Dr.

Yudi Fadilah, SpPD

PEMBAHASAN
Introduction
Definisi
Etiologi dan Faktor Resiko
Tipe hipertensi
Patofisiologi
Manisfestasi Klinis
Diagnostik
Penanganan

Introduction
BP is an important characteristic of our

body.
Without BP, nutrients, oxygen, and
proteins couldnot travel from the arterial
side of the body to the venous side.
Hypertension is a serious national public
health problem, but its causes are largely
unknown
Numerous potential complications of
hypertension

 Diastolic BP of 130-150 gives a 60% 2 year

mortality rate
Complications of hypertension include:
Stroke
MI
Heart Failure
Renal Failure

Only hypertensives are known about

of those known, only are on treatment,
of those on treatment, only adequately

treated

Consequences of Hypertension
CNS - Stroke, retina
damage

Heart - CHF, MI,

Sudden death, angina

Kidneys - renal
failure, proteinuria

Peripheral Vascular
disease

 Hypertension is defined as a

consistent constant elevation of

systolic or diastolic pressure above
140/90 mm Hg.

- venous

return
- extracellular fluid volume
- myocardial contractility

- vasoactive

substances
- thickening of arteriolar
wall

 Hypertension (according to JNC VII)

Normal BP
Prehypertension
Stage I HTN
Stage II HTN
(Severe HTN

<120/<80
121-139/80-89
140-159/90-99
>160/>100
>180/>110)

Severe HTN is not a JNC VII defined entity

 Hypertensive Emergency
Acute, rapidly evolving end-organ damage

associated with HTN (usu. DBP > 120)

BP should be controlled within hours and
requires admission to a critical care setting

Hypertensive Urgency
DBP > 120 that requires control in BP over 24

to 48 hours
No end organ damage

Malignant Hypertension is no longer used

Isolated Systolic Hypertension

Defined as SBP 140mmHG and DBP

90mmHG
60% of hypertensives > 80 years old
From age 35/40 many people have
elevated systolic or diastolic pressure
and this elevation leads to the
widening and stiffening of the aorta
elasticity and compliance of the
large blood vessels SBP and
DBP

Medical History
Duration and classification of

hypertension.
Patient history of cardiovascular disease.
Family history.
Symptoms suggesting causes of
hypertension.
Lifestyle factors - Ethanol intake.
Current and previous medications.

Blood Pressure Measurement

Patients should be seated with back supported

and arm bared and supported.

Patients should refrain from smoking or

ingesting caffeine for 30 minutes before

measurement.

Measurement should begin after at least 10

minutes of rest.

Appropriate cuff size and calibrated equipment

should be used.

Both SBP and DBP should be recorded.

Two or more readings should be averaged.

Blood Pressure Measurement

SUASANA SAAT PENGUKURAN

Blood Pressure Measurement

Blood pressure is quite variable
Multiple readings on multiple visits

are needed to diagnose hypertension

Home Blood Pressure readings are
more accurate

Advantages of Self-Measurement
Identifies white-coat hypertension.
Assesses response to medication.
Improves adherence to treatment.
Potentially reduces costs.
Usually provides lower readings than

those recorded in clinic.

Fig. 1 : Some of the factors involved in the control of blood pressure that
affect the basic equation : blood pressure cardiac output x peripheral
resistance.

Blood Pressure Regulation: AT system

Increased R-A-A activity

ANGIOTENSINOGENE
J-G

RENIN
ANGIOTENSIN I

ACE

VASOCONSTRICTION

ANGIOTENSIN II

ALDOSTERON
Na+ RETENTION

negative feed back

BLOOD PRESSURE

The etiology of hypertension can be classified as either

primary (essential) or Secondary
.

Primary (essential) hypertension

It is accounts more than 90 % of all cases and has no
cause.
Contributing factors
Overproduction of sodium retaining hormones and
vasoconstriction
Increased sodium intake
More than ideal body weight (central abdominal obesity)
Diabetes mellitus and excessive alcohol intake.

Risk Factors
1- Age and Sex

The risk of high blood pressure increases, as

you get older.Through early middle age, high
blood pressure is more common in men.
Women are more likely to develop high blood
pressure after menopause.

2- Race

High blood pressure is particularly common

among blacks.

3- Family History
Level of BP is strongly familial

4- Smoking
Nicotine constricts blood vessels

5- Elevated Serum Lipids

It leads to atherosclerosis. Narrowing of
arteries increases blood pressure

Aetiology cont.
Primary hypertension
6- Alcohol
Alcohol increases plasma catecholamine.
(epinephrine and no epinephrine)
7- Sedentary life styles
Regular physical activity can help control
weight and reduce cardiovascular risk.

Aetiology cont.
Primary hypertension
8- Socioeconomic status
It is more prevalent in low socioeconomic
groups and among the less educated.

9- Emotional stress
Stress stimulate sympathetic
nervous systems.

Secondary Hypertension
It develops as a consequence of a

particular underlying disease or condition.

Causes
Congenital narrowing of the aorta.
Renal diseases such as renal artery

stenosis ,renal failure, glomerulonephritis.

Endocrine disorders such as

hyperaldosteronism

Secondary Hypertension Cont.

Causes
Neurologic disorders such as brain tumour ,

head injury

Medication such as sympathetic stimulation

(cocaine), nonsteroidal anti-inflammatory

Pregnancy- induced hypertension,

generalized vasospasm may be a

contributing factor.

Obesity
Obesity= excessive glucose concentration in

the blood induces a high secretion of

insulin
Insulin (secreted by the pancreas) induces a
thickening of the vessels increase in their
rigidity increases blood pressure.
Obesity also increases cardiac output (due to
the increased secretion of adrenaline) which
the reabsorption of water and salt by the
kidney increase in blood volume
increases the blood pressure.
Obesity is also responsible for an oversensitivity to sodium increase in rigidity of
the peripheral arteries (9).

Stress
Stress causes temporarily increase in

blood pressure which usually returns

to normal once the stress is over
"white coat hypertension,
In susceptible people: brief increases in

blood pressure cause damage that

eventually results in permanent high
blood pressure(5).
So, continuous cases of acute stress lead
to hypertension

Salt
Increased salt intake renal sodium

reabsorption and retention

Sodium retention increased body
fluid volume increased preload
An increase in cardiac output due to
the increased fluid volume
elevation in blood pressure (5).

From Oparil et al. Pathogenesis of Hypertension

Ann Inn Med 2003;139:761

Pathogenesis
Blood pressure is controlled by a

complex combination of processes

that influence cardiac output (CO)
and total peripheral vascular
resistance (TPR)
Hypertension is a hemodynamic
disorder indicating a disturbance in
the ratio between CO and TPR

Pathogenesis
Rarely is a single factor in the

previous diagram found to be the only

cause of hypertension.
In Primary hypertension (Essential)
and secondary hypertension, multiple
factors play a role

Pathogenesis
90-95% of hypertension is primary or

essential hypertension.
Hypertension requires the
participation of the kidney, the heart
and blood vessels

Pathophysiology Cont.
Inability of the kidneys to excrete sodium,

resulting in factors being secreted to

promote salt excretion with the side-effect
of raising total peripheral resistance (Is the
force opposing the movement of blood
within the blood vessels ).

Pathophysiology Cont.
An overactive rennin / Angiotensin leads

to vasoconstriction and retention of

sodium and water. The increase in blood
volume leads to hypertension.
An overactive

sympathetic nervous system, leading to

increased stress responses.

Clinical Manifestations

Hypertension is called the (SILENT KILLER)

because it is a disease that usually occurs

without any symptoms until it become more
severe and target organ disease has
occurred

It include
Fatigue, reduced activity tolerance, dizziness,
palpitation, angina, and dyspnoea, early
morning headache, blurred vision,
spontaneous nose- bleed ,and depression.

Diagnostic Studies
The initial diagnosis of hypertension is

made on the basis of two or more elevated

blood pressure reading , supine and
sitting obtained on at least two separate
occasions

The diagnostic test include:

Electrolytes (sodium, potassium)
Glucose - to identify diabetes mellitus
Profile lipid (Cholesterol, HDL,LDL,TG)

Diagnostic Studies cont.

Creatinine (renal function), Testing of urine

samples for proteinuria

Also a baseline for later monitoring the

possible side-effects of certain

antihypertensive drugs.

Diagnostic Studies cont.

Electrocardiogram (EKG/ECG)

May show (left ventricular hypertrophy) or

the previous silent cardiac disease even
a myocardial infarction).
Chest X-ray - again for signs of cardiac

enlargement or evidence of cardiac

failure.

Management
P

RSM

R eduction of weight, intake chol

S top smoking
M odification of life
P harmacologic treatment

Algorithm for Treatment of

Hypertension
Lifestyle Modifications
Not at Goal Blood Pressure (<140/90 mmHg)
(<130/80 mmHg for those with diabetes or chronic kidney disease)

Initial Drug Choices

Without Compelling
Indications

Stage 1 HTN (SBP 140159 or

DBP 9099 mmHg)
Thiazide-type diuretics for most.
May consider ACEI, ARB, BB,
CCB, or combination.

With Compelling
Indications

Stage 2 HTN (SBP >160 or DBP

>100 mmHg)
2-drug combination for most
(usually thiazide-type diuretic
and
ACEI, or ARB, or BB, or CCB)

Drug(s) for the compelling

indications
Other antihypertensive drugs
(diuretics, ACEI, ARB, BB, CCB)
as needed.

Not at Goal
Blood Pressure
Optimize dosages or add additional drugs
until goal blood pressure is achieved.
Consider consultation with hypertension
specialist.

JNC 7 Express. JAMA. 2003 Sep 10; 290(10):1314

Management

Lifestyle modification.
Weight reduction and regular mild exercise
reduce resting heart rate and blood pressure.
Reducing sodium (salt) diet is proven very

effective: it decreases blood pressure in about

60% of people

diet should be rich in fruits and vegetables

and low fat .

Management
Lifestyle modification cont.

Discontinuing tobacco use and alcohol

consumption.

Relaxation therapy, such as meditation,

that reduces environmental stress,

reducing high sound levels

Treatment : Antihypertensives
ACE Inhibitors, ARBs
Beta blockers
Calcium cannel blockers
Centrally acting alpha-agonist
Diuretics
Direct Vasodilators

DRUG THERAPY
Younger patients :

Older patients :

ACEI / ATII
B blocker

Ca channel blocker
Diuretic (thiazide)

REMEMBER: combinations of drugs have an additive effect

1/3 patients need >3 classes of drugs to reach target

Dont forget aspirin and statins (for CHD risk reduction)

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
48

49 49

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

50

ACE Inhibitor
Captopril: 12,5 mg, 25 mg, 50 mg
Enalapril : 5 mg
Fosinopril
Lisinopril
Perindopril
Quinapril
Ramipril
Trandolapril

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

52

ARBs
Do not block bradykinin breakdown
less cough than ACE Inhibitors

Adverse effects:
orthostatic hypotension
renal insufficiency
hyperkalemia

53

ANGIOTENSIN II RECEPTOR
ANTAGONISTS

Losartan 50 100 mg daily

Valsartan 80 320 mg daily
Temilsartan 20 80 mg daily
Irbesartan 150 300mg daily
Olmesartan 20 40 mg daily
Candesartan 8 32 mg daily

Hypertension
Renin
Angiotensinogen
Angiotensin I

ACE

X
X

Aldosterone
secretion
Renal tubular
reabsorption of
sodium and water

Angiotensin II

Non-ACE alternate
pathways (eg, chymase)

ARB

Vasoconstriction

AT1 receptors

Catecholamine
secretion

Antidiuretic hormone
(vasoprressin)
secretion

X
X

Stimulation of thirst center

BP

56 56

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
57

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

58

Renin Inhibitor
1st agent FDA approved in 2007: aliskiren
Inhibits angiotensinogen to angiotensin I conversion
FDA approved as monotherapy & combination

therapy
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

59

60 60

 -Blockers
Inhibit renin release
weak association with antihypertensive effect

Negative chronotropic & inotropic cardiac

effects reduce CO

-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

61

 -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
62

 -Receptors
Distributed throughout the body
concentrate differently in certain organs & tissues
1 receptors:
heart, kidney
stimulation increases HR, contractility, renin

release
2 receptors:
lungs, liver, pancreas, arteriolar smooth muscle
stimulation causes bronchodilation & vasodilation
mediate insulin secretion & glycogenolysis

63

Cardioselective -Blockers
Greater affinity for 1 than 2 receptors
inhibit 1 receptors at low to moderate dose
higher doses block 2 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 -blockers for HTN

64

 -Blockers
Cardioselective
atenolol, betaxolol, bisoprolol, metoprolol,

nebivolol

Nonselective
nadolol, propranolol, timolol

Intrinsic sympathomimetic activity

acebutolol, carteolol, penbutolol, pindolol

Mixed - and -blockers

carvedilol, labetolol
65

Nonselective -Blockers
Inhibit 1 & 2 receptors at all doses
Can exacerbate bronchospastic

disease
Additional benefits in:
essential tremor
migraine headache
thyrotoxicosis

66

Intrinsic sympathomimetic activity

Partial -receptor agonists
do not reduce resting HR, CO, peripheral

blood flow
No clear advantage except patients with
bradycardia who must receive a -blocker
Contraindicated post-myocardial infarction &
for patients at high risk for coronary disease
May not be as cardioprotective as other blockers
Rarely used

67

Mixed - & -blockers

Carvedilol reduces mortality in

patients with systolic HF treated with

diuretic & ACE inhibitor
Adverse effects:
additional blockade produces more

orthostatic hypotension

68

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
69

CCBs
Dihydropyridines:
amlodipine, felodipine, isradipine,

nicardipine, nifedipine, nisoldipine,

clevidipine

Non-dihydropyridines:
diltiazem, verapamil

Adverse effects of non-dihydropyridines:

bradycardia
atrioventricular block
systolic HF
70

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
71

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
72

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
73

 1-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
Na+/H2O retention
74

 1-Blockers
1st dose at bedtime
Used with diuretics to minimize edema
Caution in elderly patients
Reduce benign prostatic hypertrophy

symptoms

block postsynaptic 1-adrenergic receptors

on the prostate

relaxation
decreased urinary outflow resistance
75

Central 2-Agonists
Stimulate 2-adrenergic receptors in

the brain

reduces sympathetic outflow from the

brains vasomotor center

increases vagal tone

peripheral stimulation of presynaptic 2-

receptors may further reduce sympathetic

tone
decrease HR, CO, TPR, plasma renin
activity, baroreceptor activity
76

Central 2-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)

77

Central 2-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/discontinuation

78

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 -blocker
clonidine if -blocker contraindicated
79

Direct Arterial Vasodilators

Adverse effects:
sodium/water retention
angina

Hydralazine can cause lupus-like

syndrome
Minoxidil can cause hypertrichosis

80

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

81

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

82

Direct Arterial Vasodilators

Use with diuretic (preferably thiazide)

& -blocker to reduce fluid retention

& reflex tachycardia
minoxidil
more potent vasodilator
hydralazine

83

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

84

Diuretics
Thiazide
chlorthalidone, hydrochlorothiazide (HCTZ),

indapamide, metolazone

Loop
bumetanide, furosemide, torsemide

Potassium-sparing
amiloride, triamterene

Aldosterone antagonists
eplerenone, spironolactone
85

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 < 30 mL/min
Chlorthalidone 1.5 to 2 times as potent as HCTZ

8686

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

87

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

88

Aldosterone antagonists
Dose in AM or afternoon to avoid nocturnal diuresis
Due to increased risk of hyperkalemia, eplerenone

contraindicated in CrCl < 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

89

Orthostatic Hypotension
Decrease in SBP > 20 mmHg or DBP > 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
90

Monitoring Antihypertensives
Class

Parameters

Diuretics

blood pressure
BUN/serum creatinine
serum electrolytes (K+, Mg2+, Na+)
uric acid (for thiazides)

-Blockers

blood pressure
heart rate

Aldosterone antagonists
ACE inhibitors
Angiotensin II receptor
blockers Direct Renin
inhibitors

blood pressure
BUN/serum creatinine
serum potassium

Calcium channel blockers

blood pressure
heart rate

DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM: Pharmacotherapy:A Pathophysiologic Approach, 7th
91
Edition: http://www.accesspharmacy.com/

Cara menulis resep

R/ Captopril 25 mg no xx/s2dd1
R/ Amlodipin 10 mg no x/ s1dd1
R/ Hct 25 mg no x/s1dd