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B. Mo.B. Mo.

IntroIntro

Arterial BP

Cardiac OutputPeripheralResistance

Heart Rate ContractilityFilling

PressureArteriolarVolume

Blood Volume Venous Tone

Hypertension

Systolic BloodPressure (SBP)

Diastolic BloodPressure (DBP)

>140 mmHg >90 mmHg

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ContCont……

Categories ofHypertension

Normal< )120< / 80(

Prehypertension )120-139 / 80-89(

Stage 1 Hypertension

)140-159 / 90-99(

Stage 2 Hypertension

)≥160 / ≥100(

MainComplications

Congestive HeartFailure

MyocardialInfarction

Renal DamageCerebrovascular

Accidents

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ContCont……Types of

Hypertension

Essential Secondary

A disorder of unknown origin affecting theBlood Pressure regulating mechanisms

Secondary to other disease processes

Environmental Factors

Stress Na+ Intake Obesity Smoking

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Mechanisms for Controlling Mechanisms for Controlling BPBP

BaroreflexesBaroreflexesRenin-Angiotensin-aldosteron Renin-Angiotensin-aldosteron systemsystem

MediatedMediated

ByBy

The sympathetic NSThe sympathetic NSThe kidneyThe kidney

ResponsibleResponsible

forfor

Rapid, moment-to-moment Rapid, moment-to-moment regulationregulation

Long-term controlLong-term control

Place ofPlace of

receptorsreceptors

Aortic archAortic arch & &

carotid sinusescarotid sinuses

The kidneyThe kidney

MechanismMechanism

A fall in Blood Pressure causes the A fall in Blood Pressure causes the baroreceptors to send impulses to baroreceptors to send impulses to the cardiovascular centers which the cardiovascular centers which

willwill::

Sympathetic & parasympatheticSympathetic & parasympathetic

outputoutput

The baroreceptors in the kidney The baroreceptors in the kidney will activate the Renin-will activate the Renin-

Angiotensin-aldosteron system, Angiotensin-aldosteron system, which will causewhich will cause::

-- Vasoconstriction by angiotensin IIVasoconstriction by angiotensin II

-- renal sodium reabsorptionrenal sodium reabsorption& &

blood volume by aldosteroneblood volume by aldosterone

Treatment StrategiesTreatment Strategies The goal of antihypertensive therapy is to reduceThe goal of antihypertensive therapy is to reduce cardiovascularcardiovascular && renalrenal

morbidity and mortality.morbidity and mortality.

Usually we use one drugUsually we use one drug (thiazide diuretic)(thiazide diuretic) unless it is inadequate tounless it is inadequate to control the blood pressure so we add a second drugcontrol the blood pressure so we add a second drug ((ββ-blocker)-blocker) and maybe and maybe thirdthird (vasodilator)(vasodilator)..

Individualized Care:Individualized Care: some people respond better to one class of drug than they do to another: some people respond better to one class of drug than they do to another: 1) Black patients:1) Black patients: respond well torespond well to diureticsdiuretics && Ca++ channel blockersCa++ channel blockers,, but but ββ-blocker-blocker oror ACE inhibitorsACE inhibitors is less effective. is less effective.

2) Elderly:2) Elderly: respond well torespond well to ACE inhibitorsACE inhibitors && diureticsdiuretics, while , while ββ--blockerblocker && αα-antagonists-antagonists are less tolerated. are less tolerated.

3) Concomitant diseases:3) Concomitant diseases: hypertension may coexist with other diseaseshypertension may coexist with other diseases that can be aggravated by the drugs that can be aggravated by the drugs (f 19.4)(f 19.4)..

ContCont……

Patient Compliance:Patient Compliance:

-- Lack of patient complianceLack of patient compliance is the most common reason for failure ofis the most common reason for failure of

antihypertensive therapy.antihypertensive therapy.

- Therapy is generally to- Therapy is generally to preventprevent the disease rather than to relieving thethe disease rather than to relieving the

patient’s discomfort.patient’s discomfort.

- The main adverse affect between middle-aged & elderly men is- The main adverse affect between middle-aged & elderly men is

decreasing the libidodecreasing the libido and inducingand inducing impotenceimpotence..

DiureticsDiuretics Recommended as the Recommended as the first-linefirst-line drug therapy for hypertension. drug therapy for hypertension.

Diuretics are Diuretics are superiorsuperior to to ββ-blockers in older adults.-blockers in older adults.

DiureticsDiuretics

Thiazide Loop

[Ca ]++in urine [Ca ]++in urine

Used in patientswith inadequatekidney function

Renal vascularresistance

Renalblood flow

Thiazide DiureticsThiazide Diuretics Example:Example: hydrochlorothiazidehydrochlorothiazide . .

Action:Action: - lower BP by increasing Na+ & water - lower BP by increasing Na+ & water excretionexcretion.. - - SpironolactoneSpironolactone is often used with thiazides because it has the is often used with thiazides because it has the additional benefit of diminishing the cardiac remodelation. additional benefit of diminishing the cardiac remodelation.

Therapeutic uses:Therapeutic uses: - decrease BP in both - decrease BP in both supinesupine & & standingstanding position. position. (postural hypotension is rarely observed except in elderly)(postural hypotension is rarely observed except in elderly)

- Useful in - Useful in combinationcombination with other antihypertensive with other antihypertensive drugs that cause water & Na+ retention. drugs that cause water & Na+ retention.

- - Useful:Useful: black & elderly. black & elderly. Not useful:Not useful: patients with inadequate kidney function. patients with inadequate kidney function.

ContCont…… Pharmacokinetics:Pharmacokinetics: - - orallyorally active. active.

- absorption & elimination rates - absorption & elimination rates varyvary.. - may - may competecompete with uric acid for elimination. with uric acid for elimination. (ligands for the organic acid secretory system of the nephron) (ligands for the organic acid secretory system of the nephron)

AdverseEffects

Hypokalemia (70%)

Hyperuricemia) 70% (

Hyperglycemia) 10% (

Hypomagnesemia

K+ levels shouldbe monitored in

patients predisposedto cardiac arrhythmias

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