by Dr Charles Nansel

 

 

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 during pregnancy.

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

EPIDEMIOLOGY

¨More than 90% of pregnant women take prescribed or non-prescribed (OTC) medicine or use social drugs (like tobaco and alcohol) or illicit drugs at some time during pregnancy.

¨About 2-3% of all birth defects result from drugs that are taken to treat disorders or symptom

PRINCIPLES OF THERAPY

¨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.

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

¨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.

DRUG EFFECTS ON THE PREGNANCY

ØThe fetus is very sensitive to any drugs, and drugs may cause teratogenicity or other adverse effects.

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

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

MECHANISM OF ACTION OF DRUGS IN PREGNANCY

¨They can act directly on the fetus, causing damage, abnormal development (leading to birth defects), or death.

¨They can alter the function of the placenta, usually by causing blood vessels to narrow (constrict) and thus reducing the supply of oxygen and nutrients to the fetus from the mother. Sometimes the result is a baby that is underweight and underdeveloped.

¨They can cause the muscles of the uterus to contract forcefully, indirectly injuring the fetus by reducing its blood supply or triggering preterm labour and delivery.

¨They can also affect the fetus indirectly. For example, drugs that lower the mother’s blood pressure may reduce blood flow to the placenta and thus reduce the supply of oxygen and nutrients to the fetus.

TERATOGEN

¨A teratogen is defined as any agent that results in structural or functional abnormalities in the fetus, or in the child after birth, as a consequence of maternal exposure during pregnancy

TERATOGENICTY

ØTeratogenicity is the ability of a substance to cause abnormal development of the fetus when taken by pregnant women.

Ø Drug can affect fetus at three stages:

¨1. stage of fertilization and implantation

¨2. stage of organogenesis

¨3. stage of growth and development

CATEGORY

¨The U.S. Food and Drug Administration has generated a grading system in 1974 for medications used during pregnancy. The categories are A, B, C, D, and X.

FDA CATEGORIES FOR THE TERATOGENIC EFECTS OF DRUGS

vCategory A:

¨Adequate studies in human demonstrate no risk (Thyroxine, magnesium sulfate)

vCategory 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 (penicillin, amoxicillin, erythromycin)

vCategory 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 (morphine, codeine, atropine) 

    vCategory D:

    ¨There is evidence of human fetal risk, but the potential benefits to the mother may be acceptable (Aspirin, phenytoin, methotrexate)

    vCategory X

    ¨Contraindicated in pregnancy: Proven fetal risks clearly outweigh any possible benefits. drugs in this group are: Alcohol, ACE inhibitors, Lithium, Methotrexate, Valproic acid, Mifepristone, Diazole, Isotretinoin,Radioactive iodine and others.

    COMMONLY USED DRUGS IN PREGNANCY AND THEIR CATEGORIES

  • ¨ANALGESICS & ANTIPYRETICS: paracetamol [cat B].

    ¨NAUSEA & VOMITING: metoclopramide, ondensetron, meclizine [catB].

    ¨ANTIDIARRHEAL: loperamide [cat B].

    ¨HEARTBURN &DYSPEPSIA: Non absorbable antacid like aluminium hydroxide [catB], H2 blockers [cat B], ALL PPIS-catB except Omeprazole [cat C].

  • ¨DRUGS FOR CONSTIPATION: Bulk laxatives [catB].

    ¨DRUGS FOR HYPERTENTION:

    üMethyldopa [catB].

    üBeta blockers[cat C] like atenolol, labetolol & acebutolol.

    üHypertensive emergencies- hydralazine[cat C].

    üACE inhibitors  [cat D]-contraindicated.

    üDiuretics: furosemide-cat C, Thiazide-cat D, Sipronolactone-cat B.

  • SOME MEDICATIONS CONTRAINDICATED IN
    PREGNANCY AND SIDE EFFECT
  • ØThalidomide –

    ¨Causes seal-like limbs and other defects

    ØWarfarin (Wafrin) –

    ¨Causes multiple birth defects

    ØSimvastatin (Avastin)and other statins –

    ¨Cholesterol is needed for fetal growth and its reduction by statins could harm the fetus

    ØOral contraceptives-

    ¨Can cause birth defects.

  • ØAspirin

    ¨Acetylsalicylate, a common ingredient in many OTC painkillers, may make a pregnancy last longer and may cause severe bleeding before and after delivery. High doses in the last few weeks cause premature closure of ductus arteriosus, persistent pulmonary hypertension and kernicterus in newborn.

    ØVitamin A and its derivatives

    ¨can cause birth defects.

    CONCLUSION¨If “safe use of a drug in pregnancy has not been established, It should not be administered to woman of childbearing age unless in opinion of treating physician, expected benefits to patient markedly outweigh possible hazard to child or fetus”

    ¨Always consider risk of untreated maternal condition.

  • REFRENCES
  • ¨Goodman &Gilman’s The Pharmacological Basis of Therapeutics 12TH Edition

    ¨Lippincott illustrated Reviews: Pharmacology 6th Edition.

    ¨Center for disease control and national birth defects prevention network(NBDPN). Preventing birth defects.available at http://www.nbdpn.org/current/2008pd/prevbdbroch.pdf

    ¨FDA drug safety communication:selective serotonin reuptake inhibitor(SSRI) antidepresseant use during pregnancy at http://www.fda.gov/drugs/drugsafety/ucm283375.htm