Manila Central University

College of Medicine
Department of Pharmacology
3MD - GROUP 2 - Dr. Keithley Bryan A. Perez

ADENA, CZARLYN MARIS CAYABYAB MANDAPAT, JAMES ALISON LEGASPI

CABITAC, ZHON REINIEL CASTRO PALALAY, JOANNA VICTORIA VENTURANZA
DAMANIA, DISHA VATSAL QUIMBA, EMERSON JR.
ESPLANADA, CHRISTINE FATIMA NICOLE MARANAN SAMBILAY, DENISE SISON
GUINTO, YVES MIGEL PILLE SORITA, IVAN LAWRENCE CERTEZA
LANDICHO, RYAN CHRISTOPHER MANLUSOC VERZOLA, VIANCA MARIZ SIBUCAO

RDU on Hypertension in Pregnant

LEARNING OBJECTIVE:
1. Diagnose the case presented
2. Create a concept map explaining the pathophysiology of the case
3. Formulate the therapeutic objectives and treatment
4. Justify the drug you choose for the case
5. Create a prescription appropriate for the patient
6. Plan your counseling technique for the patient
STUDENTS SHOULD HAVE PRIOR KNOWLEDGE ON:
1. Basic Pharmacology of Antihypertensive Agents
2. Principles of Rational Drug Use
3. Pathophysiology of hypertension in pregnant women
4. Principles of Prescription Writing
5. If available, include Clinical Practice Guidelines, WHO guidelines, JNCs, GINA, Different local
disciplines.

CASE: “DIGNA’S PREGNANCY DILEMMA”

Digna, a 24 year old, primigravid, on her 3rd trimester, consulted at your clinic for prenatal
check-up. Upon reviewing her history, her LMP was last February 7, 2021 and the positive pregnancy
test was done on March 20. Her first ultrasound AOG was compatible with the AOG by LMP. Her past
medical history was unremarkable. Family history revealed that her mother was hypertensive when she
was pregnant with her. All her routine initial lab work ups were unremarkable. She is maintained on
Folate, Ferrous and maternal multivitamins.

Upon routine physical examinations, her BP was noted to be persistently 170/100 mmHg. She
denies any untoward signs and symptoms felt at this time. FH was 29 cm. FHT: 142 / min at the left
quadrant. You immediately did a urinary protein dipstick which revealed +1
 1. What is your diagnosis?

Definition of Terms: eclampsia or high blood pressure

caused by preeclampsia
1) Primigravid - Woman who is pregnant
for the first time Salient Features:
2) AOG - Describes how far along the
● Digna, 24 years old, primigravid, on her
pregnancy is (normal: 38-42 weeks)
3rd trimester
3) LMP - To the first day (onset of
● LMP: February 7, 2021
bleeding) of your last menstrual period
● PMH: unremarkable
before falling pregnant
● Gestational Age: ~ 30 weeks
4) FH or fundal height - Typically done to
● Family history: her mother was
determine if a baby is small for its
hypertensive when she was pregnant
gestational age, measurement is
with her
distance in centimeters from the pubic
● Unremarkable routine initial lab workups
bone to the top of the uterus.
● Maintained on Folate, Ferrous and
5) FHT or fetal heart tones - In the fetus,
maternal multivitamins
the number of heartbeats per minute,
● PE: BP was persistently 170/100
normally 120-160. Fetoscope is used to
mmHg; no other signs and symptoms
measure the fetal heart tones.
● FH - 29 cm; FHT - 142/min at the left
6) Urinary protein dipstick - Test
quadrant
measures the presence of proteins,
● Urinary protein dipstick grade of +1
such as albumin, in a urine sample. If in
large amounts during pregnancy, this
can be an indication for seizures due to

Urine Protein Dipstick Test

Table 1. Grades of proteinuria as provided by manufacturers of random urine dipstick tests (International
Journal of Hypertension)
GRADES OF PROTEINURIA INTERPRETATION

0 absent

Traces 15-30 mg/dL

1+ 30-100 mg/dL

2+ 100-300 mg/dL

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 3+ 300-1000 mg/dL

4+ > 1000 mg/dL

Table 2. Classification of Hypertension in Pregnancy

PREGNANCY-INDUCED PREGNANCY-AGGRAVATED

● Pre-eclampsia (if >20 weeks) ● Chronic Hypertension

● Eclampsia ● Superimposed Preeclampsia on Chronic
● Gestational Hypertension Hypertension

Table 3. Differential Diagnosis

DIAGNOSIS AOG OF OCCURENCE PROTEINURIA

Pre-eclampsia >20 week AOG +

Gestational Hypertension >20 week AOG -

Chronic Hypertension <20 week AOG -

Pertinent Diagnosis

Figure 1. Indicators of Preeclampsia Severity. Source: Leveno, K.

J., Spong, C. Y., Casey, B. M., Hoffman, B. L., Cunningham, F. G.,
Bloom, S. L., & Dashe, J. S. (2018). Williams obstetrics (25th ed.).
McGraw-Hill Education / Medical.

Pertinent Diagnosis: PU 30weeks AOG G1P0

NIL preeclampsia

Preeclampsia is a syndrome characterized

by the following:

1. Hypertension
a. 140 mm Hg or greater systolic or 90 mm Hg
or greater diastolic on two separate
occasions four hours apart, or
b. 160 mm Hg or greater systolic or 110 mm
Hg or greater diastolic minutes apart.
2. Proteinuria
a. greater than 0.3 g/L in a 24-hour urine
specimen that occurs after 20 weeks of gestation in previously normotensive women,
b. protein/creatinine ratio greater than or equal to 0.3, or
c. urine dipstick of +1

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2. How will you explain, in a concept map form, what is happening to Digna?

Figure 2. Concept Map

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3. What are your therapeutic objectives in managing her condition?

1. Gradua lowering of the blood pressure

2. Prevent cerebrovascular and cardiovascular events in the mother without compromising the fetal
well being.

3. Close monitoring of the maternal and fetal status

4. Prevent complications such as Eclampsia and bleeding (HELLP syndrome)

5. Determine the etiology of Pregnancy induced hypertension

4. How will you manage her both pharmacologically and non-pharmacologically?

NON PHARMACOLOGICAL TREATMENT

● BP monitoring - Excessive lowering of BP may lead to uteroplacental insufficiency. It is

recommended that the systolic BP must be maintained at less than 160 mmHg and diastolic at
less than 110 mmHg.
● Laboratory tests

- CBC: A platelet count of < 100,000/uL is diagnostic for preeclampsia. It is considered a

sign of worsening disease and is an indication for delivery.
- Creatinine level: Pre eclampsia may lead to kidney disease so it is best to monitor kidney
function
- ALT and AST: elevated levels may indicate organ damage from preeclampsia
● Fetal non stress testing - It is a non invasive test to monitor the baby's health by checking the
heart rate and oxygen supply

● Amniotic fluid index - Used to assess the sufficiency of amniotic fluid quantity in pregnancy. This
is monitored because pre eclampsia can cause low amniotic fluid which is a sign of poor blood
supply to the baby and it can increase the risk of intrauterine growth restriction.

● Fetal growth ultrasonography - To monitor the growth of the baby because preeclampsia affects
the arteries carrying blood to the placenta and if the placenta doesn't get enough blood, oxygen,
and nutrients this can lead to fetal growth restriction, low birth weight, and preterm birth.

● Lifestyle modification (fat and salt intake reduction)

● Bed rest

● Dimming of lights to prevent possible seizure of the patient.

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PHARMACOLOGICAL TREATMENT

Table 4. Pharmacological Treatment under consideration

DRUG CLASSIFICATION MECHANISM OF DOSAGE
ACTION

Methyldopa Sympatholytic: ● Converts Initially, 250mg 2-3

alpha-methyldopa to times daily; gradually
Alpha-2 Agonist
methylnorepinephrin increase at intervals of
e centrally, Alpha-2 2 or more days, if
Agonist action from necessary
the CNS reduces
adrenergic outflow,
resulting in lower
TPR and lower BP

Labetalol Beta-blockers ● Relaxes blood 200-1200mg/day in 2-3

vessels and reduces divided doses (max
HR. 220mg total)

● Competitively binds
to
alpha-1-adrenergic
receptors

● Inhibits adrenergic
stimulation of
endothelial function
and vasoconstriction
of peripheral blood
vessels.

Hydralazine Vasodilator ● Induces arteriolar 10mg orally 4 times a

vasodilation by day for the first 2-4
preventing oxidation days; increase to 25mg
of NO. orally 4 times a day for
the balance of the first
● Relaxes vascular

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 smooth muscle. week.

2nd week: 50 mg orally

4 times a day (max of
50mg 4 times a day)

Nifedipine Calcium- channel ● Relaxes blood Initially 30-60mg/day,

blocker vessels, controls titrate 30-90mg/daily
chest pain by
(max of 90-120mg
increasing supply of
daily)
oxygen

● Calcium ion influx

inhibitor, which
inhibits
transmembrane
influx of calcium ions
into vascular smooth
muscles and cardiac
muscles.

● Reduces arterial
blood pressure,
peripheral vascular
resistance

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 5. How will you select your drug for Digna on the basis of comparing efficacy, suitability, safety
and cost?

Table 5. Choosing the p-treatment based on the four parameters of Rational Drug Use
DRUG Efficacy Safety Suitability Cost Total

Sympatholytics

α adrenergic agonist +++ +++ ++++ +++ 13

α-methyldopa

β-nonselective adrenergic antagonist +++ +++ +++ ++++ 13

Labetalol
Atenolol

β1-selective adrenergic antagonist ++ +++ + + 7

Esmolol

α1-selective adrenergic antagonist ++ +++ ++ +++ 10

Urapidil
Tamsulosin

Vasodilators

Arterial ++++ +++ ++++ +++ 14

Hydralazine

Ca2+ channel blocker +++ +++ ++ ++++ 12

Nifedipine
Amlodipine

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Table 6. Rationale behind the scoring in choosing the p-treatment in Table 5
RDU RATIONALE

α adrenergic agonist (α-methyldopa)

Efficacy

Safety Pregnancy Category (US FDA): IV/ Parenteral: C ; PO: B

● Adverse Reaction: Significant: Oedema, weight gain, reversible
granulocytopenia and thrombocytopenia, sedation, fever, jaundice,
depression.
● Special Precautions: Patients with severe bilateral cerebrovascular disease.
Patients undergoing surgery. Renal or history of hepatic impairment. Children
and elderly. Pregnancy and lactation.

Suitability Safe to use in pregnancy, without reports of maternal or fetal adverse effects.
Compatible with breastfeeding.
Onset of action : 12-24 hours

Cost PHP19 / 250 mg tablet

β-nonselective adrenergic antagonist (Atenolol)

Efficacy

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Safety Pregnancy Category (US FDA): IV/ Parenteral/ PO: C
● Adverse Reaction:Intraoperative floppy iris syndrome, orthostatic
hypotension, bradycardia, syncope, paraesthesia, dizziness, dyspnoea,
fatigue, vertigo, headache, nasal stuffiness, diarrhoea, abdominal pain, male
sexual dysfunction, dyspepsia, nausea, vomiting, flatulence, constipation,
taste disturbances, scalp tingling, tremor, muscle weakness, urinary retention,
hepatitis, jaundice, rash, increased transaminases, nightmares, claudication.
● Special Precautions: Patients w/ pheochromocytoma, inadequate cardiac
function and well-compensated heart failure, DM, non allergic bronchospasm.
Patients undergoing major surgery involving general anaesth. May mask
symptoms of hypoglycaemia. Avoid abrupt withdrawal as it may exacerbate
angina. Hepatic impairment. Elderly, pregnancy and lactation.

Suitability ● FDA approved use for treatment of acute or chronic arterial

hypertension in pregnant patients
● Compatible with breastfeeding
● Intravenous administration : 20mg/hr and doubled until 160mg/hr is achieved
● Onset of action : 2-5 mins IV

Cost PHP7 for every 50mg/tab; PHP12 for every 100mg/tab

β1-selective adrenergic antagonist (Esmolol)

Efficacy

Safety Pregnancy Category (US FDA): IV/ Parenteral: C

● Adverse Reaction: Hypotension, bradycardia, heart block, syncope,

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 peripheral ischaemia, pallor, flushing, nausea, vomiting, anorexia, dizziness,
somnolence, paraesthesia, diaphoresis, headache, agitation, fatigue,
asthenia, confusion, depression, anxiety, agitation, bronchospasm, wheezing,
dyspnoea, nasal congestion.
● Special Precautions: Patients w/ inadequate cardiac function,
well-compensated heart failure, bronchospastic disease, myasthenia gravis,
conduction disorder, peripheral vascular disease. May mask signs and
symptoms of hypoglycemia and hyperthyroidism. Avoid abrupt withdrawal as
it may precipitate thyroid storm or MI, and may exacerbate angina and
ventricular arrhythmias. Renal impairment. Pregnancy and lactation.

Suitability Intravenous route.

● Initial bolus: 80 mg (~1 mg/kg) IVP over 30 sec, THEN
● 0.15-0.3 mg/kg/min IV infusion

Cost PHP873 for every 10 mg/mL, 10mL vial or PHP794 for every 100 mg/mL, 10mL vial

α1-selective adrenergic antagonist (Tamsulosin)

Efficacy

Safety ● Adverse Reaction: Dizziness, nausea, headache, fatigue, orthostatic

hypotension, palpitations, nervousness, pruritus and allergic skin reactions.
● Special Precautions: Elderly, severe hepatic insufficiency. Pregnancy.

Suitability Available in oral form.

1 capsule (dutasteride 0.5 mg/ tamsulosin 0.4 mg) PO
# of doses per day : 1

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Cost PHP 25 for every 400 mcg MR Film Coated Tablet

Vasodilators (Hydralazine)

Efficacy

Safety Pregnancy Category (US FDA):IM/ IV/ Parenteral/ PO: C

● Adverse Reaction: postural hypotension, peripheral neuritis, anginal attacks,
ECG changes.Tachycardia, palpitation.
● Special Precautions: Renal and hepatic impairment. Pregnancy and
lactation. Avoid abrupt withdrawal.

Suitability ● Use should be avoided during the first 2 semesters of pregnancy

● Use is not recommended during 3rd trimester unless benefits outweigh the
risks to fetus
● Compatible with breastfeeding
● Onset of action : 15 minutes

Cost PHP230 for every 20 mg/mL, 1mL ampule

Ca2+ channel blocker (Nifedipine)

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Efficacy

Safety Pregnancy Category (US FDA): IV/ SL: C

● Adverse Reaction: Peripheral oedema, reflex tachycardia, increased angina
or MI, cardiac ischaemic pain, symptomatic hypotension with or without
syncope; impaired glucose tolerance.
● Special Precautions: Immediate-release preparations are not recommended
to manage angina or hypertension. Avoid abrupt withdrawal. Hepatic
impairment. Elderly. Pregnancy and lactation.

Suitability ● Classified as FDA Pregnancy Category C

● According to the manufacturer, drugs should be used only when benefits
outweigh risks to the fetus.
● Effective in treatment of high BP associated with pre-eclampsia, however,
with associated perinatal side effects such as maternal hypotension, placental
abruption, oliguria, neonatal thrombocytopenia and lower APGAR score.
● Compatible with breastfeeding
● Onset of action : 10-15 mins (buccal), 30-45 mins (oral)

Cost PHP5 / 10mg capsule

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6. What is the drug that you are to give her?

7. How will you counsel her about the complete drug information?

✔ Explain that the drug that will be given is used to lower blood pressure.
✔ Explain to the patient that the drug will be given parenterally through IV.
✔ FDA risk classification C, studies in animals have revealed adverse effects on the fetus and there
are no controlled studies in women. These drugs should only be given if the benefits outweigh the
potential risk to the fetus.
✔ May cause some dizziness, headache, nausea, anorexia, palpitations, sweating, and flushing.
Do not use tools or machines while affected.
✔ Consistent monitoring of blood pressure

✔ Seek medical help as soon as your vision starts to become blurry and if about to or currently in
seizure.

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 8. When will you ask her for follow-up?

OUTPATIENT: follow-up after one week/ at least once a week

- evaluate for evidence of seizures, preeclampsia with severe features and vaginal bleeding, BP, fetal
heart status

- platelet count, serum creatinine, serum liver enzyme

HOSPITALIZED: followed by an obstetrician and evaluated

POSTPARTUM: every 1 to 2 weeks with periodic BP measurement

- if still hypertensive at 6 weeks postpartum, may have chronic hypertension

REFERENCES

Leveno, K. J., Spong, C. Y., Casey, B. M., Hoffman, B. L., Cunningham, F. G., Bloom, S. L., & Dashe, J.
S. (2018). Williams obstetrics (25th ed.). McGraw-Hill Education / Medical.
McPherson, R. and Pincus, M. (2017). Henry’s Clinical Diagnosis and Management by Laboratory
Methods, 23rd Edition. Elsevier
Sapna V. Amin, Sireesha Illipilla, Shripad Hebbar, Lavanya Rai, Pratap Kumar, Muralidhar V. Pai,
"Quantifying Proteinuria in Hypertensive Disorders of Pregnancy", International Journal of
Hypertension, vol. 2014, Article ID 941408, 10 pages, 2014. https://doi.org/10.1155/2014/941408
Katzung, B. (2017). Basic and Clinical Pharmacology 14th Edition (14th ed.). McGraw-Hill Education
Medical.

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