Principles of Pharmacotherapy in Hypertension

.
.., Pharm.D., Ph.D.

1.
(cardiovascular diseases)
2.

3. the Seventh
Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood
Pressure (JNC 7)
4.

(compelling indications)

5.

6.

7.

(hypertension)
systolic / diastolic 140/90 mm Hg

..
2545 1 7.1
Prospective Studies Collaboration
Group ( 1 2) meta-analysis

observational studies 61
ischemic heart disease stroke
systolic 115 mm
Hg diastolic 75 mm Hg (40-89 )
systolic 20 mm
Hg diastolic 10 mm Hg

1 10

2|Page

 2 10

hemodynamic parameters 2
cardiac output (CO) total peripheral resistance (TPR) 2 parameters
arterial blood pressure (ABP) ABP = CO x TPR
CO ABP 3 Cardiac output (
) (heart rate)
(stroke volume)
heart rate
sympathetic parasympathetic
stroke volume
(ventricular force of contraction cardiac contractility
) (venous return)
(venous capacitance)
(intravascular volume)
Venous capacitance

intravascular volume

(total
peripheral resistance) 2 (arteriolar radius)
(blood viscosity)
(local regulation) (regional regulation) (systemic regulation)
TPR
3|Page

3
early response, intermediate response late response
1. Early response
sympathetic parasympathetic

Venous capacitance
Force of contraction

Venous Return
Intravascular volume

Stroke Volume

Cardiac Output

Heart Rate

Total Peripheral Resistance

ARTERIAL BLOOD PRESSURE

3

baroreceptor
vasomotor center brainstem (medulla)
sympathetic outflow
TPR () CO
( heart rate venous capacitance) sympathetic
outflow parasympathetic outflow
baroreceptor reflex
chemoreceptor reflex volume receptor reflex
2. Intermediate response
renin-angiotensin-aldosterone system (RAAS) antidiuretic hormone (ADH)
hypothalamus renin (
afferent arteriole baroreceptor reflex, sympathetic outflow macula
4|Page

densa)
Renin angiotensinogen
angiotensin I angiotensin II angiotensin converting enzyme (ACE)

Angiotensin II
aldosterone

ADH hypothalamus
baroreceptor reflex angiotensin II
3. Late response



arterial pressure CO TPR



2
1. Primary hypertension
(no identifiable cause) 90-95%
primary hypertension
2. Secondary hypertension
(lesion)
oral contraceptives, oral decongestants
secondary hypertension 1
Primary hypertension secondary
hypertension (risk factors) primary hypertension 2

1. (Hereditary factors)

(genetic defect)

5|Page

 1 secondary hypertension
Renal and Genitourinary Disease
Renoparenchymal disease
Renovascular disease
Chronic kidney disease
Obstructive uropathy

Vascular causes
Coarctation of Aorta
Vasculitis

Endocrine causes
Primary aldosteronism
Pheochromocytoma
Thyrotoxicosis

Neurogenic causes
Psychogenic
Increased intracranial pressure

Drug-induced causes
Adrenocorticosteroids
Monoamine oxidase inhibitors
Alcohol
Non-steroidal anti-inflammatory drugs
Appetite suppressants
Oral contraceptives
Cyclosporine
Oral decongestants
Estrogens
Tacrolimus
Erythropoietin
Tricyclic antidepressants (TCAs)

- sodium
- sodium/calcium transport

- angiotensinogen renin
catecholamines, insulin, endothelin (receptor)
2. (environmental factors) (smoking),
(obesity) (hyperlipidemia), (excessive salt intake),
(physical inactivity), (emotional stress),
(excessive alcohol intake)
primary hypertension 4

6|Page

 Defect in sodium excretion

Defect in sodium/calcium transport of smooth muscle cell
Defect causing increased in humoral factors e.g. angiotensin II, renin,
catecholamines, insulin, endothelin or their receptors

+
Excess salt intake

Salt and water retention

Increased vascular reactivity

Increased plasma &

extracellular fluid volume

Vasoconstriction

Increased cardiac output

autoregulation

Increased total peripheral

resistance

HYPERTENSION
4 Hypothetical theory for pathogenesis of primary hypertension

target organ damage
atherosclerosis
arteriosclerosis
(cardiac hypertrophy)

arteriosclerosis afferent arteriole,

glomerulosclerosis (tubulointerstitial injury)
2

7|Page

Ischemic heart disease (angina, myocardial infarction)

Heart failure
Left ventricular hypertrohy

Cerebrovascular disease (stroke, transient ischemic attack)

Hypertensive encephalopathy
Dementia

Chronic nephrosclerosis

Hypertensive retinopathy

Peripheral arterial disease

Dissecting aortic aneurysm

systolic pressure diastolic
pressure systolic diastolic pressure pulse
pressure 50 mm Hg aorta
(aortic compliance) pulse pressure

systolic pressure diastolic

pressure systolic pressure/diastolic pressure 140/90 ( /
over) mean arterial pressure
(MAP)
MAP = diastolic pressure + 1/3 pulse pressure

8|Page

 ()
sphygmomanometry sphygmomanometer
brachial artery
(cuff) stethoscope
cuff systolic pressure
turbulent flow
Korotkoff sound
systolic blood pressure (SBP) cuff
diastolic blood pressure (DBP)
diastolic pressure Korotkoff sound auscultatory method
systolic palpatory method
SBP radial artery stethoscope
cuff SBP DBP palpatory method

non-mercury sphygmomanometer

JNC 7 3

5 sphygmomanometer

9|Page

 (blood pressure classification) JNC 7

4 4
2 (visit) 1
SBP DBP category category
category 160/92
stage 2 hypertension prehypertension

prehypertension
(lifestyle modification)
hypertension
140/90 mm Hg stage 1 2
(target organ damage)
JNC 7
5
isolated
systolic hypertension SBP 140 mm Hg DBP
90 mm Hg SBP
50 SBP DBP
diastolic hypertension 50 systolic hypertension
50 SBP

JNC 7 Antihypertensive and
Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Controlled Onset Verapamil
Investigation of Cardiovascular Endpoints (CONVINCE) DBP
90 SBP 6070
(primary care physicians) 75 SBP
140-159 mm Hg SBP 140 mm Hg
DBP SBP
SBP
JNC7
European Society of Hypertension (ESH) European Society of Cardiology (ESC) 6

10 | P a g e

 3 JNC 7



30

5

cuff
cuff bladder 80%
cuff
SBP palpatory method radial artery
auscultatory method cuff palpatory method 2030 mm Hg
(cuff deflation) 2 mm Hg Korotkoff sound
2 systolic pressure
diastolic pressure
2 2 2
5 mm Hg

(postural hypotension) postural
hypotension
postural hypotension

4 18 JNC 7
BP classification
Normal
Prehypertension
Stage 1 hypertension
Stage 2 hypertension

SBP (mm Hg)

<120
120-139
140-159
160

DBP (mm Hg)

<80
80-89
90-99
100

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 5
target organ damage

(mm Hg)
Normal
Prehypertension

Stage 1 hypertension

Stage 2 hypertension

2
1
( )
target
organ damage
2

1
180/110 mm Hg
1

6 18 ESH/ESC
BP classification

Optimal
Normal
High normal
Stage 1 hypertension
Stage 2 hypertension
Stage 3 hypertension
Isolated systolic hypertension

SBP (mm Hg)

<120
120-129
129-139
140-159
160-179

DBP (mm Hg)

<80
80-84
85-89
90-99
100-109

180

/
/
/
/
/

140

90

110

12 | P a g e


(1) (identifiable cause) (2)
target organ damage
(3)

target organ damage
(vital signs) JNC 7 optic fundi, body mass index
(BMI), auscultation carotid artery , abdominal aorta, femoral artery
, ,

blood chemistry
sodium, potassium, glucose, blood urea nitrogen (BUN), creatinine, calcium, magnesium, lipid profile

urinary albumin excretion albumin-to-creatinine ratio



serum thyroid
thyroid disease
6 target organ damage JNC
7

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 6 target organ damage

( 55 65 )

LDL-C ( total cholesterol) HDL-C

(estimated GFR) 60 ml/
( 55
65 )
albumin (microalbuminuria)
(BMI 30 kg/m2) ()
(physical inactivity)

Target organ damage

Left ventricular hypertrophy
Angina/myocardial infarction
Prior coronary revascularization
Heart failure
Stroke/transient ischemic attack
Dementia
Chronic kidney disease
Peripheral arterial disease
Retinopathy

1

1. 45 3 5
1 BP 140/98 mm Hg
2 BP 150/100 mm Hg
3 BP 146/98 mm Hg
BUN 12 mg/dL, Scr 1.1 mg/dL, Total cholesterol 180 mg/dL HDL-C 55 mg/dL, LFTs: within
normal limit

2. 46 2 5
1 BP 152/100 mm Hg

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 2 BP 150/96 mm Hg

3. 42 2 5
160/100 mm Hg 3 5

1 BP 152/98 mm Hg
2 BP 146/92 mm Hg
3 BP 154/100 mm Hg

4. 220/120 mm Hg

5. 45 ST-depression inverted
T-wave 200/110 mm Hg troponin T (+)
6. 40 2 5 130/80 mm Hg
total cholesterol 210 mg/dL, triglyceride 200 mm Hg, HDL-C 35 mg/dL, FBS 118 mg/dL, electrolytes
are within normal limit

(goal of therapy) (1)

(2)
(goal blood pressure)

140/90 mm
Hg (chronic kidney disease)
130/80 mm Hg JNC 7 National Kidney Foundation
Guideline
140/80 mm Hg American Diabetes Association
.. 2013
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 JNC 7
140/90 mm Hg
( 120/80 mm Hg normal blood pressure)


European Society of Cardiology/European Society of Cardiology (2007)

130/80 (World Health
Organization)
130/80
target organ damage







(lifestyle modification)
JNC 7 7




7

JNC 7
6 8

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DASH

BMI 18.5-22.9* kg/m2

saturated fat
100 (2.4 6
)

aerobic 30

30

720 (4.5%), 300 (10%), 90 80proof (40%)

systolic BP
5-20 mm Hg
10 kg
8-14 mm Hg
2-8 mm Hg
4-9 mm Hg
2-4 mm Hg

DASH = Dietary Approach to Stop Hypertension Sacks FM, et al. Effects on blood pressure of reduced dietary sodium and the
Dietary Approaches to Stop Hypertension (DASH) diet. N Engl J Med. 2001; 344: 3-10.
* JNC 7 BMI 18.5-24.9 kg/m2

17 | P a g e

<140/90 mmHg <130/80 mmHg

Stage 1 hypertension
- Thiazide diuretics

thiazides
ACEIs,
ARBs, BBs, CCBs
- 2
thiazide

Stage 2 hypertension
- 2
thiazide diuretics
ACEIs,
ARBs, BBs CCBs

(
10)

( diuretics, ACEIs, ARBs,
BBs, CCBs)

1
6 (algorithm) JNC 7

18 | P a g e

()

12.5-25
12.5-50
1.25-2.5

1
1
1

Hypokalemia, Hypomagnesemia,
Hyperuricemia, Hyperglycemia,
Dyslipidemia, Impotence

Loop diuretics
Bumetanide
Furosemide

0.5-2
2080

1-2
1-2

Hypokalemia, Hypomagnesemia,
Hyperuricemia, Hyperglycemia, Impotence

Potassium-sparing diuretics
Amiloride
Triamterene

5-10
50-100

1-2
1-2

Hyperkalemia, Impotence

Aldosterone receptor antagonists

Eplerenone
Spironolactone

50-100
25-50

1
1

Hyperkalemia, Gynecomastia

Beta-blockers (BBs)
Atenolol
Bisoprolol
Metoprolol
Propranolol
Propranolol long-acting

25-100
2.5-10
50-200
40-160
60-180

1
1
1-2
2-3
1

Bradycardia, Bronchoconstriction,
Hyperglycemia, Dyslipidemia,
Negative inotropic effect,
Decreased peripheral blood flow,
Impotence, Masking hypoglycemia
symptoms in diabetes

1-16
2-20
1-20

1
2-3
1-2

First-dose hypotension,
Orthostatic hypotension,
Dizziness, Headache, Edema

12.5-50

200-800

First-dose hypotension,
Orthostatic hypotension, Dizziness,
Bronchoconstriction, Hyperglycemia
Bradycardia

Thiazide diuretics
Chlorthalidone
Hydrochlorothiazide
Indapamide

Alpha-1-blockers
Doxazosin
Prazosin
Terazosin
Combined alpha- and beta-blockers
Carvedilol

Labetalol

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 8 ()

Calcium channel blockers (CCBs)-Dihydropyridines

Amlodipine
Felodipine
Isradipine
Nicardipine long acting
Nifedipine long acting
Calcium channel blockers (CCBs)Nondihydropyridines
Diltiazem long acting
Verapamil long acting
Verapamil

()

2.5-10
2.5-20
2.5-10

1
1
2

Headache,
Dizziness,
Orthostatic hypotension,
Peripheral edema

60-120
30-60

2
1

120-540
120-480
80-320

1
1-2
2-3

Bradycardia, Dizziness, Headache,

Peripheral edema
Constipation ( verapamil),
Negative inotropic effect

Angiotensin-converting enzyme inhibitors (ACEIs)

Captopril
Enalapril
Fosinopril
Lisinopril
Peridopril
Quinapril
Ramipril
Angiotensin receptor blockers (ARBs)
Candesartan
Irbesartan
Losartan
Telmisartan
Valsartan

25-100
5-40
10-40
10-40
4-8
10-80
2.5-20

2-3
1-2
1
1
1
1
1

Hyperkalemia,
Dry cough,
Taste disturbances,
Angioneurotic edema,
Worsening renal function

8-32
150-300
25-100
20-80
80-320

1
1
1-2
1
1-2

Hyperkalemia,
Worsening renal function

Direct rennin inhibitors

Aliskiren

150-300

Hyperkalemia (?)
Worsening renal function (?)

Arterial direct vasodilators

Hydralazine
MInoxidil

25-100
2.5-80

3-4
1-2

First-dose hypotension,
Orthostatic hypotension, Headache,
Dizziness, Tachycardia,
Peripheral edema,
Lupus-like syndrome (hydralazine),
Hirsutism (minoxidil)

20 | P a g e

 8 ()

()

0.1-0.8

Methyldopa

250-1000

Reserpine

0.1-0.25

Headache, Drowsiness, Rebound

hypertension upon sudden withdrawal
Headache, Sedation, Bradycardia,
Impotence, Hemolytic anemia,
Peripheral edema
Sedation, Depression,
Peptic ulcer disease

Centrally-acting agents
Clonidine

JNC7
6
(initial first-line
antihypertensive agents) 5 Thiazides, Beta-blockers (BBs), Calcium channel
blockers (CCBs), Angiotensin-converting-enzyme inhibitors (ACEIs) Angiotensin receptor blockers
(ARBs)
JNC7
( preferred initial antihypertensive agent) thiazide diuretics hydrochlorothiazide
stage 1 hypertension
thiazide diuretics
stage 2 hypertension 2 (
SBP 10 mm Hg)
1 thiazide diuretics (
ACEIs, ARBs, BBs CCBs thiazide diuretics) 1 2

1
thiazide ACEIs, ARBs, BBs CCBs ALLHAT 60
2 140/90 mm Hg 30
3

21 | P a g e

 1
(orthostatic hypotension)

autonomic dysfunction

1 1
2

JNC 7 thiazide diuretics (preferred initial
antihypertensive agent)
thiazides (ACEIs, ARBs, BBs, CCBs)

ALLHAT 40,000 thiazide-like diuretics
(chlorthalidone) ACEIs (lisinopril) CCBs
(amlodipine) thiazides ( 25 mg
hydrochlorothiazide)
hypokalemia impotence thiazide metabolic
adverse effects hyperglycemia, dyslipidemia hyperuricemia
thiazides
JNC 7 thiazide

European Society of Cardiology/European Society of Hypertension
(2007) ( preferred intial agent)
ACEIs, ARBs, BBs CCBs thiazide diuretics
thiazides beta-blocker
metabolic syndrome National Institute of Health and Clinical Excellence (NICE)
British Society of Hypertension
(.. 2011) ACEIs ARBs preferred initial agent
55 CCBs Thiazides preferred initial agent
55 2
( 9)

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 9 NICE guideline

compelling indication
JNC 7 (heart failure)
(post-myocardial infarction) (high coronary
disease risk) (stroke transient ischemic attack)



BBs, ACEIs aldosterone receptor blockers


BBs ACEIs aldosterone antagonists




10 JNC 7
23 | P a g e



1
stage 2


3 6 JNC 7 serum
creatinine serum potassium 1-2
10 JNC 7

Diuretics BBs
Heart failure

Post-myocardial
infarction
High coronary disease
risk
Diabetes
Chronic kidney
disease
Recurrent stroke
prevention

ACEIs ARBs

CCBs

Aldo
ANT

MERIT-HF, COPERNICUS, CIBIS, SOLVD, AIRE, TRACE,

ValHEFT, RALES, CHARM

BHAT, SAVE, CAPRICON, EPHESUS

ALLHAT, HOPE, ANBP2, LIFE, CONVINCE, EUROPA,

INVEST

UKPDS, ALLHAT
Captopril Trial, RENAAL, IDNT, REIN, AASK
PROGRESS

BB = beta-blockers, ACEI = angiotensin-converting enzyme inhibitors, ARB = angiotensin receptor blockers, CCB = calcium channel
blockers, Aldo ANT = aldosterone receptor antagonists

24 | P a g e


(HYPERTENSIVE PATIENTS WITH COMPELLING INDICATIONS)
stable coronary artery disease (CAD)



(angina) CAD
stable CAD
(1) (2)

stable CAD
BBs
BBs oxygen
demand heart rate cardiac contractility

CCBs 2 (1) CAD BBs
CCBs nondihydropyridines heart rate (2) CAD BBs
CCBs dihydropyridine CCBs BBs
negative inotropic negative chronotropic effects
CCBs
CAD (long-acting) (short-acting)
sympathetic outflow reflex tachycardia
ACEIs
ventricular systolic dysfunction ( ejection fraction < 40%) ACEIs
ACEIs
ARBs
(post-myocardial infarction; post-MI)

(coronary artery)


25 | P a g e




BBs

CCBs BBs
CCBs (long-acting)
(short-acting) sympathetic outflow BBs
CCBs non-dihydropyridines BBs
bradycardia negative inotropic effect 2 ( CCBs
10 post-MI
post-MI 2 )
ACEIs
ventricular systolic dysfunction ( ejection fraction 40%)
ACEIs
ACEIs ARBs
Aldosterone antagonists ventricular
systolic dysfunction (EF 40%)
eplerenone (EPHESUS trial)
(chronic heart failure)

(ventricular systolic dysfunction)

(
)

ACEIs, ARBs, BBs, diuretics, aldosterone antagonists.

26 | P a g e

ACEIs ACEIs
angioneurotic edema ARBs
Diuretics
loop diuretics
BBs
ACEIs diuretics
Aldosterone antagonists spironolactone
(NYHA class III-IV )
CCBs

( non-dihydropyridines verapamil, diltiazem)

systolic BP 110-130 mm Hg

2 insulin resistance





ACEIs, ARBs, BBs, CCBs,
diuretics
ACEIs ARBs
(renoprotective effects) ACEIs
ARBs

CCBs ACEIs ARBs

BBs hyperglycemia dyslipidemia

BBs
1 BBs 2 BBs
27 | P a g e

 (precaution)
BBs
Diuretics ALLHAT thiazide diuretics
ACEIs
CCBs
thiazides thiazide diuretics
hyperglycemia thiazides

American Diabetes Association
.. 2013 140/80 mm Hg ( 130/80 mm Hg ADA
130/80 mm Hg
)
(chronic kidney disease)
JNC 7
(1) 60 ml/min/1.73 m2
(2) albumin (albuminuria) 300
albumin creatinine (urinary albumin-to-creatinine ratio) 200
creatinine
(1) (2) National Kidney Foundation (NKF)
guideline (kidney damage) , renal imaging
study, urine protein urine sediment 3
GFR

(end-stage renal disease)

ACEIs ARBs
(diabetic nephropathy)
(proteinuria) ACEIs ARBs
diuretics loop diuretics (GFR 30 ml/min/1.73 m2)
CCBs BBs

28 | P a g e

 11 NKF

(
)

Diabetic kidney disease

Nondiabetic kidney disease
spot urine
protein-to-creatinine 200 mg/g
Nondiabetic kidney disease
spot urine
protein-to-creatinine <200 mg/g

ACEIs ARBs
ACEIs ARBs

diuretics BBs CCBs

diuretics BBs CCBs

diuretics ACEIs, ARBs,

BBs CCBs

CCB, diuretics, BBs, ACEIs, ARBs

Kidney disease

11
NKF
130/80 mm Hg
(cerebrovascular disease)

(ischemic stroke transient ischemic attack; TIA)
(hemorrhagic stroke)

35-40

(stroke TIA) JNC 7
thiazide diuretics ACEIs (PROGRESS trial)
American Stroke Association thiazides thiazides ACEIs

2

1. 35
PMH: asthma since childhood
SH: cigarette 1 pack per day, (-) EtOH
FH: 50
All: NKDA

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Meds: paracetamol PRN for headache, ENO 2

PE: Weight 75 kg Height 1.75 m, BP 145/95 mm Hg, RR 18, P 75 bpm, T 37.6 C
ROS are all non-contributory
143 98
12
Labs:
90
4.7

23

1.0

TC 190 mg/dL, TG 160 mg/dL, HDL 40 mg/dL

2. 45 (BP 150/100 mmHg)
HPI:
PMH: hypertension x 1 month
SH: (-) cigarette, (-) EtOH,
FH: non-contributory
All: NKDA
Meds: hydrochlorothiazide 12.5 mg PO AM
1-2
PE: Weight 75 kg Height 1.65 m, BP 144/94 mm Hg, RR 16, P 70 bpm
ROS are all non-contributory
Labs: all are within normal limit
3. 50 1

HPI:
PMH: hypertension x 5 , dyslipidemia x 5 , mild COPD x 2
SH: 1 , (-) EtOH,
FH: non-contributory
All: NKDA
Meds: Aspirin 80 mg PO AM, Atorvastatin 10 mg PO PM, Berodual Q6H PRN dyspnea

PE: BP 140/90 mm Hg, P 70 bpm
Labs: BUN 12 mg/dL, Scr 1.2 mg/dL
4.

58
(MI) 2
HPI: 2

PMH: hypertension, dyslipidemia, s/p MI

SH: (-) cigarette, (-) EtOH,
FH: non-contributory
All: NKDA
Meds: Aspirin 80 mg PO AM, Simvastatin 20 mg PO PM, Clopidogrel 75 mg PO AM, isosorbide mononitrate 60 mg PO
AM , Metoprolol 100 mg PO BID, Isosorbide dinitrate 5 mg SL PRN
PE: BP 146/90 mm Hg, P 70 bpm
Labs: BUN 14 mg/dL, Scr 1.1 mg/dL, ECHO (2 ):80%

30 | P a g e

5. 45 DM, hypertension, dyslipidemia

PMH: DM, hypertension, dyslipidemia
SH: (-) cigarette, (-) EtOH,
FH: non-contributory
All: NKDA
Meds: Aspirin 80 mg PO AM, Simvastatin 20 mg PO PM, HCTZ 25 mg PO AM, glipizide 5 mg PO BID
PE: Wt 76 kg, Ht 174 cm, P 70 bpm, BP 138/84 mm Hg ( 140/90 136/86 mm Hg)
143 98
16
Labs:
130
4.5

23

1.3

6. 60 chronic heart failure

HPI:
PMH: DM, hypertension, dyslipidemia, CHF (ECHO 35%)
SH: (-) cigarette, (-) EtOH,
FH: non-contributory
All: NKDA
Meds: Aspirin 80 mg PO AM, Simvastatin 40 mg PO PM, HCTZ 25 mg PO AM, Enalapril 10 mg PO BID,
Glimepiride 4 mg PO AM, pioglitazone 15 mg PO AM
PE: Wt 76 kg, Ht 172 cm, BP 138/86 mm Hg, P 75 bpm
Labs:
143 98
20
128
4.7

23

1.4

7. 50 chronic stable CAD

HPI:
PMH: DM, hypertension, dyslipidemia, stable angina
Meds: Aspirin 80 mg PO AM, Simvastatin 20 mg PO PM, Atenolol 100 mg PO AM,
Glipizide 5 mg PO AM, Metformin 850 mg PO BID, Isosorbide mononitrate 60 mg PO AM,
Isosorbide dinitrate 5 mg SL PRN,
PE: Wt 72 kg, Ht 172 cm, BP 142/90 mm Hg, P 65 bpm
Labs:
143
4.5

98
23

14
130
1.1

8. 60 chronic heart failure, chronic stable angina

HPI:
PMH: DM, hypertension, CHF (ECHO 30%), stable CAD
All: NKDA
Meds: Aspirin 80 mg PO AM, Furosemide 20 mg PO AM, Enalapril 10 mg PO BID, atenolol 100 mg PO AM,
Glimepiride 4 mg PO AM
143 98 20
PE: Wt 76 kg, Ht 174 cm, BP 140/86 mm Hg, P 70 bpm Labs:
128
4.7

23

1.4

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(OTHER SPECIAL SITUATIONS)
(pregnancy)


12

methyldopa BBs ACEIs ARBS
( stage 1
hypertension) target organ damage


preeclampsia

target organ damage

150 mm Hg systolic BP 100 mm Hg
diastolic BP (drug of first choice) methyldopa
BBs atenolol
(pregnancy category D) labetalol
()
methyldopa diuretics CCBs ACEIs
ARBs 2 3

32 | P a g e

 12
Chronic hypertension

BP 140 mm Hg systolic 90 mm Hg diastolic 20

12

Preeclampsia

BP 140 mm Hg systolic 90 mm Hg diastolic (proteinuria)

300 24 20
preeclampsia eclampsia eclampsia
4
preeclampsia

Chronic hypertension
with superimposed
preeclampsia

20
()

20

- 2-3
-
- (thrombocytopenia)
- AST ALT

Gestational
hypertension

20 proteinuria
temporary diagnosis preeclampsia

Transient hypertension

BP 12

(hypertensive crises)

1. (hypertensive emergency)
(BP > 180/120 mm Hg) target organ damage
hypertensive encephalopathy, intracerebral hemorrhage, acute myocardial infarction, acute left
ventricular failure with pulmonary edema, unstable angina pectoris, dissecting aortic aneurysm,
eclampsia

(mean arterial pressure) 25
1
160/100-110 mm Hg 2-6

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 160/100 mm Hg
24-48
rebound hypertension
13
2. (hypertensive urgency)
( DBP > 120
mm Hg) target organ damage
, , (epistaxis)

(non-compliance) (inadequate
therapy)
24-48
captopril, labetalol clonidine
( 1-2 )
DBP < 120 mm Hg

1-2 JNC 7


shorting-acting nifedipine

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 13

3
1. 52 Dyslipidemia, HTN, DM
EKG ST-depression acute coronary syndromes
BP 220/130 mmHg, RR 20, P 86, Temp 37.6 amlodipine 10 mg
AM, HCTZ 25 mg AM, glipizide 10 mg/day, aspirin 80 mg/day, atorvastatin 10 mg HS

2. 45 Dyslipidemia, HTN amlodipine 10 mg AM

BP
220/120 mmHg, RR 20, P 86, Temp 37.6
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Guidelines & Review Articles
Chobanian AV, Bakris GL, Black HR. et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation
and Treatment of High Blood Pressure. Hypertension. 2003; 42: 1206-52.
The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European
Society of Cardiology (ESC). 2007 Guidelines for the Management of Arterial Hypertension. Journal of Hypertension 2007, 25:
11051187.
National Institute for Health and Clinical Excellence. NICE clinical guideline 127 Hypertension: clinical management of primary
hypertension in adults. Downloaded from www.nice.org.uk/guidance/CG127.
Rosendorff C. et al. Treatment of hypertension in the prevention and management of ischemic heart disease. Circulation. 2007; 115:
2761-2788.
World Health Organization, International Society of Hypertension Writing Group. 2003 World Health Organization (WHO)/International
Society of Hypertension (ISH) statement on management of hypertension. J Hypertens. 2003;21:19831992.
Research Articles
Barnett AH, Bain SC, Bouter P, Karlberg B, Madsbad S, Jervell J, Mustonen J for the Diabetics Exposed to Telmisartan and Enalapril
Study Group. Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. N Engl J
Med. 2004;351:19521961.
Black HR, Elliott WJ, Grandits G, et al, for the CONVINCE Research Group. Principal results of the controlled onset verapamil
investigation of cardiovascular end points (CONVINCE) trial. JAMA. 2003;289:20732082.
Brenner BM, Cooper ME, De Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2
diabetes and nephropathy. N Engl J Med. 2001;345:861 869.
Brown MJ, Palmer CR, Castaigne A, et al. Morbidity and mortality in patients randomised to double-blind treatment with a longacting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension
Treatment (INSIGHT). Lancet. 2000;356:366 372.
Hansson L, Hedner T, Lund-Johansen P, for the NORDIL Study Group. Randomised trial of effects of calcium antagonists compared
with diuretics and -blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study.
Lancet. 2000;356:359 365.

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Hansson L, Lindholm LH, Niskanen L, et al. Effect of angiotensin converting-enzyme inhibition compared with conventional therapy
on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial. Lancet.
1999;353:611616.
Julius S, Kjeldsen SE, Weber M, et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based
on valsartan or amlodipine: the VALUE randomized trial. Lancet. 2004; 363:20222031.
Lewis EJ, Hunsicker LG, Clarke WM, et al, for the Collaborative Study Group. Renoprotective effect of the angiotensin-receptor
antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851 860.
Lithell H, Hansson L, Skogg I, et al. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized
double-blind intervention trial. J Hypertens 2003;21:875 886.
Parving HH, Lenhert H, Mortensen JB, et al for the Irbesartan in patients with type 2 diabetes and microalbuminuria study group.
The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001;345:870
878.
Pfeffer MA, Swedberg K, Granger CB, et al. Effects of candesartan on mortality and morbidity in patients with chronic heart failure:
the CHARM-Overall programme. Lancet. 2003;362:759 766.
Pepine CJ, Handberg EM, Cooper-DeHoff RM, et al. A calcium antagonist vs a non-calcium antagonist hypertension treatment
strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized
controlled trial. JAMA. 2003;290:28052816.
PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105
individuals with previous stroke or transient ischaemic attack. Lancet. 2001 Sep 29; 358(9287):1033-41.
Turnbull F and the Blood Pressure Lowering Treatment Trialists Collaboration. Effects of different blood-pressure-lowering regimens
on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet. 2003;362:15271535.
The 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. 2002;288:29812997.
The European trial on reduction of cardiac events with perindopril in stable coronary artery disease Investigators. Efficacy of perindopril in
reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled,
multicentre trial (the EUROPA study). Lancet. 2003;362:782788.
Wing LM, Reid CM, Ryan P, et al, and the Second Australian National Blood Pressure Study Group. A comparison of outcomes with
angiotensin-converting-enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med. 2003;348:583592.
Wright JT Jr, Bakris G, Greene T, et al. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive
kidney disease. Results from the AASK trial. JAMA. 2002;288: 24212431.

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Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJV, et al. Effects of candesartan in patients with chronic heart failure
and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet. 2003;362:777781.
Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G, for The Heart Outcomes Prevention Evaluation Study Investigators. Effects
of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342:145
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