DRUG USED IN PREGNANCY

We Are In Era Of E. B. M. Absence of Evidence is

NOT An Evidence of Absence

Pregnancy - Whether planned or unplanned , a pleasant or an unpleasant surprise always brings concerns about prescription and over the counter drugs.

oesophageal & duodenal atresia. primarily phocomelias – Other effects included: • facial hemangiomata.000 birth defects.History • Thalidomide: probably the most notorious human teratogen • Marketed as a sedative in late 1950’s – Associated with up to 12. renal agenesis & anomalies of the external ear . teratology of Fallot.

Thalidomide • No malformations if taken before the 34th day after last menstruation & • Usually no malformations if taken after the 50th day • Sensitive time period: day 35 to day 49 – – – – Day Day Day Day 35 39 43 46 – – – – 37: 41: 44: 48: absence of ears & deafness absence of arms phocomelia with three fingers thumbs with three joints If taken throughout the sensitive period: severe defects of the ears. arms & legs & internal malformations often leading to early death (40% died before their 1st birthday) Continue .

Belgium. Canada.g. Finally withdrawn in Japan in Sept 1962 – Peak in epidemic occurred in Japan at a time when epidemic had ended in Germany Continue . Withdrawn in Germany at the end of Nov 1961 – end of malformation ‘epidemic’ seen in July 1962 (as predicted) Thalidomide continued to be sold for several Months in some countries e. Italy & Japan.Continue Association between thalidomide and human teratogenicity suspected by Lenz (Germany) in November 1961 & endorsed By a letter by McBride to the Lancet in November 1961. Brazil.

Continue • 20% of pregnancies exposed during this period resulted in anomalies • Administration to female rabbits did not show any adverse effects on fertility – There was an increase in early pregnancy loss (equivalent to miscarriage) – There were no thalidomide-associated malformations in surviving foetuses .

Overview • All drugs should be avoided in pregnancy unless they are ‘essential’ • In practice. the risks almost always outweigh the (often trivial) benefits . the risks may be largely unknown or unquantifiable – For minor conditions. it may not be easy to know what treatment is really necessary or whether a particular medicine is an appropriate choice • Requires a balanced approach: – Being over-cautious may deny a beneficial therapy – Lack of due caution might harm babies as a consequence of drug exposure • Benefits of treatment need to be weighed against the risks of giving no medication – Note: while the benefits of Tx may be clear.

The problem • 80% of women use prescribed or OTC drugs during pregnancy – 3 – 8 different drugs (partly prescribed and partly self-medication) • The risks of drug use in pregnancy has lagged far behind advances in other areas of pharmacotherapy • Main reasons: epidemiological difficulties in establishing causality and ethical barriers to prospective RCTs .

it is not totally immune to exposure from exogenous substances. women have been advised to avoid drug usage in pregnancy because of possible harm to the fetus.INTRODUCTION Since antiquity. .Though the uterine environment is priviledged. .

The overriding concern is the potential effects of medication fetus. Radiation Drugs) so-called .A Teratogen is defined as a drug or other agent that causes abnormal development: (Rubella virus. on the developing TERATOGENESIS ..

Tetratogenesis (Greekword) is the origin or mode of production of a monster or a disturbed growth process involved in the production of a monster (Teras: meaning monster Genesis: meaning origin. .

.Teratogenesis may be classified as • Morphologic – classical teratogenesis • Functional teratogenesis • Behavioural teratogenesis * In human being the classic teratogenesis is from approximately day 17 to day 54 post conception.

The timing of exposure to a teratogen determines the nature and extent of adverse effects. 2.e damage to all or most cells leads to death. i. .Tends to be an ‘all or nothing effect’.Factors to consider in Drug prescription in Pregnancy 1. (a) Pre-embryonic phase (days 0-14 after conception) . Most drugs. with molecular weight >1000 cross the placenta and are excreted in breast milk.

Most crucial period of organogenesis and therefore the time of greatest theoretical risk of congenital malformation.- If small no of undifferentiated cells are involved. (c) Fetal phase (9th week to birth) . normal development is likely. .Fetal growth and development can be impaired by drugs taken during this phase. (b) Embryonic phase (3-8weeks) .

warfarin may cause Haemorrhage some drugs given close to term may affect the neonate e.- Drugs which cross the placenta may have direct actions on the fetus e. Even non prescription drugs such as cough medianes conaining lodides can be harmful . 3.g.g. diazepam or pethidine.

Prescribe drugs which have been well tried in pregnancy in preference to newer preparations. Use the smallest effective dose for the . avoid all drugs in the first trimester. PRINCIPLES FOR PRESCRIBING DURING PREGNANCY AND LACTATION. 3. 2.1. Drugs to be given only when he indications are clear and specific and the expected benefit to the mother is greater than the risk to the fetus If at all possible. 4.

based on controlled studies in pregnancy e. CATEGORY A . food and Drug Administration) 1. Hydrolorothiazide . L-Thyroxine 2.Safe in animals but not confirmed in human studies e.CATEGORISATION OF DRUGS IN PREGNANCY: (According to US. CATEGORY B .g.Essentially safe.g.

CATEGORY C .3.Animal studies reveal adverse effects on the fetus (embryocidal. Theophylline Nifedipin. • Use only if potential benefits justifies risk to fetus e. teratogenic) No controlled studies in women or studies in women not available.g. .

Cytoxan despite risk .Contraindicated in women who are or may become pregnant e.Benefit may be acceptable.4.g. CATEGORY D .Drug may be necessary in life – threatening situations.g. CATEGORY E . Aminopterin oral contraceptive . e. 5.Positive evidence of human fetal risk .

. ACE inhibitors. carbamazepine. aminopterine. warfarin. methotrexate. phenytoin. lithium. Alcohol.POTENTIAL FETAL EFFECTS OF SOME DRUGS I. - Drugs with human Teratogenic potential Thalidomide. Angiotesin receptor blockers.

II. (c) Aminoglycosides – affect fetal vestibular and auditory systems. (d) Quinolone antibiotics – skeletal abnormalities in rat (e) Immunosuppressives Fetal toxicity . Other Drugs to Avoid drug pregnancy (a) Methimazole .Aplasia cutis. fetal goiter (b) Tetracycline Bone and tooth enamel effects in 2nd trimester.

zidovudine. Beta blockers Acyclovir. Drugs without Conclusive Adverse Effects Acetaminophen. cephalosporins. Hydrochlorothiazide calcium channel blockers. macrolydes (erythromycin) metronidazole. Penicillin derivatives.III. .

.May require pre-conceptional counselling and informed choice for patients to know the risk to her unborn child if some medications are not taken .Drug Usage in Pregnancy can be (1)Prophylactic (2)Therapeutic Prophylactic – To prevent certain adverse consequences during pregnancy.

Necessary component for proper hematopoiesis.Deficiency leads to ↑ed risk of neural tube defects Fe.g. Folic Acid . .g Excess B6 causing Neurotoxicity at doses exceeding 200mg/day or Vitamin A may be teratogenic at doses exceeding 8000µg/day .e. . e.Vitamin supplement: Excesses of these vitamins may be bad in pregnancy.

.Therapeutic Medications Advances in Medicine and technology have led many patients with chronic medical illness to get pregnant and carry their pregnancy successfully to viability and the need to continue their medication in pregnancy is imperative.

Has a high molecular weight and charge Does not cross placenta and is not teratogenic No fetal risks Maternal risks -osteopenia or osteoporosis . Heparin: .Some of the Medications in use include: (a) Anticoagulants – particularly in patient with thromboembolic disease or who are at high risk for thromboembolic disease.parenterally administered anticoagulant .

scoliosis.Heparin is the preferred anticoagulant in 1st trimester and some few weeks towards delivery.Warfarin (Coumadin) . epiphyseal stippling.Contraindicated in first trimesters .Teratogenic (Warfarin embryopathy) causing nasal hypoplasia. . . optic atrophy. mental retardation and microcephaly.

additional folic acid must also be given.B.Morphine and pethidine given within 2-3hrs of delivery will depress the fetal respiratory center. . C Sedatives and Analgesics . Anticonvulsants Phenytoin (Epanutin): • given to control epilepsy • is a folic acid antagonist and if used in pregnancy.

Indomethacin may inhibit prostaglandin synthesis and produce premature closure of the fetal ductus arteriosus. and there is hypotonia after delivery.Before delivery will depress the fetal medullary centers and cause loss of the normal baseline variation of he heart rate. Diazepam .g.. . They may postpone onset of labour.Aspirin and other non steroidal antiinflammatory drugs e.

D. Antihypertensives: Alphamethydopa is a category B drug while others such as bethanidine.damages 8th cranial nerve  congenital deafness. guanethidine and hydralazine are category C drugs but seem to have no harmful effect on the fetus. Penicillin – safe in pregnancy . E. Antibiotics Sulfonamides compete with billirubin for binding sites or serum Albumin and ↑ risk of kernicterus. Streptomycin .

G. Antithyroid drugs – cause fetal goitre – or hypothyroidism e. When mothers are addicted babies of low birth weight are delivered with ↑ chance of neonatal and infant mortality. Alcohol During Preg. Thiouracil.should not be used in pregnancy H.F. .g. Cytotoxic and Alkylating Agents – may harm the fetus .

a long upper lip and a small lower jaw with mental retardation.a few will have fetal Alcohol syndrome with characteristic facial appearance with a broad base to the nose. I Smoking – • harmful to the fetus and gives rise to LBW. . epicanthic folds. • CO interferes with 02 transport • Nicotine causes vasoconstrive effect of placental bed..

viral load Benefits of its use outweighs their risk. Long term study is necessary to determine their full effects on the fetus. *Marijuana * Heroine * Cocaine K. - - . They all reduce: vertical transmission of HIV. Antiretroviral Therapy Has become more common place during pregnancy to prevent MTCT. A lot of them are being used in various combination.J.

Excellent communication between health care providers and recipients is essential to optimize pregnancy outcome. The contribution of effective preconception counselling to improving pregnancy outcome can not be emphasized. .CONCLUSION Medication use in pregnancy creates a challenge for the health care provider as well as the patient. Judging benefits and risks can be objective but in many instances is largely subjective.