3. GI Tract
Constipation 25% - 50% of pregnant women
• First-line treatments
– Bulk-forming agents(Psyllium, methylcellulose)
– Osmotic laxatives (Polyethylene glycol, lactulose,
sorbitol)
• Second-line treatment
– Stimulant laxatives (Senna, bisacodyl)
• Contraindication
– Castor oil (stimulate uterine contraction)
– Mineral oil (impairment of maternal
fat-soluble vitamin absorption)
4. GI Tract
Hemorrhoids
• First-line management
– Laxatives, stool softeners
– Topical anesthetics, skin protectants, astringents
for irritation and pain
– Hydrocortisone cream to reduce inflammation
and pruritus
5. GI Tract
GERD 40-80% of pregnant women
• First-line
– Antacids (aluminium, calcium, magnesium
prepartions)
• Second-line
– H2 blockers (ranitidine and cimetidine)
• Reserve
– Famotidine and nizatidine
– Proton pump inhibitors
6. GI Tract
Nausea and vomiting 90% of pregnancy
• First-line management
– Pyridoxine, Doxylamine
• Alternatives
– Phenothiazines, Metoclopramide (risk of sedation
and extrapyramidal effects)
– Ondansetron
– Corticosteroids (for hyperemesis gravidarum)
7. Gestational diabetes
• Prevalence – 1-14%
• First-line treatment
– Insulin
• Alternatives
– Glyburide and metformin
• Intravenous drip insulin should be used during
labor
8. Hypertension
• Approximately 10% of pregnancies
• SBP > 140 mmHg or DBP > 90 mmHg (two or
more measurements at least 4 hours apart)
• Preeclampsia – hypertension + proteinuria (>300
mg/24 hr)/ thrombocytopenia/ serum creatinine
> 1.1 mg/dL / elevated liver tansminases
– Low dose aspirin – prevent preeclampsia in high-risk
patient
– Calcium supplement – prevent preeclampsia
9. Hypertension
• Eclampsia – occurrence of seizures
superimposed on preeclampsia
• Magnesium sulfate – recommended to
prevent and treat eclampsia
– 4-6 g IV over 15-20 min followed by 2 g/hr
continuous infusion for 24 hrs
10. Nonsevere hypertension
Drug Dosage Comments
First choices
Methyldopa 250-500 mg orally 2-4 x
daily
May cause orthostatic
hypotension, drowsiness,
depression, hemolytic
anemia
Labetalol 100-400 mg orally 2-4 x
daily
Maternal adverse reactions
– headache, flushing,
dizziness, transient
hypotension, pulmonary
edema
Hydralazine 5 mg IV or IM:
could be repeated every 30
min (total 30 mg)
May cause tachycardia,
headaches, hypotension
Second choices
Clonidine 0.05-0.2 mg orally (max:
0.8 mg daily)
May cause hypotension,
drowsiness
11. Severe hypertension
Drug Dosage Comments
First choices
Labetalol 10-20 mg IV over 2 min:
could be repeated every
15-30 min (total 30 mg)
Not for asthmatic women
May cause fetal
bradycardia
Nifedipine (short acting) 5-10 mg orally:
could be repeated after 30
min
Maternal adverse reactions
– headache, flushing,
dizziness, transient
hypotension, pulmonary
edema
Hydralazine 5 mg IV or IM:
could be repeated every 30
min (total 30 mg)
May cause tachycardia,
headaches, hypotension
Second choices
Clonidine 0.05-0.2 mg orally (max:
0.8 mg daily)
May cause hypotension,
drowsiness
13. Thyroid Abnormalities
Hyperthyroid
• Propylthiouracil – first trimester
• Methimazole – second and third trimesters
• Contraindication
– Iodine131 – risk of thyroid damage in fetus
Hypothyroid
• Thyroid replacement therapy
– Levothyroxine (0.1 mg/day)
14. Thromboembolism
• Risk increases five- to tenfold over
nonpregnant women
• First-line management
– LMWH throughout pregnancy and for 6 wk after
delivery
• To avoid
– Warfarin (between 6 and 12 wk)
– Unfractionated heparin
– Injectable direct thrombin inhibitors
15. Acute care issues in Pregnancy
• Urinary tract infection
• Sexually transmitted infections
• Headache
16. Urinary tract infections
• Associated with higher risks of hypertension,
low birth weight, and preterm delivery
Asymptomatic bacteriuria and cystitis
acute pyelonephritis
Septic shock and acute respiratory distress
syndrome
18. Urinary tract infections
• Nitrofurantoin – contraindicated in
pyelonephritis
• Trimethoprim-sulfamethoxazole
– During organogenesis (congenital malformation)
– Near term (risk of neonatal jaundice)
• Quinolones
– Reserved for resistant infections (concerns of
arthropathy)
20. Bacterial vaginosis
Recommended
Metronidazole
500 mg orally two times daily x 7 days
250 mg orally three times daily x 7 days
Clindamycin 300 mg orally two times daily x 7 days
Recommended
Azithromycin 1 g orally x 1 dose
Ceftriaxone 250 mg IM x 1 dose
Erythromycin 500 mg orally three times daily x 7 days
Chancroid
Recommended Metronidazole 2 g orally x 1 dose
Trichomoniasis
21. Chlamydia
Recommended
Azithromycin
1 g orally x 1 dose
Amoxicillin 500 mg orally x 7 days
Recommended
Azithromycin 1 g orally x 1 dose
Ceftriaxone 250 mg IM x 1 dose
Alternative
Cefixime
+
Azithromycin
400 mg orally x 1 dose
1 g orally x 1 dose
Gonorrhea
Alternatives Erythromycin 500 mg orally three times daily x 7 days
22. Syphilis
Recommended Benzathine penicillin G 2.4 millions unit IM x 1 dose
Recommended
Benzathine
penicillin G
2.4 millions units IM x 3 doses weekly
Tertiary, late latent
Primary, secondary, early latent
Recommended
Aqueous
penicillin G
3-4 millions unit IV every 4 hr or continuous
IV x 10-14 days
Alternative
Procaine penicillin
+
Probenecid
2.4 millions unit IM daily x 10-14 days
500 mg orally four times daily x 10-14 days
Neurosyphilis
24. Headache
Unresponsive patients
• Sumatriptan (little safety information of other
triptans)
Contraindication
• Ergotamine and dihydroergotamine
Migraine-associated nausea
• Promethazine, Prochlorperazine,
metocloperamide
25. Headache
Prevention of severe migrainous headache
• Agent of choice
– Propranolol (lowest effective dose)
• Alternatives
– Tricyclic antidepressants (amitriptyline,
nortriptyline)
26. Malaria Prophylaxis and treatment in
pregnancy
• Safe drugs
– Quinine, Chloroquine, Proguanil, Clindamycin
• Uncomplicated malaria
– First trimester - Quinine plus clindamycin
– Second and third trimester – Artemisinin
derivatives
27. Malaria Prophylaxis and treatment in
pregnancy
• Reserve medications
– Amodiaquine, atovaquone, dapsone,
lumefantrine, mefloquine, piperaquine,
pyrimethamine plus sulfadoxine
• Caution and contraindication
– Halofantrine and primaquine
– Doxycycline
28. Specific antimalarial drugs
• Artemisinin derivatives
– Relatively safe in second and third trimester
• Mefloquine
– Throughout the pregnancy for prophylaxis and
treatment
• Proguanil
– Throughout the pregnancy for prophylaxis and
treatment
29. Specific antimalarial drugs
• Quinine
– Drug of choice for chloroquine-resistant malaria
• Lumifantrine, Amodiaquine, Atovaquone
– Reserve medication
31. Asthma
• Common chronic illnesses in pregnancy
• Diagnosis and staging of asthma is same as in
nonpregnant women
• Risks of medication use are lower than the
risks of untreated asthma
32. Asthma
• Intermittent - Short acting β2 agonist
(albuterol is preferred)
• Persistent – step-appropriate doses (low,
medium, high) of inhaled corticosteroids
(Budesonide is preferred)
33. Asthma
• Long acting β2 agonist –considered safe
• Cromolyn – less effective
• Leukotriene receptor antagonists – less
experience in clinical trials
• Theophylline – more potential toxicity
• Systemic corticosteroids – for the most severe
asthma
34. Allergic rhinitis
• Approximately 20% of pregnancy are
impacted
• Vascular engorgement in nasal passages and
hormonal effects on mucus secretion – nasal
congestion
• Treatment strategies – similar to those used in
nonpregnant women
36. Diabetes
• Poorly controlled diabetes can cause fetal
malformations, fetal loss and maternal
morbidity
• Women with diabetes should use effective
contraception until optimal glycemic control is
achieved before attempting pregnancy
• Target organ problems may become worsen
during pregnancy
37. Diabetes
• Insulin is drug treatment of choice
• Women receiving insulin glargine or detemir
should be switched to NPH insulin
• Glyburide and metformin may be alternatives,
but not recommended by the American
Diabetes Association
38. Epilepsy
• Seizures may become frequent because of
changes in maternal hormones, sleep
deprivation, and medication adherence
problems
• Changes in free serum concentrations of
antiepileptic drugs
39. Epilepsy
• Carbamazepine and lamortigine – safest
• Valporic acid – risk of neural tube defects,
facial clefts, and cognitive teratogenicity
• Phenobaribital – cardiac malformation
• Polytherapy – greater rate of major
malformations than monotherapy
40. Epilepsy
• If drug withdrawal is planned, it should be
attempted at least 6 months before
attempting to conceive
• Folic acid supplementation – all women taking
antiepileptic drugs
41. HIV
• Generally, pregnant women should be treated
as nonpregnant women, with some
exceptions
• Efavirenz – avoid during first trimester
• Drugs that cross placental barrier
– Abacavir, Emtricitabine, Lamivudine, Tenofovir,
Zidovudine
43. HIV
• Women currently receiving ARV treatment should
be continued on their regimen
• For ARV-naïve women, use of three-drug
combination regimen
– Two nucleoside/nucleotide reverse transcriptase
inhibitors (NRTIs) with high transplacental passage
(preferred: Zidovudine, Lamivudine: alternatives:
emtricitabine, tenofovir, abacavir)
– A protease inhibitor (preferred: Atazanavir plus low-
dose ritonavir, lopinavir/ritonavir; alternative:
Darunavir or saquinavir, both with low-dose ritonavir)
44. HIV
• NNRTI (Nevirapine)
– Alternative to protease inhibitor
– Risk of severe rash and life-threatening or fatal
hepatotoxicity
• After discussion of risks and benefits, ARV
may be delayed until after first trimester to
avoid potential teratogenic complications
45. HIV
• Caesarean section before the onset of labor is
recommended to reduce the risk of perinatal
HIV transmission
• IV Zidovudine should be initiated with a 1-
hour loading dose followed by a continuous
infusion for 2 hours (cesarean) or until
delivery (for vaginal delivery)
• IV Zidovudine should still be administered in
the presence of resistance to oral Zidovudine
46. Preterm labor
• Preterm birth especially before 32 weeks of
pregnancy
• Major cause of short- and long-term neonatal
mortality and morbidity
47. Preterm labor
Antenatal corticosteroids
• Single course of corticosteroids – between 24
and 34 weeks gestation to women at risk of
preterm delivery within 7 days
• To decrease incidence and severity of neonatal
respiratory distress syndrome, intraventricular
hemorrhage, necrotizing enterocolitis, and
death
48. Tocolytic agents
• Used to buy time to complete a course of
corticosteroids
• To delay delivery to allow transfer of the
patient to a center with neonatal intensive
care unit facilities
• No clear first-line tocolytic drugs – based on
maternal status and potential adverse drug
reaction
Preterm labor
49. Tocolytic agents
• Magnesium sulfate, terbutaline,
indomethacin, nifedipine
• Magnesium sulfate
– Prevent neonatal risk of cerebral palsy
• Indomethacin
– Prolongs pregnancy, particularly beneficial in
women with hydramnios
Preterm labor
50. Tocolytic agents
• Terbutaline
– Risk of serious side effects (increased heart rate,
transient hyperglycemia, hypokalemia, cardiac
arrhythmias, pulmonary edema, myocardial
ischemia)
• Nifedipine
– Best benefit to risk ratio
Preterm labor
51. Antibiotics
• Parenteral/ Oral ampicillin or amoxicillin and
erythromycin
– In PROM (before 34 wk gestation)
– Delay in delivery and reduce maternal and
neonatal morbidity
Preterm labor
52. Progesterone
• To prevent preterm birth in women with
previous preterm delivery
• Also useful in women with sonographic short
cervix
Preterm labor
53. References
• Christof Schaefer, Paul Peters, Richard K Miller.
Drugs during pregnancy and lactation.
3rd edition. Elsevier; 2015.
• Joseph T DiPiro et al., Pharmacotherapy, A
pathophysiologic approach. 10th edition.
McGraw Hill; 2017.
• Katzung B G, Masters S B, Trevor A J. Basic and
clinical pharmacology. 13th edition. McGraw
Hill; 2015.
Bulk-forming agents (eg, psyllium,
methylcellulose, and polycarbophil) are safe for long-term use because they are not absorbed.
Osmotic laxatives (eg, polyethylene glycol, lactulose, and sorbitol) and stimulant laxatives (eg, senna
and bisacodyl) can also be used.
Use of magnesium and sodium salts may cause electrolyte
imbalance.
CLASSIFICATION
1. Bulk forming
Dietary fibre: Bran, Psyllium (Plantago)
Ispaghula, Methylcellulose
2. Stool softener
Docusates (DOSS), Liquid paraffin
3. Stimulant purgatives
(a) Diphenylmethanes
Phenolphthalein, Bisacodyl, Sodium
picosulfate
(b) Anthraquinones (Emodins)
Senna, Cascara sagrada
(c) 5-HT 4 agonist
Prucalopride
(d) Fixed oil
Castor oil
4. Osmotic purgatives
Magnesium salts: sulfate, hydroxide
Sodium salts: sulfate, phosphate
Sod. pot. tartrate
Lactulose
Conservative treatment (ie, high dietary fiber intake, adequate oral fluid intake, and use of sitz baths) should betried first. Laxatives and stool softeners can be used if conservative management is inadequate for
preventing or treating constipation. Topical anesthetics, skin protectants, and astringents (eg, witch
hazel) can be used for anal irritation and pain. Hydrocortisone may reduce inflammation and
pruritis.
Lifestyle and dietary modifications (eg, small, frequent meals; alcohol and tobacco avoidance; food avoidance before bedtime; elevation of the head of the bed).
Antacids (eg, aluminum, calcium, or magnesium preparations) or sucralfate are acceptable; however, sodium bicarbonate and magnesium trisilicate should be avoided.
The use of proton pump inhibitors (PPIs) during pregnancy does not appear to increase the risk of major birth defects; most data comes from use of omeprazole. Since more data and clinical experience are available for H2 antagonists, use of PPIs should be reserved for women with inadequate response to H2 antagonists.
NVP usually begins between weeks 4 and 6 of gestation and usually resolves by weeks 16 to 20; peak symptoms occur between weeks 8 and 12.
Hyperemesis gravidarum (HG; ie, unrelenting
vomiting causing weight loss of more than 5% prepregnancy weight, dehydration, electrolyte
imbalance, and ketonuria) occurs in 0.5% to 2% of women.
CLASSIFICATION
1. Anticholinergics Hyoscine, Dicyclomine
2. H 1 antihistaminics Promethazine,
Diphenhydramine, Dimenhydrinate,Doxylamine,Meclozine (Meclizine),Cinnarizine.
Neuroleptics Chlorpromazine,(D2 blockers) Triflupromazine,Prochlorperazine,Haloperidol, etc.
Prokinetic drugs Metoclopramide,Domperidone,Cisapride, Mosapride,Itopride
5-HT 3 antagonists Ondansetron,Granisetron,
Palonosetron,Ramosetron
6. NK 1 receptor antagonists Aprepitant,Fosaprepitant
7. Adjuvant antiemetics Dexamethasone,
Benzodiazepines, Dronabinol, Nabilone
Gestational diabetes mellitus (GDM) is diabetes diagnosed in the second or third trimester that is not overt diabetes.
KDT 259
Risks of GDM are many and include fetal loss, increased risk of major malformations, and fetal macrosomia.
Overt diabetes occurs if the
A1C is greater than or equal to 6.5% (0.065; 48 mmol/mol Hgb),
fasting plasma glucose (FPG) is
greater than or equal to 126 mg/dL (7.0 mmol/L), or 2-hour plasma glucose 200 mg/dL (11.1 mmol/L)
or greater during an oral glucose tolerance test (OGTT), or
if random plasma glucose (RPG) is greater
than or equal to 200 mg/dL (11.1 mmol/L) in a patient with hyperglycemic crisis or classic hyperglycemic symptoms.
Signs of more severe preeclampsia include: persistent severe headache, vomiting; hyperreflexia, chest pain or dyspnea, and HELLP (hemolysis, elevated liver enzymes, low platelets). Treatment of hypertension in women with preeclampsia depends upon the blood
pressure measurement and follows the same principles discussed under Chronic Illnesses in Pregnancy.
During pregnancy, stimulation of the thyroid gland may occur because of hCG’s structural similarity to thyroid-stimulating hormone (TSH; thyrotropin). In some women, gestational transient thyrotoxicosis (GTT) may result. Occurrence of GTT is often associated with HG. By 20 weeks of gestation, GTT usually resolves as production of hCG declines. Treatment with antithyroid medicationis not usually needed. Nausea and vomiting can be treated as for patients without this pseudohyperthyroid state.
Causes of hypothyroidism include autoimmune diseases (eg, Hashimoto’s thyroiditis), iodine deficiency (uncommon in the United States), and thyroid
dysfunction following surgery or ablative therapy for previous hyperthyroidism.
Treatment should be continued throughout pregnancy and for 6 weeks after delivery; the minimum total duration of therapy should not be less than 3 months. Fondaparinux and injectable direct thrombin inhibitors
(eg, lepirudin and bivalirudin) should be avoided unless a severe allergy to heparin (eg, heparin-induced thrombocytopenia) is present. The novel oral anticoagulants (eg, dabigatran, rivaroxaban, and apixaban) are not recommended. Warfarin is not used because it causes nasal hypoplasia, stippled epiphyses, limb hypoplasia, and eye abnormalities; the risk period appears to be between 6 and 12 weeks of gestation. CNS anomalies are associated with second- and third-trimester exposure.
Bacterial vaginosis
adverse pregnancy outcomes – PROM, chorioamnionitis, preterm birth, postpartum endometritis
Tx is recommeded in all symptomatic women and in asympatomatic women at high risk of preterm delivery
Trichomoniasis is caused by the protozoa, Trichomonas vaginalis. Infection with T. vaginalis is associated with an increased risk of premature rupture of the membranes, preterm delivery, and low birth weight. Treatment may prevent respiratory or genital infection in the neonate.
Cmplications of C. trachomatis include pelvic inflammatory disease (PID), ectopic pregnancy, and infertility. C. trachomatis infects the newborn through exposure to the infected cervix during delivery. Perinatal infection most commonly causes conjunctivitis that develops 5 to 12 days postpartum. A subacute, afebrile pneumonia with an onset at ages 1 to 3 months may occur.
Gonorrheal infection can cause PID, a known risk for infertility. Perinatal gonococcal infection results from exposure to the infected cervix during birth. Symptoms usually manifest within 2 to 5 days after delivery. Milder manifestations include rhinitis, vaginitis, and urethritis. More severe presentations include ophthalmia neonatorum and sepsis.50 Identification and treatment of the infection in neonates is crucial, as permanent sequelae such as blindness can occur.
Syphilis is caused by Treponema pallidum; complications are many (eg, mucocutaneous lesions, altered mental status, visual and auditory abnormalities, gumma, cranial nerve palsies).
If a penicillin allergy is present, women with IgE-mediated hypersensitivity can undergo desensitization. Penicillin effectively prevents transmission to the fetus and treats the fetus, if already infected. Treatment during the second half of pregnancy may increase the risk for preterm labor and fetal distress because a Jarisch-Herxheimer reaction may occur; however, treatment should not be withheld or delayed.
Migraine headaches are associated with estrogen fluctuations in women of childbearing age.
Between 60% and 70% of pregnant women with a history of migraine headaches experience symptom improvement during pregnancy; 20% experience complete cessation. Improvement is more likely in women who have migraine without aura and in women with a history of menstrual migraine.
All NSAIDs are contraindicated in the third trimester because of the potential for premature closure of the ductus arteriosus. Aspirin should be avoided in the third trimester because, in addition to its effects on the
ductus arteriosis, it can cause maternal and fetal bleeding as well as decreased uterine contractility (hence, prolonged labor). Opioids are rarely used.
For migraines that are not responsive to other treatments, triptans may be used; sumatriptan is the triptan of choice because for other triptans, there is relatively little information about use in pregnancy. Ergotamine and dihydroergotamine are contraindicated because of effects on uterine tone.
Streptomycin – ototoxic to fetus
Health consequences of untreated or poorly treated asthma include preterm labor, preeclampsia, intrauterine growth restriction, premature birth, low birth weight, and stillbirth; therefore, the treatment goal is to achieve and maintain control of asthma symptoms. Asthma is controlled when there are no daytime symptoms, limitations of activities, nocturnal symptoms, short-acting β2-agonist use, or exacerbations, and there is normal pulmonary function.
Intranasal corticosteroids are most effective Rx, low risk of systemic effect (Beclomethasone, Budesonide are most widely studied)
Second gen Antihistamines do not appear to increase fetal risk but are less extensively studied than first generation products.
Diabetic retinopathy may worsen, hypertension may develop, renal function may deteriorate.
Diabetes in pregnancy includes pregestational and gestational diabetes. Women with pregestational diabetes should be counseled about
Increase risk of complications such as miscarriage, fetal/neonatal death, malformations, macrosomia, preeclampsia, need for cesarean section.
Euglycemia at conception and during pregnancy is the best approach in preventing poor pregnancy outcomes.
Women with type 2 DM may be started with insulin therapy before pregnancy if they do not achieve optimal control of DM.
Gestational DM is associated with neonatal macrosomia, PE, cesarean section but not with major fetal malformations.
Diabetic retinopathy may worsen, hypertension may develop, renal function may deteriorate.
Intravenous drip insulin should be used during labor.
Increase maternal volume of distribution, decrease protein binding from hypoalbuminaemia,
increase hepatic metabolism, increased renal drug clearance – changes in free serum concentrations of antiepileptic drugs.
A woman’s clinical condition and her free serum
concentrations of antiepileptic drug should be the basis for dose adjustments.
Only single course. Current guidelines do not support the use of repeated courses of corticosteriods.