Pregnancy and Prescribing Flashcards
What are general pre-pregnancy advise that a GP should provide to their patients?
- Vitamins & minerals – folic acid (400 mcgm), Vitamin C, Vitamin D,
- Alcohol – 2 units per week
- Diet – Greens and fruits
- Lifestyle – weight loss if appropriate
- Consider the impact of underlying health conditions – diabetes, hypertension, clotting disorders
- Vaccinations
- Screen for sickle cell and thalassemia
What problems normally arise during the…
1. Early embryonic phase
2. Main embryonic phase
3. Fetal period
- Early embryonic phase (weeks 1-2) - death of embryo/abortion
- Main embryonic phase (weeks 3-8) - Major congenital abnormalities
- Fetal period (weeks 9-38) - Functional defects and minor anomalies
Why is folic acid important during pregnancy? Common consequence of low folic acid? What is the recommended amount?
Required for purine and pyrimidine synthesis - DNA synthesis - especially important when there is loads of rapid cell divisions taking place
Consequence
- Closure of neural tube requires rapid proliferation of neuroepithelial cells - hence a lack of folic acid increases the liklihood that the neural tube fails to close.
Recommendations
- Women advised to take folic acid 400 mcgms daily when trying to conceive until 12 weeks of pregnancy
Is any level of alcohol consumption safe? What consequence might arise from alcohol consumption during pregnancy?
No safe level of consumption!
High levels of alchol exposure causes fetal alcohol syndrome - leading preventable cause of birth defects
Facial dysmorphism is common - low nasal bridge, thin upper lip, smooth philtrum and small palebral fissures
Why does alcohol do this?
Alcohol is a teratogen with irreversible CNS effects
How does methotrexate interfer with DNA synthesis?
DMARD - Common drug in treatment of rheumatoid arthritis
Methotrexate inhibits
1. DHFR - Dihydrofolate reductase
2. TYMS - Thymidine synthetase
Both of these result in the inhibition of de-novo thymidine residues
3. ATIC involved in purine synthesis - reduces the synthesis of adenosine and guanidine precursors from the pentose-phosphate pathway
The net result is reduced DNA synthesis
What is the function of Dihydrofolate reductase?
Converts dihydrofolate to tetrahydrofolate - Tetrahydrofolate is involved in purine and pyrimidine synthesis
Methotrexate is competitive inhibitor of DHF, hence this results in…
1. Reduces amino acid synthesis
2. Antagonizes action of folic acid
3. Reduced cell division
What should patients on methotrexate that want conceive do?
Pre-pregnancy counselling - rheumatologist and obstetrician
Patients should be off methotrexate for 3 months before conception - allow it to be eliminated from the system
Important to keep the disease under control with other safe DMARDS, such as…
1. Hydroxychloroquine
2. Sulfasalazine
What condition is sodium valproate normally used to treat?
Used in treatment of epilepsy
Note - A seizure is sudden change in behaviour caused by electrical hypersynchronization of neuronal networks in the cerebral cortex
Epilepsy is recurrent seizures
What are the consequences of using sodium valporate during pregnancy?
Increases the risk of neural tube like defects - occur in 1-2% of fetuses (20x risk of general population)
Also associated with cardiac, oral and urogenital malformations
Must NOT be used in women or girls of child-bearing age unless in a Pregnancy Prevention Programme - counselling + information leaflet to inform & ensure highly effective contraception
What are ACE inhibitors used for?
ACEi used for:
Hypertension
Heart failure
Renal disease
ACEi - prevents conversion of AngI to AngII
Angiotensin receptor blockers (ARBs) have similar uses - prevents AngII from exerting effect
What effects do ACEi and ARBs have during pregnancy?
Exposure in second and third trimester associated with:
1. Oligohydramnios (reduced amount of amniotic fluid)
2. Renal failure - fetal circulation has low perfusion pressures - normally AngII is used to increase to maintain renal function - interfering with this
3. Low blood pressure
4. Reduce placental blood flow - Reduced fetal growth
4. Pulmonary hypoplasia - underdeveloped lungs
5. Respiratory distress syndrome - occurs in babies with underdeveloped lungs
Are ACEis and ARBs safe to use in the first trimester?
Data is less clear as to whether it should be used in the first trimester
So what do we do?
1. Explain the data to the patient
2. Use alternative if possible - Not always possible in diabetic renal disease
3. If planning on conceiving detect pregnancy early - e.g. if period delayed, withhold ACEi/ARB and get a pregnancy test
4. Stop for duration of any pregnancy
Why should NSAIDs be avoided in the third trimester?
Fetal structure - Ductus arteriosus enables oxygenated blood to pass from pulmonary artery to aorta, thereby bypassing the lung (blood is oxygenated when entering from the placenta)
Ductus arteriosus closes after birth.
- Functional closure in 24 hours
- Complete anatomic closure takes 2-3 weeks
Prostaglandins (PGE) keeps blood vessel open - (causes vascular smooth muscle to relax) - PGE drops after birth to allow closure of Ductus arteriosus
Hence…
As NSAIDs is a COX inhibitor - it prevents endoperoxidase formation and consequently prostaglandin production - resulting in the loss of PGE - leading to the premature closure of the ductus arteriosus
Consequences of early ductus arteriosus closure?
Cardiac output directed through the pulmonary circulation
Leads to pulmonary hypertension
- Cardiac failure
- Fetal hydrops (fluid accumulation in tissues and organs)
