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Done byDone by
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
****************************************************
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
****************************************************
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
****************************************************
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
Done byDone by
B. Mo.B. Mo.