Hypertension Chapter 15

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Hypertension Chapter 15
Pharmacotherapy A Pathophysiologic Approach
The McGraw-Hill Companies
2
Abbreviations
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Overview

• Definition, classification of hypertension (HTN)
• Goals of therapy
• Compelling indications
• Lifestyle modifications
• Hypertension in pregnancy
• Treatment
• Orthostatic hypotension
• Hypertensive crisis
• Monitoring antihypertensive drug therapy

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Hypertension

• Persistent elevation of arterial blood pressure
  (BP)
• National Guideline
• 7th Report of the Joint National Committee on the
  Detection, Evaluation, and Treatment of High
  Blood Pressure (JNC7)
• 72 million Americans (31) have BP gt 140/90 mmHg
• Most patients asymptomatic
• Cardiovascular morbidity mortality risk
  directly correlated with BP antihypertensive
  drug therapy reduces cardiovascular mortality
  risk

Chobanian AV, Bakris GL, Black HR, et al. Seventh
report of the Joint National Committee on
Prevention, Detection, Evaluation, and Treatment
of High Blood Pressure. Hypertension
200342(6)12061252.
5
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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Etiology

• Essential hypertension
• gt 90 of cases
• hereditary component
• Secondary hypertension
• lt 10 of cases
• common causes chronic kidney disease,
  renovascular disease
• other causes Rx drugs, street drugs, natural
  products, food, industrial chemicals

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Causes of 2 Hypertension

• Diseases
• chronic kidney disease
• Cushing's syndrome
• coarctation of the aorta
• obstructive sleep apnea
• parathyroid disease
• pheochromocytoma
• primary aldosteronism
• renovascular disease
• thyroid disease

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Causes of 2 Hypertension

• Prescription drugs  
• prednisone, fludrocortisone, triamcinolone
• amphetamines/anorexiants phendimetrazine,
  phentermine, sibutramine
• antivascular endothelin growth factor agents
• estrogens usually oral contraceptives
• calcineurin inhibitors cyclosporine, tacrolimus
• decongestants phenylpropanolamine analogs
• erythropoiesis stimulating agents
  erythropoietin, darbepoietin

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Causes of 2 Hypertension

• Prescription drugs
• NSAIDs, COX-2 inhibitors
• venlafaxine
• bupropion
• bromocriptine
• buspirone
• carbamazepine
• clozapine
• ketamine
• metoclopramide

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Causes of 2 Hypertension

• Situations
• ß-blocker or centrally acting a-agonists
• when abruptly discontinued
• ß-blocker without a-blocker first when treating
  pheochromocytoma
• Food substances  
• sodium
• ethanol
• licorice

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Causes of 2 Hypertension

• Street drugs, other natural products  

• cocaine
• cocaine withdrawal
• ephedra alkaloids (e.g., ma-huang)
• herbal ecstasy
• phenylpropanolamine analogs
• nicotine withdrawal

• anabolic steroids
• narcotic withdrawal
• methylphenidate
• phencyclidine
• ketamine
• ergot-containing herbal products
• St. John's wort

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Mechanisms of Pathogenesis

• Increased cardiac output (CO)
• increased preload
• increased fluid volume
• excess sodium intake
• renal sodium retention
• venous constriction
• excess RAAS stimulation
• sympathetic nervous system overactivity

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Mechanisms of Pathogenesis

• Increased peripheral resistance (PR)
• functional vascular constriction
• excess RAAS stimulation
• sympathetic nervous system overactivity
• genetic alterations of cell membranes
• endothelial-derived factors
• structural vascular hypertrophy
• excess RAAS stimulation
• sympathetic nervous system overactivity
• genetic alterations of cell membranes
• endothelial-derived factors
• hyperinsulinemia due to obesity, metabolic
  syndrome

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Arterial Blood Pressure

• Sphygmomanometry indirect BP measurement
• MAP 1/3 (SBP) 2/3 (DBP)
• BP CO x TPR
• 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 Pressure Determinants
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Adult Classification
Chobanian AV, Bakris GL, Black HR, et al. Seventh
report of the Joint National Committee on
Prevention, Detection, Evaluation, and Treatment
of High Blood Pressure. Hypertension
200342(6)12061252.
18
Clinical Controversy

• White coat hypertension elevated BP in clinic
  followed by normal BP reading at home
• Aggressive treatment of white coat hypertension
  is controversial
• Patients with white coat hypertension may have
  increased CV risk compared to those without such
  BP changes

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Classification for Adults

• Classification based on average of gt 2 properly
  measured seated BP measurements from gt 2 clinical
  encounters
• If systolic diastolic blood pressure values
  give different classifications, classify by
  highest category
• gt 130/80 mmHg above goal for patients with
  diabetes mellitus or chronic kidney disease
• Prehypertension patients likely to develop
  hypertension

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Clinical Controversy

• Ambulatory BP measurements may be more accurate
  better predict target-organ damage than manual BP
  measurements using a sphygmomanometer in a clinic
  setting (gold standard)
• many patients may be misdiagnosed, misclassified
  
• poor technique, daily BP variability, white coat
  HTN
• Validated ambulatory BP monitoring role in the
  routine HTN management unclear

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Treatment Goals

• Reduce morbidity mortality
• Select drug therapy based on evidence
  demonstrating risk reduction

Chobanian AV, Bakris GL, Black HR, et al. Seventh
report of the Joint National Committee on
Prevention, Detection, Evaluation, and Treatment
of High Blood Pressure. Hypertension
200342(6)12061252.
22
2007 AHA Recommendations

• More aggressive BP lowering for high risk patients

Rosendorff C, Black HR, Cannon CP, et al.
Treatment of hypertension in the prevention and
management of ischemic heart disease A
scientific statement from the American Heart
Association Council for High Blood Pressure
Research and the Councils on Clinical Cardiology
and Epidemiology and Prevention. Circulation
2007115(21)27612788.
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ALLHAT

• Antihypertensive and Lipid-Lowering Treatment to
  Prevent Heart Attack Trial (ALLHAT)
• Primary endpoints
• fatal CHD
• nonfatal MI
• Secondary endpoints
• other hypertension-related complications
• HF
• stroke

ALLHAT Officers and Coordinators for the ALLHAT
Collaborative Research Group. Major outcomes in
high-risk hypertensive patients randomized to
angiotensin-converting enzyme inhibitor or
calcium channel blocker vs diuretic The
Antihypertensive and Lipid-Lowering Treatment to
Prevent Heart Attack Trial (ALLHAT). JAMA
2002288(23)29812997.
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ALLHAT

• Prospective, double-blind trial
• randomized patients to
• chlorthalidone
• amlodipine
• doxazosin
• lisinopril-based therapy
• 42,418 patients age gt 55 yr with HTN 1
  additional CV risk factor (mean subject
  participation 4.9 years)
• Thiazide-type diuretics remain unsurpassed for
  reducing CV morbidity mortality in most
  patients

ALLHAT Officers and Coordinators for the ALLHAT
Collaborative Research Group. Major outcomes in
high-risk hypertensive patients randomized to
angiotensin-converting enzyme inhibitor or
calcium channel blocker vs diuretic The
Antihypertensive and Lipid-Lowering Treatment to
Prevent Heart Attack Trial (ALLHAT). JAMA
2002288(23)29812997.
25
JNC7 Recommendations

• Thiazide-like diuretics preferred 1st line
  therapy based on clinical trials showing
  morbidity mortality reductions
• ALLHAT confirms 1st line role of thiazide
  diuretics
• Compelling indications comorbid conditions where
  specific drug therapies provide unique long-term
  benefits based on clinical trials
• drug therapy recommendations are in combination
  with or in place of a thiazide diuretic

Chobanian AV, Bakris GL, Black HR, et al. Seventh
report of the Joint National Committee on
Prevention, Detection, Evaluation, and
Treatment of High Blood Pressure.
Hypertension 200342(6)12061252.
26
Clinical Controversy

• Avoiding Cardiovascular Events through
  COMbination Therapy in Patients LIving with
  Systolic Hypertension (ACCOMPLISH)
• Endpoint composite of death from CV causes,
  hospitalization for angina, nonfatal MI or
  stroke, coronary revascularization,
  resuscitation after cardiac arrest
• Prospective, double-blind, industry sponsored
  trial
• randomized patients to benazepril amodipdine or
  benazepril HCTZ
• 11,506 patients with HTN high CV risk
• Combination benazepril amlodipine superior to
  benazepril HCTZ for reducing CV events in high
  risk patients

Jamerson KA, Weber MA, Bakris GL, et al.
Benazepril plus amlodipine or hydrochlorothiazide
for hypertension. N Engl J Med.
2009359(23)2417-2428.
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Compelling Indications

• Heart Failure
• Post Myocardial Infarction
• High Coronary Disease Risk
• Diabetes Mellitus
• Chronic Kidney Disease
• Recurrent Stroke Prevention

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Recommendations Evidence

• Strength of recommendations
• A good, B moderate, C poor
• Quality of evidence
• 1 more than 1 properly randomized, controlled
  trial
• 2 at least 1 well-designed clinical trial with
  randomization cohort or case-controlled analytic
  studies dramatic results from uncontrolled
  experiments or subgroup analyses
• 3 opinions of respected authorities, based on
  clinical experience, descriptive studies, or
  reports of expert communities

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ACE angiotensin-converting enzyme ARB
angiotensin receptor blocker CCB calcium
channel blocker DBP diastolic blood pressure
SBP systolic blood pressure
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Lifestyle Modifications
DASH, Dietary Approaches to Stop Hypertension. a
Effects of implementing these modifications are
time and dose dependent and could be greater for
some patients.
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells
BG, Posey LM PharmacotherapyA Pathophysiologic
Approach, 7th Edition http//www.accesspharmacy.c
om/
32
Clinical Controversy

• Prehypertension patients do not have HTN but at
  risk for developing it
• Trial of Preventing Hypertension (TROPHY) showed
  treating prehypertension with candesartan
  decreased progression to stage 1 hypertension
• Unknown whether managing prehypertension with
  drug therapy and lifestyle modifications
  decreases CV events or if this approach is
  cost-effective

Julius S, Nesbitt SD, Egan BM, et al. Feasibility
of treating prehypertension with an
angiotensin-receptor blocker. N Engl J Med
2006354(16)16851697.
33
Hypertension in Pregnancy

• Important to differentiate preeclampsia from
  chronic, transient, gestational hypertension
• Preeclampsia gt140/90 mmHg after 20 weeks
  gestation with proteinuria
• restricted activity, bed rest, close monitoring
  beneficial
• definitive treatment delivery
• Methyldopa drug of choice

34
Chronic HTN in Pregnancy
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells
BG, Posey LM PharmacotherapyA Pathophysiologic
Approach, 7th Edition http//www.accesspharmacy.c
om/
35
Diuretics

• Exact hypotensive 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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Diuretics

• Thiazide
• chlorthalidone, hydrochlorothiazide (HCTZ),
  indapamide, metolazone
• Loop
• bumetanide, furosemide, torsemide
• Potassium-sparing
• amiloride, triamterene
• Aldosterone antagonists
• eplerenone, spironolactone

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Thiazide Diuretics

• Dose in morning to avoid nocturnal diuresis
• Adverse effects
• hypokalemia, hypomagnesemia, hypercalcemia,
  hyperuricemia, hyperuricemia, hyperglycemia,
  hyperlipidemia, sexual dysfunction
• lithium toxicity with concurrent administration
• More effective antihypertensives than loop
  diuretics unless CrCl lt 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, 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 lt 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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ACE Inhibitors

• 2nd line to diuretics 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
• 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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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
• hyperkalemia particularly in patients with CKD
  or DM
• 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
• aldosterone antagonists

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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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Clinical Controversy

• CV events risk further reduced when ARB combined
  with an ACE inhibitor for patients with left
  ventricular dysfunction
• Data supports ACE/ARB combination therapy for
  patients with severe forms of nephrotic syndrome
• Combination ACE/ARB therapy not well studied as
  standard treatment for HTN
• Significantly higher risk of adverse effects such
  as hyperkalemia

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Clinical Controversy

• ONgoing Telmisartan Alone and in combination with
  Ramipril Global Endpoint Trial (ONTARGET)
• Endpoint composite of death, dialysis, SCr
  doubling
• Prospective, randomized, multicenter,
  double-blind trial patients randomized patients
  to ramipril, telmisartan, combination of both
• 25,620 patients gt age 55 yr with diabetes
  end-organ damage or established atherosclerotic
  vascular disease
• Combination therapy reduces proteinuria more than
  monotherapy but worsens major renal outcomes

Mann JF, Schmieder RE, McQueen M, et al. Renal
outcomes with telmisartan, ramipril, or both, in
people at high vascular risk (the ONTARGET
study) a multicentre, randomised, double-blind,
controlled trial. Lancet 2008372547-543.
51
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
• less cough than ACE Inhibitors
• Adverse effects orthostatic hypotension,
  hyperkalemia

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ß-Blockers

• Inhibit renin release
• weak association with antihypertensive effect
• Negative chronotropic inotropic cardiac effects
  reduce CO
• ß-blockers with intrinsic sympathomimetic
  activity (ISA)
• do not reduce CO
• lower BP
• decrease peripheral resistance
• Membrane-stabilizing action on cardiac cells at
  high enough doses

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ß-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,
  Raynauds phenomenon

55
ß-Receptors

• Distributed throughout the body
• concentrate differently in certain organs
  tissues
• ß1 receptors
• heart, kidney
• stimulation increases HR, contractility, renin
  release
• ß2 receptors
• lungs, liver, pancreas, arteriolar smooth muscle
• stimulation causes bronchodilation vasodilation
  
• mediate insulin secretion glycogenolysis

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Cardioselective ß-Blockers

• Greater affinity for ß1 than ß2 receptors
• inhibit ß1 receptors at low to moderate dose
• higher doses block ß2 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 ß-blockers for HTN

57
ß-Blockers

• Cardioselective
• atenolol, betaxolol, bisoprolol, metoprolol,
  nebivolol
• Nonselective
• nadolol, propranolol, timolol
• Intrinsic sympathomimetic activity
• acebutolol, carteolol, penbutolol, pindolol
• Mixed a- and ß-blockers
• carvedilol, labetolol

58
Nonselective ß-Blockers

• Inhibit ß1 ß2 receptors at all doses
• Can exacerbate bronchospastic disease
• Additional benefits in
• essential tremor
• migraine headache
• thyrotoxicosis

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Intrinsic sympathomimetic activity

• Partial ß-receptor agonists
• do not reduce resting HR, CO, peripheral blood
  flow
• No clear advantage except patients with
  bradycardia who must receive a ß-blocker
• Contraindicated post-myocardial infarction for
  patients at high risk for coronary disease
• May not be as cardioprotective as other
  ß-blockers
• Rarely used

60
Clinical Controversy

• Meta-analyses suggest ß-blocker based therapy may
  not reduce CV events as well as other agents
• Atenolol t½ 6 to 7 hrs yet it is often dosed
  once daily
• IR forms of carvedilol metoprolol tartrate have
  6- to 10- 3- to 7-hour half-lives respectively
  always dosed at least BID
• Findings may only apply to atenolol
• may be a result of using atenolol daily instead
  of BID

61
Mixed a- ß-blockers

• Carvedilol reduces mortality in patients with
  systolic HF treated with diuretic ACE inhibitor
• Adverse effects
• additional blockade produces more orthostatic
  hypotension

62
CCBs

• 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

63
CCBs

• Dihydropyridines
• amlodipine, felodipine, isradipine, nicardipine,
  nifedipine, nisoldipine, clevidipine
• Non-dihydropyridines
• diltiazem, verapamil
• Adverse effects of non-dihydropyridines
• bradycardia
• atrioventricular block
• systolic HF

64
CCBs

• 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

65
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

66
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
• Additional benefits in Raynauds syndrome
• Effective in older patients with isolated
  systolic HTN

67
a1-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

68
a1-Blockers

• 1st dose at bedtime
• Used with diuretics to minimize edema
• Caution in elderly patients
• Reduce benign prostatic hypertrophy symptoms
• block postsynaptic a1-adrenergic receptors on the
  prostate
• relaxation
• decreased urinary outflow resistance

69
Central a2-Agonists

• Stimulate a2-adrenergic receptors in the brain
• reduces sympathetic outflow from the brains
  vasomotor center
• increases vagal tone
• peripheral stimulation of presynaptic
  a2-receptors may further reduce sympathetic tone
• decrease HR, CO, TPR, plasma renin activity,
  baroreceptor activity

70
Central a2-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)

71
Central a2-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/disconti
  nuation

72
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 ß-blocker
• clonidine if ß-blocker contraindicated

73
Direct Arterial Vasodilators

• Adverse effects
• sodium/water retention
• angina
• Hydralazine can cause lupus-like syndrome
• Minoxidil can cause hypertrichosis

74
Reserpine

• Peripheral adrenergic antagonist
• depletes norephinephrine from sympathetic nerve
  endings blocks norephinephrine transport into
  storage granules
• reduces norephinephrine release into synapse
  following nerve stimulation
• reduced sympathetic tone
• peripheral vascular resistance reduction
• decreased BP
• depletes catecholamines from brain myocardium
• Maximum antihypertensive effect 2 to 6 weeks

75
Reserpine

• Adverse effects
• sedation
• depression
• decreased CO
• sodium/water retention
• increased gastric acid secretion
• diarrhea
• bradycardia
• Use with diuretic (preferably thiazide) to avoid
  fluid retention

76
Direct Arterial Vasodilators

• Use with diuretic (preferably thiazide)
  ß-blocker to reduce fluid retention reflex
  tachycardia
• minoxidil
• more potent vasodilator
• hydralazine

77
Orthostatic Hypotension

• Decrease in SBP gt 20 mmHg or DBP gt 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

78
Hypertensive Crisis

• BP gt 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

79
Hypertensive Emergency
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells
BG, Posey LM PharmacotherapyA Pathophysiologic
Approach, 7th Edition http//www.accesspharmacy.c
om/
80
Hypertensive Emergency
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells
BG, Posey LM PharmacotherapyA Pathophysiologic
Approach, 7th Edition http//www.accesspharmacy.c
om/
81
Monitoring Antihypertensives
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells
BG, Posey LM PharmacotherapyA Pathophysiologic
Approach, 7th Edition http//www.accesspharmacy.c
om/
82
Combination Therapy

• Most patients require gt 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)
• Resistant hypertension failure to achieve BP
  goal on full doses of 3 drug regimen including a
  diuretic

83
Acknowledgements

• Prepared By/Series Editor April Casselman,
  Pharm.D.
• Editor-in-Chief Robert L. Talbert, Pharm.D.,
  FCCP, BCPS, FAHA
• Chapter Authors Joseph J. Saseen, Pharm.D.,
  FCCP, BCPS
• Eric J. Maclaughlin, Pharm.D., BS Pharm
• Section Editor Robert L. Talbert, Pharm.D.,
  FCCP, BCPS, FAHA