HYPERTENTIONBY: M ABUBAKAR

MPHIL PHARMACY PRACTICEQUAID E AZAM UNIVERSITY ISLAMABD

Hypertension DefinitionPersistent elevation of arterial blood pressure is called as hypertension. High blood pressure is said to be present if it is often at or

above 140/90 mmHg.• Blood pressure = CO X TPR• Cardiac output = stroke vol X heart rate Types of BP:• Systolic BP ( contraction).• Diastolic BP ( relaxation). Normal BP • Systolic BP = 120 mmHg• Diastolic BP =80 mmHg

Blood Pressure SBP DBPClassification mmHg mmHg• Normal <120 and <80• Prehypertensi

on120–139 or 80–89

• Stage 1Hypertension

140–159 or 90–99

• Stage 2Hypertension

≥160 or ≥110

Classification of BP according to JNC 7 Its the Seventh Report of the Joint National Committee (USA) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure .

Epidemiology• Overall, approximately 20% of the world’s adults are

estimated to have hypertension, when hypertension is defined as BP in excess of 140/90 mm Hg.

• The prevalence dramatically increases in patients older than 60 years.

• In many countries, 50% of individuals in this age group have hypertension.

• Worldwide, approximately 1 billion people have hypertension, contributing to more than 7.1 million deaths per year.

• National health surveys in various countries have shown a high prevalence of poor control of hypertension.

Age Distribution for Hypertension :A progressive rise in BP with increasing age is observed. Age-related hypertension appears to be predominantly systolic rather than diastolic.Cardiovascular disease risk : According to the JNC in individuals older than 50 years : • SBP of greater than 140 mm Hg is a more important cardiovascular

disease risk factor than DBP.• Beginning at a BP of 115/75 mm Hg, the cardiovascular disease

risk doubles for each increment of 20/10 mm Hg. Prevalence of Hypertension by Race :• Black individuals have a higher prevalence and incidence of

hypertension than white persons .• The prevalence of hypertension has been reported to be increased

by 50% in blacks.

To understand ethnic influence, an understanding of the renin-angiotensin system (RAS) is essential.

Renin secretion is suppressed when the kidney detects that the amount of sodium excretion is increased; thus, this is a clue to the excess sodium in the circulation.

• Black people tend to develop hypertension at an earlier age and have lower renin activity.

• Genetics of Hypertension :• There are rare forms of hypertension due to genetic mutations.• These involve mutations in the epithelial sodium channel (ENaC) in

the distal renal tubule (Liddle syndrome). involves abnormal kidney function, with excess reabsorption of sodium and loss of potassium from the renal tubule, and is treated with a combination of low sodium diet and potassium-sparing diuretic drugs (e.g., amiloride)

• The inheritance of the mutation almost always results in the development of hypertension.

Age Groups (y)

All Races White BlackMen (%)

Women (%)

Total (%)

Men (%)

Women (%)

Total (%)

Men (%)

Women (%)

Total (%)

18-24 2.6 4.6 0.7 2.5 4.6 0.5 2.6 4.1 1.425-34 5.4 8.4 2.4 4.9 8.1 1.6 8.2 10.6 6.235-44 13.0 16.0 10.2 11.3 14.3 8.5 25.9 29.5 22.945-54 27.6 30.0 25.2 25.8 29.1 22.6 46.9 44.3 48.855-64 43.7 44.2 43.2 42.1 43.0 41.4 60.0 58.0 63.065-74 59.6 55.8 62.7 58.6 54.9 61.7 71.0 65.2 75.675+ 70.3 60.5 76.2 69.7 59.0 76.1 75.5 71.3 77.9Total 23.4 23.5 23.3 23.2 23.4 23.1 28.1 27.9 28.2

National Estimates of HypertensionNational High Blood Pressure Education ProgramThe prevalence according to age group, sex, and race is shown in Table :

HTN in Pakistan • The National Health Survey of Pakistan estimated that

hypertension affects 18% of adults and 33% of adults above 45 years old.

• In another report, it was shown that 18% of people in Pakistan suffer from hypertension with every third person over the age of 40 increasingly effected to HTN.

• It was also mentioned that only 50% of the people with hypertension were diagnosed and that only half of those diagnosed were ever treated.

• Thus, only 12.5% of hypertension cases were adequately controlled.

MECHANISM• The renin-angiotensin system (RAS) or the

renin-angiotensin-aldosterone system (RAAS) is a hormone system that regulates blood pressure and water (fluid) balance.

• When blood volume is low, juxtaglomerular cells in the kidneys activate their prorenin and secrete renin directly into circulation.

• Plasma renin then carries out the conversion of angiotensinogen released by the liver to angiotensin I.

• It is subsequently converted to angiotensin II by the enzyme angiotensin-converting enzyme found in the lungs.

• Angiotensin II is a potent vaso-active peptide that causes blood vessels to constrict, resulting in increased blood pressure.

• Angiotensin II also stimulates the secretion of the hormone aldosterone from the adrenal cortex.

• Aldosterone causes the tubules of the kidneys to increase the reabsorption of sodium and water into the blood.

• This increases the volume of fluid in the body, which also increases blood pressure.

• If the renin-angiotensin-aldosterone system is abnormally active, blood pressure will be too high.

Types of HypertensionPrimary HTN.Secondary HTN.• Drugs related HTN.• Food related HTN.• Chemicals related HTN.

Primary HTN• It may be from an underlying pathophysiologic

mechanism of unknown cause.• Also called essential or idopathic HTN. • 95 % cases no cause of HTN is found.• Uncommon before age 20.• Onset is between ages 25 and 55 years.• Life long persist.

Multiple factors may contribute to the development of primary hypertension :✓ Abnormalities involving the renin-angiotensin-aldosterone system.

✓ A pathologic disturbance in the CNS, like stress. Abnormalities in either the renal or tissue autoregulatory processes

for sodium excretion, plasma volume, and arteriolar constriction. A high sodium intake .

✓ Increased intracellular concentration of calcium, leading to altered vascular smooth muscle function and increased peripheral vascular resistance.

✓ A deficiency in the local synthesis of vasodilating substances in the vascular endothelium, such as prostacyclin, bradykinin , and nitric oxide, or an increase in production of vasoconstricting substances such as angiotensin II.

Secondary HTNIdentifible causes revealed by :• History• Physical examination• Routine lab tests.• In 5% cases causes of HTN discovered.• Over age 50 years.

Disease related HTN chronic kidney disease or renovascular disease (2-

6%) :• Chronic glomerular nephritis. • Polycystic kidney disease. is characterized by the presence of multiple

cysts• chronic pyelonephritis. an inflammation of the renal parenchyma, calyces

, and pelvis.[ Endocrine disorders (1- 2%) :• Pheochromocytoma.• Cushing’s syndrome.• Hyperthyroidism.• primary aldosteronism.

Renovascular HTN or muscular disorders (1-2%) :

• coarctation of aorta.

• Atherosclerosis.• Renal artery

stenosis. Miscellenous:• obesity• obstructive sleep

apnea

Food related • Sodium• Ethanol.

CHEMICALS• Lead• Mercury• Lithium• thallium

DRUGSCorticosteroids.Estrogen.NSAID,s.Cyclosporins.Amphetamine.MAOI,s.TCA.Cocaine. Oral contraceptives.Nicotine.

Diagnosis of HTN

• Take history of patient.• Measurement

of BP.• Physical

examination.• Lab findings.

PHYSICAL EXAMINATION• Frequently, the only sign of primary hypertension on

physical examination is elevated BP.• The diagnosis of hypertension should be based on the

average of two or more readings taken at each of two or more clinical encounters.

• As hypertension progresses, signs of end-organ damage begin to appear chiefly related to pathologic changes in the :

o Eye.o Brain.o Heart. o Kidneys. o peripheral blood vessels.

• Cardiopulmonary examination may reveal :o Abnormal heart rate or rhythm.o Left ventricular (LV) hypertrophy.o Third and fourth heart sounds.• Peripheral vascular examination can detect evidence of : o Atherosclerosis.o Distended veins.• Patients with Cushing’s syndrome may have the classic physical features of :o Moon face o Buffalo humpo Hirsutism o Abdominal striae.

• Baseline hypokalemia may suggest mineralocorticoid-induced hypertension.

• The presence of protein, blood cells, and casts in the urine may indicate renovascular diseases.

• Laboratory findings that should be obtained in all patients prior to initiating drug therapy include :o Urine analysis.o complete blood cell count.o serum chemistries (sodium, potassium, creatinine, fasting

glucose).o These tests are used to assess other risk factors and to

develop baseline data for monitoring drug-induced metabolic changes.

Tests to Evaluate the Heart. An electrocardiogram (ECG) : It records the electrical activity of the heart. The heart produces tiny electrical impulses which

spread through the heart muscle to make the heart contract.

These impulses can be detected by the ECG machine. The machine amplifies the electrical impulses that

occur at each heartbeat, and records them on to a paper or computer.

An ECG recording is painless and harmless. The ECG machine records electrical impulses coming

from your body, it does not put any electricity into your body.

An exercise tolerance test (ETT) records the electrical activity of your heart while you exercise.How is an exercise tolerance test done?Small electrodes are stuck on to your chest. Wires from the electrodes are connected to the ECG machine. You will then be asked to exercise on a treadmill or on an exercise bike. The exercise starts at a very easy pace, and is gradually made more strenuous by increasing the speed and incline of the treadmill, or by putting some resistance on the bike wheel.While you exercise, ECG tracings are made and you will also have your blood pressure measured from time to time. The test lasts about 15-20 minutes.

Why is an exercise tolerance test done?The ETT helps to diagnose and assess the severity of ischaemic heart disease (sometimes called coronary heart disease or coronary artery disease). This disease is due to narrowing of the coronary arteries. It can cause angina (chest pains) and other problems. So, if you develop chest pains you may be advised to have an ETT to help to clarify the cause.

Investigations For

Pheochromocytoma:• Plasma norepinephrine.• Urinary metanephrine

levels Plasma. (PCC) is a neuroendocrine tumor of the medulla of the adrenal glands

primary aldosteronism:

• urinary aldosterone levels for Plasma renin activity.

For renovascular disease

• Captopril stimulation test.• Renal vein renins . Renal

artery angiography.Doppler or duplex test.

A Doppler ultrasound is a noninvasive test that can be used to estimate your blood flow through blood vessels by bouncing high-frequency sound waves (ultrasound) off circulating red blood cells. A regular ultrasound uses sound waves to produce images, but can't show blood flow.A Doppler ultrasound may help diagnose many conditions, including:o Blood clotso Poorly functioning valves in your leg veins, which can cause blood or

other fluids to pool in your legs (venous insufficiency)o Heart valve defects and congenital heart diseaseo A blocked artery (arterial occlusion)o Decreased blood circulation into your legs (peripheral artery

disease)o Narrowing of an artery.

• A Doppler ultrasound can estimate how fast blood flows by measuring the rate of change in its pitch (frequency).

• A Doppler ultrasound test may also help your doctor check for injuries to your arteries or to monitor certain treatments to your veins and arteries.

CLINICAL PRESENTATIONS• Patients with uncomplicated primary hypertension are usually

asymptomatic.• Patients with secondary hypertension may complain of symptoms

suggestive of the underlying disorder. Patients with pheochromocytoma may

have a history of :o headacheso Sweatingo Tachycardia o Palpitationso Orthostatic hypertension.

In primary aldosteronism :Hypokalemic symptoms of muscle cramps and weakness. Patients with hypertension secondary to

Cushing’s syndrome may complain of :o weight gain.o Polyuria.o Edema.o Menstrual irregularities.o Acne.o Muscular weakness. Symptoms of complications such as : o heart failure.o Stroke.o renal failure.

Complications of HTNCentral nervous

system • Stroke.• Hypertensive

encephalopathy.• Subarachnoid hemorrhage.• Multi infarct dementia. Heart :• Ventricular hypertrophy.• Ischemic heart disease.• Heart failure.

Kidneys:• Nephropathy.• Proteinuria.• Renal failure.Eyes related

problems :• Retina grade 1 to 4.• Sometimes blindness.

Symptoms of Malignant HypertensionIn rare cases (fewer than 1% of all patients with hypertension), the blood pressure rises quickly resulting in malignant or accelerated hypertension. This is a life-threatening condition and must be treated

immediately. People with uncontrolled hypertension or a history of

heart failure are at increased risk for this crisis.People should call a doctor immediately if these symptoms occur:o Drowsinesso Confusiono Headacheo Nauseao Loss of visiono Respiratory distress (difficulty breathing)

DESIRED OUTCOME• The overall goal of treating hypertension is to reduce morbidity and mortality by the possible means. Goal BP values are <140/90 for most

patients, but <130/80 for patients with :o Diabetes mellitus.o Significant chronic kidney disease.o Coronary artery disease .o Myocardial infarctiono Angina.

Patients with LV dysfunction have a : o BP goal of <120/80 mm Hg.o SBP is a better predictor of CV risk than DBP and

must be used as the primary clinical marker of disease control in hypertension.

Treatment NONPHARMACOLOGIC THERAPY• All patients with prehypertension and

hypertension should be prescribed lifestyle modifications, including :

• Weight reduction if overweight.• Adoption of the Dietary Approaches (eating plan) to Stop

Hypertension.• Dietary sodium restriction .• Regular aerobic physical activity.• Moderate alcohol consumption (two or fewer drinks per day)• Smoking cessation.

• Lifestyle modifications alone is appropriate therapy for patients with prehypertension. Patients diagnosed with stage 1 or 2 hypertension should be placed on lifestyle modifications and drug therapy concurrently.

Pharmacological therapy• Initial drug selection depends on the degree of BP

elevation and the presence of compelling indications for selected drugs.

• Most patients with stage 1 hypertension should be treated initially with :

• Thiazide diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB), or calcium channel blockers (CCB).

• Combination therapy is recommended for patients with stage 2 disease, with one of the agents being a thiazide-type diuretic unless contraindications exist.

• Diuretics, ACE inhibitors, ARBs, and CCBs are primary agents acceptable as first-line options based on outcome data demonstrating CV risk reduction benefits . β-Blockers may be used either to treat a specific compelling indication or as combination therapy with a primary antihypertensive agent for patients without a compelling indication.α1-Blockers, direct renin inhibitors, central α2-agonists, peripheral adrenergic antagonists, and direct arterial vasodilators are alternatives that may be used in select patients after primary agents .

Preclampsia or Eclampsia • Hypertension occurs in approximately 8–10% of pregnancies.• High BP in pregnancy may usually be due to pre-existing HTN or pre-

eclampsia.• Two blood pressure measurements in six hours an apart of greater than

140/90 mm Hg is considered diagnostic of hypertension in pregnancy. • Pre-eclampsia is characterised by increased blood pressure and the

presence of protein in the urine. proteinuria (≥300 mg/24 hours), can lead to life-threatening complications for both the mother and fetus.

• It occurs in about 5% of pregnancies and is responsible for approximately 16% of all maternal deaths globally.

• Usually there are no symptoms in pre-eclampsia and it is detected by routine screening.

When symptoms of pre-eclampsia occur the most common are :• Headache• Visual disturbance .• Vomiting.• Epigastric pain• Edema.Eclampsia can occasionally progress to life-threatening which is a hypertensive emergency and has several serious complications including :• vision loss• cerebral edema• seizures or convulsions• renal failure• pulmonary edema• intravascular coagulation (a blood clotting disorder)

TREATMENT :• Methyl dopa is safe in pregnancy.• Beta blockers are effective and safe in 3rd trimester

of pregnancy.• Modified release preparations of nifidipine are also

used in HTN in pregnancy.• IV labetolol or hydralazine can be used to control

hypertensive crisis.• Mg sulphate is drug of choice to prevent seizures in

preclampsia.• ACE inhibitors and ARB,s are contraindicated

because they cross placenta.

HTN with Diabetes

HTN with Asthma & COPD

HTN with liver disease • All hypertensive drugs can be used except methyldopa.

HTN with gout All hypertensive drugs can be used.But all diuretics can increase serum uric acid level.So diuretics should be avoided if possible.

White coat HTN also known as white coat syndrome : It is a phenomenon in which patients exhibit elevated blood pressure in a clinical sitting but not in other sittings.It is believed that this is due to the anxiety some people experience during a clinic visit. In general, individuals with white coat hypertension have lower morbidity than patients with sustained hypertension. White coat" hypertension do not require even very small doses of antihypertensive therapy as it may result in hypotension, but must still be careful as patients may show signs of vascular changes and may eventually develop hypertension.The term "masked hypertension" can be used to describe the contrasting phenomenon, where blood pressure is elevated during daily living, but not in an office sitting.

Measurement of BP• Arterial pressure is most commonly measured via a

sphygmomanometer which historically used the height of a column of mercury to reflect the circulating pressure.

• Systolic and diastolic arterial blood pressures are not static but undergo natural variations from one heartbeat to another and throughout the day (in a circadian rhythm).

• They also change in response to :o Stress. o Nutritional factors.o Drugs.o Disease.o Exercise.

Hypertensive urgencies

• Severe HTN without or with minimal symptoms and controlled slowly in 24 hours.

• It is ideally managed by adjusting maintenance therapy by adding a new antihypertensive and/or increasing the dose of a present medication.

• Acute administration of a short-acting oral drug (captopril, clonidine, or labetalol) followed by careful observation for several hours to ensure a gradual BP reduction is an option.

Hypertensive emergencies :• Hypertensive emergency is severe HTN with

symptomatic end organ damage require immediate BP reduction to limit new or progressing target-organ damage.

• The goal is not to lower BP to normal; instead, the initial target is a reduction in mean arterial pressure of up to 25% within minutes to hours.

• If BP is then stable, it can be reduced toward 160/100– 110 mm Hg within the next 2 to 6 hours.

• If BP reduction is well tolerated, additional gradual decrease toward the goal BP can be attempted after 24 to 48 hours.

• Nitroprusside is the agent of choice :for minute-to-minute control in most cases. It is usually given as a continuous IV infusion at a rate of 0.25 to 10 mcg/kg/min.

• Its onset of hypotensive action is immediate and disappears within 1 to 2 minutes of discontinuation.

• When the infusion must be continued longer than 72 hours, serum thiocyanate levels should be measured, and the infusion should be discontinued if the level exceeds 12 mg/dL.

• The risk of thiocyanate toxicity is increased in patients with impaired kidney function.

Refractory HTNThe more common cause of treatment failure

in HTN :• Non compliance i.e patient is not taking drug regularly.• Inadequate therapy.• Failure to recognize secondary causes of HTN e.g renal

artery stenosis & pheochromocytoma.• Use of antagonistic drugs e.g NSAIDSo Steroidso cocaine • Increase alcohol intake.

EVALUATION OF THERAPEUTIC OUTCOMES

• Clinic-based BP monitoring is the standard for managing hypertension.

• BP response should be evaluated 2 to 4 weeks after initiating or making changes in therapy.

• More frequent evaluations are required in patients with a history of :

Poor control. Non adherence Progressive target-organ damage Symptoms of adverse drug effects.• These techniques are currently recommended only for select

situations such as suspected white coat hypertension.

Monitoring for adverse drug effects should typically occur 2 to 4 weeks after starting a new agent or dose increases, and then every 6 to 12 months in stable patients.

Additional monitoring may be needed for other concomitant diseases.

Patients taking aldosterone antagonists should have potassium concentration and kidney function assessed . Patients should be questioned periodically about changes

in:o their general health perception.o energy level.o physical functioning. o overall satisfaction with treatment..