Read from Dr. Wong Pei Se’s notes

Diseases that require treatment during pregnancy

  • Thromboembolic disease
  • Hypertension
  • Diabetes mellitus
  • STD
  • Recurrent pregnancy loss
  • URTI
  • Asthma
  • Epilepsy
  • Migraine
  • Psychosis
  • Depression/anxiety

Common illness during pregnancy

  • Nausea & vomiting
  • abdominal bloating
  • heartburn
  • headache
  • constipation

Teratogens

  • drugs, environmental hazards
    • produces a characteristic set of malformations
    • exerting it’s effects during the specific period of organogenesis
  • carbamazepin
  • isotretinoin
  • Mechanisms:
    • directly act on differentiation process in foetal tissus
    • interfere with passage of oxygen/nutrients via placenta
    • RNA/DNA damage
    • directly act on maternal tissues
      • secondarily act on foetal tissues

Factors in determining the effects of drug exposure in pregnancies

  • Teratogen specificity
    • Thalidomide: limb defects
    • Valproate: neural tube defects
    • ACE inhibitors: fetal hypotension, renal tubular dysplasia etc
    • Warfarin: skeletal features of foetal warfarin syndrome, haemorrhage
    • Lithium: Cardiac (Ebstein’s complex)
    • Phenytoin: Carniofacial, limb
    • Carbamazepine: Carniofacial, limb, renal failure
    • Retinoic acid: CNS, absent ears, eyesight, cleft palate
    • Sodium Valproate: Neural tube
    • Antithyroid: Fetal hypothyroidism
    • Tetracycline: bone & teeth
    • NSAIDS: constriction of ductus arteriosus
  • Psychochemical properties
    • determine chances of reaching fetus( cross placenta)
      • low molecular weight
      • high lipid solubility drugs
      • intoxicating/sedating agents (cocaine etc)
      • long duration of action
  • Timing of exposure
    • critical period of organogenesis
  • Intensity of exposure
    • dose, frequency
  • Differences in susceptibility
    • age, nutritional status
  • Genetic variation
    • metabolism
  • Concomitant problems & use of other drugs

Foetal development & the effects of teratogen

  • 1st trimester
    • All effect
    • No effect
  • 2nd trimester
    • Gross structural malformations (deformity)
      • organogenesis
  • 3rd trimester
    • interference of functional development

Effect of pregnancy on drug absorption

  • Gastro-intestinal absorption
    • decrease intestinal motility
    • delayed onset of drug action
      • quicker response by IV

Effect of pregnancy on drug distribution

  • Affects drug solubility, tissue affinity & protein binding
  • increase in body water
    • reduced concentration
  • increase body fat
    • accumulation of lipophilic drug
  • less protein bound
    • previously high protein bound drugs, now more free fraction
      • more active

Effect of pregnancy on drug metabolism

  • Liver blood flow remained unchaged
    • extraction of drug by liver remained unchanged
  • Hormonal changes –> alteration of enxymes
    • Progesterone inhibit CY1A2 (theophylline)
    • Progesterone increase CY3A4 (phenytoin)

Effect of pregnancy on drug clearance by kidney

  • Renal blood flow increased
    • increase clearance of drugs

Drugs used for diseases

  • Diabetes mellitus
    • insulin does not cross placenta
    • monitor glucose level
    • large baby: macrosomia
  • Blood pressure
    • Methyldopa: preferred drug

Use of drugs during lactation

  • Mother
    • decrease risk of breast cancer
    • more delayed ovulation
  • Infant
    • increase in immunocompetence
    • Increase IQ (neurodevelopmental advantage)
  • Some drugs can cause effects
    • aspirin: Reye’s syndrome
  • Drug effects on milk secretion
    • affect prolactin
    • Decrease mik secretion
      • Ethinyloestradiol
      • Bromocriptine
    • Increase milk secretion (inhibit dopamine action)
      • Antipsychotic
      • Domperidone
      • Metoclopramide
  • Drug reaching milk
    • usually greatly distributed in mother’s body before reaching milk
    • factors affecting distribution of milk
      • lipid solubility
      • low molecular weight
      • less protein bound
      • longer half life
      • absorption & bioavailability
        • degraded by baby’s highly acidic GI tract

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