THE USE OF

BETA BLOCKER
IN PREECLAMPSIA
Febrina Pritayuni,
Rizqiyanti R., S.Farm.,
S.Farm., Apt
Apt
Dessy Surya S., S.Farm., Mareta Rindang, S.Farm.,
Apt
Apt
Rahmawati Raising,
Nur Hadiyanti, S.Farm.,
S.Farm., Apt
Apt
Fitria W, S.Farm., Apt
Febriansyah N.U.,
MasterB.,of Clinical
Pharmacy
Hargus Haraudi
S.Farm., Apt
S.Farm., Apt
Faculty of Pharmacy
Laurin Anastasia W.,
Adinugraha A., S.Farm.,
University ofS.Farm.,
Airlangga:
Apt
Apt

2014/2015

Background and objective

Background: Beta Blockers as
antihypertensive agents changes the
systemic perfusion that may be benefit or
even harmful for pregnant women with
preeclampsia
Objective: To analyze the use of beta
blockers
in preeclampsia

Definition
A spesific-pregnancy syndrome in which
there are an evident of proteinuria (>
300mg/ 24h or +1 dipstick) and elevated
maternal
blood
pressure
(BP
>
140mmHg/90mmHg)
Arises after 20 weeks of gestation
Cunningham, et al., 2014

Classification and Clinical

Manifestation
Mild preeclampsia
SBP >140 mmHg or DBP >90
mmHg
Proteinuria > 300mg/24 h or >1
to >2 on dipstick

Severe Preeclampsia

SBP > 160mmHg or DBP >

110mmHg
Proteinuria 5g / 24 h or > +3
on dipstick
Pulmonary Edema
Oligouria < 500ml/24 h
Thrombocytopenia < 100,000
pl/ml
Visual changes
Severe headache
Hemolytic anemia
IUGR
RUQ
Pain 2013
Callahan and
Caughey,
Elevated liver AST, ALT

Pathogenesis
2010)

(Redman, et al.,

SOGC, 2014

ESC, 2011
The thresholds for antihypertensive treatment an SBP of
140 mmHg or a DBP of 90 mmHg in women with:
gestational hypertension (with or without proteinuria)
pre-existing hypertension with the superimposition of
gestational hypertension
hypertension with subclinical organ damage or
symptoms at any time during pregnancy.(Class: 1; level
of evidence: C).
In severe hypertension (values ranging between 160 and
180 mmHg/>110 mmHg), drug treatment with
intravenous labetalol or oral methyldopa or nifedipine is
recommended (Class: 1; level of evidence: C).

PNPK Preeklamsia
Antihipertensi diberikan pada tekanan
darah sistolik 140 mmHg atau diastolik
90 mmHg (Level evidence I a,
Rekomendasi A ).

Adrenergic Receptor Antagonists

Brunton, et al., 2011

Pharmacodinamics and
Pharmacokinetics Properties of beta
blockers (Brunton et al., 2011)
drug

ISA Lipid
Oral
Solubility Avaibility
(%)

Plasma Pregnanc
T1/2
y
(Hours) Category
Risk

Non selective -Blocker : First Generation

Nadolol
0
Low
30-50
20-24
C
Penbutolol +
High
~100
~5
C
Pindolol

+++ Low

Propranolol 0
Timolol
0

High
Low to
moderate

~100

3-4

30
75

3-5
4

C
C

drug

ISA Lipid
Oral
Plasma Pregnancy
Solubility Avaibility T1/2
Category
(%)
(Hours) Risk
1- Selective Blockers : Second Generation

Acebutolol

Low

20-60

3-4

B, D in 2 &
3 trimester

Atenolol

Low

50-60

6-7

Bisoprolol

Low

80

9-12

Esmolol

Low

NA

0,15

C, D in 2&3
trimesters

metoprolol

moderate

40-60

3-7

drug

ISA

Lipid
Solubility

Oral
Plasma
Avaibilit T1/2
y (%)
(Hours)

Pregnan
cy
Categor
y Risk

Non selective -Blocker with additional action : Third Generation

Carteolol

++

Low

85

Carvedilol 0

Moderate

~30

7-10

C, D

Labetalol

Low

~33

3-4

1- Selective Blockers with additional action : Third Generation

Betaxolol

Moderate

~80

15

Celiprolol

Low

30-70

Nebivolol

Low

NA

11-30

No
1.

Author

Xie, et.
al., 2014

PICO

P = pregnant women
with hypertension
I = treatment with
labetalol (n = 416)
C = treatment with
metildopa (n =
1000)
O = Small for
gestational age
(SGA) and
hospitalisation
during infancy

Results

For infants born to

mothers with chronic
hypertension, compared
with those treated by
methyldopa alone,
those treated by betablockers appear to be at
increased rates of
SGA and hospitalisation
during infancy

No
2.

Author

Verma, et.
al., 2012

PICO

Results

P = pregnant patient (20-40

weeks of pregnancy)
newly diagnosed with
140/90 mmHg
I = treatment with labetalol
(n = 45)
C = treatment with
methyldopa (n = 45)
O = blood pressure
reduction

Labetalol is
equally
efficacious and
better tolerated
compared to
methyldopa in the
treatment of new
onset
hypertension
during pregnancy
(p > 0,05)

N
o
3.

Author

PICO

Dharwadk P = pregnant women

ar, et. al.,
with preeclampsia
2014
and gestational
hypertension with
140/90 mmHg
I = treatment with
labetalol (n = 40)
C = treatment with
methyldopa (n =
40)
O = blood pressure
controlling,
prevention of

Results

Labetalol is safer,
quicker in achieving
adequate control of
blood pressure with
considerable
prolongation of the
duration of
pregnancy with fewer
side effects on the
mother as well as the
neonate when used
the management
hypertensive

Cochrane Collaboration (1)

No
1.

Author
Duley L,
HendersonSmart DJ,
Meher S., 2007.

Results
Labetalol was associated with a
lower risk of hypotension (one
trial 90 women; RR 0.06, 95% CI
0.00 to 0.99) and caesarean
section (RR 0.43, 95% CI 0.18 to
1.02) than diazoxide.
Data were insufficient for reliable
conclusions about other outcomes.

Cochrane Collaboration (2)

No
2.

Author
Abalos E,
Duley L,
Steyn DW,
HendersonSmart DJ.,
2007

Results
Nineteen trials (1282 women) compared one
antihypertensive drug with another.
Beta blockers seem better than methyldopa
for reducing the risk of severe hypertension
(10 trials, 539 women, RR 0.75 (95 % CI 0.59 to
0.94); RD -0.08 (-0.14 to 0.02); NNT 12 (6 to
275)).
There is no clear difference between any of the
alternative drugs in the risk of developing
proteinuria/pre-eclampsia. Other outcomes were
only reported by a small proportion of studies, and
there were no clear differences..

Cochrane Collaboration (3)

No
3.

Author

Results

Magee L, Duley
L., 2012

Oral beta-blockers decrease the risk of

severe hypertension (relative risk (RR) 0.37,
95% confidence interval (CI) 0.26 to 0.53; 11
trials, N = 1128 women) and the need for
additional antihypertensives (RR 0.44, 95% CI
0.31 to 0.62; 7 trials, N = 856 women).
Beta-blockers seem to be associated with an
increase in small-for-gestational-age (SGA)
infants (RR 1.36, 95% CI 1.02 to 1.82; 12 trials; N
= 1346)
In 13 trials (854 women), beta-blockers were
compared with methyldopa. Beta-blockers
appear to be no more effective and probably
equally as safe.

Conclusion
Beta blockers of which can be used in
preeclampsia is labetalol
Labetalol is used in mild to moderate
preeclampsia, unless it is contraindicated.
Labetalol is as effective and safe as
methyldopa

References
Duley L, Henderson-Smart DJ, Meher S., 2007. Drugs for treatment of very high
blood pressure during pregnancy (Review). Cochrane Database of Systematic
Reviews, Issue 3. Art. No.: CD001449
Abalos E, Duley L, Steyn DW, Henderson-Smart DJ., 2007.) Antihypertensive drug
therapy for mild to moderate hypertension during pregnancy (Review.)
Cochrane Database of Systematic Reviews, Issue 1. Art. No.: CD002252
Magee L, Duley L., 2012. Oral beta-blockers for mild to moderate hypertension
during pregnancy (Review). Cochrane Database of Systematic Reviews 2003,
Issue 3. Art. No.: CD002863
Xie, et al., 2014. Beta-Blockers increase the risk of being born small for
gestational age or of being institutionalised during infancy. European Journal
of Obstetrics & Gynecology and Reproductive Biology 175: 124128
Callahan, T.L. and Caughey, A.B. 2013. Blueprints Obstetrics & Gynecology 6 th Ed.
Ch.8 pp. 111-114. Baltimore: Lippincott Williams & Wilkins
Cunningham, F.G., Leveno, K.J., Bloom, S.L., Spong, C.Y., Dashe, J.S., Hoffman,
B.L., Casey, B.M. and Sheffield, J.S. 2014. Williams Obstetrics 24 th Ed. New
York : McGraw Hill Education pp. 728-741
Magee, L.A., Pels, A., Helewa, M., Rey, E. and von Dadelzsen, P. 2014. Diagnosis,
evaluation and management of the hypertensive disorders of pregnancy.
Pregnancy Hypertension : An International Journal of Womens
Cardiovascular Health Vol. 4 pp. 118-121
Redman, C.G.W., Jacobson, S. and Russell.,R. 2010. Hypertension in pregnancy. In:
Powrie, R.O., Greene, M.F. and Camann, W. (Eds). De Swiets Medical
Disorders in Obstetric Practice 5 th Ed. Oxford : Wiley-Blackwell. Pp. 153-160
Brunton, et al., 2011. Goodman & Gilmans The Pharmacological Basis of
Therapeutics, 12th edition. California: McGraw-Hills Company Inc

THANK YOU

Etiopathogenesis

(Cunningham, et al., 2014)

Hypertension in Pregnancy
Types
Gestational
hypertensi
on
Chronic
hypertensi
on
Preeclamps
ia and
eclampsia
syndrome

Characteristics
BP > 140/90 mmHg after 20 weeks in
previously normotensive women,
proteinuria (-)
BP 140/90 mmHg before pregnancy or
before 20 weeks of pregnancy

Preeclampsia :
BP > 140/90 mmHg after 20 weeks ,
proteinuria (+)
Eclampsia :
Preeclampsia + convulsion
Preeclamps A woman with chronic hypertension who
ia
develops signs of preeclampsia after the
Cunningham, et al., 2014
superimpos
20th weeks of pregnancy

PREECLAMPSIA

Gestational age 37 weeks

At 34 weeks gestation:
Severe pre-eclampsia
Labour or rupture of membranes
Abnormal fetal testing
Severe oligohydramnions or fetal
growth restriction

MATERNAL AND FETAL ASSESSMENT

YES

DELIVER

NO
MILD DISEASE
Hospital or office
management
Maternal and fetal
assessment

Worsening maternal
or fetal condition
38 weeks
Labour or rupture of
membranes

Severe disease

23 - 32 weeks

Steroids
Antihypertensives
Daily assessment of
maternal-fetal conditions
Delivery at 34 weeks

< 23 weeks

33 - 34 weeks

Steroids
Delivery
after
48 h

Severe Pre-Eclampsia
Management

(Sibai, 2003)

Antihypentensive for gestasional or chronic hypertension

(Podymow & August, 2008)

Nifedipine vs Labetalol
Arch Gynecol Obstet

(Gianubillo et al, 2012)

Association between labetalol use for hypertension in pregnancy and adverse

infant outcomes
European Journal of Obstetric & Gynecologic and Reproductive Biology
(Xie et al, 2014)

Continue..

NHBPEP, 2000

NICE, 2011
Moderate hypertension (150/100 to
159/109 mmHg): With oral labetalol
as first-line treatment to keep: diastolic
blood pressure between 80100 mmHg
systolic blood pressure less than 150
mmHg
Severe hypertension (160/110 mmHg or
higher): With oral labetalol as first-line
treatment to keep: diastolic blood
pressure between 80100 mmHg
systolic blood pressure less than 150
mmHg