HIPERTENSI

Angiotensin II (Ang II) generated

in the afferent arteriole interacts
with AT1 receptors on cellular
components of the nephron

Angiotensinogen

Ang I

ACE

Renin

Ang II

AT1R

= AT1 Receptor
Slide Source
Hypertension Online
www.hypertensiononline.or
g

Discussion

Classification

Why BP should be controlled?

Hypertension Assessment

Target Blood Pressure

Non-pharmacologic Treatment

Pharmacologic Treatment based on

Algorhythm
6

Classification of
Hypertension (JNC VII)
Category

Systolic
(mm Hg)

Normal

< 120

Prehypertension 120-139

Diastolic
(mm Hg)
and

<80

or

80-89

Hypertension
Stage 1

140-159

or

90-99

Stage 2

> 160

or

100
7

SH/ESC Classification of BP

Category

Systolic

Diastolic

Optimal
Normal

120

and

80

120-129

and/or

80-84

High Normal

130-139

and/or

85-89

Grade 1 Hypertension

140-159

and/or

90-99

Grade 2 Hypertension

160-179

and/or

100-109

Grade 3 Hypertension

180

and/or

110

Isolated Systolic
Hypertension

140

and

90

Mancia G, et al. J Hypertens 2007;25:1105-1187

Slide Source Hypertension Online

ndonesian Classification of BP

Category

Systolic

Diastolic

120

and

80

Pre Hipertensi

120-139

and/or

80-89

Grade 1 Hypertension

140-159

and/or

90-99

Grade 2 Hypertension

160-179

and/or

100

140

and

90

Normal

Isolated Systolic
Hypertension
Sumber, Sani,2008

Slide Source Hypertension Online

Discussion

Classification

Why BP should be controlled?

Hypertension Assessment

Target Blood Pressure

Non-pharmacologic Treatment

Pharmacologic Treatment based on

Algorhythm
10

Complications of Hypertension:
End-Organ Damage
Hypertension
Hemorrhage,
Stroke

Retinopathy

LVH, CHD, CHF

Peripheral
Vascular
Disease

CHD = coronary heart disease

CHF = congestive heart failure
LVH = left ventricular hypertrophy
Chobanian AV, et al. JAMA. 2003;289:2560-2572.

Renal
Failure,
Proteinuria
Slide Source
Hypertension Online
www.hypertensiononline.or
g

11

Discussion

Classification

Why BP should be controlled?

Hypertension Assessment

Target Blood Pressure

Non-pharmacologic Treatment

Pharmacologic Treatment based on

Algorhythm
12

Assessment of Hypertensive
Patients
Contributing factors
Complications of hypertension
Causes of secondary hypertension
Target of blood pressure

13

Assessment of Hypertension
Assess and manage contributive factor in
hypertensive patients i.e.
Dislipidemia
Disglycemia (e.g. impaired fasting glucose,
diabetes)
Obesity
Unhealthy eating
Physical inactivity
2009 Canadian Hypertension Education Program
Recommendations
Slide Source
Hypertension Online
www.hypertensiononline.or
g

14

Assessment of Hypertension
Search for exogenous potentially modifiable factors that
can induce/aggravate hypertension
Prescription Drugs:
NSAIDs, including COXIBS (e.g. celecoxib)
Corticosteroids and anabolic steroids
Oral contraceptive and sex hormones
Vasoconstricting/sympathomimetic decongestants
Calcineurin inhibitors (cyclosporin, tacrolimus)
Erythropoietin and analogues
Monoamine oxidase inhibitors (MAOIs)
Other sympathomemetics e.g. Midodrine

Other:
Licorice root
Stimulants including cocaine
Salt
Excessive alcohol use
Sleep apnea

2009 Canadian Hypertension Education Program

15

Discussion

Classification
Background: Why BP should be
controlled?

Hypertension Assessment

Target Blood Pressure

Non-pharmacologic Treatment

Pharmacologic Treatment based on

Algorhythm
16

17

Discussion

Classification
Background: Why BP should be
controlled?

Hypertension Assessment

Target Blood Pressure

Non-pharmacologic Treatment

Pharmacologic Treatment based on

Algorhythm
18

Lifestyle Modification
Modification

Recommendation

Decrease of
Sistolic Blood
Pressure

Body weight

Maintain normal body 5-20 mm Hg every

weight (BMI 18.5-24.9) decrease of 10 kg BW

DASH diet

Consumption of fruits,
vegetables, low fat
8-14 mm Hg
milk and low fat cheese

Reducing
salt/sodium intake

Reducing sodium to
not more than 2.4 g/
day or NaCl 6 g/day

Increasing physical
activity

Aerobic exercise ie.

Walking
(30 min/day 4-5 days in 4-9 mm Hg
a week)

Reducing alcohol
consumption

Limiting alcohol
consumption to not
more than 2 oz/day for
man and 1 oz / day for
women.

Source: The Seventh Report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure JNCVII. JAMA. 2003;289:2560-2572.

2-8 mm Hg

2-4 mm Hg

19

DASH DIET
Food Group

Daily Serving Examples and Notes

Grains

78

Whole wheat bread, oatmeal, popcorn

Vegetables

45

Tomatoes, potatoes, carrots, beans,

peas, squash, spinach

Fruits

45

Apricots, bananas, grapes, oranges,

grapefruit, melons

Low-fat or fat-free dairy

foods

23

Fat-free (skim)/low-fat (1%)milk, fatfree,/low fat yogurt, fat free/low fat

cheese

Meats, poultry, fish

Select only lean meats, trim away fats;

broil, roast, or boil, no frying and remove
skin from poultry

Nuts, seeds, dry beans

4 5 / week

Almonds, peanuts, walnuts, sunflower

seeds, soybeans, lentils

Fats and oils

23

Soft margarines, low fat mayonaise,

vegetables oil (oil, corn, canola, or
safflower)

Sweets

5 / weeks

Maple syrup, sugar, jelly, jam, hard candy,

sorbet

DASH eating plan available at: http://www.nhibi.nih.gov/health/public/heart/hpb/dash/new_dash.pdf

20

Discussion

Classification
Background: Why BP should be
controlled?

Hypertension Assessment

Target Blood Pressure

Non-pharmacologic Treatment

Pharmacologic Treatment based on

Algorhythm
21

History of antihypertensive drugs

Effectiveness and general tolerability

1940s

1950

Direct
vasodilators
Peripheral
sympatholytics
Ganglion
blockers
Veratrum
alkaloids

1957

1960s

1970s

1980s

Alphablockers
Thiazide
diuretics
Central 2
agonists
Calcium
antagonistsnon-DHPs

1990s 2000 2007

ARBs
ACE
inhibitors

DRI

Calcium
antagonistsDHPs

Beta-blockers
DHP, dihydropyridine;
ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor
blocker

22

First line classes of antihypertensive

drugs

Diuretics

Calcium-channel antagonists

Inhibit stimulation of beta-adrenergic receptors

Angiotensin-converting enzyme (ACE) inhibitors

Inhibit influx of calcium into cardiac and smooth muscle

Beta-blockers

Inhibit the reabsorption of salts and water from kidney tubules

into the bloodstream

Inhibit formation of angiotensin II

Angiotensin II receptor blockers (ARBs)

Inhibit binding of angiotensin II to type 1 angiotensin II

Receptors

23

Thiazide Diuretics
Veins

Mechanism: inhibit Na/K pumps in

the distal tubule
Examples:
Hydrocholorthiazide 12.5-25 mg daily
Chlorthalidone 12.5-50 mg daily

Effective first line agent

Thiazides

As single agent more effective if

CrCl >30 ml/min
Compelling indications: HF, High
CAD risk, DM, Stroke, ISH
24

Loop Diuretics
Veins

Mechanism: Inhibit Na/K/Cl

ATPase in ascending loop of
henle
Examples:
Furosemide 20 mg BID

Thiazides
Loops

Typically only beneficial in

patients with resistant HTN and
evidence of fluid overload;
effective if CrCl <30 ml/min
MUST be dosed at least twice
daily (Lasix = Lasts six hours)
Administer morning and lunch25

Aldosterone Receptor
Antagonists
Mechanism: inhibit receptor
Veins

aldosterone reducing Na &

water retention
Examples:
Spironolactone 25 mg daily

Thiazides
Loops
Aldosterone Ant.

Can provide as much as 25 mmHg

BP reduction on top of 4 drug
regimen in resistant hypertension
Monitor SCr and K
Compelling indications: HF
26

Am J Hypertension. 2003; 16:925-930.

Beta Blockers
Heart

Mechanism: Competitively inhibit

the binding of catecholamines to
beta-adrenergic receptors
Examples:
Atenolol 25-100 mg QD, Metoprolol 25
-100 mg BID, Bisoprolol 2.5 10 mg QD
Carvedilol 6.25-50 mg (alfa+Beta) BID

Beta Blockers

Monitor: HR, Blood Glucose in DM

Not contraindicated in asthma or
COPD but use caution
Compelling indications: HF, post-MI,
High CAD risk, DM
27

CCB Non-Dihydropyridine:
Diltiazem and Mechanism:
Verapamil
Decrease calcium influx
Heart

Arteries

into cells of vascular smooth muscle

and myocardium
Examples:
Diltiazem Long acting; CD 100 -400 mg
Verapamil 60-480 mg, long acting SR

Diltiazem
Verapamil

Monitor: HR
Verapamil causes constipation
Relatively contraindicated in HF
Compelling indications: DM, High
CAD risk
28

CCB: Dihydropyridine
Arteries

Mechanism: Decrease calcium influx

into cells of vascular smooth muscle
Examples:
Amlodipine 2.5-10 mg PO daily
Felodipine 2.5-10 mg PO daily
OROS/GITS. Do not use immediate
release nifedipine

Dihydropyridine
CCBs
Monitor: Peripheral edema, HR (can
cause tachycardia)
Good add on agent if cost is not an
issue
29

ACE Inhibitors
Veins
Arteries

Mechanism: inhibiting synthesis of

angiotensin II inhibit
vasoconstriction
Examples:
ACEI: Captopril 12.5 -50 BID, Enalapril 2.540 mg daily BID, Lisinopril 5 40 mg daily,
Imidapril 5-10 QD, Perindopril 4-8 mg QD,
Ramipril 2.5-20 mg

ACEI

Monitor: S Cr, K
Compelling indications: HF, post-MI,
High CAD risk, DM, CKD, Stroke
30

ARBs
Veins
Arteries

Mechanism: blocking action of

angiotensin II inhibit
vasoconstriction
Examples:
ARB: Irbesartan 150-300 mg QD, Losartan
25-100 mg BID, Olmesartan 20-40 mg,
Telmisartan 20-80 mg, Valsartan 90-160
mgQD

ARB

Monitor: S Cr, K
Compelling indications: HF, post-MI,
High CAD risk, DM, CKD, Stroke
31

Alpha1 Blockers
Arteries

Mechanism: Inhibit peripheral

post-synaptic alpha1 receptors
vasodilation
Examples:
Terazosin 1 20 mg daily
Doxazosin 1 16 mg daily

Alpha1 Blockers

Cause marked orthostatic

hypotension, give dose at bedtime
Consider only as add on therapy
Can be beneficial in patients with
BPH
32

Central Acting Agents

Heart

Mechanism: false neurotransmitters

reduce sympathetic outflow
reducing sympathetic tone
Examples:

Central Acting
Mechanism:
Clonidine

Clonidine 0.75-0.6 mg bid, Methyldopa

250 mg-1000 mg BID (Pregnancy),
Reserpin 0,1 -0,25 mg QD

Monitor: HR (bradycardia)
Side effects often limiting: Dry
mouth, orthostatic, sedation
Withdrawal/Rebound effect
33

Vasodilators
Arteries

Mechanism: Direct vasodilation of

arterioles via increased intracellular
cAMP
Examples:
Hydralazine 20-400 mg BID-QID
Minoxidil 2.5-40 mg PO daily-BID

Dihydropyridine
CCBs
Monitor: HR (can cause reflex
Hydralazine
tachycardia), Na/Water retention
Minoxidil
Hydralazine is an alternative in HF if
ACEI contraindicated
Consider minoxidil in refractory
patients on multi-drug regimens
34

NEWER ANTIHYPERTENSIVE AGENTS

Direct Renin Inhibitor; ALISKIREN
Monotherapy effective in lowering SBP and DBP
in hypertensive patients
Effective also in combination with a thiazide
diuretic, a CCB and an ACE inhibitor or an ARB
Protect against subclinical organ damage when
combined with an ARB
= the available evidence justifies its use in hypertension, in
combination with other agents.
Mancia et al.Reappraisal of ESC Hypertension Guidelines 2007

35

Hypertension treatment strategy: JNC VII

Lifestyle modifications
Not at goal blood pressure (<140/90 mmHg)
(<130/80 mmHg for patients with diabetes or chronic kidney disease)
Initial drug choices
Without compelling
indications
Stage 1 hypertension
(SBP 140-159 or DBP
90-99 mmHg)
Thiazide-type diuretics
for most. May consider
ACE-I, ARB, BB, CCB
or combination

Stage 2 hypertension
(SBP 160 or DBP 100 mmHg)
Two-drug combination for
most (usually thiazide-type
diuretic and ACE-I or
ARB, or BB, or CCB)

With compelling
indications
Drug(s) for the
compelling indications
Other antihypertensive
Drugs (diuretics, ACE-I,
ARB, BB, CCB) as needed

Not at blood pressure goal

Optimize dosages or add additional drugs until goal blood pressure is achieved.
Consider consultation with hypertension specialist.
SBP, systolic blood pressure; DBP, diastolic blood pressure;
ACE-I, angiotensin-converting enzyme inhibitor; ARB,
angiotensin II receptor blocker; BB, beta-blocker; CCB, calcium-

36

JNC VII. JAMA 2003;289:2560-2572

Treatment initiation: JNC VII

Stage 1 hypertension
Stage 2 hypertension
Normal Pre-hypertension
Lifestyle modification
Encourage

Yes

Yes

Yes

Initial drug therapy

hout compelling
Thiazide-type
No
indication
antihypertensive
Two-drug
diureticsdrug
combination
for most;
indicated
may
forconsider
most (usually
ACE-I, thiazide-type
ARB, BB, CCB,
diure
or

h compelling
Drug(s)
indications
Drug(s)
for compelling
for compelling
indications;
indications
other antihypertensive drugs (diuretics,
ACE-I, angiotensin-converting enzyme inhibitor; ARB,
angiotensin II receptor blocker; BB, beta-blocker; CCB,

37

JNC VII. JAMA 2003;289:2560-2572

38

39

40

Follow-up

Hypertensive patients are recommended

to be followed at least every month
Follow-up visits are used to:

Increase the intensity of lifestyle and drug

therapy,

Monitor the response to therapy

Assess adherence

41

Summary

Hypertension is becoming a burden to the

community due to impact on target organs
& premature death.
Treatment has proven to reduce morbidity
& mortality, but majority of patients were
not treated adequately.
Aggressive treatment shown benefit in
achieving target blood pressure.
More frequent follow up will be necessary
for patients with stage 2 hypertension or
patients with comorbid conditions.
42

Thank you