Obstetrics Flashcards
1
Q
What is teratogenesis?
A
- Dysgenesis of foetal organs either structurally or functionally e.g. brain function
- Can include restricted growth or death of the foetus, carcinogenesis and malformations
- Usually dose dependent
2
Q
What are 3 known teratogens and what effect do they have?
A
- Carbamazepine causes neural tube defects (brain, spine and spinal cord)
- Phenytoin cases growth retardation, CNS defect
- Warfarin causes skeletal and CNS defects, Dandy walker syndrome (brain defect)
3
Q
Name 3 drugs that were thought to be teratogens but found to be safe
A
- Diazepam was thought to increase the risk of oral clefts – no evidence
- Oral contraceptives- thought it increased risk of birth defects however no association was found between first trimester exposure and malformations
- Spermicides- limb defects, tumours, Down’s syndrome but found no risk
4
Q
What is the pre-embryonic phase and how does this relate to drugs?
A
Exposure to a drug during the pre-embryonic phase (until 17 days after conception) will result in survival or death – all or nothing
5
Q
When is the embryo most vulnerable to teratogens?
A
The embryo is most vulnerable to teratogens during the embryonic phase, days 18-55 when cells differentiate, and the major organs are formed
6
Q
What is the foetal period and what are the risks?
A
Day 56-birth, organs such as the cerebral cortex and renal glomeruli continue to develop and susceptible to damage. Risk of pre-term birth
7
Q
What is an advantage and disadvantage of drug testing in rodents?
A
- Rodents are usually used to evaluate the safety of drugs in pregnancy, their physiology, metabolism and development are different to humans
- Cannot be assumed that because it is not teratogenic in rodents, that it is safe in humans
- However, if a drug causes foetal toxicity in animal species, this is an indicator that the same effects may occur in man
8
Q
What is the role of the placenta?
A
- Nutrition
- Excretion
- Immunity
- Endocrine function
9
Q
What kind of drugs like to cross the placenta?
If a drug doesn’t cross the placenta, can it still cause toxicity to the foetus?
A
- It is estimated that 99% of drugs will cross the placenta, mostly because of simple diffusion
- Non-ionised, lipid soluble drugs will cross in preference to polar, ionised, hydrophilic compounds
- Drugs with a high MW e.g. insulin, heparins tend not to cross
- A drug does not need to cross to cause toxicity e.g. any drug that causes vasoconstriction of the placental vasculature can harm the foetus
10
Q
How can you minimise the risk with drug use during pregnancy?
A
- Consider non-drug treatment
- Avoid in first trimester
- Use lowest effective dose
- Avoid known teratogens
11
Q
What respiratory changes do you see in pregnancy?
A
- Respiratory rate increases and hit steady point around week 12
- Tidal volume continues to increase during pregnancy
- Minute and alveolar ventilation continues to increase during pregnancy
12
Q
What cardiology changes do you see in pregnancy?
A
- Increase in cardiac output
- Problem in those with an existing cardiac condition as pregnancy puts an additional strain on the heart
- Blood flow to skin increases
13
Q
What renal and liver changes do you see in pregnancy?
A
- Increase in renal blood flow and in GFR by 50% by the end of the first trimester, normalises after delivery
- Some evidence of alterations in the metabolic enzymes in the liver
14
Q
How is distribution affected in pregnancy?
A
Plasma volume and total body water increases
Decreased albumin concentration
15
Q
Name some conditions where drug therapy is continued during pregnancy
A
- Diabetes
- HIV
- Hypertension
- Asthma
- DVT/PE
- Transplant patients
- Epilepsy
16
Q
What are the benefits of breastfeeding to a mother?
A
- Money saving
- 500 calories burnt a day - weight loss
- Reduces risk of breast and ovarian cancer
- Bond between mother and baby
- Reduces osteoporosis
17
Q
What are the benefits of breastfeeding to a baby?
A
Less chance of:
- D and V
- Infections
- Constipation
- Becoming obese and developing type 2 diabetes
- Eczema
- Infection due to transfer of antibodies
- Risk and allergies
- Colic
18
Q
Some drugs are safer to to prescribe in breastfeeding because they won’t pass into the breast milk/safe to use. What sort of properties do these drugs have?
A
- Highly protein bound
- Shorter half-life
- Drugs prescribed for neonates and children
- Drugs with a low milk: plasma ratio (lower the ratio, less that reaches the milk). Also links with milk intake and infant drug clearance
19
Q
How do you calculate exposure index?
A
(100 x MP x A) / Infant drug clearance
20
Q
Cationic drugs favour excretion of drug into milk. True of false?
A
True
21
Q
How are the biochemical characteristics of breast milk different to plasma?
A
Higher pH and lipid contents
22
Q
What factors do you need to consider when deciding whether a breastfeeding mother should be on a drug?
For the baby, mother and the drug
A
Baby:
- What is the potential risk?
- Is the drug licensed in children?
- What gestation was the baby at birth?
- How old?
- How often is the baby being breast fed? (volume)
- Age and maturity of the baby- are the liver and renal systems fully functioning?
Mother:
- Is the medicine essential?
- Was she taking it during pregnancy?
- Chronic/acute use?
- What does she think?
Drug:
- Licensed for BF?
- PK and PD
- Side effects and contraindications
- Available safety data
23
Q
What % of adult clearance do the following ages have?
- 2-3 months premature
- Term
- 1-2 months
- 3-6 months
- > 6 months
A
- 10 %
- 33%
- 50%
- 66%
- 100%
24
Q
How are drugs transported into the breast milk and what factors affect this?
A
- Mostly passive diffusion although drug transporters are increasingly recognised as playing a role
- Maternal PK, physiological composition of blood versus milk, and characteristics of the drug all affect diffusion of drug into milk
25
Name some drugs that have known breast milk problems and their effect
* Atenolol- XS beta blockage
* Caffeine- irritability, poor sleep
* Ergotamine- V and D
* Fluoxetine- irritability, poor weight gain
* Nicotine- shock, vomiting
* Phenobarbital- sedation
* Salicylate- metabolic acidosis
* Theophylline- irritability
* Lithium- near therapeutic levels in infants
* Cocaine- marked irritability
26
What are the analgesics of choice in BF ?
Paracetamol
Ibuprofen
Morphine
27
What is the glucocorticoid choice in BF?
Prednisolone
28
What is the antihistamine of choice in BF?
Loratadine
29
What are the beta blockers of choice in BF?
Labetalol and propranolol (non-selective)
30
How is absorption affected in pregnancy?
* Decreased gastric and intestinal motility
* Reduced gastric acid secretion so increased gastric pH (less acidic)
* Nausea and vomiting (hyperemesis gravidarum)
31
Why might compliance be poor in pregnancy?
Fear of harming the foetus
32
What should be essential for all women receiving long-term treatment with medicines?
Pre-pregnancy counselling
Discussing the consequences of stopping treatment
33
What are the risks with obesity in pregnancy?
1. Higher rates of congenital abnormalities:
High dose folic acid supplementation pre-pregnancy and during first trimester – 5mg daily
2. Vitamin D deficiency – supplementation of at least 1000 units a day:
* Could be associated with pre-eclampsia
* Glucose intolerance-associated with gestational diabetes
* Neonatal tetany – hypocalcaemic seizures
* Impaired foetal growth and long bone development – rickets
* Effects on foetal lung development (childhood wheeze and allergy)
3. Increased risk of pre-eclampsia:
* Disorder of pregnancy characterised by the onset of high BP and significant amount of protein in the urine.
* 75 mg aspirin daily throughout
4. Increased risk of gestational diabetes:
Much greater risk of complications as the mother gets older, as well as the presence of comorbidities
34
What is the different between direct and indirect causes in maternity death?
* Indirect causes – not related to pregnancy as such
| * Direct causes – would not have died if they weren’t pregnant. E.g. haemorrhage, thrombosis
35
What is perinatal mental health?
* Woman’s mental health during pregnancy and the first year after birth
* Leading cause of maternal deaths
36
What are the risks of treating severe mental illness in pregnancy?
Major malformation (1st trimester exposure)
Neonatal toxicity and withdrawal effects (3rd trimester exposure)
Long term neurobehavioural effects and growth impairment
Miscarriage- spontaneous abortion
37
What are the benefits in treating severe mental illness in pregnancy?
Reducing harm to the mother. Poor self-care, self-harm, impulsive acts, poor judgement and substance misuse
Reducing harm to baby (neglect, killing)
38
For psychotropic medicines, what do you need to consider for pregnancy and what precautions can you take?
* Unlicensed in pregnancy and BF
* Need to document consent
* Consider psychological interventions (non-drug)
* Choose drug with the lowest risk profile for the woman, foetus and baby
* Lowest effective dose
* Monotherapy if possible
* Dose may need changing in pregnancy- do you need to monitor the levels?
* 1st trimester- early screening, counselling about continuing the pregnancy
39
What do you need to consider when treating a pregnant lady who has epilepsy?
* Pre-conception counselling to optimise seizure control before pregnancy
* Folic acid 5mg daily before and during pregnancy
* Monotherapy if possible, as malformation risk increases with polytherapy and higher doses
* Avoid sodium valproate if possible due to neurodevelopmental disorders and congenital malformations – MHRA
* Monitoring of levels and dose adjustment e.g. lamotrigine
40
What should you do if you are dispensing sodium valproate for the first time in a child bearing age woman?
Give her a patient card to read and enter her name and date to reinforce its her own accountability (if she has not done so already).
41
For diabetes, what is the risk for the mother?
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Miscarriage
Pre-eclampsia
Pre-term labour
Induction of labour/caesarean
Diabetic retinopathy may worsen
Birth trauma
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42
For diabetes, what is the risks for the baby?
```
Birth trauma
Perinatal death
Neonatal hypoglycaemia
Obesity
Diabetes developing from childhood
Macrosomia- larger than average baby
```
43
How should you control diabetes in pregnancy?
* Pre-conception- measure Hb1ac monthly and aim for <48 mmol/mol
* Folic acid 5mg pre and during
* Maintain tight blood glucose control during
* Isophane= long acting insulin of choice (but detemir and glargine can be continued if good control)
* Metformin= benefit outweighs risk
44
Should you continue ACEis, ARBs and statins during pregnancy?
No- stop before conception or as soon as pregnancy is confirmed
45
What is the risk with gestational diabetes?
Increased risk of Type 2
46
How do you manage gestational diabetes?
* Diet, exercise
* Insulin, metformin
* Glibenclamide (sulphonylurea) if blood glucose targets not achieved, insulin declined or metformin not tolerated
47
What are the risks associated with acei in pregnancy?
- 1st trimester has increased risk of congenital cardiac or CNS malformations
- 2nd and 3rd trimesters- foetal hypotension and renal failure – risk of death
48
What are the risks associated with beta blockers in pregnancy?
Increased risk of growth restriction
49
How would you diagnose pre-eclampsia?
* Hypetension and proteinuria
* PCR (protein creatinine ratio)
* 24 hour urine collection
50
How do you treat pre-eclampsia?
- Labetalol
- Nifedipine
- Methyldopa
- Hydralazine
51
How do you prevent pre-eclampsia?
75 mg aspirin OD
52
What are the risks associated with anticoagulation treatment options and what would be the treatment of choice in pregnancy?
* Warfarin teratogenicity
– exposure between weeks 6-9 -defective bone ossification (bone remodelling)
- 2nd and 3rd trimester - CNS abnormalities e.g. microhaemorrhages in the brain
* LMWH acceptable
* DOACs not recommended due to animal toxicity or no human data
53
What would you use for VTE prophylaxis in pregnancy?
What risk score do you need to have to go on this?
LMWH
Score of 3 or more in pregnancy
Score of 2 or more postnatally
54
Elective caesareans decrease the risk of HIV transmission from mother to baby. True or false?
True
55
What are the risk factors in pregnancy for mother to baby transmission?
* Viraemia (virus in blood)
* Mode of delivery
* Duration of membrane rupture
* Deliver <32 weeks
56
What is the post exposure prophylaxis regimen for a baby whose mother is HIV positive?
Zidovudine (AZT) 4mg/kg BD for 4 weeks
Nevirapine +/- lamivudine (or alternatives if resistance)
57
Is the flu vaccine safe in pregnancy?
Yes
58
Can the flu virus cross the placenta?
Yes
59
There was a case of a pregnant lady not attending her GP flu vaccine appointment and later dying. Where else could the flu vaccine be offered?
Antenatal care
60
What FDA category is Tamiflu?
Should you use this in pregnancy?
What is an advantage of it over zanamivir when deciding what one to use for pregnancy?
C - potential placental transfer
Use if potential benefit outweighs risk
Tamiflu has neonatal dosing from 2 months whereas zanamivir has no neonatal dosing
61
What are the PKs of Tamiflu?
Pro drug via hepatic metabolism
Renal elimination
Nausea and vomiting side effects
62
What are the PKs of Zanamivir?
What is a disadvantage of its inhaled powder form?
* Oral bioavailability low
* Low systemic exposure from inhaled dose (10-20%)
* Inhaled powder contains lactose which may cause bronchospasm
* Not metabolised and excreted unchanged via kidneys
* Use if potential benefit outweighs the risk
63
What is used in the treatment of ectopic pregnancies?
Methotrexate
64
What is used in combination for medical termination of pregnancy?
* Mifepristone (antiprogesterone)– yellow, cylindrical 200mg tablets
* Misoprostol (Prostaglandin E1 analogue) white, hexagonal 200 mcg tablets
65
What sources can we use to see if a drug is safe in pregnancy?
* Europe- SPC
* America- pregnancy letter categories have been removed as they are confusing and simplistic. Instead, there is the Pregnancy and lactation labelling rule for both males and females
* Signposting to pregnancy exposure registers
* Companies should update recommendations as new human data becomes available
66
What are the FDA category risks for pregnancy?
A= controlled studies in pregnant women, no risk shown
B= no risk shown in animal studies but no controlled studies in pregnancy
OR some fetal risk in animal studies but no risk shown in human studies
C= some risk shown in animal studies but no human studies OR no animal or human studies. Benefit may outweigh risk
D= human data shows risk. Benefits may outweigh risk
X= animal or human data have demonstrated foetal harm
67
What does WHO say about babies being breastfed?
Infants should be exclusively breast fed for the first 6 months of life to achieve optimal growth, development and health
68
What are the psychological aspects of BF?
The thought of “poisoning” baby if they give formula instead, or take drugs during BF, am I a good mum?
69
Codeine is restricted for use as an analgesic in children/BF women.
Why?
What alternatives are there?
What should you monitor in the baby?
Fatal respiratory depression is a side effect
Morphine, tramadol
Check baby is feeding well, waking up to be fed, gaining
weight, not appearing limp
70
How is codeine metabolised?
CYP2D6
71
What are the PKs of beta blockers?
* Water soluble, low protein binding, renally excreted
| * Half life 6-7 hours
72
What is the risk of using a beta blocker whilst BF and what is the general advice given?
* XS beta blockade?
* Baby may be at risk of hypoglycaemia and bradycardia
* Monitoring needed but it has been found the amount in breast milk is small
73
What ACEi should be avoided in the first few weeks after delivery?
What ACEi is contraindicated in BF?
What should you monitor in the baby?
Captopril, enalapril and quinapril
Ramipril is C/I
BP monitoring due to hypotension risk
74
Can diuretics be given in BF ?
No-avoid
75
If the patient is hypertensive, what monitoring should do you when the baby is born?
Assess wellbeing of the baby and how well they are being fed daily for the first 2 days after birth
76
What antihypertensives have no known side effects on BF babies?
* Labetolol, atenolol, metoprolol
* Nifedipine
* Enalapril, captopril
77
Should statins be given in BF?
No information available
Manufacturers advise avoid
78
What is the risk of aspirin in BF?
Risk of Reye’s syndrome and regular high doses could impair platelet function and produce low prothrombin levels in infant if neonatal vitamin K stores are low
May allow BF is taking low dose aspirin 75 mg/day but advise not to BF if child has a temperature or is unwell
79
How would you manage epilepsy in BF?
Lamotrigine- up to 200mg probably safe
Monitor serum concentrations, as slow neonatal elimination is possible (glucuronidation) Can cause sedation and a rash
Avoid abrupt withdrawal
* Carbamazepine, phenytoin, valproate, and levetiracetam is acceptable in BF
80
Should you restart any medicines stopped before pregnancy whilst BF?
No
81
How should you manage Type 1 diabetes after a woman has given birth?
Reduce insulin doses immediately after birth and monitor blood glucose levels to establish an appropriate dose
82
What is the risk of BF in type 1 diabetes?
Increased risk of hypoglycaemia especially when breastfeeding so need to have a meal/snacks before feeds
83
How should you manage Type 2 diabetes after a woman has given birth and for BF?
* Resume or continue to take metformin and glibenclamide immediately after birth
* Avoid any other oral diabetic meds when BF
84
How should you manage gestational diabetes after a woman has given birth?
Stop blood glucose lowering therapy immediately after birth
85
What needs to be considered with azathioprine in BF in terms of its PK?
* Immunosuppressant
* Concern is cytotoxic properties
* Metabolised to 6-mercaptopurine then to active metabolites
* TPMT (metabolises the drug) genotype in mother needs to be considered
* If decreased TPMT activity, increase in toxic metabolites and side effects e.g. bone marrow suppression
* 6-MP Present in low concentrations in milk, in small studies has shown no harm
* Use if potential benefit outweighs risk
86
What medication is used to stimukate breast milk production?
* 10 mg TDS domperidone or metoclopramide for 7 days and review
87
What medication can be used to suppress/prevent breast milk production?
* Bromocriptine and cabergoline however this can be treated with breast support
* 1mg cabergoline single dose on first day postpartum for prevention or 250 mcg every 12 hours for 2 days to suppress – not recommended for routine suppression
88
What does compatible mean in terms of drug and milk?
Either the drug is not excreted in clinically significant amounts into breast milk or its use during lactation does not/not expected to cause toxicity in infant
89
What are the Thomas Hale lactation risk strategies?
L1- safest (lots of studies)
L2- safer (limited studies)
L3- moderately safe (possible risk)
L4- hazardous (evidence of risk)
L5- contraindicated
90
How is carbamazepine a teratogenic?
Neural tube defects
91
How is phenytoin a teratogenic?
Growth retardation, CNS defect
92
How is warfarin a teratogenic?
Skeletal and CNS defect
Dandy walker syndrome
93
What drug causes dandy walker syndrome?
Warfarin
