Drug Use in Pregnancy , Lactation, And Extremes of Age-student Lectures Latest

8/6/2019 Drug Use in Pregnancy , Lactation, And Extremes of Age-student Lectures Latest

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DRUGS IN PREGNANCY,

LACTATION AND EXTREMESOF AGEDR E.O.ORJI

Associate Professor/ConsultantObstetrician & Gynaecologist


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AIMS

To update pharmacy students oncurrent opinion relating to the

prescribing of drugs in pregnancy,breastfeeding and extremes of age.


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OBJECTIVES

To be aware of the background and relevance of this specialised area of prescribing

To be able to find information regarding currentdrug use in pregnancy, breast feeding andextremes of ageTo be able to interpret this in day to day cases

encountered in working - practice.


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INTRODUCTION

Thalidomide

Foetal malformations occur in 2% of population

65% - 70% of malformations are of unknown cause


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- Women have been advised to avoiddrug usage in pregnancy because of

possible harm to the fetus.- Though the uterine environment is

priviledged, it is not totally immune toexposure from exogenoussubstances.


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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 abnormal development:(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: meaningorigin.


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Teratogenesis may be classified asMorphologic classical teratogenesis

Functional teratogenesis

Behavioural teratogenesis


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* In human being the classicteratogenesis is from

approximately day 17 to day 54post conception.


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PRINCIPLES OF TERATO GENESIS

Teratogenic agents may be synergistic.

Teratogenicity is usually dose dependent

A teratogen may be harmless to the mother but

devastating to the embryo.

Placental barrier does not exist

Timing and exposure is critical

Susceptibility to teratogenesis is genetically determined


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Factors to consider in Drugprescription in Pregnancy

1. Most drugs, with molecular weight >1000 crossthe placenta and are excreted in breast milk.

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

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

conception)- 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 are involved,normal development is likely.

(b)Embryonic phase (3-8weeks)- Most crucial period of organogenesis and

therefore the time of greatest theoretical risk of congenital malformation.

(c)Fetal phase (9 th 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 may havedirect actions on the fetus e.g. warfarinmay cause Haemorrhage some drugsgiven close to term may affect the neonatee.g. diazepam or pethidine.

3.Even non prescription drugs such ascough medicines containing iodides canbe harmful


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PRINCIPLES FOR PRESCRIBINGDURING PREGNANCY AND

LACTATION.1. Drugs to be given only when the indicationsare clear and specific and the expected benefitto the mother is greater than the risk to thefetus

2. If at all possible, avoid all drugs in the firsttrimester.

3. Prescribe drugs which have been well tried inpregnancy in preference to newer

preparations.4. Use the smallest effective dose for the shortesttherapeutic time.


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:(According to US, food and

Drug Administration )1. CATEGORY A - Essentially safe,based on controlled studies in

pregnancy e.g. L-Thyroxine2 . CATEGORY B - Safe in animals

but not confirmed in human studiese.g. Hydrochlorothiazide


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CATEGORY C - Animal studies revealadverse effects on the fetus (embryocidal,

teratogenic) No controlled studies inwomen or studies in women not available.

Use only if potential benefits justifies risk

to fetus e.g. Theophylline


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4 . CATEGORY D- Positive evidence of human fetal risk

- 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


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OF SOME DRUGS

Drugs with human Teratogenicpotential

- Thalidomide, warfarin, methotrexate,aminopterine, phenytoin, carbamazepine,lithium, ACE inhibitors, Angiotesin receptor

blockers, Alcohol.


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t er rugs to vo rugpregnancy

(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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Drugs without ConclusiveAdverse Effects

Acetaminophen, Penicillin derivatives,cephalosporins, macrolydes

(erythromycin) metronidazole,Hydrochlorothiazide calcium channelblockers, Beta blockers Acyclovir,

zidovudine.


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Drug Usage in Pregnancy can be(1) Prophylactic(2) TherapeuticProphylactic To prevent certain adverse consequences

during pregnancy.- May require pre-conceptional counselling and

informed choice for patients to know the risk toher unborn child if some medications are nottaken


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e.g. Folic Acid- Necessary component for proper hematopoiesis.

- Deficiency leads to oed risk of neural tube defectsFe.

- Vitamin supplement:

Excesses of these vitamins may be bad in pregnancy.

e.g Excess B6 causing Neurotoxicity at doses exceeding 200mg/dayor Vitamin A may be teratogenic at doses exceeding 8000 Qg/day


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Therapeutic Medications

Advances in Medicine and technology

have led many patients with chronicmedical illness to get pregnant and carrytheir pregnancy successfully to viabilityand the need to continue their medicationin pregnancy is imperative.


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Some of the Medications in

use include:(a) Anticoagulants particularly in patient with

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 risksMaternal risks -osteopenia or osteoporosis


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W arfarin (Coumadin)- Teratogenic (Warfarin embryopathy) causingnasal hypoplasia, optic atrophy, scoliosis,epiphyseal stippling, mental retardation andmicrocephaly.

- Contraindicated in first trimesters

- Heparin is the preferred anticoagulant in1 st trimester and some few weeks towardsdelivery.


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B. AnticonvulsantsPhenytoin (Epanutin):given to control epilepsyis a folic acid antagonist and if used inpregnancy, additional folic acid must alsobe given.

C Sedatives and Analgesics- Morphine and pethidine given within 2-

3hrs of delivery will depress the fetalrespiratory center.


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

produce premature closure of the fetalductus arteriosus. They may postponeonset of labour.

Diazepam - Before delivery will depress the

fetal medullary centers and cause loss of the normal baseline variation of he heartrate, and there is hypotonia after delivery.


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Antihypertensives: Alphamethydopa is a category B drugwhile others such as bethanidine, guanethidine andhydralazine are category C drugs but seem to have noharmful effect on the fetus.

E.AntibioticsSulfonamides compete with billirubin for binding

sites or serum Albumin and o risk of kernicterus.Streptomycin - damages 8 th cranial nerve

congenital deafness.Penicillin safe in pregnancy


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Antithyroid drugs cause fetal goitre or hypothyroidisme.g. Thiouracil.

G.Cytotoxic and Alkylating Agents may harm the fetus

- should not be used in pregnancyH. Alcohol During Pregnancy .

When mothers are addicted babies of low birth weightare delivered with o chance of neonatal and infantmortality.


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- a few will have fetal Alcohol syndrome withcharacteristic facial appearance with abroad base to the nose, epicanthic folds, a

long upper lip and a small lower jaw withmental retardation.I Smoking

harmful to the fetus and gives rise to LBW.

CO interferes with 02 transportNicotine causes vasoconstrive effect of placentalbed.


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PRINCIPLES OF PRESCRIBING

Use drugs which have been widely used inpregnancyUse the lowest effective dose for as shorta time as possible. Consider need fordosing changes needed during pregnancy

Evaluate every drug prescribed

Medico-legal


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In medico-legal terms a Doctor isimmune from civil liability for theeffects on the fetus of a drug if thedrug is currently given in pregnancyas established medical practice.


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PROBLEMS ENCOUNTERED

1. Anxious and emotional patients should be ahappy time often however anxious andconcerned.

2. Medico legal implications would your peershave provided this advice?

3. Defensive Pharmaceutical Companies- noclinical trials on pregnant patients.

4. Poor quality data data skewed as we reportadverse outcomes only dont or rarely reportcases where good outcomes occur.


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5. Media Scares. E.g. phytomenadionescare in 1990s where use of a cover doseof vit K IM to babies was linked with laterdevelopment of childhood leukaemia.Later papers disputed this finding but hadlong term effect on parents confidence inthe product and as a result many babiesreceived no cover or cover with oralvitamin K.

All these show the need for betterprescribing information


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F ACTORS TO TAKE INTO CONSIDERATION

Pregnant, planning pregnancyScript neededConsider period of gestation

Medicate only if benefits outweigh the risksAvoid new drugsUse a single drug if possibleUse lowest effective dose

Involve and counsel patient


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DRUG USE IN LACTATION

Breast feeding can lead to toxicity in the infant if the drug enters the milk in pharmacologicalquantities.

Milk concentration of some drugs (e.g. iodides)may exceed the maternal plasma concentration,but the total dose delivered to the baby is usuallyvery small. However, drugs in breast milk maycause hypersensitivity reactions even in very lowdose.


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Virtually all drugs that reach the maternal systemiccirculation will enter breast milk, especially lipid-solubleunionized low molecular weight drugs.Milk is weakly acidic, so drugs that are weak bases areconcentrated in breast milk by trapping of the chargedform of the drug (cf. renal elimination). The resultingdose administered to the fetus in breast milk is however usually clinically insignificant although some drugs arecontraindicated and breast feeding should cease duringtreatment if there is no safer alternative.


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The infant should be monitored if b-adrenoceptor antagonists, corticosteroidsor lithium are prescribed to the mother. b-

Adrenoceptor antagonists rarely causesignificant bradycardia. In high dosescorticosteroids can affect the infants

adrenal function and lithium may causeintoxication.


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Bromocriptine and diuretics suppresslactation and adverse effects outweighbenefits in women who chose not to breastfeed. Metronidazole gives milk anunpleasant taste.


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Some drugs to be avoided duringbreast feeding

Vitamin A/retinoid analogs (e.g. etretinate)AmiodaroneStimulant laxatives

BenzodiazepinesChloramphenicolCiprofloxacinCombined oral contraceptivesCyclosporinCytotoxicsSulfonylureasThiazide diuretics


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DRUGS IN THE ELDERLY

The elderly are subject to a variety of complaintsmany of which are chronic and incapacitating,and so they receive a great deal of drug

treatment.. Adverse drug reactions become more commonwith increasing age. In one study 11,8% of patients aged 41-50 years experienced adversereactions to drugs but this increased to 25% inpatients over 80. There are several reasons for this:


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1. Elderly people take more drugs. In onesurvey in general practice, 87% of patientsover 75 were on regular drug therapy with34% taking three to four different drugsdaily2. Pharmacokinetics change withincreasing age and concomitant diseaseleading to higher plasma concentrations of drugs and increased liability to side effects


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3. Homeostatic mechanisms become lesseffective with advancing age, so individuals areless able to compensate for adverse effects

such as unsteadiness or postural hypotension.4. The central nervous system becomes moresensitive to the actions of sedative drugs.5. Increasing age produces changes in theimmune response that cause an increasedliability to allergic reactions.


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P ractical aspects of prescribing

Improper prescription of drugs is a commoncause of morbidity in elderly persons. Common-sense rules for prescribing have been suggested(and apply not only for the elderly).1. Take a full drug history which should includeany adverse reactions and use of over-the-counter drugs.

2. Know the pharmacological action of the drugemployed.3. Use the lowest effective dose.


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4. Use the fewest drugs a patient needs.5. Drugs should not be used to treat symptoms withoutfirst discovering the cause of the symptoms, i.e. firstdiagnosis, then treatment.

6. Drugs should not be withheld because of old age, butit should be remembered that there is no cure for old ageeither.7. A drug should not be continued if it is no longer necessary.8. Do not use a drug if the symptoms it causes are worsethan those it is meant to relieve.9. It is seldom sensible to treat the side effects of onedrug by prescribing another.


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In the elderly it is often important to pay attentionto matters such as the formulation of the drug tobe used: many old people tolerate elixirs andliquid medicines better than tablets or capsules.Supervision of drug taking may be necessarysince an old person with a serious physical or mental disability cannot be expected to complywith any but the simples drug regimen.Containers require especially clear labelling andshould be easy to open: child-proof containersare often also grandparent proof!

DRUGS IN INFANTS AND


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DRUGS IN INFANTS ANDCHILDREN

Children are not miniature adults in terms

of drug handling because of differences inbody constitution, drug absorption andelimination, and sensitivity to adversereactions.


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ABSORPTIONReduced gastric acidity in neonates results ingreater oral absorption of certain antibiotics, for example amoxycillin. The major practicaldifferences in children is the more frequent useof oral liquid preparations resulting in lessaccurate dosing, more rapid rate of absorption(although minimal difference in bioavailability).


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DISTRIBUTION

Fat content is relatively low in children leading toa lower volume of distribution of fat-solubledrugs (e.g. diazepam) in babies. Plasma proteinbinding of drugs is reduced in neonates due to alower plasma albumin concentration which is notgenerally of clinical significance although thedanger of kernicterus caused by displacement of bilirubin from albumin by sulfonamides is wellrecognized.


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METABOLISM

At birth the hepatic microsomal enzyme systemis relatively immature (particularly in the preterminfant) but after the first 4 weeks it maturesrapidly. Chloramphenicol can produce graybaby syndrome in neonates due to high plasmalevels secondary to inefficient glucuronidation.Drugs administered to the mother can induceneonatal enzyme activity, for examplebarbiturates. In children there is evidence thataspirin metabolism is relatively impaired whilstphenobarbitone metabolism is increased


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EXCRETION

All renal mechanisms (filtration, secretionand reabsorption) are reduced in babiesand renal excretion of drugs is relativelyreduced in the newborn. Glomerular filtration rate (GFR) rapidly increasesduring the first 4 weeks of life with

consequent changes in rate of drugelimination


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CONCLUSION

The principle of drug use in pregnancy,lactation and extremes of age differs fromdrug use in other stages of life. Theseperiods are delicate with a far reachingimplications for morbidity and mortality.Dose adjustments must be done and

drugs with widely known efficacy, safetyand acceptability must be used in the bestinterest of the recipients.

Drug Use in Pregnancy , Lactation, And Extremes of Age-student Lectures Latest

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