Nifedipine attenuates the hypertensive

response to tracheal intubation in

pregnancy-induced hypertension
N Kumar, YK Batra, I Bala and S Gopalan
Department of Anaesthesiology, Postgraduate Institute of Medical Education and
Research, Chandigarh, India.
Thirty women with pregnancy-induced hypertension (PIH) scheduled
for Caesarean section under general anaesthesia were studied to
evaluate the efficacy of sublingual nifedipine in attenuating the pressor
response to laryngoscopy and tracheal intubation. The patients were
randomly given either the contents of a nifedipine capsule 10 mg or
placebo sublingually 20 min before induction of anaesthesia. Blood
pressure and heart rate were recorded at various time intervals. There
was a decrease in mean arterial blood pressure (MAP) after
pretreatment with nifedipine (P < 0.01). The increase in MAP during
laryngoscopy and intubation was higher in the control group compared
with nifedipine pretreatment group (P < 0.01). During laryngoscopy
and intubation, MAP decreased by 3 mmHg in the nifedipine
pretreatment group, while there was an increase of 14 mmHg in the
control group. Heart rate increased in both the groups during the
laryngoscopy and tracheal intubation (P < 0.01) but the increase was
higher in the nifedipine group than in the control group (P < 0.05).
Neonatal Apgar scores in both the groups were comparable. These
results suggest that sublingual nifedipine is effective in attenuating the
hypertensive response to laryngoscopy and intubation but not the
tachycardiac response in parturients with PIH.

Nifedipine as a second line

antihypertensive drug in pregnancy
• G. CONSTANTINE Research Registrar11Department of Obstetrics and Gynaecology, Dudley Road
Hospital, Birmingham,
• A. L. REYNOLDS Consultant11Department of Obstetrics and Gynaecology, Dudley Road Hospital,
Birmingham,
• D. M. LUESLEY Senior Lecturer11Department of Obstetrics and Gynaecology, Dudley Road Hospital,
Birmingham,
• D. G. BEEVERS Reader22Department of Medicine, Dudley Road Hospital, Birmingham
 • 1
Department of Obstetrics and Gynaecology, Dudley Road Hospital,
Birmingham2Department of Medicine, Dudley Road Hospital, Birmingham

Correspondence: Dr G. Constantine

Abstract

Summary. Slow-release nifedipine has been used in the treatment of severe

hypertension in 23 pregnant women. In 22 this was in combination with other drugs, in
18 including atenolol. Good control of blood pressure was achieved in 20 women. The
perinatal mortality of the group was 130/1000, with a high caesarean section rate (71%
of live-births), a high rate of abnormal CTGs, a high rate of premature delivery, and a
high rate of infants who were small-for-dates. Whether this is due to the disease process
or the medication is uncertain. For the present time these combinations should only be
used in severe hypertensives or in the context of a controlled trial.

Pregnancy-Induced Hypertension Complicated by Postpartum Renal

Failure and Pancreatitis: A Case Report.

Article

American Journal of Perinatology. 19(4):177-179, June 2002.

Marcovici, Iacob M.D. 1,2; Marzano, David M.D. 1

Abstract:
Reported causes of pancreatitis in pregnancy include:
gallstone disease, hyperlipidemia, alcohol ingestion, viral,
and idiopathic. Few reports associate pancreatitis with
pregnancy-induced hypertension. A 35-year-old women
with pregnancy-induced hypertension and spontaneous
rupture of membranes was admitted for induction of labor.
Her postpartum course was complicated by acute renal
failure that responded well to treatment with Lasix and
Albumin. Subsequently, the patient developed acute
pancreatitis and recovered following conservative
treatment. It is possible that the pancreatic ischemia due
to generalized vasoconstriction of preeclampsia and loop
diuretics in the setting of oliguria with renal failure, had a
synergistic effect on the pancreas. Therefore, we suggest
that in postpartum women with pregnancy-induced
hypertension and acute renal failure, diuretics should be
cautiously used because they may increase the risk of
pancreatitis.

A comparison of nifedipine with methyldopa in

pregnancy induced hypertension.

• Jayawardana J,
• Lekamge N.

General Hospital, Peradeniya, Sri Lanka.

OBJECTIVE: To compare nifedipine (group 1) with methyldopa (group 2)
in the management of pregnancy induced hypertension (PIH). DESIGN: A
prospective clinical trial. SETTING: Obstetric Unit, General Hospital,
Peradeniya. PATIENTS: A total of 126 patients with PIH were allocated
alternately to either group. The patients in group 1 received nifedipine 30
to 90 mg/day and in group 2 methyldopa 750 to 2000 mg/day.
MEASUREMENTS: Blood pressure, the extra days added to the pregnancy,
number of patients treated for acute hypertensive episodes, maturity of
 fetus at birth, mode of delivery, birth weight, intrauterine deaths, Apgar
score, maternal side effects and complications. RESULTS: The two groups
on admission to the study had similar periods of gestation (group 1, 33.6
+ 5.9, group 2, 34.1 + 4.2), systolic blood pressure in mmHg (151 + 22,
and 154 + 24) and diastolic blood pressure (108 + 12, and 108 + 12).
The results showed no differences between the two groups, with respect
to maturity of fetus at delivery (35.1 + 5.5, and 35.7 + 2.9), mode of
delivery, number of intrauterine deaths, average systolic blood pressure in
mmHg (148 + 14 and 152 + 16), average diastolic blood pressure (102 +
8 and 104 + 9), highest systolic blood pressure (169 + 24 and 167 + 30),
highest diastolic blood pressure (115 + 12 and 116 + 11), birth weight in
kg (2.015 + 0.957, and 1.922 + 0.660) and number of days added to the
pregnancy (7 + 7, 9 + 11). The Apgar score for group 2 was better than
in group 1, and less patients in group 2 required treatment for acute
hypertension during the period of study. CONCLUSIONS: The results of
our study indicate that nifedipine is as effective as methyldopa in the
treatment of PIH.

Nifedipine trials: effectiveness and safety

aspects
• Herman P. van Geijn,
• Joris E. Lenglet,
• Annemieke C. Bolte
• Department of Obstetrics and Gynaecology, Vrije Universiteit Medical Center
(VUmc), De Boelelaan, Amsterdam, The Netherlands

Professor H. P. van Geijn, Department of Obstetrics and Gynaecology, Vrije Universiteit

Medical Center (VUmc), De Boelelaan 1117, 1007 MB Amsterdam, The Netherlands.
Abstract
Nifedipine (Adalat) is marketed as an anti-hypertensive agent. Nifedipine inhibits
voltage-dependent L-type calcium channels, which leads to vascular (and other) smooth
muscle relaxation and negative inotropic and chronotropic effects on the heart.
Vasodilation, followed by a baroreceptor-mediated increase in sympathetic tone then
results in indirect cardiostimulation. Nifedipine was introduced as a tocolytic agent at a
time when β-agonists and magnesium sulphate dominated the arena for the prevention
of preterm birth. The oral administration route, the availability of immediate and slow-
release preparations, the low incidence of (mild) side effects, and its limited costs
explain the attraction to this medication from the obstetric field and its rapid and
widespread distribution. Currently, over 40 studies have been published on nifedipine's
tocolytic effectiveness, including seven meta-analyses. The quality of the studies suffers
particularly from performance bias because the majority of them failed to ensure
adequate blinding to treatment both for providers and patients. Concerns about other
methodological flaws include measurements, outcome assessment and attrition bias. In
particular, the safety aspects of nifedipine for tocolysis have been underassessed.
Conclusions from the meta-analyses, favouring the use of nifedipine as a tocolytic agent,
are not supported by close examination of the data. The tocolytic effectiveness and
'safety' of nifedipine has been studied primarily in normal pregnancies. Based on its
pharmacological properties, one should be cautious to administer nifedipine when the
maternal cardiovascular condition is compromised, such as with intrauterine infection,
twin pregnancy, maternal hypertension, cardiac disease, etc. Life-threatening pulmonary
oedema and/or cardiac failure are definite risks and have been reported. Under such
circumstances, the baroreceptor-mediated increase in sympathetic tone may not balance
the cardiac-depressant activity of nifedipine

Long-Acting Lacidipine Versus Short-Acting Nifedipine in the

Treatment of Asymptomatic Acute Blood Pressure Increase.

Articles

Journal of Cardiovascular Pharmacology. 33(3):479-484, March

1999.
Sanchez, M. *; Sobrino, J.; Ribera, L.; Adrian, M. J.; Torres, M.;
Coca, A. +

Abstract:
Summary: We compared antihypertensive efficacy and safety of a
single administration of equipotent doses of lacidipine versus
nifedipine in the hypertensive urgencies. Twenty-nine
asymptomatic essential hypertensive patients (nine men, 20
women) with a mean age of 55.03 +/- 11.19 years and baseline
 diastolic blood pressure (DBP) of >=120 mm Hg after resting 30
min, not taking antihypertensive drugs for the last 24 h, were
randomized in a single-blind fashion to receive lacidipine, 4 mg
(LCD, 15 patients) or short-acting nifedipine, 20 mg (NFD, 14
patients) in a single dose. Blood pressure (BP) and heart rate
(HR) were taken every 30 min during the first 8 h and every 2 h
until 24 h of follow-up. Baseline BP values were similar in the two
groups (LCD, 222.5 +/- 32.8/124.6 +/- 8.4 mm Hg vs. NFD, 215.9
+/- 20.6/128 +/- 7.7 mm Hg; p = NS). Both drugs promoted a
significant reduction of systolic blood pressure (SBP; 169.6 +/-
27.8 vs. 170.6 +/- 25.3 mm Hg) and diastolic blood pressure
(DBP; 104.1 +/- 16 vs. 102.9 +/- 12.4 mm Hg) after 8 h. However,
either SBP (165 +/- 27.3 vs. 190.6 +/- 18.2 mm Hg; p = 0.008) and
DBP (99.9 +/- 12.3 vs. 117.2 +/- 11.4 mm Hg; p = 0.001) were
significantly higher in the NFD group after 24-h dosing. Eleven
patients in the LCD group had a decrease in BP >25% of the
baseline value both 8 and 24 h after the dose. Although 10
patients showed the same response in the NFD group 8 h after
the dose, only four patients maintained these values at 24 h. One
patient treated with NFD had a transient cerebrovascular ischemic
attack. No adverse effects were observed in the LCD group. We
conclude that the long-acting calcium antagonist lacidipine was
more effective than the short-acting nifedipine in both controlling
BP and maintaining this BP reduction over 8 h in essential
hypertensive patients with acute asymptomatic BP increase.

Acute effects of nitrendipine in

pregnancy-induced hypertension
• JIM ALLEN11Department of Obstetrics and Gynaecology and Pharmacology, University of Aarhus,
Denmark,
• SVEND MAIGAARD11Department of Obstetrics and Gynaecology and Pharmacology, University of
Aarhus, Denmark,
• AXEL FORMAN11Department of Obstetrics and Gynaecology and Pharmacology, University of
Aarhus, Denmark,
• PREBEN JACOBSEN11Department of Obstetrics and Gynaecology and Pharmacology, University of
Aarhus, Denmark,
• LENNART T. JESPERSEN11Department of Obstetrics and Gynaecology and Pharmacology, University
of Aarhus, Denmark,
• KARL PETER BROGAARD HANSEN11Department of Obstetrics and Gynaecology and Pharmacology,
University of Aarhus, Denmark,
• KARL ERIK ANDERSSON22Department of Clinical Pharmacology, University of Lund, Sweden
• 1
Department of Obstetrics and Gynaecology and Pharmacology, University of
Aarhus, Denmark2Department of Clinical Pharmacology, University of Lund,
Sweden

Correspondence: Jim Allen, M. D., Dept Obstetrics & Gynaecology, Aarhus

Kommunehospital, DK-8000 Aarhus C, Denmark.

Abstract

Summary. The acute effects of a single, 20 mg oral dose of nitrendipine were studied in
10 women at between 32 and 42 weeks gestation with stable pregnancy-induced
hypertension (PIH). Blood pressure (BP), maternal heart rate and fetal heart rate (FHR)
were assessed for 8 h after nitrendipine intake together with the plasma levels of
nitrendipine, noradrenaline, adrenaline, plasma renin activity (PRA) and vasopressin.
The mean initial systolic/diastolic BP was 158 (SEM 3.7)/ 108 (SEM 2.7) mmHg. Within 1
h stable, reduced mean BP-levels of 141–145/90–95 mmHg were reached and
maintained for 4 h after medication. This antihypertensive effect was closely related to
the maternal plasma concentration of nitrendipine, which reached a maximum of 9.1
(SEM 2.6) ng/ml 3 h after tablet intake. After 4 h, systolic and diastolic BPs slowly
increased in parallel to a successive decrease in plasma concentrations of nitrendipine.
Maternal heart rate increased by less than 10%, while FHR remained unchanged. No
hypotensive incidents occurred. The initial mean plasma concentrations of noradrenaline,
adrenaline, vasopressin and PRA did not change during the treatment. No major
maternal and no fetal side-effects were observed. Three of 10 patients experienced mild,
transient facial flushing.

24-hour ambulatory blood pressure monitoring: a

comparison between transdermal glyceryl-trinitrate
and oral nifedipine.

• Neri I,
• Valensise H,
• Facchinetti F,
• Menghini S,
• Romanini C,
• Volpe A.

Department of Obstetrics and Gynecology, University of Modena, Italy.

The objective of the present study is to compare the effectiveness of
transdermal glyceryl-trinitrate versus oral nifedipine in lowering blood
pressure in patients affected by pregnancy-induced hypertension (PIH).
Thirty-six consecutive pregnant women have been evaluated at different
gestational ages after the diagnosis of PIH or preeclampsia (PE). After a
24-h ambulatory blood pressure monitoring, patients were allocated to
three groups: those receiving oral nifedipine and those receiving
transdermal glyceryl-trinitrate in a continuous (24 h/day) or intermittent
(16 h/day) administration. A second blood pressure monitoring was
performed after 2 weeks of treatment. Systolic and diastolic blood
pressure were compared by using the Cosinor method looking at mesor,
amplitude, and acrophase. Baseline systolic and diastolic blood pressure
was similar among the three groups. Neither the transdermal glyceryl-
trinitrate administered for 24 or 16 h nor oral nifedipine affected systolic
and diastolic blood pressure. Analysis of variance showed that the
posttreatment values were similar among the groups. Further studies are
needed to verify the possible use of transdermal glyceryl-trinitrate as an
antihypertensive drug during pregnancy.