Drug use in pregnancy and lactation (1)

Drug Use inPregnancy and lactation (1)

By

M.H.Farjoo M.D. , Ph.D.Shahid Beheshti University of Medical Science

M.H.FarjooM.H.Farjoo

Drug Use in Pregnancy and lactation (1)

Introduction Principles of Therapy Physiologic – pharmacokinetics Changes Maternal – Fetal Circulation Drug Effects On The Fetus Drug Categories in Pregnancy Fetal Therapeutics Dietary Supplements Pregnancy-Associated Problems


Introduction

Drug use during pregnancy and lactation requires special consideration because both the mother and the child are affected.

Few drugs are considered safe, and drug use is generally contraindicated.

Many pregnant or lactating women take drugs for acute or chronic disorders or habitual use of alcohol and tobacco.


Principles of Therapy: Pregnancy

Give medications only when clearly indicated, weighing benefits to the mother against the risks to the fetus.

Any drugs used during pregnancy should be given in the lowest effective doses and for the shortest effective time.

The choice of drug should be based on the stage of pregnancy and drug information.


Principles of Therapy: Pregnancy (Cont,d)

During the first trimester, an older safe drug is preferred over a newer drug of unknown teratogenicity.

Counsel pregnant women about the use of immunizations during pregnancy.

Teratogenicity is the ability of a substance to cause abnormal fetal development when taken by pregnant women



Live virus vaccines (measles, mumps, polio, rubella) should be avoided because of possible harmful effects to the fetus.

Inactive virus vaccines (influenza, rabies, hepatitis B) and toxoids (diphtheria, tetanus) are considered safe for use.

Hyperimmune globulins can be given to pregnant women who are exposed to hepatitis B, rabies, tetanus, or varicella.



Hyperimmune immunoglobulin are IGIVs with high titers of antibodies against viruses or toxins.

Hyperimmune IGIVs are available for hepatitis B virus, rabies, tetanus, and digoxin overdose.

Intravenous administration of the hyperimmune globulins reduces risk or severity of infection.


Principles of Therapy: Lactation

Most systemic drugs taken by the mother reach the infant in breast milk.

For some, the amount of drug is too small for others effects are unknown or potentially adverse.

Give medications only when clearly indicated. For contraindicated drugs, the mother should

stop the drug or stop breast feeding.


Principles of Therapy: Lactation (Cont,d)

Any drugs used during lactation should be given in the lowest effective dose for the shortest effective time.

Stopping breast feeding during maternal drug therapy is not recommend unless necessary.

In some instances, mothers may pump and discard breast milk while receiving therapeutic drugs, to maintain lactation.

Women with HIV infection should not breast-feed. The virus can be transmitted to the nursing infant.


Physiologic – Pharmacokinetics Changes

In the pregnant woman, physiologic changes alter drug pharmacokinetics.

Drug effects are less predictable than in the nonpregnant state.

The physiologic and related pharmacologic changes are as follows:


Physiologic – Pharmacokinetics Changes (Cont,d)

Physiologic Change: 50% Increase in plasma volume and body water.

Pharmacokinetic Change: Water soluble drugs are distributed and “diluted”

more than in the nonpregnant state.

Drug dosage requirements may increase.

This effect may be offset by other pharmacokinetic changes of pregnancy.



Physiologic Change: Increased weight (~14 Kg) and body fat

Pharmacokinetic Change: Fat-soluble drugs are distributed more widely.

Drugs distributed to fatty tissues tend to linger in the body because they are slowly released from storage sites.



Physiologic Change: Decreased serum albumin. The rate of albumin production is increased. However,

serum levels fall because of plasma volume expansion. Many plasma protein-binding sites are occupied by

hormones that increase during pregnancy.

Pharmacokinetic Change: More free drug is available for therapeutic or adverse

effects on the mother and for placental transfer to the fetus. A given dose of a drug is likely to produce greater effects

than it would in the nonpregnant state.

Protein binding Pic.



Physiologic Change: Increased renal blood flow and glomerular filtration rate

secondary to increased cardiac output.

Pharmacokinetic Change: Increased excretion of drugs by the kidneys, especially

those excreted primarily unchanged in the urine (digoxin, lithium).

In late pregnancy, the increased size of the uterus decreases renal blood flow in supine position.

This results in decreased excretion and prolonged effects of renally excreted drugs.


Maternal – Fetal Circulation On the maternal side, arterial blood pressure carries blood and

drugs to the placenta. Drugs readily cross the placenta, mainly by passive diffusion. Placental transfer begins approximately the fifth week after

conception. Drugs given on a regular schedule, equilibrate with fetal blood

which contains 50% - 100% of the maternal blood. After entering the fetal circulation, large amounts of drugs are

active because albumin levels are low and thus low levels of drug is bound.


Maternal – Fetal Circulation (Cont,d)

Drug molecules are distributed in two ways: liver and kidney.

Most are transported to the liver, where they are metabolized.

Metabolism is slow because the fetal liver is immature Drugs metabolized by the fetal liver are excreted by

fetal kidneys into amniotic fluid. Excretion also is inefficient owing to immature fetal

kidneys. The fetus swallows some amniotic fluid, and some

drug molecules are recirculated.


Maternal – Fetal Circulation (Cont,d)

Drug molecules are also distributed to the brain.

Drugs enter the brain easily because the blood–brain barrier is poorly developed in the fetus.

Umbilical arteries transport half of the drug-containing blood to the placenta where reenters the maternal circulation.

Thus, the mother can metabolize and excrete some drug molecules for the fetus.


Drug Effects On The Fetus

The fetus which is exposed to any drugs circulating in maternal blood, is very sensitive to drug effects

Drugs may cause teratogenicity or other adverse effects.

Drug teratogenicity most likely occurs during the first trimester, when fetal organs are formed.

During the 2nd and 3rd trimesters, drug adverse effects are: growth retardation, respiratory problems, infection, or bleeding.


Drug Effects On The Fetus (Cont,d)

Overall, effects are determined mainly by: The type and amount of drugs The duration of exposure The level of fetal growth and development when

exposed to the drugs.

Both therapeutic and nontherapeutic drugs may affect the fetus.


Drug Categories in Pregnancy

Category A: Adequate studies in human demonstrate no risk.

Category B: Animal studies indicate no risk, but there are no

adequate studies in human. Animal studies show adverse effects, but adequate

studies in human have not demonstrated a risk.


Drug Categories in Pregnancy (Cont,d)

Category C: A potential risk, when:

Animal studies have not been performed or, Animal studies indicated no adverse effects and, There are no data from human studies.

These drugs may be used when potential benefits outweigh the potential risks.


Drug Categories in Pregnancy (Cont,d)

Category D: There is evidence of human fetal risk, but the

potential benefits to the mother may be acceptable.

Category X: Studies in animals or humans or adverse reaction

reports or both have demonstrated fetal abnormalities.

The risk of use in a pregnant woman clearly outweighs any possible benefit.


Fetal Therapeutics

A few drugs are given to the mother for their therapeutic effects on the fetus, They include: Digoxin for fetal tachycardia or heart failure

Levothyroxine for hypothyroidism

Penicillin for exposure to maternal syphilis

Prenatal Betamethasone to promote surfactant production in preterm infants.


Dietary Supplements

Pregnancy increases nutritional needs and vitamin and mineral supplements are commonly used.

Folic acid supplementation is especially important, to prevent neural tube birth defects (spina bifida).

Such defects occur early in pregnancy, often before the woman realizes she is pregnant.


Dietary Supplements (Cont,d)

It is recommended that all women of childbearing potential ingest at least 400 mcg daily from food and/ or a supplement.

In addition, pregnancy increases folic acid needs by 5 to 10 fold and deficiencies are common.

A supplement is usually needed to supply adequate amounts.

For deficiency states, 1 mg or more daily may be needed.


Pregnancy-Associated Problems

Anemia Constipation Gastroesophageal Reflux Gestational Diabetes Nausea & Vomiting Pregnancy-Induced Hypertension


Anemia

Three types of anemia are common during pregnancy: Physiologic

Iron- deficiency

Megaloblastic

Results from expanded blood volume• Iron preparations should be given

with food to decrease gastric irritation.

• Citrus juices enhance absorptionCaused by folic acid deficiency


Constipation

Constipation occurs from decreased peristalsis. Preferred treatment, if effective, is to increase

exercise and intake of fluids and high-fiber foods.

If a laxative is required, a bulk forming agent is the most physiologic because it is not absorbed.

A stool softener or an occasional saline laxative (milk of magnesia) may also be used.


Constipation (Cont,d)

Mineral oil should be avoided because it interferes with absorption of fat-soluble vitamins.

Reduced absorption of vitamin K can lead to bleeding in newborns.

Castor oil should be avoided because it can cause uterine contractions.

Strong laxatives or any laxative used in excess may initiate uterine contractions and labor.


Gastroesophageal Reflux

Often occurs in the later months of pregnancy.

Nonpharmacologic interventions (eating small meals; avoiding gas producing food and drinks) are recommended.

Antacids may be used if necessary. Because little systemic absorption occurs.

Cimetidine, ranitidine, or sucralfate may also be used.


Gestational Diabetes

Some women first show signs of diabetes during pregnancy. This is called gestational diabetes.

Women without risk factors, or whose initial test was normal, should be tested between 24 and 28 weeks of gestation.

Initial management includes nutrition and exercise interventions and calorie restriction for obese women.

If drug is necessary, recombinant human insulin is needed to keep blood sugar levels as nearly normal as possible.


Gestational Diabetes (Cont,d)

Oral antidiabetic drugs are generally contraindicated, although acarbose, metformin, and miglitol are almost safe.

These women may revert to a nondiabetic state when pregnancy ends.

They are at increased risk for development of overt diabetes within 5 to 10 years.

Gestational diabetes usually subsides within 6 weeks after delivery.


Nausea & Vomiting Dietary management and maintaining fluid and

electrolyte balance are recommended.

Antiemetic drugs should be given only if nausea and vomiting are severe enough to threaten the mother’s nutritional status.

Dimenhydrinate, 50 mg every 3 to 4 hours, are thought to have low teratogenic risks.

Pyridoxine (vitamin B6) also may be helpful 10 to 25 mg daily.


Pregnancy-Induced Hypertension

Pregnancy-induced hypertension includes preeclampsia and eclampsia.

They endanger the lives of mother and fetus.

Preeclampsia occurs during the last 10 weeks of pregnancy, during labor, or within the first 48 hr after delivery.

It is manifested by edema, hypertension, and proteinuria.


Pregnancy-Induced Hypertension (Cont,d)

Drug therapy includes IV hydralazine or labetalol for blood pressure and magnesium sulfate for seizures.

Eclampsia, occurs if preeclampsia is not treated effectively.

Delivery of the fetus is the only known cure for preeclampsia or eclampsia.

Thank youAny question?

Drug use in pregnancy and lactation (1)

Health & Medicine

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