HYPERTENSION

By : Tewolde (B.Pharma,MSC)
Address =0970922524

31-Oct-23
Learning objectives
Upon completion of this lesson, the students will be able to:

Identify guideline-based treatment goals for patients with hypertension.

Recognize underlying causes and contributing factors in the development of

hypertension.

Describe the appropriate measurement of blood pressure (BP).

Classify BP levels after appropriate measurement.

Recommend appropriate lifestyle modifications.

Determine patient-centered pharmacotherapy for individuals with hypertension.

Construct an appropriate monitoring plan to assess hypertension treatment.

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Introduction

• Hypertension is a common disease that is simply defined as persistently elevated

arterial blood pressure (BP).

• Increasing awareness and diagnosis of hypertension, and improving control of BP

with appropriate treatment are considered critical public health initiatives to
reduce CV morbidity and mortality.

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Introduction

• Cardiovascular morbidity & mortality risk directly correlated with BP

- Starting at a BP of 115/75 mm Hg, risk of CV disease doubles with every 20/10

mm Hg increase

- Even patients with prehypertension have an increased risk of CV disease

- Antihypertensive drug therapy reduces cardiovascular & mortality risk

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Epidemiology

• The definition of hypertension changed with the 2017 ACC/AHA guideline from a
BP of ≥140/90 mm Hg to ≥130/80 mm Hg.

• The overall incidence of hypertension is similar between men and women but
varies depending on age.

• The prevalence of high BP is higher in men than women before the age of 65 and
is similar between the ages 65 and 74.

• However, after the age of 74, more women have high BP than men

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Epidemiology

• BP values increase with age, and hypertension is very common in older patients.

• The lifetime risk of developing hypertension among those 55 years of age and
older who are normotensive is higher than 90%.

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Etiology

• Essential hypertension/ primary hypertension

• results from unknown pathophysiologic etiology

• This form of hypertension cannot be cured, but it can be controlled

• Most individuals with high BP (over 90%) have essential or primary hypertension.

• Genetic factors may play a role in the development of essential hypertension by

affecting sodium balance or other BP regulating pathways.

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 Secondary Hypertension

where either a comorbid disease or a drug (or other product) is responsible

for elevating BP.

much less common than primary hypertension (up to 10%).

In most of these cases, renal dysfunction resulting from severe chronic

kidney disease (CKD)

renovascular disease is the most common secondary cause.

Certain agents (drugs or other products), either directly or indirectly, can

increase BP and cause or exacerbate hypertension.
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Secondary Causes of Hypertension*

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Secondary Causes of Hypertension*

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Secondary Causes of Hypertension*

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Pathophysiology

• Multiple physiologic factors control BP.

• These include malfunctions in either

humoral (ie, the renin–angiotensin–aldosterone system [RAAS])

vasodepressor mechanisms

abnormal neuronal mechanisms, defects in peripheral autoregulation

disturbances in sodium, calcium, and natriuretic hormones.

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Arterial BP

• Arterial BP is the pressure in the arterial wall measured in millimeters of mercury

(mm Hg).

• The two arterial BP values are systolic BP (SBP) and diastolic BP (DBP).

• SBP represents the peak value, which is achieved during cardiac contraction.

• DBP is achieved after contraction when the cardiac chambers are filling, and
represents the nadir value.

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Arterial BP

• The absolute difference between SBP and DBP is called the pulse pressure and is
a measure of arterial wall tension.

• Mean arterial pressure (MAP) is the average pressure throughout the cardiac
contraction cycle
• During a cardiac cycle, two-thirds of the time is spent in diastole and one-third in
systole.
• Therefore, the MAP is calculated by using the following equation:

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Arterial BP

Arterial BP is hemodynamically generated by the interplay between

blood flow and the resistance to blood flow.
It is mathematically defined as the product of cardiac output (CO) and
total peripheral resistance (TPR) according to the following equation:

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 MAP: Mean Arterial Pressure

SBP: Systolic Blood Pressure

DBP: Diastolic Blood Pressure

BP: Blood Pressure

CO: Cardiac Output

TPR: Total Peripheral Resistance

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Arterial BP

• CO is the major determinant of SBP, whereas TPR largely determines DBP.

• In turn, CO is a function of stroke volume, heart rate, and venous capacitance.

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Potential Mechanisms of Pathogenesis

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The interrelationship between the kidney, angiotensin II, and regulation of blood
pressure

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Classification for HTN Adults

• The classification of BP in adults (age 18 years and older) is based on the average
of two or more properly measured BP values from two or more clinical encounters

• According to ACC/AHA, there are four BP categories:

• normal BP

• Prehypertension(elevated ): patients likely to develop hypertension

• stage 1 hypertension

• stage 2 hypertension
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Classification of Blood Pressure in Adults (Age ≥18 Y ears)

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Classification for HTN Adults
• If systolic & diastolic blood pressure values give different classifications, classify
by highest category

• Hypertensive crises are clinical situations where patients have extreme BP

elevations, typically >180/120 mm Hg.

• They are categorized as either hypertensive emergency or hypertensive urgency

• Hypertensive emergencies are extreme BP elevations that are accompanied by

acute or progressing end-organ damage.

• Hypertensive urgencies are extreme BP elevations without acute or progressing

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end-organ injury.
Classification for HTN Adults
• White coat hypertension

• Approximately 15% to 20% of patients have white coat hypertension, where BP

values rise in a clinical setting but are normal in nonclinical environments as
measured with home or ambulatory BP (ABP) monitors

• Masked hypertension

• With masked hypertension, home BP is much higher than the in office BP

measurement.

This situation may lead to undertreatment or lack of treatment for hypertension

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Classification for HTN Adults

• Moreover, patients with either white coat or masked hypertension are at higher
risk of progressing to sustained hypertension

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Classification for HTN Adults

• Patients are considered to have isolated systolic hypertension when their SBP
values are elevated (ie, ≥130 mm Hg) and DBP values are not (ie, <80 mm Hg).

• systolic hypertension is believed to result from pathophysiologic changes in the

arterial vasculature consistent with aging.

• These changes decrease the compliance of the arterial wall and portend an
increased risk of CV morbidity and mortality.

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Humoral Mechanisms

• Humoral abnormalities involved in the development of essential hypertension.

• The Renin angiotensin aldosterone system

• Natriuretic hormone

• Hyperinsulinemia

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The Renin–Angiotensin–Aldosterone System

• A complex endogenous system that is involved with most regulatory components

of arterial BP.

• Activation and regulation are primarily governed by the kidney

• The RAAS regulates sodium, potassium, and blood volume.

• Therefore, this system significantly influences vascular tone and sympathetic

nervous system activity, and is the most influential contributor to the homeostatic
regulation of BP.

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 FIGURE Diagram representing the renin–angiotensin–aldosterone system
Renin secretion from the juxtaglomerular cells in the afferent arterioles is regulated by three major factors that trigger conversion of
angiotensinogen to angiotensin.The primary sites of action for major antihypertensive agents are included: 1 ACE inhibitor; 2 angiotensin
31-Oct-23 II receptor blocker;3 β-blocker; 4 calcium channel blocker; 5 thiazide;6 mineralocorticoid receptor antagonist 28
The Renin–Angiotensin–Aldosterone System
• Renin is an enzyme that is stored in the juxtaglomerular cells, which are located in
the afferent arterioles of the kidney

• The release of renin is modulated by several factors: intrarenal factors (eg, renal
perfusion pressure, catecholamines, angiotensin II) and extrarenal factors (eg,
sodium, chloride, potassium).
• Juxtaglomerular cells function as a baroreceptor-sensing device.
• Decreased renal artery pressure and kidney blood flow are sensed by these cells
and stimulate secretion of renin
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The Renin–Angiotensin–Aldosterone System
• A decrease in sodium and chloride delivered to the distal tubule stimulates renin
release.
• Renin catalyzes the conversion of angiotensinogen to angiotensin I in the blood.

• Angiotensin I is then converted to angiotensin II by angiotensin converting

enzyme (ACE).

• After binding to angiotensin II type 1 [AT1] or angiotensin II type 2 [AT2]

subtypes), angiotensin II exerts biologic effects in several tissues.

• The AT1 receptor is located in the brain, kidneys, myocardium, peripheral

vasculature, and the adrenal glands.
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The Renin–Angiotensin–Aldosterone System

• Circulating angiotensin II can elevate BP through pressor and volume effects.

• Pressor effects include direct vasoconstriction, stimulation of catecholamine

release from the adrenal medulla, and centrally mediated increases in sympathetic
nervous system activity.

• Angiotensin II also stimulates aldosterone synthesis from the adrenal cortex,

leading to sodium and water reabsorption that increases plasma volume, TPR, and
ultimately BP.

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Natriuretic Hormone
• Natriuretic hormone inhibits sodium and potassium ATPase and thus interferes
with sodium transport across cell membranes.

• Inherited defects in the kidney’s ability to eliminate sodium can cause increased
blood volume.

• A compensatory increase in the concentration of circulating natriuretic hormone

theoretically could increase urinary excretion of sodium and water.
• However, this hormone might block the active transport of sodium out of arteriolar
smooth muscle cells.
• The increased intracellular sodium concentration ultimately increases vascular
tone and BP
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 Neuronal Regulation

• Central and autonomic nervous systems are intricately involved in the regulation
of arterial BP.

• The α and β presynaptic receptors play a role in negative and positive feedback to
the norepinephrine-containing vesicles.

• Stimulation of presynaptic α-receptors (α2) exerts a negative inhibition on

norepinephrine release.

• Stimulation of presynaptic β-receptors facilitates norepinephrine release.

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Neuronal Regulation

• Stimulation of postsynaptic α-receptors (α1) on arterioles and venules results in

vasoconstriction.

• There are two types of postsynaptic β- receptors, β1 and β2.

• Stimulation of β1-receptors in the heart increases heart rate (chronotropy) and

force of contraction (inotropy), whereas stimulation of β2-receptors causes

vasodilation in arteries and veins.

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Neuronal Regulation
• The baroreceptor reflex system is the major negative feedback mechanism that
controls sympathetic activity.

• Baroreceptors are nerve endings lying in the walls of large arteries, especially in
the carotid arteries and aortic arch

• Changes in arterial BP rapidly activate baroreceptors that then transmit impulses

to the brain stem through the ninth cranial nerve and vagus nerve.

• In this reflex system decrease in arterial BP stimulates baroreceptors, causing

reflex vasoconstriction, increased heart rate, and increased force of cardiac
contraction
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Clinical presentation and diagnosis of hypertension

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Clinical presentation and diagnosis of hypertension

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Diagnosis
• Hypertension is called the silent killer because most patients do not have
symptoms

• The primary physical finding is persistently elevated BP.

• The diagnosis of hypertension cannot be made based on one elevated BP

measurement.

• The average of two or more measurements taken during two or more clinical
encounters is required to diagnose hypertension

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Diagnosis
• The minimal laboratory testing required for the initial evaluation of hypertension
is determination of blood electrolyte, fasting glucose, and serum creatinine levels
(with calculated glomerular filtration rate [GFR]), a fasting lipid panel, hematocrit,
spot urinalysis (including urine albumin-to-creatinine ratio), and a resting 12-lead
electrocardiogram (ECG)

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Target-Organ Damage

• Brain: stroke, transient ischemic attack, dementia

• Eyes: retinopathy

• Heart: left ventricular hypertrophy, angina

• Kidney: chronic kidney disease

• Peripheral Vasculature: peripheral arterial disease

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Target-Organ Damage

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Measuring BP

• The appropriate procedure to indirectly measure BP is described by the AHA.

• It is imperative that the measurement equipment (ie,inflation cuff, stethoscope,

and manometer) meet national standards to ensure maximum quality and precision
with measurement.

• The AHA stepwise technique is recommended:

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Measuring BP
1. Patients should ideally refrain from nicotine and caffeine ingestion for 30 minutes
and sit with lower back supported in a chair.
Their bare arm should be supported and rest near heart level
2. Measurement should begin only after a 5-minute period of rest.
3. Neither the patient nor the clinician measuring the BP should talk during
measurement.
4. A properly sized cuff should be used. The inflatable rubber bladder should be at
least 80% of arm circumference and a width that is at least 40% of arm
circumference.
5. The palpatory method should be used to estimate the SBP:
a. Place the cuff on the upper arm with the bottom resting 2 to 3 cm
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Measuring BP

• 6. The stethoscope (either diaphragm or bell) should be placed on the bare skin of
the antecubital fossa, directly over where the brachial artery is palpated.

• 7. The clinician should listen for Korotkoff sounds with the stethoscope. The first
phase of Korotkoff sounds is the initial presence of clear tapping sounds. Note the
pressure at the first recognition of these sounds. This is the SBP. As pressure
deflates, note the pressure when all sounds disappear, right at the last sound. This
is the DBP.

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Measuring BP

8. Measurements should be rounded up to the nearest 2 mm Hg (eg, 145 mm Hg

rounded up to 146 mm Hg).

9. A second measurement should be obtained after at least 1 minute. If the two

measurements (SBP and/or DBP) differ by more than 5 mm Hg.

10. When first establishing care with a patient, BP should be measured in both arms.
If consistent inter-arm differences exist, the arm with the higher value should be
used.

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Treatment

• Overall Goal of Treatment

• The overall goal of treating hypertension is to reduce morbidity and mortality

from CV events (eg, coronary events, cerebrovascular events, HF) and kidney
disease.

• Therefore, the specific selection of antihypertensive drug therapy should be based

on evidence demonstrating a reduction in morbidity and mortality, not merely a
reduction in BP.

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Surrogate Targets—Blood Pressure Goals

• Treating patients with hypertension to achieve a desired goal BP is a surrogate

goal of therapy.

• Reducing BP to goal does not guarantee prevention of hypertension-associated

complications, but is associated with a lower risk.

• Targeting a goal BP is how clinicians evaluate response to therapy.

• It is the primary method that is used to determine the need for titration and
regimen modification.

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Surrogate Targets—Blood Pressure Goals

• The 2017 ACC/AHA guideline recommends a goal BP of <130/80 mm Hg for the

management of hypertension in most patients

• The American Diabetes Association recommends a goal of <140/90 mm Hg for

most patients with diabetes, with a lower goal of <130/80 mm Hg for certain
individuals (eg, those at high risk of ASCVD) if achieved without undue treatment
burden.

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Surrogate Targets—Blood Pressure Goals

• The Kidney Disease Improving Global Outcomes (KDIGO) guidelines

recommend a BP goal of ≤140/90 mm Hg for patients with hypertension and CKD
(nondialysis), with a lower BP goal of ≤130/80 mm Hg only for those patients
who have persistent albuminuria (≥30 mg urine albumin excretion per 24 hours or
equivalent) as a therapeutic option.

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Surrogate Targets—Blood Pressure Goals

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General Approach to Treatment

• Most patients should be placed on both lifestyle modifications and drug

therapy concurrently after a diagnosis of hypertension is made

• Lifestyle modification alone is appropriate for most patients with

prehypertension.

• lifestyle modifications alone may not be adequate for patients with

hypertension and either additional CV risk factors or hypertension-
associated target-organ damage

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General Approach to Treatment

• The threshold when drug therapy should be started for these low-risk patients is
when the BP is ≥140/90 mm Hg with a goal BP of <130/80 mm Hg.

• For patients with stage 1 or 2 hypertension who already have ASCVD (secondary
prevention) or who have an elevated 10-year ASCVD risk ≥10% (including most
patients with diabetes and most patients with CKD), the threshold for starting drug
therapy is ≥130/80 mm Hg with a goal BP of <130/80 mm Hg.

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Nonpharmacologic Therapy

• All patients with elevated blood pressure and hypertension should be prescribed
lifestyle modifications.

• However, they should never be used as a replacement for antihypertensive drug

therapy for patients with hypertension who are not at goal BP.

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Lifestyle Modifications to Prevent and Manage Hypertension

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Pharmacologic therapy

• Lowering systolic blood pressure by 10–12 mmHg and diastolic blood pressure by
5–6 mmHg confers relative risk reductions of

35–40% for stroke .

12–16% for CHD within 5 years of the initiation of treatment

heart failure >50%

hypertension control is the single most effective intervention for slowing the rate
of progression of hypertension-related kidney disease

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Choice of antihypertensive drugs

• Selection and combinations of antihypertensive agents should be individualized,

taking into account

- Age

- severity of hypertension,

- Other cardiovascular disease risk factors

- comorbid conditions

- practical considerations related to cost, side effects , and frequency of dosing

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Pharmacologic therapy………

The choice of initial drug therapy depends on the degree of BP elevation, age, race and
presence of compelling indications
6 major compelling indications

Heart Failure

Post Myocardial Infarction

High Coronary Disease Risk

Diabetes Mellitus

Chronic Kidney Disease

Recurrent Stroke Prevention

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Pharmacologic therapy

Compelling Indications

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Compelling Indications

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Certain combination therapies have synergistic effects &/or are proven
regimens

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Pharmacologic therapy……..

• An ACEi, ARB, CCB, or a thiazide are the preferred first-line antihypertensive

agents for most patients.

• These agents should be used to treat the majority of patients with hypertension
because of evidence demonstrating CV event reduction.

• β-Blocker therapy should be reserved to either treat a specific compelling

indication or used in combination with one or more of those mentioned above
first-line antihypertensive agents for patients without a compelling indication.

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Pharmacologic therapy

• Other antihypertensive drug classes are considered alternative drug classes that
may be used in select patients after implementing first-line agents.

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Diuretics

• Exact hypertensive mechanism unknown

• Initial BP drop caused by diuresis

• reduced plasma & stroke volume decreases CO and BP
• causes compensatory increase in peripheral vascular resistance

• Extracellular & plasma volume return to near pretreatment levels with chronic use
• peripheral vascular resistance becomes lower than pretreatment values
• results in chronic antihypertensive effects

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Reabsorption of solutes and water

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Diuretics

• Thiazide

• chlorthalidone, hydrochlorothiazide (HCTZ), indapamide, metolazone

• Loop

• bumetanide, furosemide, torsemide

• Potassium-sparing

• amiloride, triamterene

• Aldosterone antagonists
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• eplerenone, spironolactone
Thiazide diuretics

• Dose in morning to avoid nocturnal diuresis

• Adverse effects:
• hypokalemia, hypomagnesemia, hypercalcemia, hyperuricemia,
hyperglycemia, hyperlipidemia, sexual dysfunction
• lithium toxicity with concurrent administration

• More effective antihypertensives than loop diuretics unless CrCl < 30 mL/min

• Chlorthalidone 1.5 to 2 times as potent as HCTZ

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Loop diuretics

• Dose in AM or afternoon to avoid nocturnal diuresis

• Higher doses may be needed for patients with severely decreased glomerular
filtration rate or heart failure

• Adverse effects:

• hypokalemia, hypomagnesemia, hypocalcemia, hyperuricemia

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Potassium sparing diuretics

Dose in AM or afternoon to avoid nocturnal diuresis

Generally reserved for diuretic-induced hypokalemia patients
Weak diuretics, generally used in combination with thiazide diuretics to minimize
hypokalemia
Adverse effects:
may cause hyperkalemia especially in combination with an ACE inhibitor,
angiotensin-receptor blocker or potassium supplements
avoid in patients with CKD or diabetes

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Aldosterone antagonists
• Dose in AM or afternoon to avoid nocturnal diuresis
• Due to increased risk of hyperkalemia, eplerenone contraindicated in CrCl < 50
mL/min & patients with type 2 diabetes & proteinuria
• Adverse effects:
• may cause hyperkalemia especially in combination with ACE inhibitor,
angiotensin-receptor blocker or potassium supplements
• avoid in CKD or DM patients
• Gynecomastia: up to 10% of patients taking spironolactone
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Diuretics for hypertension

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Angiotensin-Converting Enzyme Inhibitors (ACEi)

• First line for most patients

Block angiotensin I to angiotensin II conversion

ACE (Angiotensin Converting Enzyme) distributed in many tissues

primarily endothelial cells

blood vessels: major site for angiotensin II production

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Angiotensin-Converting Enzyme Inhibitors

Block bradykinin degradation; stimulate synthesis of other

vasodilating substances such as prostaglandin E2 & prostacyclin

Prevent or regress left ventricular hypertrophy by reducing

angiotensin II myocardial stimulation

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Angiotensin-Converting Enzyme Inhibitors

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ACE inhibitors

• Monitor serum K+ & SCr within 4 weeks of initiation or dose increase

• Adverse effects:
• cough
• up to 20% of patients
• due to increased bradykinin
• angioedema (lip and tongue swelling, laryngeal edema and possibly difficulty
breathing)..blacks and smokers
• hyperkalemia: particularly in patients with CKD or DM

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ACE inhibitors

• neutropenia, agranulocytosis, proteinuria, glomerulonephritis, acute renal failure

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ARBS

• Angiotensin II Receptor Blockers

• Angiotensin II generation
• renin-angiotensin-aldosterone pathway
• alternative pathway using other enzymes such as chymases

• Inhibit angiotensin II from all pathways

• directly block angiotensin II type 1 (AT1) receptor
• ACE inhibitors partially block effects of angiotensin II

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ARBS

• Do not block bradykinin breakdown

• less cough than ACE Inhibitors

• Adverse effects:

• orthostatic hypotension

• renal insufficiency

• hyperkalemia

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ACE Inhibitor/ARB Warnings
• Reduce starting dose 50% in some patients due to hypotension risk
• patients also taking diuretic
• volume depletion
• elderly patients
• May cause hyperkalemia in:
• CKD patients
• patients on other K+ sparing medications
• K+ sparing diuretics
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ACE Inhibitor/ARB Warnings

• Can cause acute kidney failure in certain patients

• severe bilateral renal artery stenosis

• severe stenosis in artery to solitary kidney

• Pregnancy category C in 1st trimester

• Pregnancy category D in 2nd & 3rd trimester

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Renin Inhibitor

• 1st agent FDA approved in 2007: aliskiren

• Inhibits angiotensinogen to angiotensin I conversion

• FDA approved as monotherapy & combination therapy with other

antihypertensives

• Efficacy demonstrated with other antihypertensives including amlodipine, HCTZ,

ACEIs/ARBs

• Does not block bradykinin breakdown

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• less cough than ACE Inhibitors
RENIN INHIBITORS

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B –Blockers

• Inhibit renin release

• weak association with antihypertensive effect

• Negative chronotropic & inotropic cardiac effects reduce CO

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B-Blockers

• Adverse effects:
• bradycardia
• atrioventricular conduction abnormalities
• acute heart failure
• abrupt discontinuation may cause rebound hypertension or unstable angina,
myocardial infarction, & death in patients with high coronary disease risk
• bronchospastic pulmonary disease exacerbation
• may aggravate intermittent claudication, Raynaud’s phenomenon

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B-Receptors

• Distributed throughout the body

• concentrate differently in certain organs & tissues

• β1 receptors:

• heart, kidney

• stimulation increases HR, contractility, renin release

• β2 receptors:

• lungs, liver, pancreas, arteriolar smooth muscle

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• stimulation causes bronchodilation & vasodilation
Cardioselective β-Blockers

• Greater affinity for β1 than β2 receptors

• inhibit β1 receptors at low to moderate dose
• higher doses block β2 receptors

• Safer in patients with bronchospastic disease, peripheral arterial disease, diabetes

• may exacerbate bronchospastic disease when selectivity lost at high doses
• dose where selectivity lost varies from patient to patient

• Generally preferred β-blockers for HTN

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β-Blockers

• Cardioselective

• atenolol, betaxolol, bisoprolol, metoprolol, nebivolol

• Nonselective

• nadolol, propranolol, timolol

• Mixed α- and β-blockers

• carvedilol, labetolol

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Nonselective β-Blockers

• Inhibit β1 & β2 receptors at all doses

• Can exacerbate bronchospastic disease

• Additional benefits in:

• essential tremor

• migraine headache

• thyrotoxicosis

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Mixed α- & β-blockers

• Carvedilol reduces mortality in patients with systolic HF treated with diuretic &
ACE inhibitor

• Adverse effects:

• additional blockade produces more orthostatic hypotension

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Calcium channel blockers

• Calcium Channel Blockers

• Inhibit influx of Ca2+ across cardiac & smooth muscle cell membranes
• muscle contraction requires increased free intracellular Ca2+ concentration
• CCBs block high-voltage (L-type) Ca2+ channels resulting in coronary &
peripheral vasodilation
• dihydropyridines vs non-dihydropyridines
• different pharmacologically
• similar antihypertensive efficacy
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Calcium channel blockers
• Dihydropyridines:
• amlodipine, felodipine, isradipine, nicardipine, nifedipine, nisoldipine,
clevidipine
• Non-dihydropyridines:
• diltiazem, verapamil
• Adverse effects of non-dihydropyridines:
• bradycardia
• atrioventricular block
• systolic HF
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Calcium channel blockers

• Dihydropyridines:
• baroreceptor-mediated reflex tachycardia due to potent vasodilating effects
• do not alter conduction through atrioventricular node
• not effective in supraventricular tachyarrhythmias

• Non-dihydropyridines:
• decrease HR, slow atrioventricular nodal conduction
• may treat supraventricular tachyarrhythmias

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Non-dihydropyridine CCBs

• ER products preferred for HTN

• Block cardiac SA & AV nodes: reduce HR

• May produce heart block

• Not AB rated as interchangeable/equipotent due to different release mechanisms &

bioavailability

• Additional benefits in patients with atrial tachyarrhythmia

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Dihydropyridine CCBs

• Avoid short-acting dihydropyridines

• particularly IR nifedipine, nicardipine

Dihydropyridines more potent peripheral vasodilators than nondihydropyridines

may cause more reflex sympathetic discharge: tachycardia, dizziness,

headaches, flushing, peripheral edema

Effective in older patients with isolated systolic HTN

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Dihydropyridine CCBs

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α1-Blockers
• Not appropriate monotherapy for HTN
• Inhibit smooth muscle catecholamine uptake in peripheral
vasculature: vasodilation & BP lowering
• Adverse effects:
• orthostatic hypotension
• 1st dose phenomenon: transient dizziness, faintness, palpitations, syncope
within 1 to 3 hours of 1st dose
• lassitude, vivid dreams, depression
• priapism
• Na+/H2O retention

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α1-Blockers

• 1st dose at bedtime

• Used with diuretics to minimize edema

• Caution in elderly patients

• Reduce benign prostatic hypertrophy symptoms

• block postsynaptic α1-adrenergic receptors on the prostate
• relaxation
• decreased urinary outflow resistance

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Central α2-Agonists

• Stimulate α2-adrenergic receptors in the brain

• reduces sympathetic outflow from the brains vasomotor center

• increases vagal tone

• peripheral stimulation of presynaptic α2-receptors may further reduce

sympathetic tone

• decrease HR, CO, TPR, plasma renin activity, baroreceptor activity

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Central α2-Agonists
• Adverse effects:
• sodium/water retention
• abrupt discontinuation may cause rebound HTN
• depression
• orthostatic hypotension
• dizziness
• Clonidine: anticholinergic side effects
• Methyldopa: can cause hepatitis, hemolytic anemia (rare)

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Central α2-Agonists
• Most effective if used with a diuretic
• minimizes fluid retention

• Use caution in elderly patients

• Clonidine transdermal patch: placed weekly

• may result in fewer adverse effects
• avoids high peak serum drug concentrations
• delayed onset: 2 to 3 days
• overlap with PO formulation at initiation/discontinuation

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Direct Arterial Vasodilators
• Direct arterial smooth muscle relaxation causes antihypertensive effect (little or no
venous vasodilation)

• reduce impedence to myocardial contractility

• potent reductions in perfusion pressure activate baroreceptor reflexes

• baroreceptor activation: compensatory increase in sympathetic outflow;

tachyphylaxis can cause loss of antihypertensive effect
• counteract with concurrent β-blocker

• clonidine if β-blocker contraindicated

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Direct Arterial Vasodilators

• Adverse effects:

• sodium/water retention

• angina

• Hydralazine can cause lupus-like syndrome

• Minoxidil can cause hypertrichosis

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Orthostatic Hypotension

• Decrease in SBP > 20 mmHg or DBP > 10 mmHg when changing from supine to
standing position

• Older patients with isolated systolic hypertension at risk at initiation of drug

therapy

• Prevalent with diuretics, ACE inhibitors, ARBs

• Treatment should remain the same with low initial doses & gradual dose titrations

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Hypertensive Crisis
• BP > 180/120 mmHg
• reduce gradually

• Hypertensive urgency
• elevated BP
• no acute or progressing target-organ injury

• Hypertensive emergency
• acute or progressing target-organ damage
• encephalopathy, intracranial hemorrhage, acute left ventricular failure with pulmonary edema, dissecting aortic
aneurysm, unstable angina, eclampsia

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Combination Therapy

• Most patients require > 2 agents to control BP

• A thiazide-type diuretic should be one of these agents unless contraindicated

• Combination regimens should include a diuretic (preferably a thiazide)

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Resistant hypertension

• Patients failing to achieve goal BP despite adherence to optimal doses

of three antihypertensive agents of different classes (ideally, one being
a diuretic) have resistant hypertension
• Or when four or more antihypertensive drugs are needed to achieve
BP control
• should be evaluated for secondary causes of hypertension

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Resistant hypertension

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Resistant hypertension

there are treatment philosophies that are germane to the management of resistant
hypertension:

(a) assuring adequate diuretic therapy

(b) appropriate use of combination therapy,

(c) using alternative antihypertensive agents when needed.

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Hypertension in Pregnancy

• Hypertension during pregnancy is a major cause of maternal and neonatal

morbidity and mortality

• Hypertension during pregnancy is categorized as

• preeclampsia-eclampsia,

• chronic hypertension (of any cause),

• chronic hypertension superimposed preeclampsia,

• gestational hypertension

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Hypertension in Pregnancy

• Preeclampsia is defined as hypertension (elevated BP ≥140/90 mm Hg on more

than two occasions at least 4 hours apart after 20 weeks’ gestation or ≥160/110
mm Hg confirmed within a short interval) in association with
thrombocytopenia,impaired liver function, new-onset renal insufficiency,
pulmonary edema, or new-onset cerebral or visual disturbances.

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Hypertension in Pregnancy

• It can lead to life-threatening complications for both mother and fetus.

• Eclampsia, the onset of convulsions in preeclampsia, is a medical emergency

• Chronic hypertension is hypertension that predates pregnancy; superimposed

preeclampsia is chronic hypertension associated with preeclampsia

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Hypertension in Pregnancy

• Gestational hypertension is defined as new-onset hypertension arising after 20

weeks of gestation in the absence of proteinuria or other systemic findings (eg,
thrombocytopenia, renal insufficiency, pulmonary edema, cerebral or visual
disturbances).

• Definitive treatment of preeclampsia is delivery.

• Labor induction is indicated if pending or frank eclampsia is present

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Hypertension in Pregnancy
• Labetalol, long-acting nifedipine, or methyldopa is recommended as a first-line
agent due to favorable safety profile.

• Other β-blockers (not atenolol) and CCBs are also reasonable alternatives.

• An ACEi, an ARB, and a direct renin inhibitor are known teratogens and are
absolutely contraindicated.

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Treatment of Chronic Hypertension in Pregnancy

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Hypertension in Older People

• Hypertension often presents as isolated systolic hypertension in older patients.

• Epidemiologic data indicate that CV morbidity and mortality are more directly
correlated to SBP than to DBP for patients aged 50 and older.

• This population is also at high risk for hypertension-associated complications.

• Older patients are more sensitive to volume depletion and sympathetic inhibition
than younger patients

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Hypertension in Older People

• (JNC 8) recommended a less strict BP goal of <150/90 mm Hg in patients older

than 60 years.

• A recent meta-analysis examining the risks and benefits of lower BP compared to

a“relaxed” goal of <150 mm Hg found similar results

• Therefore, based on the totality of evidence older, ambulatory patients should be

treated to a SBP goal of <130 mm Hg

• The treatment of hypertension in older patients should follow the same principles
that are outlined for general care of hypertension.
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Hypertension in Older People

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Routine Monitoring for Select Antihypertensive Agents

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Case studies

• Case #1.
You are seeing a 60-year-old man for the first time. He has untreated hypertension (168/106 mm
Hg and blood pressure has been elevated on at least 3 occasions). There is currently no evidence of
target organ dysfunction (heart, neurological, or eye grounds).

• From a therapeutic perspective, what is the best initial approach?

• A. Initiate treatment with 25 mg of hydrochlorothiazide.

• B. Consider initiating treatment with a 2-agent combination pill.

• C. Delay pharmacologic intervention and treat with salt restriction.

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Case studies
• Case #2.
You evaluate a woman with chronic hypertension whose blood pressure remains above target
despite a daily regimen of benazepril 20 mg, chlorthalidone 25 mg, and amlodipine 10 mg. Your
next step should be:

A. Add an agent from another class, such as hydralazine or clonidine.

B. Characterize the patient as having resistant hypertension and initiate therapy with 25 mg of
spironolactone (potassium levels permitting).

C. Add an ARB.

D. Switch from amlodipine to verapamil.

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 Thank you!!!!

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