Hypertension

Pharmacologic Management of Hypertension &CHF

John A. Kenna, MS, ACNPAssistant Clinical ProfessorUniversity of Rhode Island3/25/2014

OverviewCardiac Output/Venous Return

Hypertension

Heart Failure

Cardiac OutputCO= HR x SVRCardiac output: The quantity of blood pumped into the aorta each minute by the heart Also the quantity of blood that flows through the circulation Perhaps the most important factor to consider in relation to circulation

Normal Values for Cardiac Output Varies widely with the level of activity The following factors directly affect COBasic level of body metabolismWhether the person is exercisingAgeSize of the bodyYoung healthy men resting CO about 5.6L/minFor women, about 4.9L/min

Cardiac IndexCI = CO/BSA

The CO per square meter of body surface area

The normal range of cardiac index in rest is 2.6 - 4.2 L/min per square meter

Control of Heart Rate (HR)The SA node of the heart is innervated by both sympathetic and parasympathetic nervesParasympathetic fibers release acetylcholineDecrease HRSympathetic release norepinephrine and release of epinephrine from the adrenal medulla. Increase HR

Control of Stroke Volume (SV)The ventricles of the heart empty only about 50% of their volume during systole.During periods of exercise, the heart fills up with more blood and the heart contracts more strongly. Stroke volume is increased by 2 mechanisms:increase in end-diastolic volumeincrease in sympathetic system activity

Control of Cardiac Output by Venous Return This means it is NOT the heart itself that is the primary controller of COPeripheral factors usually more important in controlling COHeart will pump regardless the amount of blood flowing into the right atriumFrank-Starling lawAs a result of increased quantities of volume the heart will stretch and eject blood with increased forceStretch of the right atrium with stretch the sinus node and increase heart rate (remember for Afib)

End-diastolic VolumeEnd- diastolic Volume: Volume of blood in the ventricles at the end of diastoleLarger end-diastolic volume will stretch the heartStretching the muscles of the heart optimizes the length-strength relationship of cardiac fibers, resulting in stronger contractility and greater stroke volume

Frank Starling Law

Regulation of Blood Volume by the KidneysRegulation of water excretion directly affects blood volumeRegulated by the kidneys, controlled by anitdiuretic hormone (ADH)ADHProduced by the hypothalamus and secreted by the posterior pituitary Regulated by hypothalamus based on plasma osmolality

Regulation of Blood FlowBlood flow = Pressure / ResistanceIf pressure in a vessel increases flow will increaseHowever if resistance in vessel increases flow will decreaseResistance in the vessels effected by:Length of the vessel (the longer the vessel the greater the resistanceViscosity of the blood (greater the viscosity the greater the resistanceRadius of the vessel (smaller the radius the greater the resistance

Of all of the factors that effect blood flow, the radius of the blood vessel is the most potent. Blood flow is proportional to the 4th power of vessel radius. This means that if the radius of a blood vessel doubles (by vasodilation) then the flow will increase 16 fold (2 to the 4th power is 16). On the other hand, if the radius of a vessel is reduce in half (by vasoconstriction), then the blood flow will be reduced 16 fold13

Regulation of Blood FlowExtrinsic regulation Sympathetic control of arteriolar radiusNorepinephrine causes vasoconstriction Vasodilation accomplished by decreased sympathetic stimulationEndocrine control of arteriolar radiusEpinephrine secreted by adrenals in response to sympathetic responseIntrinsic regulationSome organs regulate their own blood flow regardless of what is happening elsewhere

Effect of Peripheral Resistance on the Long-Term COCO= Arterial Pressure/Total Peripheral ResistanceUnder most normal conditions the long term cardiac output level varies reciprocally with changes in total peripheral resistanceAs resistance increase the CO decreases and vice versa

Mean Arterial PressureAverage blood pressure in an individual3 most important variables effecting MAPTotal peripheral resistanceCardiac output Blood volume

MAP= (COxSVR) + CVPMAP= ((2x DP) + SP)/3

Total Peripheral Resistance (TPA)TPA refers to the sum of total vascular resistance to flow of blood in the systemic circulationArterioles given their small radii provide the greatest resistanceIf resistance increases then pressure increases

Cardiac Output/Blood VolumeCO is a measure of blood flow and directly proportional to pressure. Therefore an increase in CO will cause an increase in pressure (MAP)Blood volume is directly related to blood pressureAs stroke volume goes up -> CO goes up -> BP rises

Summary of Factors the Effect MAP

Baroreceptor Reflexes Regulation of MAPIs controlled on a minute-to-minute basis by baroreceptor reflexesSpecialized stretch receptors located in the carotid sinus and aortaCommunicate with the brain stem to normalize BP

Baroreceptor Response in Increased BP

EPIDEMIOLOGY HTN AFFECTS ABOUT 58 MILLION AMERICANS33.5% non-Hispanic blacks28.9% non-Hispanic whites20% in Mexican Americans

PREVALENCE OF HTN INCREASING AS THE POPULATION AGES

ESTIMATED ABOUT 1% OF HYPERTENSIVE PATIENTS WILL DEVELOP A HYPERTENSIVE EMERGENCY

UNABLE TO KNOW FOR SURE THE PERCENTAGE OF OCCURANCE OF HYPERTENSIVE URGENCY

ED PRESENTATION- 2-3% OF VISITS ANNUALLY 70% URGENCY, 3% EMERGENCY

BOTH ENVIRONMENTAL AND GENETIC FACTORS MAY CONTRIBUTE TO REGIONAL AND RACIAL VARIATIONS

HYPERTENSION IS EXTREMELY COMMON

Ed PRESENTATIONS 2-3 % OF ALL VISITS ANNUALLY, 70% URGENCY, 30 % EMERGENCY24

Hypertension

Objectives

Describe drug therapy options for chronic and acute hypertension

Explain the clinical pharmacology of commonly used antihypertensive drugs

Chronic HypertensionPrimary or essentialNo identifiable causeAlso know as essential HTNAccounts for ~90% of cases

SecondaryIdentifiable causeCRI, Cushings, pheochromocytoma, oral contraceptives, etc.

Causes of Hypertension ESSENTIAL HYPERTENSIONMEDICATION NONCOMPLIANCE/UNDERTREATEDSECONDARY HYPERTENSIONAORTIC COARCTATIONCUSHINGS SYNDROMEELEVATED ICPSLEEP APNEARENAL DYSFUNCTION/OBSTRUCIVE UROPATHYPREGNANCY HYPERPARATHYROIDISMHYPERTHYROIDISMPHEOCHROMOCYTOMAPRIMARY ALDOSTERONISMMEDICATIONS-(OCS, MOAIS, TCAS, STEROIDS, NSAIDS, NASAL DECON, COLD REMEDIES AND COCAINE, APPITITE SUPPRESS)DC OF MEDS (BB, CLONIDINE)SPINAL CORD DISORDERS (GUILLAIN BARRE)POST OP-(Cardiovascular)

ALPHA ADRENERGIC AGONISTS Causes:The most common hypertensive emergency is a rapid unexplained rise in BP in a patient with chronic essential HTN. Other causes include: Renal parenchymal disease - Chronic pyelonephritis, primary glomerulonephritis, tubulointerstitial nephritis (accounts for 80% of all secondary causes); Systemic disorders with renal involvement - Systemic lupus erythematosus, systemic sclerosis, vasculitides; Renovascular disease - Atherosclerotic disease, fibromuscular dysplasia, polyarteritis nodosa; Endocrine - Pheochromocytoma, Cushing syndrome, primary hyperaldosteronism; Drugs - Cocaine, amphetamines, cyclosporin, clonidine withdrawal, phencyclidine, diet pills, oral contraceptive pills.Drug interactions - Monoamine oxidase inhibitors with tricyclic antidepressants, antihistamines, or tyramine- containing food; CNS - CNS trauma or spinal cord disorders, such as Guillain-Barr syndrome; Coarctation of the aorta; Preeclampsia/eclampsia; Postoperative hypertension.SLEEP APNEA

Sci-pts are prone to autonomic overactivity syndrome manifested by severe htn, bradycardia, HA and diaphoresis The syndrome is triggered by stimulation of dermatomes or muscles innervated by nerves below the sc lesion28

Risk FactorsAge > 60 yearsMale genderSmokingDiabetesFamily historyHeart failurePVDHyperlipidemiaRenal Disease

Mechanism of HypertensionIntravascular VolumeAutonomic Nervous SystemRenin-Angiotensin-AldosteroneVascular Mechanisms

Intravascular Volume

BP = CO x Peripheral Vascular ResistanceAutoregulation: (ie. Kidneys and Brain)If constant blood flow is to be maintained in the face of increased arterial pressure, resistance within that bed must increaseInitial in BP is in response to vascular volume due to increased CO; however reverts back to normal over time (peripheral resistance remains elevated likely to due to epithelial damage)

Intravascular VolumePressure- NatriuresisIncreased urinary excretions of sodium along with water to maintain normal BPInvolves subtle increase in GFRDecreased absorbing capacity in renal tubulesHormonal factor (atrial natriuretic factor/peptide)

Autonomic Nervous SystemMaintains cardiovascular hemostasis via:Pressure, Volume, Chemoreceptor signals3 endogenous catecholamines NorepinephrineEpinephrineDopamineAlpha & Beta receptors 1,2

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HypertensionDiagnosisA sustained elevation of SBP 140mm Hg or DBP 90 at least 3 times on two different occasions.

Systolic BPDiastolic BPNormal< 120< 80Prehypertension121-13980-89Stage 1140-15990-99Stage 2 160 100

Blood Pressure Classification

Treatment Goals

Prevent end-organ damage

Reduce risk of cardiovascular events

Maintain SBP < 140 and DBP < 90 mmHg

HypertensionTarget Organ DamageIndependent predisposing factor for heart failure, coronary artery disease, stroke, renal disease, and peripheral artery disease

HypertensionHeartHeart disease is most common cause of death in hypertensive patientsStructural DamageLVHDiastolic dysfunctionCHFCADArrhythmias

HypertensionBrainImportant risk factor for infarction and hemorrhageIncidence of stroke increases with increase in BPTreatment decreases incidence of both ischemic and hemorrhagic strokeAssociated with impaired cognition in aging populationMay cause hypertensive encephalopathy Can lead to stupor, coma, seizures, death

HypertensionKidneyRisk factor for renal injury and ESRDThe atherosclerotic, HTN-related vascular lesionsResulting in glomerular ischemia and atrophyMacro (urine albumin/creatinine ratio >300 mg/g) and microalbuminuria (30-300 mg/g)

HypertensionPeripheral ArteriesMay be asymptomaticIntermittent claudicationAching pain in calves relieved by rest

Lifestyle ModificationsDietDASH diet rich in fruit, vegetables and low-fat dairy foodsReduce sodium intake to 2.4 grams/dayLimit alcohol consumption

ExerciseAerobic and weight-bearing activity

Stop smoking!

Drug Dosing

Start low and go slow!

No need to drop BP immediately unless in an emergency

Hypertensive Emergencies and UrgenciesEmergencies (>180/120)Require immediate BP reduction to limit target organ damage (TOD)Encephalopathy, ICH, AMI, pulmonary edema, aortic aneurysm, eclampsia, etc.

Urgencies (>180/120)Reduce BP over 1-2 days to prevent TOD

Goals of TherapyReduce MAP by no more than 25% (within 2 minutes to 2 hours)

Achieve BP of 160/90 within 6 hours (drastic drops in BP may induce ischemia)

Elevated BP alone without target organ damage or symptoms rarely requires emergency therapy

ManagementUse parental drugs for HTN emergency:EnalaprilatEsmololFenoldopamLabetalolNicardipineNitroglycerinNitroprussidePhentolamine

Use fast-acting, oral agents for HTN urgency:Loop diureticsBBs and CCBs ACE-IsAlpha-2 agonists (clonidine)