Part 1 Science Notes
MRCOG Part 1
Pharmacology
Pharmacology in Obstetrics and Gynaecology
Teratogenic Drugs
| Drug | Effect | Critical Period |
|---|---|---|
| Warfarin | Nasal hypoplasia, stippled epiphyses (warfarin embryopathy); CNS abnormalities | 6-12 weeks (skeletal); 2nd/3rd trimester (CNS) |
| Retinoids (isotretinoin) | Craniofacial, cardiac, CNS defects | First trimester |
| Sodium valproate | Neural tube defects (1-2%), craniofacial, neurodevelopmental impairment | First trimester; NDD risk throughout |
| Methotrexate | Aminopterin syndrome: cranial dysostosis, limb defects | First trimester |
| ACE inhibitors / ARBs | Renal agenesis, oligohydramnios, pulmonary hypoplasia, skull ossification defects | 2nd/3rd trimester |
| Carbamazepine | Neural tube defects (0.5-1%), craniofacial | First trimester |
| Phenytoin | Fetal hydantoin syndrome: craniofacial, digital hypoplasia | First trimester |
| Lithium | Ebstein's anomaly (right heart) | First trimester |
| Thalidomide | Phocomelia (limb reduction); historical | 20-36 days post-conception |
| Mycophenolate | Ear, facial, cardiac defects | First trimester |
| Statins | Potentially teratogenic; limited data | Throughout |
| Misoprostol | Moebius syndrome (cranial nerve palsies) if used as abortifacient | First trimester |
Safe Drugs in Pregnancy
| Category | Safe Drugs |
|---|---|
| Analgesics | Paracetamol (first-line); codeine (short-term); avoid NSAIDs after 28 weeks (premature closure of ductus arteriosus) |
| Antibiotics | Penicillins, cephalosporins, erythromycin (NOT erythromycin estolate), nitrofurantoin (avoid at term — neonatal haemolysis) |
| Antihypertensives | Labetalol, nifedipine, methyldopa |
| Antiemetics | Cyclizine, prochlorperazine, ondansetron (first-line for hyperemesis) |
| Antidiabetics | Insulin (does not cross placenta), metformin (crosses placenta but no evidence of harm) |
| Anticoagulants | LMWH (does not cross placenta) |
| Antithyroid | Propylthiouracil (1st trimester; lower risk of aplasia cutis); carbimazole (2nd/3rd trimester) |
| Antiepileptics | Lamotrigine, levetiracetam (lowest teratogenic risk) |
Uterotonics
Oxytocin
- Synthetic nonapeptide; acts on oxytocin receptors in myometrium
- Uses: labour induction/augmentation, PPH prevention and treatment, caesarean section
- Side effects: uterine hyperstimulation, water retention (antidiuretic effect at high doses — hyponatraemia), nausea
- Dose: 5 IU slow IV for PPH; 10 IU IM for 3rd stage; titrated infusion for augmentation
Ergometrine
- Ergot alkaloid; sustained uterine contraction
- Contraindicated: hypertension, pre-eclampsia, cardiovascular disease
- Side effects: hypertension, nausea, vomiting, vasospasm
Carboprost (Hemabate / 15-methyl PGF2-alpha)
- Prostaglandin F2-alpha analogue; potent uterotonic
- IM injection (250mcg, max 8 doses)
- Contraindicated: ASTHMA (causes bronchospasm); active cardiac/hepatic/renal disease
- Side effects: diarrhoea, pyrexia, bronchospasm
Misoprostol (PGE1 analogue)
- Multiple routes: oral, sublingual, vaginal, rectal
- Uses: PPH (800-1000mcg sublingual/rectal), cervical priming, medical management of miscarriage, induction of labour
- Advantages: cheap, stable at room temperature, no refrigeration needed
- Side effects: diarrhoea, pyrexia, shivering
Magnesium Sulphate
- Mechanism: calcium antagonist; stabilises cell membranes; reduces neuromuscular excitability
- Eclampsia: loading 4g IV over 5-15 min, maintenance 1g/hr for 24h
- Neuroprotection: same dosing; indicated <30 weeks when preterm delivery imminent
- Therapeutic range: 2-4 mmol/L
- Toxicity: loss of deep tendon reflexes (first sign) → respiratory depression → cardiac arrest
- Monitoring: hourly reflexes, respiratory rate (>16/min), urine output (>25ml/hr)
- Antidote: 10ml 10% calcium gluconate IV
Methotrexate in O&G
- Folic acid antagonist; inhibits dihydrofolate reductase → blocks DNA synthesis
- Uses: ectopic pregnancy (medical management), gestational trophoblastic disease, medical termination (in combination)
- Dose for ectopic: 50mg/m2 IM single dose
- Side effects: stomatitis, nausea, bone marrow suppression, hepatotoxicity
- Contraindications: hepatic/renal impairment, immunodeficiency, breastfeeding, active infection
- Avoid folic acid, NSAIDs, alcohol during treatment
- Contraception for 3 months after treatment (teratogenic)
Important Facts for MRCOG
- Warfarin embryopathy: nasal hypoplasia, stippled epiphyses (6-12 weeks)
- ACE inhibitors: 2nd/3rd trimester — renal agenesis, oligohydramnios
- Carboprost contraindicated in ASTHMA
- Ergometrine contraindicated in HYPERTENSION
- Paracetamol: first-line analgesic in pregnancy
- LMWH does not cross placenta; warfarin does
- MgSO4 toxicity sequence: reflexes lost → resp depression → cardiac arrest; antidote = calcium gluconate
- Methotrexate for ectopic: 50mg/m2 IM; contraception for 3 months after
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