Drug Safety in Pregnancy

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Drug Safety in Pregnancy

• Mother
• Child

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Adverse Drug Reactions
An appreciably harmful or unpleasant reaction,
resulting from an intervention related to the use
of a medicinal product, which predicts hazard
from future administration and warrants
prevention or specific treatment, or alteration
of the dosage regimen, or withdrawal of the
product
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Adverse Drug Reactions

• Common
• 6.2 of all hospital admissions
• gt100,000 deaths in the US p.a.
• Occupy 7 800-bed hospitals in the UK

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Drug Safety in Pregnancy

• Pre-existing disorders, e.g. epilepsy
• Infections, e.g. urinary tract infections
• Disorders of pregnancy
• Treatment of foetus

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Physiological changes in Pregnancy
Absorption
Decrease in intestinal motility Decreased gastric
emptying Emesis/reflux - decreased absorption
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Physiological changes in Pregnancy
Distribution
Increased plasma volume by 45 (32 wks) Total
body fat increased Protein concentration
decreased Uterine blood flow increased (lt1 to
16-25)
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Physiological changes in Pregnancy
Excretion

• 50 Increase in glomerular filtration rate by mid
  pregnancy
• Increased excretion of drugs, increased dose
  requirements

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Bacteriuria in pregnancy

• 6 of normal pregnant women have asymptomatic
  bacteriuria
• 23-40 of these will develop acute
  pyelonephritis
• Screening at initial visit
• E. coli commonest

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Bacteriuria in pregnancy
Treatment

• Asymptomatic
• Trial of single dose therapy
• If fails, 7-day course
• Safe Penicillins and nitrofurantoin
• Contraindicated Quinolones, tetracycline and
  trimethoprim

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Bacteriuria in pregnancy
Treatment

• Symptomatic UTI 1-2 of pregnant women
• Prevent complication to mother and foetus
• Prevent recurrence
• Ampicillin 10-14 day course

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Adverse Effects of Penicillins

• Nausea
• Pregnancy can cause nausea
• UTI may cause nausea
• Drug can cause nausea

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Adverse Effects of Penicillins

• Diarrhoea
• Vary in severity
• Mild to fulminant colitis

Pseudomembranous Colitis Clostridium difficile
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Adverse Effects of PenicillinsRash
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Causality

• Pregnancy-related?
• Disease-related?
• Drug-related?

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Causality

• Temporal relationship
• Rechallenge
• Exclusion of other causes
• Previous reports
• ALWAYS CONSIDER DRUGS IN DIFFERENTIAL DIAGNOSIS
  OF NEW SYMPTOMS

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Placental Circulation
Maternal
Foetal
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Placental transfer

• Molecular weight of drug lt500 daltons
• Lipid solubility
• Degree of ionisation of drug
• Extent of plasma protein binding

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Placental transfer

• Type I - equal concentrations
• complete transfer profile
• Type II - higher foetal than maternal
• plasma concentrations
• Type III - higher maternal concentrations
  incomplete transfer profile

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Teratogenicity

• Regard every drug as being potentially
  teratogenic
• 1-5 of all congenital anomalies are caused by
  drugs
• Thalidomide disaster
• Yellow card adverse drug reaction reporting scheme

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YELLOW CARDS

• Introduced in 1964
• 500,000 reports
• 20,000 reports per year

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Teratogenicity
Screening for teratogenicity

• Animals used as models for man
• 2 species (rat or mouse and rabbit)
• 3 dose levels
• Period of organogenesis
• Males tested for effect on fertility
• Females administered drug in 3rd trimester to
  assess effects on foetal growth

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Teratogenicity
Stage of pregnancy

• Period of organogenesis
• Late stages may lead to fetal growth retardation
  and/or mental retardation

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Teratogenicity

• Alcohol
• Anticonvulsants
• Thalidomide
• Corticosteroids
• Vitamin A and derivatives

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Sources of Information
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Sources of information

• Dug Information Centres
• National Teratology Information Centre, The
  Regional Drug and Therapeutic Centre, Wolfson
  Unit, Claremont Place, Newcastle-upon-Tyne. Tel
  No. 0191 232 1525

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Prescribing in pregnancy

• Disease pre-pregnancy
• - does drug therapy need to be continued?
• - does it need to be altered?
• Try non-drug treatment first
• Avoid multiple drugs
• Select the safest and most efficacious drug
• Dose changes may be necessary

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Adverse drug reaction in pregnancy

• Consider stopping drug
• Treat mother
• If harm to the foetus suspected, get specialist
  advice
• Communication with mother
• Report the adverse reaction