Pharmacology and Medications used in pregnancy. FDA categories and which medications are safe to use in pregnancy.

1. Pharmacology and
Medications in Pregnancy
M. TENO
MBBS, DGO
31st July 2023

2. Outline
 Introduction
 Physiological Changes in Pregnancy
 Placental transfer of drugs
 Critical period in fetal development and teratogenesis
 FDA categories of drug use in pregnancy
 Commonly used drugs
 References

3. Introduction
 Medications or drugs are only used in pregnancy when “indicated.”
 Physiological changes during pregnancy affect drug therapy including
pharmacokinetics
 Use of drugs is associated with 2-3% of all birth defects other than alcohol.
 Medications are essential when medical conditions are superimposed on
pregnancy.

4. Physiologcial Changes in Pregnancy
System Changes
GIT Nausea & vomiting, ↓ gastric motility and emptying
CVS CO ↑ 30-50%, SBP & DBP ↓ in T2, plasma volume ↑ 45%
Resp ↑O2 consumption (32-58mls), ↑ TV 40%, ↓PaCO2 27%
Liver No change in size/blood flow. ↓ serum albumin levels, ↓
colloid osmotic pressure
Renal ↑ in size/blood flow 60-80%, ↑ GFR
Coagulation System Hyper-coagulable state
Weight ↑ BMR 15-20%, weight gain

5. Impact of Pregnancy on maternal pharmacokinetics
PHARMACOKINETIC
PROPERTY
PHYSIOLOGOGICAL PARAMETER EFFECT
Absorption ↓ GI motility
↓ gastric emptying time
Hypertrophy of duodenal villi
↑ gastric acid pH
↑ systemic absorption of medications
Distribution ↑ palsma vol
↑ adipose tissue volume
↑ cardiac output
↑ volume distribution
↓ plasma drug concentration
Excretion ↑ GFR and renal blood flow ↑ clearance of drugs that are cleared
through the kidney (especially in T3)
Protein binding ↓ albumin concentration ↑ free drug concentration of high protein
bound drugs
↑ drugs total clearance
Metabolism &
bioavailability
Blood flow to liver is unchanged ↑ hepatic metabolism occurs for some
drugs, ↓ bioavailability or no change

6. TRANSFER OF DRUGS ACROSS PLACENTA
Rate of transfer of a drug depends on:
Molecular size
Lipid solubility
pH difference (7.0 vs 7.4): ionic trapping of weak
basic drugs (e.g. morphine)
Ionization of drugs

7. William’s Obstetrics (22nd Edition). 2005. McGraw-Hill Companies. Inc
• Placenta is capable of
metabolizing drugs
• Little relevance to mother
• Protective effect on fetus

8. Drugs can affect the fetus in several ways:
1. Act directly on the fetus, causing damage, abnormal
development (birth defects, or death.
2. Alter function of placenta, by constricting blood vessels
and ↓ oxygen and nutrient supply.
3. Stimulate forceful uterine contractions, which can affect
the fetus by ↓ blood supply and stimulating preterm
delivery

9. Effect of toxic Drugs on the fetus
No effect
Little effect
Serious fetal toxicity
Spontaneous abortion
Death
Fetal malfunction/malformation

10. Harmful effects depends on
 Nature of drug, dose and route of administration
 Trimester of pregnancy at which drug is administered
 Genetic constitution and susceptibility of fetus
 Directly on the fetus – birth defects or death
 Alter the function of the placenta - by constricting blood
vessels, ↓ blood supply of O2 and nutrients to the fetus
 Contract uterus:
↓ blood supply to fetus
Trigger pre-term labour and delivery

11. Gestation is divided into 4 stages
Blastocyst formation (0-16days or first 2 weeks)
Teratogen(s) can either:
Inhibit cell division and kill embryo or
Normal subsequent development, if embryo survives exposure to
drug
Organogenesis (17-60days or week 3 to 8)
Teratogen causes gross structural malformation

12.  Histogenesis and maturation (final stage)
 Teratogens have a deleterious effect on growth and maturation
 e.g.
DES (diethylstilbesterol)– dysplasia, vaginal Ca in female offsprings
Androgen exposure - masculinization of female infants
 Short labour and delivery
 Drug administration poses the risk of neonatal toxicity.

14. What is a teratogen?
 Terato = teras (Greek) + gen = genesis ----- teratogen
Something unsual or abnormal in size, composition or appearance
 Congenital anomalies caused by teratogens and visible at birth
 Exert its effect on a particular stage of fetal development
 Show dose dependent incidence
 Include radiation, maternal infections, chemicals and drugs.

15. Examples of teratogenic agents
Drugs • Thaliomide
• Sodium Valproate
• Methotrexate
• Lithium
• Warfarin
Environmental agents • Ionizing radiation
• fever
Infections • Rubella
• Cytomegalovirus (CMV)
• Parvovirus
• Syphilis
Toxins • Alcohol
• Phenylalanine
• Lead
• Mercury
Nutrients • Folic Acid
• Vitamin A

16. Fetal Warfarin Syndrome:
Chondrodysplasia Punctata
Aminopterin
Thalidomide
Disorders of musculoskeletal
system: phocomelia or amelia
Anencephaly,
hydrocephalus, cleft lip
and palate
Nasal hypoplasia, limb
hypoplasia, optic atrophy, bone
abnormalities, neurological
impairement
Clinical Pharamcology during Pregnancy. 2013

17. Rubella
Syphillis
Classic triad of rubella: cataract, cardiac
abnormalities & deafness
Anomalies and deformations of musculoskeletal
system: Amelia
Clinical Pharamcology during Pregnancy. 2013

18. Fetal Alcohol Syndrome

19. (U.S Food and Drug Administration)
• Folic Acid
• Vitamin B12
• Acetaminophen or
paracetamol
• Insulin
• Famotidine
• Fluconazole
• ciprofloxacin
• Phenytoin
Medications that are
contraindicated: Warfarin,
Methotrexate,
Medroxyprogesterone (Depo)
Medications that can be
used

20. DRUGS WITH PROVEN TERATOGENIC EFFCTS
DRUGS EFFECTS
Phenytoin • Fetal Hydantoin Syndrome
• Cleft Lip/palate and CHD
Vitamin A-
derivatives
• Isotretinon, etretinate
• ↑ risk of miscarriage and other significant anomalies
ACEIs • Renal damage and oligohydramnios in T2/T3
• Anomalies of face, limbs and lungs
Valproate and
carbamazepine
• CNS defects: spina bifida, anencephaly, encephalocele
Warfarin • Fetal warfarin syndrome
• Nasal hypoplasia, depressed nasa; bridge & hemorrhagic
disorders in fetus
NSAID’s
(diclofenac,
ibuprofen,
naproxen)
After 20 weeks:
• Premature closure of ductus arteriosus
• Kidney problems  Oligohydramnios
(Aspirin is only used when indicated)

21. Clinical Pharamcology during Pregnancy. 2013
Bilateral cleft Lip Palate

22. Clinical Pharamcology during Pregnancy. 2013
Meningocele Mylomeningocele

23. COMMONLY USED DRUGS IN
PREGNANCY

24. Category Drugs used Contraindications
Developed
Countries
LMICs
Analgesics &
antipyeretics
Acetaminophen,
phenacetin, aspirin
Acetaminophen (panadol) NSAID’s avoided towards end of
pregnancy: risk of PDA
Anti-emetics Cyclizine, meclizine,
ondansteron
Metoclopromide
(maxalon)
Antibiotics Beta-lactam, nitrofurantoin, erythromicin
Antiamoebic Metronidazole
Antimalarials Coartem, Quinine Primaquine (for mixed infection)
Anti-TB FDC: Isoniazid, Rifampicin and Ethambutol Streptomycin and Kanamycin –
ototoxicity, , Amikacin –
congenital otoxicity
Anti-fungal Nystatin,
miconazole
Nystatin, miconazole,
clotrimazole
Ketoconazole – fetal
malformation

25. Category Drugs used Contraindications
Developed
Countries
LMICs
Anti-asthmatic Beta-agonist, glucocorticoids
(salbutamol, prednisolone, dexamethasone,
cortisone)
Cardiac Digoxin and quinidine
Anti-
hypertensives
Methyldopa,
labetalol
Methyldopa, Nifedipine Enalapril - oligohydramnios
Anti-coaguant Low molecular weight heparin (LMWH) Warfarin
Anti-
Helminithic
Piperazine, pyrantel Albendazole
Anti-
convulsants
Magnesium Sulphate (MgSo4) Phenytoin, carbamazepine,
phenobarbiturate

26. References
 Carachi and Doss. Clinical Embryology – An Atlas of Congenital Malformations.
2019. Springer Internataional Publishing AG, United Kingdom.
 Currie, D. Drug Therapy During Pregnancy [PowerPoint slides]. SlideShare
 Donald Mattison. Clinical Pharmacology During Pregnancy. 2013. Alsevier Inc,
London, UK.
 Karch, A. Lippincott’s Nursing Drug Guide. 2011. Wolters Kluwer – Lippincott
Williams & Wilkins, Philadelphia, US.
 Manjuprasad. Drug Therapy in Pregnancy [PowerPoint slides]. slideShare