Principles of Pharmacotherapy in Hypertension

. .

...., , PPhhaarrmm..DD..,, PPhh..DD..

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.

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(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

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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

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3

early response, intermediate response late response

1. Early response

sympathetic parasympathetic

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

Force of contraction Venous Return

Venous capacitance

Intravascular volume

Stroke Volume Heart Rate

Cardiac Output Total Peripheral Resistance

3

ARTERIAL BLOOD PRESSURE

X

X

X

Force of contraction Venous Return

Venous capacitance

Intravascular volume

Stroke Volume Heart Rate

Cardiac Output Total Peripheral Resistance

3

ARTERIAL BLOOD PRESSURE

X

X

X

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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)

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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

Alcohol

Appetite suppressants

Cyclosporine

Estrogens

Erythropoietin

Monoamine oxidase inhibitors

Non-steroidal anti-inflammatory drugs

Oral contraceptives

Oral decongestants

Tacrolimus

Tricyclic antidepressants (TCAs)

- sodium

- sodium/calcium transport

- angiotensino-

gen renin

catecholamines, insulin, endothelin (receptor)

2. (environmental factors) (smoking),

(obesity) (hyperlipidemia), (excessive salt intake),

(physical inactivity), (emotional stress),

(excessive alcohol intake)

primary hypertension 4

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target organ damage

atherosclerosis

arteriosclerosis

(cardiac hypertrophy)

arteriosclerosis afferent arteriole,

glomerulosclerosis (tubulointerstitial injury)

2

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 Increased total peripheral

resistance

HYPERTENSION

4 Hypothetical theory for pathogenesis of primary hypertension

autoregulation

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 Increased total peripheral

resistance

HYPERTENSION

4 Hypothetical theory for pathogenesis of primary hypertension

autoregulation

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2

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

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()

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

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(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 60-

70

(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

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3 JNC 7

30

5

cuff cuff bladder 80%

cuff

SBP palpatory method radial artery

auscultatory method cuff palpatory method 20-

30 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 SBP (mm Hg) DBP (mm Hg)

Normal

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5

target organ damage

(mm Hg)

Normal 2

Prehypertension 1

()

target

organ damage

Stage 1 hypertension 2

Stage 2 hypertension 1

180/110 mm Hg

1

6 18 ESH/ESC

BP classification SBP (mm Hg) DBP (mm Hg)

Optimal

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(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

14 | P a g e

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

17 | P a g e

7

systolic BP

BMI 18.5-22.9* kg/m2 5-20 mm Hg

10 kg

DASH

saturated fat

8-14 mm Hg

100 (2.4 6

)

2-8 mm Hg

aerobic 30

4-9 mm Hg

30

720 (4.5%), 300 (10%), 90 80-

proof (40%)

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

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8

()

Thiazide diuretics

Chlorthalidone 12.5-25 1 Hypokalemia, Hypomagnesemia,

Hyperuricemia, Hyperglycemia,

Dyslipidemia, Impotence

Hydrochlorothiazide 12.5-50 1

Indapamide

1.25-2.5 1

Loop diuretics

Bumetanide 0.5-2 1-2 Hypokalemia, Hypomagnesemia,

Hyperuricemia, Hyperglycemia, Impotence

Furosemide 2080 1-2

Potassium-sparing diuretics

Amiloride 5-10 1-2 Hyperkalemia, Impotence

Triamterene

50-100 1-2

Aldosterone receptor antagonists

Eplerenone 50-100 1 Hyperkalemia, Gynecomastia

Spironolactone

25-50 1

Beta-blockers (BBs)

Atenolol 25-100 1 Bradycardia, Bronchoconstriction,

Hyperglycemia, Dyslipidemia,

Negative inotropic effect,

Decreased peripheral blood flow,

Impotence, Masking hypoglycemia

symptoms in diabetes

Bisoprolol 2.5-10 1

Metoprolol 50-200 1-2

Propranolol 40-160 2-3

Propranolol long-acting 60-180 1

Alpha-1-blockers

Doxazosin 1-16 1 First-dose hypotension,

Orthostatic hypotension,

Dizziness, Headache, Edema

Prazosin 2-20 2-3

Terazosin

1-20 1-2

Combined alpha- and beta-blockers

Carvedilol 12.5-50 2 First-dose hypotension,

Orthostatic hypotension, Dizziness,

Bronchoconstriction, Hyperglycemia

Labetalol 200-800 2 Bradycardia

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8 ()

()

Calcium channel blockers (CCBs)-Dihydropyridines

Amlodipine 2.5-10 1 Headache,

Dizziness,

Orthostatic hypotension,

Peripheral edema

Felodipine 2.5-20 1

Isradipine 2.5-10 2

Nicardipine long acting 60-120 2

Nifedipine long acting 30-60 1

Calcium channel blockers (CCBs)-

Nondihydropyridines

Diltiazem long acting 120-540 1 Bradycardia, Dizziness, Headache,

Peripheral edema

Constipation ( verapamil),

Negative inotropic effect

Verapamil long acting 120-480 1-2

Verapamil 80-320 2-3

Angiotensin-converting enzyme inhibitors (ACEIs)

Captopril 25-100 2-3 Hyperkalemia,

Dry cough,

Taste disturbances,

Angioneurotic edema,

Worsening renal function

Enalapril 5-40 1-2

Fosinopril 10-40 1

Lisinopril 10-40 1

Peridopril 4-8 1

Quinapril 10-80 1

Ramipril 2.5-20 1

Angiotensin receptor blockers (ARBs)

Candesartan 8-32 1 Hyperkalemia,

Worsening renal function Irbesartan 150-300 1

Losartan 25-100 1-2

Telmisartan 20-80 1

Valsartan

80-320 1-2

Direct rennin inhibitors

Aliskiren 150-300 1 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)

21 | P a g e

8 ()

()

Centrally-acting agents

Clonidine 0.1-0.8 2 Headache, Drowsiness, Rebound

hypertension upon sudden withdrawal

Methyldopa 250-1000 2 Headache, Sedation, Bradycardia,

Impotence, Hemolytic anemia,

Peripheral edema

Reserpine

0.1-0.25 1 Sedation, Depression,

Peptic ulcer disease

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

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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

1

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

24 | P a g e

1

stage 2

3 6 JNC 7 serum

creatinine serum potassium 1-2

10 JNC 7

Diuretics BBs ACEIs ARBs CCBs Aldo

ANT

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

ValHEFT, RALES, CHARM

Post-myocardial

infarction

BHAT, SAVE, CAPRICON, EPHESUS

High coronary disease

risk

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

INVEST

Diabetes UKPDS, ALLHAT

Chronic kidney

disease

Captopril Trial, RENAAL, IDNT, REIN, AASK

Recurrent stroke

prevention

PROGRESS

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

blockers, Aldo ANT = aldosterone receptor antagonists

25 | 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 non-

dihydropyridines 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)

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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.

27 | 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

28 | 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

29 | P a g e

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

11 NKF

(

)

Diabetic kidney disease ACEIs ARBs diuretics BBs CCBs

Nondiabetic kidney disease

spot urine

protein-to-creatinine 200 mg/g

ACEIs ARBs diuretics BBs CCBs

Nondiabetic kidney disease

spot urine

protein-to-creatinine

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143 98 12

4.7 23 1.090

143 98 12

4.7 23 1.090

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

Labs:

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%

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143 98 16

4.5 23 1.3130

143 98 16

4.5 23 1.3130

143 98 14

4.5 23 1.1130

143 98 14

4.5 23 1.1130

143 98 20

4.7 23 1.4128

143 98 20

4.7 23 1.4128

143 98 20

4.7 23 1.4128

143 98 20

4.7 23 1.4128

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)

Labs:

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:

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:

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

PE: Wt 76 kg, Ht 174 cm, BP 140/86 mm Hg, P 70 bpm Labs:

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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

33 | 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

34 | P a g e

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

35 | P a g e

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

36 | P a g e

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 long-

acting 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

153.