1. Pharmacologic
Management of
Hypertension &CHF
John A. Kenna, MS, ACNP
Assistant Clinical Professor
University of Rhode Island
3/25/2014

2. Overview
 Cardiac Output/Venous Return
 Hypertension
 Heart Failure

3. Cardiac Output
 CO= HR x SVR
 Cardiac 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

4. Normal Values for Cardiac
Output
 Varies widely with the level of activity
 The following factors directly affect CO
 Basic level of body metabolism
 Whether the person is exercising
 Age
 Size of the body
 Young healthy men resting CO about 5.6L/min
 For women, about 4.9L/min

5. Cardiac Index
 CI = 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

6. Control of Heart Rate (HR)
 The SA node of the heart is innervated by both sympathetic
and parasympathetic nerves
 Parasympathetic fibers release acetylcholine
 Decrease HR
 Sympathetic release norepinephrine and release of
epinephrine from the adrenal medulla.
 Increase HR

7. 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 volume
 increase in sympathetic system activity

8. Control of Cardiac Output by
Venous Return
 This means it is NOT the heart itself that is the primary
controller of CO
 Peripheral factors usually more important in controlling CO
 Heart will pump regardless the amount of blood flowing into
the right atrium
 Frank-Starling law
 As a result of increased quantities of volume the heart will stretch
and eject blood with increased force
 Stretch of the right atrium with stretch the sinus node and
increase heart rate (remember for Afib)

9. End-diastolic Volume
 End- diastolic Volume: Volume of blood in the ventricles
at the end of diastole
 Larger end-diastolic volume will stretch the heart
 Stretching the muscles of the heart optimizes the
length-strength relationship of cardiac fibers, resulting
in stronger contractility and greater stroke volume

10. Frank Starling Law

12. Regulation of Blood Volume by
the Kidneys
 Regulation of water excretion directly affects blood volume
 Regulated by the kidneys, controlled by anitdiuretic
hormone (ADH)
 ADH
 Produced by the hypothalamus and secreted by the posterior
pituitary
 Regulated by hypothalamus based on plasma osmolality

13. Regulation of Blood Flow
 Blood flow = Pressure / Resistance
 If pressure in a vessel increases flow will increase
 However if resistance in vessel increases flow will decrease
 Resistance in the vessels effected by:
 Length of the vessel (the longer the vessel the greater the
resistance
 Viscosity of the blood (greater the viscosity the greater
the resistance
 Radius of the vessel (smaller the radius the greater the
resistance

14. Regulation of Blood Flow
 Extrinsic regulation
 Sympathetic control of arteriolar radius
 Norepinephrine causes vasoconstriction
 Vasodilation accomplished by decreased sympathetic
stimulation
 Endocrine control of arteriolar radius
 Epinephrine secreted by adrenals in response to sympathetic
response
 Intrinsic regulation
 Some organs regulate their own blood flow regardless of
what is happening elsewhere

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

18. Mean Arterial Pressure
 Average blood pressure in an individual
 3 most important variables effecting MAP
 Total peripheral resistance
 Cardiac output
 Blood volume
MAP= (COxSVR) + CVP
MAP= ((2x DP) + SP)/3

19. Total Peripheral Resistance
(TPA)
 TPA refers to the sum of total vascular resistance to
flow of blood in the systemic circulation
 Arterioles given their small radii provide the greatest
resistance
 If resistance increases then pressure increases

20. Cardiac Output/Blood Volume
 CO 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 pressure
 As stroke volume goes up -> CO goes up -> BP rises

21. Summary of Factors the
Effect MAP

22. Baroreceptor Reflexes
Regulation of MAP
 Is controlled on a minute-to-minute basis by
baroreceptor reflexes
 Specialized stretch receptors located in the carotid
sinus and aorta
 Communicate with the brain stem to normalize BP

23. Baroreceptor Response in
Increased BP

24. EPIDEMIOLOGY
 HTN AFFECTS ABOUT 58 MILLION AMERICANS
 33.5% non-Hispanic blacks
 28.9% non-Hispanic whites
 20% 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

25. Hypertension

26. Objectives
 Describe drug therapy options for chronic and acute
hypertension
 Explain the clinical pharmacology of commonly used
antihypertensive drugs

27. Chronic Hypertension
 Primary or “essential”
 No identifiable cause
 Also know as essential HTN
 Accounts for ~90% of cases
 Secondary
 Identifiable cause
 CRI, Cushing’s, pheochromocytoma, oral
contraceptives, etc.

28. Causes of Hypertension
 ESSENTIAL HYPERTENSION
● MEDICATION NONCOMPLIANCE/UNDERTREATED
 SECONDARY HYPERTENSION
● AORTIC COARCTATION
● CUSHING’S SYNDROME
● ELEVATED ICP
● SLEEP APNEA
● RENAL DYSFUNCTION/OBSTRUCIVE UROPATHY
● PREGNANCY
● HYPERPARATHYROIDISM
● HYPERTHYROIDISM
● PHEOCHROMOCYTOMA
● PRIMARY ALDOSTERONISM
● MEDICATIONS-(OC’S, MOAI’S, TCA’S, STEROIDS, NSAIDS, NASAL
DECON, COLD REMEDIES AND COCAINE, APPITITE SUPPRESS)
● DC OF MEDS (BB, CLONIDINE)
● SPINAL CORD DISORDERS (GUILLAIN BARRE)
● POST –OP-(Cardiovascular)

29. Risk Factors
 Age > 60 years
 Male gender
 Smoking
 Diabetes
 Family history
 Heart failure
 PVD
 Hyperlipidemia
 Renal Disease

30. Mechanism of Hypertension
 Intravascular Volume
 Autonomic Nervous System
 Renin-Angiotensin-Aldosterone
 Vascular Mechanisms

31. Intravascular Volume
• BP = CO x Peripheral Vascular Resistance
• Autoregulation: (ie. Kidneys and Brain)
If constant blood flow is to be maintained in the face of
increased arterial pressure, resistance within that bed must
increase
– Initial  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)

32. Intravascular Volume
 “Pressure- Natriuresis”
 Increased urinary excretions of sodium along with water to
maintain normal BP
 Involves subtle increase in GFR
 Decreased absorbing capacity in renal tubules
 Hormonal factor (atrial natriuretic factor/peptide)

33. Autonomic Nervous System
 Maintains cardiovascular hemostasis via:
 Pressure, Volume, Chemoreceptor signals
 3 endogenous catecholamines
 Norepinephrine
 Epinephrine
 Dopamine
 Alpha & Beta receptors 1,2

36. Hypertension
 Diagnosis
 A sustained elevation of SBP ≥ 140mm Hg or DBP ≥ 90 at
least 3 times on two different occasions.

37. Systolic BP Diastolic BP
Normal < 120 < 80
Prehypertension 121-139 80-89
Stage 1 140-159 90-99
Stage 2 160 100
Blood Pressure Classification

38. Treatment Goals
 Prevent end-organ damage
 Reduce risk of cardiovascular events
 Maintain SBP < 140 and DBP < 90 mmHg

39. Hypertension
 Target Organ Damage
 Independent predisposing factor for heart
failure, coronary artery disease, stroke, renal
disease, and peripheral artery disease

40. Hypertension
 Heart
 Heart disease is most common cause of death in
hypertensive patients
 Structural Damage
 LVH
 Diastolic dysfunction
 CHF
 CAD
 Arrhythmias

41. Hypertension
 Brain
 Important risk factor for infarction and hemorrhage
 Incidence of stroke increases with increase in BP
 Treatment decreases incidence of both ischemic and
hemorrhagic stroke
 Associated with impaired cognition in aging
population
 May cause hypertensive encephalopathy
 Can lead to stupor, coma, seizures, death

42. Hypertension
 Kidney
 Risk factor for renal injury and ESRD
 The atherosclerotic, HTN-related vascular lesions
 Resulting in glomerular ischemia and atrophy
 Macro (urine albumin/creatinine ratio >300 mg/g) and
microalbuminuria (30-300 mg/g)

43. Hypertension
 Peripheral Arteries
 May be asymptomatic
 Intermittent claudication
 Aching pain in calves relieved by rest

44. Lifestyle Modifications
 Diet
 DASH diet rich in fruit, vegetables and low-fat dairy foods
 Reduce sodium intake to 2.4 grams/day
 Limit alcohol consumption
 Exercise
 Aerobic and weight-bearing activity
 Stop smoking!

45. Drug Dosing
 “Start low and go slow!”
 No need to drop BP immediately unless in an
emergency

46. Hypertensive Emergencies and Urgencies
 “Emergencies” (>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

47. Goals of Therapy
 Reduce 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

48. Management
 Use parental drugs for HTN emergency:
 Enalaprilat
 Esmolol
 Fenoldopam
 Labetalol
 Nicardipine
 Nitroglycerin
 Nitroprusside
 Phentolamine
 Use fast-acting, oral agents for HTN urgency:
 Loop diuretics
 BBs and CCBs
 ACE-Is
 Alpha-2 agonists (clonidine)