Hypertension also known as high blood pressure (HBP) is a very common condition and an important risk factor for the future development of cardiovascular disease. It can be defined as a disturbance in the circulatory function associated with a persistent elevation of systolic and diastolic blood pressure (BP) above normal or to a level likely to lead to adverse consequences.
The actual level of pressure that can be considered hypertensive is difficult to define; it depends on a number of factors, including the patient’s age, sex, race, and lifestyle. As a working definition, many cardiovascular treatment centres consider that a systolic blood pressure equal to or greater than 140 mm Hg and/or diastolic blood pressure equal to or greater than 90 mm Hg represents hypertension.
- 1 Types of hypertension
- 2 Causes of high blood pressure
- 3 Drugs that may increase blood pressure
- 4 Symptoms of high blood pressure
- 5 How should blood pressure be measured?
- 6 Understanding blood pressure readings
- 7 Management of hypertension
- 7.1 Nonpharmacologic approach/ Nondrug approach of managing hypertension
- 7.2 Blood pressure medications
- 7.2.1 1. Angiotensin-Converting Enzyme Inhibitors (ACEIs)
- 7.2.2 2. Beta-blockers (Beta-Adrenergic Blockers)
- 7.2.3 3. Diuretics
- 7.2.4 4. Angiotensin II receptor blockers (ARBs)
- 7.2.5 5. Calcium channel blockers (CCBs)
- 7.2.6 6. α-Adrenoreceptor blockers
- 7.2.7 7. Central α2-agonists (Centrally acting agents)
- 7.2.8 8. Direct vasodilators
- 7.2.9 9. Direct renin inhibitors
- 7.2.10 10. Aldosterone receptor antagonists (ARAs)
- 8 References
Types of hypertension
There are two broad classifications of hypertension based on aetiology
- Primary or essential hypertension and
- Secondary hypertension.
Primary or essential hypertension occurs when the cause is not identifiable. Patients with secondary hypertension have identifiable pathology responsible for their chronically elevated blood pressure (BP).
Other types of hypertension include: white-coat hypertension, resistant hypertension, isolated systolic hypertension, and hypertensive crisis
Causes of high blood pressure
The cause of 90 – 95 % cases of hypertension (essential hypertension) is unknown. The remaining 5 – 10 % of cases is secondary to some other disease conditions. Such causes include:
- chronic kidney disease (CKD)
- renovascular disease
- coarctation of the aorta
- primary aldosteronism
- sleep apnea
- hyperthyroidism and
- Cushing syndrome.
Other cardiovascular risk factors include smoking, alcoholism and some drugs.
Drugs that may increase blood pressure
Some drugs that may increase blood pressure include
- Amphetamines (amphetamine, dexmethylphenidate, dextroamphetamine, lisdexamfetamine, methylphenidate, phendimetrazine, and phentermine)
- Antidepressants (bupropion, desvenlafaxine, and venlafaxine)
- Antihypertensive agents that are abruptly stopped (only β-blockers and central a2-agonists)
- Anabolic steroids (e.g., testosterone)
- Calcineurin inhibitors (cyclosporine and tacrolimus)
- Cocaine and other illicit drugs
- Ephedra alkaloids
- Erythropoiesis-stimulating agents (darbepoetin-alfa and erythropoietin)
- Ergot alkaloids (ergonovine and methysergide)
- Estrogen-containing oral contraceptives (ethinyl estradiol)
- Licorice (including some chewing tobacco)
- Monoamine oxidase inhibitors (isocarboxazid, phenelzine, tranylcypromine sulfate) when given with tyramine containing foods or with an interacting drug Nonsteroidal antiinflammatory drugs (all types)
- Oral decongestants (e.g., pseudoephedrine)
- Phenylephrine (ocular administration)
- Vascular endothelial growth factor inhibitor (bevacizumab)
- Vascular endothelial growth factor receptor tyrosine kinase inhibitor (sorafenib and sunitinib)
Symptoms of high blood pressure
Hypertension is asymptomatic in most cases and is often, therefore, an incidental finding when patients present with unrelated conditions or may be identified during a cardiovascular risk assessment. Patients with secondary hypertension may have symptoms of the underlying disorder. For example, patients with pheochromocytoma may have
- palpitations, and
- orthostatic hypotension
Patients with Cushing syndrome in addition to classic features (moon face, buffalo hump, and hirsutism) may have
- weight gain
- menstrual irregularities
- recurrent acne
- muscular weakness
In primary aldosteronism, hypokalemic symptoms of muscle cramps and weakness may be present.
How should blood pressure be measured?
- Blood pressure should be measured after the patient has emptied their bladder and has been seated for five minutes with back supported and legs resting on the ground (not crossed).
- Arm used for measurement should rest on a table, at heart-level.
- Use a sphygmomanometer/stethoscope or automated electronic device (preferred) with the correct size arm cuff.
- Take two readings one to two minutes apart, and average the readings (preferred).
- Measure blood pressure in both arms at initial evaluation. Use the higher reading for measurements thereafter.
Understanding blood pressure readings
The table below defines blood pressure readings for adults (age 18 years and older)
|Classification||Systolic blood pressure (mmHg)||Diastolic blood pressure (mmHg)|
|Stage 1 hypertension||140–159||or 90–99|
|Stage 2 hypertension||≥160||or ≥100|
Note: If systolic blood pressure and diastolic blood pressure are in different categories, the overall classification is determined based on the higher of the two blood pressure categories.
Management of hypertension
Hypertension is treated with both lifestyle modifications and pharmacotherapy. The overall goal in the management of hypertension is to reduce associated morbidity and mortality (also called cardiovascular or CV events) by the least intrusive means possible.
Most patients with hypertension including those with diabetes or chronic kidney disease (CKD) under age 60 years have recommended BP goal of less than 140/90 mm Hg. Lower goals may be an option in certain populations. Elderly patients (age > 60 years) have a BP goal of less than 150/90 mm Hg.
The JNC-8 is considered the “gold standard” consensus guidelines for the management of hypertension in the United States.
Nonpharmacologic approach/ Nondrug approach of managing hypertension
Lifestyle modifications are the foundation for preventing hypertension, and they are an important component of first-line therapy in all patients treated with antihypertensive drug therapy. Lifestyle advice should include
- Weight loss if overweight or obese, ideally attaining a body mass index (BMI) less than 25 kg/m2 or maintaining a desirable BMI (18.5–24.9 kg/m2) if not overweight or obese
- Adoption of the Dietary Approaches to Stop Hypertension (DASH) eating plan that is consumption of a diet rich in fruits and vegetables (8–10 servings/day), rich in low-fat dairy products (2–3 servings/day) with reduced saturated and total fat.
- Dietary sodium restriction ideally to 1.5 g/day (3.8 g/day sodium chloride)
- Increase daily dietary potassium intake to 120 mmol/day (4.7 g/day), which is the amount provided in a DASH-type diet
- Regular aerobic physical activity (at least 30 min/day, most days of the week but preferable daily)
- Moderation of alcohol consumption (2 drinks/day in men and 1 drink/day in women and lighter-weight persons), and
- Smoking cessation
In order to maximise potential benefit, patients should receive clear and unambiguous advice, including written information they can digest in their own time.
Blood pressure medications
Several antihypertensive drugs with different sites and mechanism of action are now available. Nevertheless, none can be said to be the ideal antihypertensive drug. Drug choice should aim to maximise blood-pressure-lowering effectiveness and minimise patient side effects.
The most appropriate choice of initial drug therapy depends on the age and racial origin of the patient, as well as the presence of other medical conditions. Some of the drugs used to treat hypertension include
1. Angiotensin-Converting Enzyme Inhibitors (ACEIs)
The ACEIs block conversion of angiotensin I to angiotensin II, a potent vasoconstrictor and stimulator of aldosterone secretion. This helps blood vessels relax and reduces blood pressure. ACEIs also block degradation of bradykinin and stimulate the synthesis of other vasodilating substances, including prostaglandin E2 and prostacyclin.
Examples of ACEIs used in the management of hypertension include
- Benazepril (Lotensin)
- Captopril (Capoten)
- Enalapril (Vasotec)
- Fosinopril (Monopril)
- Lisinopril (Prinivil, Zestril)
- Moexipril (Univasc) etc.
2. Beta-blockers (Beta-Adrenergic Blockers)
β-Blockers have several direct effects on the cardiovascular system. They can decrease cardiac contractility and cardiac output (CO), lower heart rate, blunt sympathetic reflex with exercise, reduce central release of adrenergic substances, inhibit norepinephrine release peripherally, and decrease renin release from the kidney. All these contribute to their antihypertensive effects.
Examples of β-Blockers include
- Atenolol (Tenormin)
- Betaxolol (Kerlone)
- Bisoprolol (Zebeta)
- Nadolol (Corgard)
- Propranolol (Inderal)
- Acebutolol (Sectral) etc.
Diuretics, also called water pills, are drugs that are employed to facilitate elimination of extracellular fluid from the body. They exert their effect directly on the kidneys and lower BP by causing diuresis. Examples include
- Chlorthalidone (Hygroton)
- Hydrochlorothiazide (Esidrix,)
- Indapamide (Lozol)
- Furosemide (Lasix)
- Torsemide (Demadex) etc.
4. Angiotensin II receptor blockers (ARBs)
While ACEIs block conversion of angiotensin I to angiotensin II, ARBs modulate the Renin-Angiotensin-Aldosterone System (RAAS) by directly blocking the angiotensin II type 1 receptor site, preventing angiotensin II-mediated vasoconstriction and aldosterone release. Examples of Angiotensin II receptor blockers include
- Candesartan (Atacand)
- Irbesartan (Avapro)
- Losartan (Cozaar)
- Olmesartan (Benicar)
- Telmisartan (Micardis)
5. Calcium channel blockers (CCBs)
These medications reduce calcium entry into smooth muscles, which causes coronary and peripheral vasodilation and lowers BP. The dihydropyridine group work almost exclusively on L-type calcium channels in the peripheral arterioles and reduce blood pressure by reducing total peripheral resistance. In contrast, the effect of verapamil and diltiazem are primarily on the heart, reducing heart rate and cardiac output. Other examples of CCBs include
- Amlodipine (Norvasc)
- Felodipine (Plendil) etc.
6. α-Adrenoreceptor blockers
These agents antagonise α-adrenoceptors in the blood vessel wall and, thus, prevent noradrenaline (norepinephrine) induced vasoconstriction. As a result, they reduce total peripheral resistance and blood pressure. Examples include
- Prazosin (Minipress)
- Doxazosin (Cardura)
- Terazosin (Hytrin)
7. Central α2-agonists (Centrally acting agents)
Central α2-agonists work in the vasomotor centres of the brain where they stimulate inhibitory neurons and decrease sympathetic outflow from the central nervous system (CNS). The resultant decrease in peripheral vascular resistance (PVR) and CO lowers BP. Examples include
- Methyldopa (Aldomet)
- Clonidine HCL (Catapres)
8. Direct vasodilators
These drugs cause direct arteriolar smooth muscle relaxation. They decrease total peripheral resistance and thus correct the hemodynamic abnormality that is responsible for the elevated blood pressure in primary hypertension. In addition, because they act directly on vascular smooth muscle, the vasodilators are effective in lowering blood pressure, regardless of the aetiology of the hypertension.
- Minoxidil (Loniten)
- Hydralazine (Apresoline)
9. Direct renin inhibitors
Similar to ACEIs or ARBs, direct renin inhibitors target the rate-limiting step in the RAAS. Aliskiren, approved in 2007, is the only direct renin inhibitor. Many of the cautions and adverse effects seen with ACE inhibitors and ARBs apply to aliskiren.
10. Aldosterone receptor antagonists (ARAs)
Aldosterone exerts its effects at the nephron through mineralocorticoid receptors, which translocate to the nucleus upon aldosterone binding and exert genomic effects leading to increased sodium reabsorption. Potent blockade of the aldosterone receptor inhibits sodium and water retention and inhibits vasoconstriction. These agents are also considered potassium-sparing diuretics. Examples of aldosterone antagonists include
- Spironolactone (Aldactone)
- Eplerenone (Inspra)
- Antman, E. and Sabatine, M. (2013). Cardiovascular Therapeutics: A Companion to Braunwald’s Heart Disease (4th). Philadelphia: Saunders.
- James, P., Oparil S., Carter B., Cushman W., Dennison-Himmelfarb C., Handler J. et al. (2014) Evidence-based guidelines for the management of high blood pressure in adults . JAMA, 311(5):507–520.
- Wells, B., DiPiro, J., Schwinghammer, T. and DiPiro, C. (2017). Pharmacotherapy Handbook. (10th). New York: McGraw-Hill Education.
- Whittlesea, C. and Hodson, K. (2019). Clinical Pharmacy and Therapeutics (6th). London: Elsevier Limited.
- Zeind, C. and Carvalho, M. (2018). Applied Therapeutics: The Clinical Use of Drugs (11th). New York: Wolters Kluwer.
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