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