drug used during pregnancy self

8/2/2019 Drug Used During Pregnancy Self

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DRUG USED IN PREGNANCY


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We Are In Era Of E. B. M.

Absence of Evidence

isNOT

An Evidence of Absence


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Pregnancy- Whether planned or unplanned ,

a pleasant or an unpleasant surprise

always brings concerns about prescription and

over the counter drugs.


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History

Thalidomide:probably the most notorioushuman teratogen

Marketed as a sedative in late 1950s Associated with up to 12,000 birth defects,

primarily phocomelias

Other effects included: facial hemangiomata, oesophageal & duodenalatresia, teratology of Fallot, renal agenesis &anomalies of the external ear


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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 35 37: absence of ears & deafness Day 39 41: absence of arms Day 43 44: phocomelia with three fingers

Day 46 48: thumbs with three jointsIf taken throughout the sensitive period: severe defects ofthe ears, arms & legs & internal malformations oftenleading to early death (40% died before their 1st birthday)

Continue


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Continue

Thalidomide continued to be sold for severalMonths in some countries e.g. Belgium, Brazil,

Canada, Italy & Japan.

Association between thalidomide and human teratogenicitysuspected by Lenz (Germany) in November 1961 & endorsedBy a letter by McBride to the Lancet in November 1961.

Withdrawn in Germany at the end of Nov 1961 end of malformation epidemic seen in July 1962 (as predicted)

Finally withdrawn in Japan in Sept 1962 Peak in epidemic occurred in Japan at a time when

epidemic had ended in Germany Continue


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20% of pregnancies exposed during this

period resulted in anomalies Administration to female rabbits did notshow 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

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Overview

All drugs should be avoided in pregnancy unlessthey are essential

In practice, it may not be easy to know whattreatment is reallynecessary 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 ofdrug exposure

Benefits of treatment need to be weighedagainst the risks of giving no medication Note: while the benefits of Tx may be clear, the risks may be

largely unknown or unquantifiable

For minor conditions, the risks almost always outweigh the(often trivial) benefits


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The problem

80% of women use prescribed or OTCdrugs during pregnancy 3 8 different drugs (partly prescribed and

partly self-medication)

The risks of drug use in pregnancy haslagged far behind advances in other areasof pharmacotherapy

Main reasons: epidemiological difficultiesin establishing causality and ethicalbarriers to prospective RCTs


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INTRODUCTIONSince antiquity, women have beenadvised to avoid drug usage in

pregnancy because of possible harm

to the fetus.

- Though the uterine environment is

priviledged, it is not totally immune toexposure from exogenous substances.


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- The overriding concern is the potential

effects of medication on the

developing fetus, so-called

TERATOGENESIS-A Teratogen is defined as a drug or

other agent that causes abnormaldevelopment: (Rubella virus, Radiation

Drugs)


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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.


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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.


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Factors to consider in Drugprescription in Pregnancy1. Most drugs, with molecular weight

>1000 cross the placenta and areexcreted in breast milk.

2. The timing of exposure to a teratogendetermines the nature and extent ofadverse effects.

(a) Pre-embryonic phase (days 0-14 afterconception)

- Tends to be an all or nothing effect, i.edamage to all or most cells leads to

death.


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- If small no of undifferentiated cells areinvolved, normal development is likely.

(b) Embryonic phase (3-8weeks)

- Most crucial period of organogenesis andtherefore the time of greatest theoreticalrisk of congenital malformation.

(c) Fetal phase (9th

week to birth)- Fetal growth and development can be

impaired by drugs taken during this

phase.


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- Drugs which cross the placenta mayhave direct actions on the fetus e.g.warfarin may cause Haemorrhage somedrugs given close to term may affect theneonate e.g. diazepam or pethidine.

3. Even non prescription drugs such ascough medianes conaining lodides can

be harmful


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PRINCIPLES FOR PRESCRIBINGDURING PREGNANCY ANDLACTATION.

1. Drugs to be given only when heindications are clear and specific and theexpected benefit to the mother is greaterthan the risk to the fetus

2. If at all possible, avoid all drugs in thefirst trimester.

3. Prescribe drugs which have been welltried in pregnancy in preference tonewer preparations.

4. Use the smallest effective dose for the


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CATEGORISATION OF DRUGS INPREGNANCY: (Acco rd i ng t o US ,f ood and D rug Adm in is t r a t i on )

1. CATEGORY A - Essentially safe,based on controlled studies inpregnancy e.g. L-Thyroxine

2. CATEGORY B - Safe in animals butnot confirmed in human studies e.g.Hydrolorothiazide


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3. CATEGORY C - Animal studiesreveal adverse effects on the fetus(embryocidal, teratogenic) No

controlled studies in women or

studies in women not available.

Use only if potential benefits justifies

risk to fetus e.g. TheophyllineNifedipin.


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4. CATEGORYD- Positive evidence of human fetalrisk

- Benefit may be acceptable, e.g.Cytoxan despite risk

- Drug may be necessary in life threatening situations.

5. CATEGORY E - Contraindicated inwomen who are or may becomepregnant e.g. Aminopterin oralcontraceptive


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POTENTIAL FETAL EFFECTS OFSOME DRUGS

I. Drugs with human Teratogenicpotential

- Thalidomide, warfarin, methotrexate,aminopterine, phenytoin,

carbamazepine, lithium, ACE inhibitors,

Angiotesin receptor blockers, Alcohol.


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II. Other Drugs to Avoid drugpregnancy(a) Methimazole - Aplasia cutis, fetal

goiter(b) Tetracycline - Bone and tooth

enamel effects in 2nd

trimester.(c) Aminoglycosides affect fetal

vestibular and auditory systems.

(d) Quinolone antibiotics skeletalabnormalities in rat(e) Immunosuppressives - Fetal

toxicity


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III. Drugs without Conclusive AdverseEffects

Acetaminophen, Penicillin

derivatives, cephalosporins,macrolydes (erythromycin)

metronidazole, Hydrochlorothiazide

calcium channel blockers, Beta

blockers Acyclovir, zidovudine.


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Drug Usage in Pregnancy can be

(1)Prophylactic(2)Therapeutic

Prophylactic To prevent certain adverse consequences

during pregnancy.

- May require pre-conceptional counsellingand informed choice for patients to knowthe risk to her unborn child if somemedications are not taken


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e.g. Folic Acid

- Necessary component for proper hematopoiesis.- Deficiency leads to ed risk of neural tube

defects

Fe.- Vitamin supplement:

Excesses of these vitamins may be bad in pregnancy.

e.g Excess B6 causing Neurotoxicity at doses exceeding

200mg/day or Vitamin A may be teratogenic at doses

exceeding 8000g/day


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Therapeutic MedicationsAdvances in Medicine and technology

have led many patients with chronic

medical illness to get pregnant andcarry their pregnancy successfully to

viability and the need to continue their

medication in pregnancy is imperative.


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Some of the Medications in useinclude:(a)Anticoagulants particularly in patientwith thromboembolic disease or who are

at high risk for thromboembolic disease.

Heparin:- parenterally administered anticoagulant

- Has a high molecular weight and charge- Does not cross placenta and is not teratogenic

No fetal risks

Maternal risks -osteopenia or osteoporosis


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Warfarin(Coumadin)- Teratogenic (Warfarin embryopathy)causing nasal hypoplasia, optic atrophy,scoliosis, epiphyseal stippling, mentalretardation and microcephaly.

- Contraindicated in first trimesters

- Heparin is the preferred anticoagulant

in 1st trimester and some few weekstowards delivery.


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B. AnticonvulsantsPhenytoin (Epanutin):

given to control epilepsy

is a folic acid antagonist and if used

in pregnancy, additional folic acidmust also be given.

C Sedatives and Analgesics- Morphine and pethidine given within

2-3hrs of delivery will depress the

fetal respiratory center.


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-Aspirin and other non steroidal anti-inflammatory drugs e.g. Indomethacin

may inhibit prostaglandin synthesisand produce premature closure of thefetal ductus arteriosus. They maypostpone onset of labour.

Diazepam - Before delivery will depress

the fetal medullary centers and causeloss of the normal baseline variation ofhe heart rate, and there is hypotonia

after delivery.


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D. Ant ihypertensives: Alphamethydopa is acategory B drug while others such as

bethanidine, guanethidine and hydralazine arecategory C drugs but seem to have no harmfuleffect on the fetus.

E. AntibioticsSulfonamides compete with billirubin for

binding sites or serum Albumin and riskof kernicterus.

Streptomycin - damages 8th cranial nerve congenital deafness.

Penici l l in safe in pregnancy


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F. Antithyroid drugs cause fetal goitre or hypothyroidism e.g. Thiouracil.

G. Cytotoxic and Alkylat ing Agents may harm the fetus

- should not be used in pregnancyH. Alcohol Dur ing Preg.When mothers are addicted babies of

low birth weight are delivered with chance of neonatal and infant mortality.


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- a few will have fetal Alcohol syndromewith characteristic facial appearance

with a broad base to the nose,epicanthic folds, a long upper lip and asmall lower jaw with mental

retardation.I Smoking harmful to the fetus and gives rise to

LBW. CO interferes with 02 transport

Nicotine causes vasoconstrive effect of

placental bed.


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J. *Marijuana* Heroine* Cocaine

K. Ant iretrovira l Therapy- Has become more common place during pregnancy to

prevent MTCT.- A lot of them are being used in various combination.

Long term study is necessary to determine their fulleffects on the fetus.

- They all reduce: vertical transmission ofHIV.

viral load

- Benefits of its use outweighs their risk.


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CONCLUSIONMedication use in pregnancy creates a

challenge for the health care provider aswell as the patient. Judging benefits andrisks can be objective but in many

instances is largely subjective. Excellentcommunication between health careproviders and recipients is essential to

optimize pregnancy outcome. Thecontribution of effective preconceptioncounselling to improving pregnancyoutcome can not be emphasized.

drug used during pregnancy self

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