2. PRE TEXT…..
Hypertension complicates almost
10% of pregnancies.
Progression from mild to severe forms of hypertension during
pregnancy is unpredictable and can be rapid.
The use of antihypertensive
drugs in pregnancy is
controversial.
3. Further, treatment of PIH often
involves adjustment between
competing concerns for maternal
health, gestational age of the
infant and fetal exposure to
antihypertensive drugs.
4. During pregnancy, the priority
regarding hypertension is in
making the correct diagnosis,
with the emphasis on distinguishing
preexisting (chronic) from pregnancy
induced (gestational hypertension
and the syndrome of preeclampsia).
American Heart Assoc. Guidelines 2008
5. Role of Antihypertensive in
Pregnancy
Antihypertensive agents are mainly used to
prevent and treat severe hypertension; to
prolong pregnancy for as long as
safely possible, thereby maximizing the
gestational age of the infant; and to
minimize fetal exposure to medications
that may have adverse effects.
American Heart Assoc. Guidelines 2008
7. Definition
Hypertension in pregnancy is
Sustained diastolic BP (DBP)
≥90mm Hg;
(most accepted)
Systolic BP ≥140mm Hg
(less commonly accepted)
Relative rise in DBP
> 15 mm of Hg (Least accepted)
8. In general, mild to moderate
hypertension in pregnancy reflects a
DBP between 90 and 109mm Hg;
severe hypertension is usually
defined as SBP ≥170mm Hg and/or
DBP ≥110mm Hg.
9. Chronic hypertension
diagnosed before pregnancy
or within the first 20 weeks' gestation,
Gestational hypertension
diagnosed after 20 weeks'
not associated with proteinuria
Pre-eclampsia
diagnosed after 20 weeks' gestation
associated with proteinuria
10. Classification of Hypertensive disorders in
pregnancy
Chronic hypertension
Gestational hypertension
Develops in 2nd half of pregnancy
Without significant proteinuria
BP normalizes by 6 weeks
post partum.
Risk of developing preeclampsia is
15-25%.
Pre-eclampsia / Eclampsia
11. Pre Eclampsia-Eclampsia
• Preeclampsia-eclampsia is a syndrome that manifests
clinically as new-onset hypertension in later pregnancy
(any time after 20 weeks, but usually closer to term.
With associated
• Proteinuria: 1 on dipstick or (300 mg /24 hr Urine)
Occurs in 5% to 8% all pregnancies and is thought to be a
consequence ofabnormalities in the maternal vessels
supplying the placenta
12. Preeclampsia/eclampsia definitions
Preeclampsia: Hypertension >140/90 with proteinuria
of at least 0.3g/24h
Severe preeclampsia: Preeclampsia with
hypertension >160/110 or proteinuria >5g/24h or
multiorgan involvement
Eclampsia: Convulsions in any woman who has, or
then presents with, hypertension in pregnancy of any
cause
13. Symptoms other than hypertension and
proteinuria in severe preeclampsia
Oliguria (<400 ml/24h)
Cerebral signs (headache, blurred vision, altered
consciousness)
Pulmonary edema, cyanosis
Epigastric or right upper quadrant pain
Impaired liver function
Hepatic rupture
Trombocytopenia
HELLP syndrome
14. Hypertension in Pregnancy:
When to treat?
CONTROVERSIES ARE….
At what level of BP treatment should be
initiated?
What is target BP for patient undergoing
treatment?
No evidence to suggest that treatment of
gestational or chronic hypertension prevents
development of Pre Eclampsia
15. When to treat
Controversy in mild to moderate
hypertension
B’COZ
Most Anti-hypertensives are in
Category C
of FDA safety list.
which states that human studies are
lacking, animal studies are either
positive for fetal risk or are lacking.
16. When to treat…
consensus that
severe hypertension
There is
in pregnancy,
defined as >160/110 mm Hg, requires
treatment, because these women are at an increased risk
of intracerebral hemorrhage, and that treatment
decreases the risk of maternal death.
T Podymow, August P. Update on the Use of Antihypertensive Drugs in
Pregnancy .Hypertension 2008; 51: 960-969.
17. When to treat…
consensus that
severe hypertension
There is
in pregnancy,
defined as >160/110 mm Hg, requires
treatment, because these women are at an increased risk
of intracerebral hemorrhage, and that treatment
decreases the risk of maternal death.
T Podymow, August P. Update on the Use of Antihypertensive Drugs in
Pregnancy .Hypertension 2008; 51: 960-969.
18. Choice of drugs
The choice of antihypertensive
drugs in pregnancy is often
limited due to fetal safety
concerns.
19. Factors affecting choice of
anti-hypertensive Drugs
Efficacy
Familiarity and experience with the drug
Knowledge of doses and interactions with the drug
Fetal and maternal adverse effects
Effect on utero-placental blood flow
Onset of action
Duration of action
Ease of administration
20. Drugs administered during gestational days
0 to 17 (during fertilisation and implantation)
or days 18 to 55 (when organogenesis
takes place) can critically interrupt fetal
structural development.
After day 55, the developing fetus is more
resistant to drugs although noxious agents
can cause fetal deformation by decreasing
cell size and number.
21. General Principles for Anti Hypertensive
drugs in Pregnancy
When possible, drugs should be avoided in the first
trimester
Monotherapy with older and familiar
antihypertensives known to have minimal or no
maternal or fetal adverse effects is preferred
Episodic treatment should be avoided
All antihypertensive drugs affect the mother and the
fetus.
22. By What To Treat
•
•
•
•
•
•
Sympatholytics:
Adrenergic receptor Blocker
Vasodilators
Ca Channel blockers
ACE Inhibitors
Angiotensin receptor blockers
24. There is
no clear consensus on the management
of mild to moderate hypertension
Methyldopa,
Labetalol
Nifedipine
Are acceptable oral antihypertensive agents
for this scenario.
26. History of severe HTN in Previous pregnancy
History of abruptio Placenta
History of still birth or unexplained neonatal death
Marked obesity
Older than 35 years
Hypertension for more than !5 years.
27. Classes Of Drugs Useful in Treatment
DIURETICS
Furosemide
Thiazides
CENTRALLY
ACTING
DRUGS
Methyl Dopa
DRUGS that Decrease
Cardiac output
Beta Blockers
Propanolol
Vasopdilators
Labetalol
Fenoldopam
Nicardipine
Nifidepine
Prazosin
Hydralazine
29. METHYL DOPA
0.5 to 3.0 g/d in 2 divided doses
Safety after first trimester well
documented, including 7 years followup of offsprings
30. Drug of first choice
r control of mild to moderate'
fo
ypertension in Pregnancy
h
Most commonly Prescribed
st documented safety record
Be
Maternal and
Fetal safety record,
(4.5 to 7.5 year)
Follow up data.
Does not alter maternal
Cardiac output
Uterine blood flow and
Renal blood flow.
31. Alpha methyl Dopa
• When to start
BP > 110 mm of Hg diastolic
Initial Dose:
250 mg 3-4 times /day
Maximum dose 2gm/day
BP not controlled : add other
drug
32. Alpha Methyl Dopa
• Side Effects:
Postural Hypertension(dose reduction)
Depression
Headache
Fatigue
Depression
Drowsiness
Salt And water retention----Rebound Htn
( add diuretics)
Abnormal LFT
34. Calcium channel Blockers
Useful In late pregnancy,
Good control of maternal BP
Including those with pre-eclampsia,
No adverse fetal or perinatal effects.
Little data regarding their safety in
early pregnancy
Nifidepine is Most Commonly used drug
35. Nifedipine/Calcium channel Blockers
30 to 120 mg/d of a slow-release preparation
..May inhibit labor
..Has synergistic action with magnesium
sulfate in BP lowering;
..Little experience with other calcium entry
blockers
36. Labetalol
Combined alpha & beta adrenergic blocker
Is a peripheral vascular dilator
As effective as Methyldopa in pre-eclamptic
and non-proteinuric hypertension in pregnancy.
as safe as methyl dopa
PROBABLY
Long term safety not established
2nd Line drug for this reason
37. Labetlol
• Non selective B blocker
• Mechanism of action
Blocks –alpha 1 , Beta 1 & 2 receptors
Decreases peripheral Vascular
resistance
No effect on utero-placental blood flow
Cardiac output not affected
•
38. Labetalol
200 to 1200 mg/d in 2 to 3 divided
doses
May be associated with fetal
growth restriction
41. Labetalol was more effective than
methyldopa and nifedipine in
controlling blood pressure in patients
with pregnancy-induced hypertension
while methyldopa and nifedipine are
equally effective in controlling blood
pressure.
IJBCP International Journal of Basic & Clinical Pharmacology.
42. Severe Hypertension
There is consensus that severe
hypertension in pregnancy, defined as
>160/110 mm Hg, requires treatment,
because these women are at an
increased risk of intracerebral
hemorrhage, and that treatment
decreases the risk of maternal
death.
43. Which Drug Is to be used ?
Do We Have any Choice
Preferrence ?
44. A recent meta-analysis of 24 trials
(2949 women) in which different
antihypertensive drugs were
compared for the treatment of severe
hypertension in pregnancy concluded
that there is insufficient data to
favor one agent over another.
47. Who require par-entral treatment
Hypertensive encephalopathy,
Hemorrhage, or
Eclampsia
Target is :
To lower
Mean Arterial Pressure
by 25% over minutes to hours
and then to further lower BP to 160/100 mm Hg over
subsequent hours
Caution: Avoid Hypotension
48. Those with hypertensive encephalopathy, hemorrhage, or eclampsia require
treatment with parenteral agents to lower mean arterial pressure by 25%
over minutes to hours and then to further lower BP to 160/100 mm Hg
over subsequent hours.
In treating severe hypertension, it
is important to avoid hypotension,
because the degree to which
placental blood flow is
autoregulated is not established,
and aggressive lowering may
49. Hydarlazine
Drug of first choice for severe HTN
ADVANTAGES ARE
No adverse effects on fetal circulation,
Long experience with the drug in this
clinical setting,
Convenient administration
50. Hydarlazine
Laimed to be Drug of first choice for
severe HTN
ADVANTAGES ARE
No adverse effects on fetal circulation,
Long experience with the drug in this
clinical setting,
Convenient administration
51. Disadvantages of Hydralazine
Adverse effects
Mimicking HEELLP Syndrome
Maternal hypotension
Fetal heart rate deceleration
Possible increased tendency to cause
serious ventricular arrhythmias compared
with labetalol
May cause neonatal thrombocytopenia
52. Hydralazine
50 to 300 mg/d in 2 to 4 divided doses
Few controlled trials,
long experience with few adverse
events documented;
useful in combination with sympatholytic
agent;
53. Labetalol
Experience with labetalol in the acute
treatment of severe hypertension in
pregnancy is less well documented.
Studies suggest that parenteral use
of labetalol is at least effective and
safe as hydralazine.
Fetal distress and neonatal bradycardia
have been reported.
54. Nifedipine
Oral/sublingual has been reported to
be as safe and effective as
intravenous hydralazine for the
acute treatment of severe
hypertension in pregnancy.
55. Nifedipine With MgSO4
Has been associated with maternal
hypotension (and fetal distress).
Neuromuscular Blockade has been
reported.
While the drugs should be used together
with caution, their combined use is
common practice in some delivery suites.
Short-acting nifedipine capsules have been
withdrawn in some countries
56. Isradipine
....a new weapon
Intravenous Isradipine has also been
shown to be effective in severe
pregnancy-associated hypertension,
although it has not been extensively
studied in this clinical setting
57. Diazoxide
Diazoxide is a potent
antihypertensive
Can interfere with glucose
metabolism.
Should be reserved for patients with
severe hypertension unresponsive to
hydralazine, nifedipine or labetalol.
59. Impending eclampsia
Severe preeclampsia with signs of cerebral
affection like visual disturbancies, headache,
increased reflexes, and clonus
BJA 1996: 76: 133-148
60. The treatment of choice for eclampsia
and prophylaxis against recurrent
convulsions is magnesium sulphate
(Lancet 1995: 345: 1456-1463)
Magnesium sulphate is also the drug of
choice for seizure prophylaxis in
patients with preeclampsia
(Lancet 2002: 359: 1877-1890)
61. Magnesium Sulphate
Drug of Choice
for T/t
Of
Eclampsia
Normal serum
concentration
s of Mg2+ are
1.5 to 2.5
mEq/L (1.8 to
3.0 mg/dL),
Has Narrow
Range of
Therapeutic
Safety
Areflexia,
particularly
loss of the
patellar deep
tendon reflex,
has been
observed at 8
to 10 mEq/L
Respiratory
Serum
paralysis
Concentrari
seen at
ons
>13 mEq/L
between
3.5-7 meq/l
62. ”Delivery of the fetus and placenta is the
definitive management of severe
preeclampsia. Once severe disease has
been established and is progressing,
delivery of the fetus and placenta must
be accomplished to limit maternal risk.”
Int Care Med 1997: 23: 248-255
64. ASPIRIN MAY PREVENT
Low-dose acetylsalicylic acid
(aspirin, 75 mg) is recommended for the
prevention of pre-eclampsia in women at
high risk of developing the
Condition
WHO Guidelibes 2010
65. Calcium Supplementation
In areas where dietary calcium intake
is low, calcium supplementation
during pregnancy (at doses of 1.5–2.0
g elemental calcium/day) is
recommended for the prevention of
pre-eclampsia in all women, but
especially those at high risk of
developing pre-eclampsia
66. Rest May Not help in prevention
weak Evidence
Advice to rest at home is not
recommended as an intervention for
the primary prevention of preeclampsia
and hypertensive disorders of
pregnancy in womenconsidered to
be at risk of developing those
condition
67. Pre Conceptional Counselling
Indicated in
Patients who are chronic Hypertensive, Planning to
have pregnancy.
ACE Inhibitors may be replaced with other drugs as
they are fetotoxic
