in hypertensive patients, and their relative roles may differ between individuals. Among the factors that have been intensively studied are salt intake, obesity and insulin resistance, the renin-angiotensin system, and the sympathetic nervous system. In the past few years, other factors have been evaluated, including genetics, endothelial dysfunction (as manifested by changes in endothelin and nitric oxide), low birth weight and intrauterine nutrition, and neurovascular anomalies.

Pharmacotherapy/Treatment Of Hypertension

There is no cure for hypertension. Main aim of treatment or lifestyle modification is to reduce blood pressure as close to normal as possible. When this is achieve, number of drugs or strength can be reduced. In some cases, all drug is stop with regular monitoring of the blood pressure. If it get high again, treatment is once again initiated.

Lifestyle Modification

Elevated and stage one blood pressure don't need drugs. Lifestyle modification alone will be able to lower it and prevent organ damage. Also, those needing drugs should also abide by lifestyle modifications to enhance the effect of the drugs.

1. Reduce weight

2. Exercise

3. Reduce sodium (salt) intake

4. Reduce total fat and cholesterol

5. Increase omega 3, folic acid, potassium, calcium and magnesium level

6. Reduce alcohol

7. Avoid cigarette, tobacco and cocaine

8. Avoid caffeine

Class Of Antihypertensive Drugs

Diuretics

These drugs remove water and other electrolytes like sodium from the blood and pass out through frequent urination. They accomplished this by altering how the kidney handles sodium. If the kidney excretes more sodium, then water excretion will also increase. Most diuretics produce diuresis by inhibiting the reabsorption of sodium at different segments of the renal tubular system. Sometimes a combination of two diuretics is given because this can be significantly more effective than either compound alone (synergistic effect). The reason for this is that one nephron segment can compensate for altered sodium reabsorption at another nephron segment; therefore, blocking multiple nephron sites significantly enhances efficacy.

1. Thiazide diuretic: Thiazide diuretics are a type of diuretic (a drug that increases urine flow). They act directly on the kidneys and promote diuresis (urine flow) by inhibiting the sodium/chloride cotransporter located in the distal convoluted tubule of a nephron. Because this transporter normally only reabsorbs about 5% of filtered sodium, these diuretics are less efficacious than loop diuretics in producing diuresis and natriuresis. An example is chlorthalidone which is the best diuretic with a long half-life and reduces cardiovascular disorder risk. Others are hydrochlorothiazide, indapamide, metolazone and chlorothiazide.

2. Potassium sparing diuretic: some of these drugs do antagonize the actions of aldosterone (aldosterone receptor antagonists) at the distal segment of the distal tubule. The reason for this is that by inhibiting aldosterone-sensitive sodium reabsorption, less potassium and hydrogen ion are exchanged for sodium by this transporter and therefore less potassium and hydrogen are lost to the urine. This causes more sodium (and water) to pass into the collecting duct and be excreted in the urine. Other potassium-sparing diuretics directly inhibit sodium channels associated with the aldosterone-sensitive sodium pump, and therefore have similar effects on potassium and hydrogen ions as the aldosterone antagonists. Their mechanism depends on renal prostaglandin production. Because this class of diuretic has relatively weak effects on overall sodium balance, they are often used in conjunction with thiazide or loop diuretics to help prevent hypokalemia. Examples are amiloride and spironolactone.

3. Loop diuretics: Loop diuretics inhibit the sodium-potassium-chloride cotransporter in the thick ascending limb. This transporter normally reabsorbs about 25% of the sodium load; therefore, inhibition of this pump can lead to a significant increase in the distal tubular concentration of sodium, reduced hypertonicity of the surrounding interstitium, and less water reabsorption in the collecting duct. Examples are furosemide and torsemide.

Carbonic Anhydrase

Carbonic anhydrase inhibitors inhibit the transport of bicarbonate out of the proximal convoluted tubule into the interstitium, which leads to less sodium reabsorption at this site and therefore greater sodium, bicarbonate and water loss in the urine. These are the weakest of the diuretics and seldom used in cardiovascular disease. Their main use is in the treatment of glaucoma. Examples are acetazolamide, methazolamide, dorzolamide, brinzolamide, diclofenamide, ethoxzolamide and zonisamide.

Beta-Blockers (Beta-adrenergic blockers)

They work by blocking the effect of epinephrine (adrenaline) thereby lowering heart rate and force. Examples are atenolol, bisoprolol, metoprolol and propranolol.

Alpha-Blockers (α-blockers or α- adrenoreceptor antagonists)

Alpha blockers lower blood pressure by keeping the hormone norepinephrine from tightening the muscles in the walls of smaller arteries and veins. Example are alfuzosin, doxazosin, prazosin and terazosin.

Alpha-Adrenoceptor Agonists (α-agonists)

Alpha-adrenoceptor agonists (α-agonists) bind to α-receptors on vascular smooth muscle and induce smooth contraction and vasoconstriction, thus mimicking the effects of sympathetic adrenergic nerve activation to the blood vessels. They are also called central acting agents. The drugs prevent the brain from signaling the nervous system to increase heart rate and narrow blood vessels. Alpha-agonists constrict both arteries and veins; however, the vasoconstrictor effect is more pronounced in the arterial resistance vessels. Example are tetrahydrozoline and α-methyldopa.

Alpha-Beta Blockers

They block the binding of catecholamine hormones to both alpha- and beta-receptors. Therefore, they can decrease the constriction of blood vessels like alpha-blockers do. They also slow down the rate and force of the heartbeat like beta-blockers do. Examples are carvedilol, labetalol and dilevalol.

Aldosterone Receptor Antagonists

An antimineralocorticoid, MCRA, or aldosterone receptor antagonists work by blocking a chemical called aldosterone. This action reduces the amount of fluids your body retains, which helps lower your blood pressure. Examples are spironolactone and eplerenone.

Direct Renin Inhibitors

A newer type of blood pressure medication is called direct renin inhibitors (DRIs). These drugs block a chemical in your body called renin. This action helps widen your blood vessels, which lowers your blood pressure. The only available one is aliskiren. They are not given together with ARB and ACE inhibitors due to risk of serious complications like stroke.

Angiotensin Converting Enzyme (ACE) Inhibitors

ACE inhibitors reduce blood pressure by blocking the action of angiotensin II in the blood vessels and other tissues. Blood vessels dilate. Examples are lisinopril, captopril, enalapril, etc.

Angiotensin Receptor Blocker (ARB)

They have similar effects with ACE inhibitors. But this time, they block the angiotensin II receptor so that angiotensin II enzyme cannot bind to it. An Example is candesartan, candesartan, irbesartan, olmesartan, losartan, valsartan, telmisartan, eprosartan, etc.

Calcium Channel Blockers

Calcium channel blockers, calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium through calcium channels. Generally classified into three groups according to their chemical structure: benzothiazepines (diltiazem); phenylalkylamines (verapamil); and the dihydropyridines (amlodipine, bepridil, felodipine, isradipine, nicardipine, nifedipine, and nisoldipine).

Vasodilator

Vasodilator drugs relax the smooth muscle in blood vessels, which causes the vessels to dilate.They affect the muscles in the walls of your arteries and veins, preventing the muscles from tightening and the walls from narrowing. There are different types of vasodilators, including;

Arterial dilators (mainly affect the arteries): Dilation of arterial (resistance) vessels leads to a reduction in systemic vascular resistance, which leads to a fall in arterial blood pressure.

Venous dilators (mainly affect the veins): Dilation of venous (capacitance ) vessels decreases venous blood pressure.

Mixed dilators (affect veins and arteries): Arterial and mixed dilation is used for hypertension than venous dilation. Example are minoxidil and hydralazine

Treatment Guide

The goal of medical intervention is to prolong life and reduce complications. The target is different for different persons. Those above 80 years of age above 260 mmHg systolic and 90 mmHg diastolic is to bring it below that figure even though normal range is far below that. This is because it is likely not possible to achieve normal range.

Read Also: Is diclofenac potassium safer in hypertension than diclofenac sodium?

There is no significant difference in the antihypertensive activities of various agents. Choice depends on other indications and responses. For example, it is wrong to give a diuretic to a patient with renal failure. It is not advisable to give two agents from the same class. And it is better to give two agents at low does than to give a single agent at high dose. Never give combinations of ACE, direct renin inhibitors and ARB together.

ACE inhibitors, ARB, CCB and thiazide diuretic are recommended for non brown skin people while CCB and thiazide for brown skin people. Beta-Blockers are no longer considered first line therapy. Those under 55 years old, ACE inhibitors or ARB are suitable. Also, those above 55 years of age or any age from Africa or Caribbean descent should be given CCB.

Elevated blood pressure does not require the use of medication but lifestyle changes should be able to work. NHS advice that blood pressure of patients less than 60 years of about 140 mmHg systolic and 90 mmHg diastolic or above 60 years of about 135/85 mmHg with no complaints should not be given any drug but encouraged to follow lifestyle modification.

But when the blood pressure at that level comes with likely complications, lifestyle modification alone will not achieve the desired results. A single antihypertensive agent should be added at the lowest possible dose. Anybody above 160 mmHg systolic and 100 mmHg diastolic should be given drugs along with lifestyle modification.

Adults with stroke or transient ischemic attack should be placed on ACE inhibitors or ARB or a combination of ACE inhibitors and thiazide diuretics. Diabetes and chronic kidney disease is best treated with ARB and ACE inhibitors. ARB or ACE inhibitors combined with potassium sparing diuretic can cause hyperkalemia. CCB can cause edema hence contraindicated in people experiencing edema.

Hypertension In Pregnancy

Women who are hypertensive before pregnancy will do well to tell their pharmacist and medical doctor on the drug they are currently taking. Most women experience hypertension from week 20. There are different stages in pregnancy. Blood pressure above 160 mmHg systolic and 100-105 mmHg diastolic should be placed on antihypertensive. Women with high risk of organ damage should be placed on antihypertensive drugs before it gets to this level. The target value depends on so many things but 140 mmHg systolic and 90 mmHg diastolic is not bad. ACE inhibitors, ARB or direct renin inhibitors are contraindicated in pregnancy. Methyldopa is best used in pregnancy. Labetalol, beta-blockers and diuretic may be considered. Others like CCB have limited information on pregnancy that they should still be avoided for the time being.

Hypertensive Crisis

Hypertensive crisis cases has dropped significantly Fromm 7 percent to 1 percent and survival have increased from 20 percent to 90 percent

In hypertensive crisis, the goal is to bring down the blood pressure to a safe level. The blood pressure should be lowered in minutes to hours by not more than 25 percent and then lowered further to 160 mmHg systolic and 100 mmHg diastolic. From here, normal prescription drugs can be used. Lowering the blood pressure too fast can lead to complications.

Drugs used in emergencies are parenteral sodium nitroprusside and hydralazine. Oral agents used sometimes are labetalol, esmolol and nifedipine. Nifedipine causes a faster than normal drop in Hypertension in some people hence caution when using it.

Resistant Hypertension

A resistant Hypertension is defined as Hypertension three antihypertensive agents are not working for. In most cases, changing the agent does the trick. It involves trial and error.

Dosage Of Oral Antihypertensive Drugs

1. Hydrochlorothiazide 12.5–50 mg daily

2. indapamide 1.25–2.5 mg daily

3. furosemide 20–80 mg two times daily

4. torsemide 2.5–10 mg daily

5. amiloride 5–10 mg daily or two times a day

6. spironolactone 25–50 mg daily

7. atenolol 25–100 mg daily

8. propranolol 60–180 mg daily

9. bisoprolol 2.5–10 mg daily

10. metoprolol 50–100 mg daily or two times a day. Extended release tablet is given daily.

11. propranolol long-acting 60–180 mg daily. Short acting is taken two times a day.

12. timolol 20–40 mg taken two times daily

13. carvedilol 12.5–50 mg taken two times daily

14. labetalol 200–800 mg two times daily

15. captopril 25–100 mg two times daily

16. enalapril 5–40 mg once or two times daily

17. lisinopril 10–40 mg daily

18. ramipril 2.5–20 mg daily

19. candesartan 8–32 daily

20. irbesartan 150–300 mg daily

21. losartan 25–100 mg daily or two times a day

22. olmesartan 20–40 mg daily

23. telmisartan 80–320 mg once or twice a day

24. valsartan 80–320 mg once or twice a day

25. amlodipine 2.5–10 mg daily

26. nifedipine long-acting 30–60 mg daily

27. doxazosin 2–20 mg two or three times a day

28. methyldopa 250–1,000 mg two times a day

29. hydralazine 25–100 mg two times a day

30. minoxidil 25–100 mg two times a day