Drugs used during Pregnancy

Question 1

What factors are to be considered in the therapeutic decision making when it comes use of drugs in pregnancy?

Answer 1

1. The health of the woman
2. The delivery of a healthy baby
3. Altered pharmacokinetics associated with pregnancy
4. Altered pharmacodynamics associated with pregnancy
5. The probable lack of information regarding the effects of drugs on the developing fetus

Question 2

What are the maternal pharmacokinetic changes in pregnancy?

Answer 2

1. Increased total body water (↑30 -40%)
2. Increased hepatic metabolism
3. Increased renal blood flow (↑30)
4. Decreased plasma protein concentrations
5. Increased cardiovascular function
6. Decreased GIT motility/tone
7. Hypercoagulation state

Question 3

Describe the physiological changes that can influence drug disposition in mother and fetus?

Answer 3

1. Maternal plasma albumin is reduced - influencing plasma binding
2. Cardiac output is increased - leading to increased renal blood flow & increased renal elimination of drugs
3. Lipophilic molecules quickly transverse the placental barrier, whereas the hydrophyllic drugs are slow.
4. The placental barrier, excludes some drugs so effectively that their chronic administration to the mother will not affect the fetus
5. Drugs that are transferred across the placental barrier are slowly eliminated. The activity of most drug metabolizing enzymes in fetal liver is much less than that in the adult.

Question 4

Is the fetal kidney and efficient route of drug elimination?

Answer 4

is not an efficient route of elimination

- the excreted drug enters the amniotic fluid, which is swallowed by the fetus

Question 5

What should always be addressed when prescribing a drug to a pregnant woman?

Answer 5

1. The probability of placenta transfer
2. How the drug will/can affect the fetus
   - Through effects on organogenesis
   - Organ development
   - Or delivery complications
3. The risk of fetus and mother, associated with the underlying maternal illness
   - Treatment of underlying illnesses of mothers should continue with drugs that have proven effective but experimenting with new drugs should be avoided

Question 6

What are the general guidelines for drug use in pregnancy?

Answer 6

1. Avoid drug use in 1st trimester whenever possible
2. If possible delay treatment of minor conditions until after delivery (e.g. worms)
3. Drug treatment only indicated when clearly required
4. Avoid new drugs (choose drugs based on safety data; well established products preferable)
5. Drugs dosed at minimum effective dose for shortest period of time
6. Avoid polypharmacy whenever possible
7. Discourage self-medication (herbal/natural remedies)

Question 7

Name pregnancy influenced issues?

Answer 7

1. Nausea and vomiting
2. Constipation
3. Haemorrhoids
4. Reflux esophagitis
5. Other conditions
   - Gestational Diabetes
   - Hypertension and pre-eclampsia
   - Venous thromboembolism
   - Gestational thyrotoxicosis

Question 8

What are the non-pharmacological treatments for nausea and vomiting?

Answer 8

1. Dietary modifications
2. Frequent, small, bland meals
3. Avoid fatty foods
   - to prevent ↓gastric emptying
4. Vitamin B6 (pyridoxine) 50 -100mg/d

Question 9

What are the pharmacological treatments of nausea and vomiting?

Answer 9

1. Multivitamins
2. Vitamin B6 (pyridoxine) 50 -100mg/d
3. Vitamin B12
4. Antihistamines: doxylamine
5. Phenothiazines & Metoclopramide

Question 10

What is the non-pharmacological management of constipation?

Answer 10

1. Education
2. Physical exercise
3. Increased dietary fibre and fluid intake

Question 11

What do you do when non-pharmacological management of constipation has failed?

Answer 11

1. Supplemental fibre
2. Stool softener
   - Lactulose
   - Sorbitol
   - Bisacodyl
   - Senna
   Note: AVOID: castor oil and mineral oil

Question 12

What are the 3 stages of fetal development?

Answer 12

1. Blastogenesis : 15 - 21 days
2. Organoogenesis : 21 - 90 days
3. Fetogenesis : more than 90 days after fertilization

Question 13

When is the fetus the most vulnerable to the effects of maternal drug therapy?

Answer 13

during first and third trimesters

Question 14

What drug properties can affect the degree of placental drug transfer?

Answer 14

1. molecular size
2. pH
3. lipid solubility

Question 15

How does molecular size affect the degree of placental drug transfer?

Answer 15

Drugs with very large molecules, e.g. Heparin do not cross the placental membrane as readily as drugs with smaller molecules

Question 16

How does the pH of the drug affect the degree of placental transfer of the drug?

Answer 16

Weakly acidic and weakly basic drugs tend to be rapidly transferred.

Question 17

How does lipid solubilty affect the degree of placental transfer?

Answer 17

generally, highly lipid-soluble compounds do not diffuse across the placental membrane as easily as less lipid soluble compounds

Question 17

How does lipid solubilty affect the degree of placental transfer?

Answer 17

generally, highly lipid-soluble compounds do not diffuse across the placental membrane as easily as less lipid soluble compounds

Question 18

Describe the physical characteristics of the placenta that affect placental transfer of the drug?

Answer 18

1. As pregnancy progresses, and the placenta ages, placental drug transfer is efficient
2. the presence of placental enzymes and the thickness of the placenta, which change during the course of pregnancy, may reduce placental transfer
3. The pH gradient between the maternal and fetal circulation

Question 19

What are embryocidal drug effects?

Answer 19

These are those that harm the developing embryo resulting in termination of pregnancy.

• Since the placenta, which provides some protection has not yet fully formed
• Some drugs may result in spontaneous abortion by causing a severe chemical insult to embryo before cell differentiation

Question 20

Name drugs that are embryocidal?

Answer 20

1. Hormones
2. Antidepressants
3. ACE inhibitors
4. Certain antiinfectives

Question 21

What are teratogenic effects?

Answer 21

These cause physical defects in the fetus
- this risk is highest in the first trimester, when organs are differentiating.
Note: Teratogenesis may lead to physical deformaties and mental abnormalities.

Question 22

What is dysmorphogenesis?

Answer 22

development of ill-shaped/otherwise malformed body structures (structural and functional defects)

Question 23

What is a congenital anomaly?

Answer 23

non-reversible birth defect caused by genetic pre-disposition/ other factors e.g. drug exposure
- examples: spina bifida, hydrocephlus

Question 24

What determines the teratogenic effects with the use of drugs in pregnancy?

Answer 24

Specific teratogenic effects depends on when the drug was ingested since organ system development occurs at different times

Question 25

Describe the incidence of birth defects with use of drugs in pregnancy?

Answer 25

1. Incidence of spontaneous malformations in neonates = 2-3% (1:40 live births)
2. Incidence of spontaneous miscarriage rates = 10-20%
3. Incidence of drug-induced birth defects estimated to be <1% (conservatively 2-3%)

Question 26

Describe the thalidomide tragedies?

Answer 26

Thalidomide is sedative-hypnotic drug: tranquiliser, pain killer
which was used as remedy for morning sickness
8000 women in 28 countries: babies born with major congenital defects
- 1/3 of babies exposed in utero

Question 27

Describe the classification system on drugs and the degrees of potential risk during pregnancy?

Answer 27

Category A – controlled studies have not demonstrated a risk in the first trimester
Category B – studies show adverse effects on animal fetuses studies but not on human studies.
Category C – teratogenic effects have been shown in animal fetuses but human studies are not available.
Category D – Evidence of human fetal risk exists, but a threat to the mothers life may warrant the use of these drugs.
Category X – The risks of using these drugs outweigh the benefits: All studies show severe harm to the fetus.

Question 28

Give examples of potentially teratogenic drugs?

Answer 28

1. Vitamin A derivatives e.g. isotertretinoin (accutane)
   - may result in severe human deformities
2. Oral antihyperglycemic agents e.g. chlorpropamide
   - these drugs should be replaced with insulin in pregnant women
   - Most toxicity problems associated with diabetic mothers are probably related to high maternal serum glucose levels
3. warfarin + derivatives
   - these drugs can be replaced by heparin which is poorly transported across the placenta, when coagulant therapy is necessary
4. Estrogen and oral contraceptives
   - These drugs (category X drugs) may cause severe genital tract malformations
5. Other hormonal agents.
   - Thyroid preparations & cortisone may affect the development of fetal endocrine glands
6. Tetracycline
   - Mottling of teeth, when it is taken after the 18th week of gestation
   - This effect does not become apparent until later in childhood when tooth eruption occurs.

Question 29

What are fetotoxic drug effects?

Answer 29

These are physiologic effects in the developing fetus

- During Fetogenesis, these are likely to occur than teratogenic effects

Question 30

Describe clinically significant fetotoxic effects include?

Answer 30

1. CNS depression
   - barbiturates, tranquilizers, antidepressants and narcotics
   - Anasthetics and analgesics used during labour may also cause significant CNS & respiratory depression in newborns.
2. Neonatal bleeding
   - Maternal ingestion of agents such as NSAIDs, antidepressants and anxiety medications may cause bleeding in newborns
3. Drug dependence
   - Habitual maternal use of barbiturates and narcotics may lead to withdrawal symptoms in the neonate.
4. Reduced birth weight
   - Pregnant women who smoke or consume large amounts of alcohol have an increased risk of delivering an underweight infant