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CDM > Obstetrics > Flashcards

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
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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)
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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
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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

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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

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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

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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
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8
Q

What is the role of the placenta?

A
  • Nutrition
  • Excretion
  • Immunity
  • Endocrine function
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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
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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
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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
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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
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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
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14
Q

How is distribution affected in pregnancy?

A

Plasma volume and total body water increases

Decreased albumin concentration

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15
Q

Name some conditions where drug therapy is continued during pregnancy

A
  • Diabetes
  • HIV
  • Hypertension
  • Asthma
  • DVT/PE
  • Transplant patients
  • Epilepsy
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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
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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
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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
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19
Q

How do you calculate exposure index?

A

(100 x MP x A) / Infant drug clearance

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20
Q

Cationic drugs favour excretion of drug into milk. True of false?

A

True

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21
Q

How are the biochemical characteristics of breast milk different to plasma?

A

Higher pH and lipid contents

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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
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23
Q

What % of adult clearance do the following ages have?

  1. 2-3 months premature
  2. Term
  3. 1-2 months
  4. 3-6 months
  5. > 6 months
A
  1. 10 %
  2. 33%
  3. 50%
  4. 66%
  5. 100%
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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
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25
Q

Name some drugs that have known breast milk problems and their effect

A
  • 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
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26
Q

What are the analgesics of choice in BF ?

A

Paracetamol
Ibuprofen
Morphine

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27
Q

What is the glucocorticoid choice in BF?

A

Prednisolone

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28
Q

What is the antihistamine of choice in BF?

A

Loratadine

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29
Q

What are the beta blockers of choice in BF?

A

Labetalol and propranolol (non-selective)

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30
Q

How is absorption affected in pregnancy?

A
  • Decreased gastric and intestinal motility
  • Reduced gastric acid secretion so increased gastric pH (less acidic)
  • Nausea and vomiting (hyperemesis gravidarum)
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31
Q

Why might compliance be poor in pregnancy?

A

Fear of harming the foetus

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32
Q

What should be essential for all women receiving long-term treatment with medicines?

A

Pre-pregnancy counselling

Discussing the consequences of stopping treatment

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33
Q

What are the risks with obesity in pregnancy?

A
  1. Higher rates of congenital abnormalities:

High dose folic acid supplementation pre-pregnancy and during first trimester – 5mg daily

  1. 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)
  2. 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
  3. Increased risk of gestational diabetes:

Much greater risk of complications as the mother gets older, as well as the presence of comorbidities

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34
Q

What is the different between direct and indirect causes in maternity death?

A
  • Indirect causes – not related to pregnancy as such

* Direct causes – would not have died if they weren’t pregnant. E.g. haemorrhage, thrombosis

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35
Q

What is perinatal mental health?

A
  • Woman’s mental health during pregnancy and the first year after birth
  • Leading cause of maternal deaths
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36
Q

What are the risks of treating severe mental illness in pregnancy?

A

Major malformation (1st trimester exposure)

Neonatal toxicity and withdrawal effects (3rd trimester exposure)

Long term neurobehavioural effects and growth impairment

Miscarriage- spontaneous abortion

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37
Q

What are the benefits in treating severe mental illness in pregnancy?

A

Reducing harm to the mother. Poor self-care, self-harm, impulsive acts, poor judgement and substance misuse

Reducing harm to baby (neglect, killing)

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38
Q

For psychotropic medicines, what do you need to consider for pregnancy and what precautions can you take?

A
  • 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
Q

What do you need to consider when treating a pregnant lady who has epilepsy?

A
  • 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
Q

What should you do if you are dispensing sodium valproate for the first time in a child bearing age woman?

A

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
Q

For diabetes, what is the risk for the mother?

A 
Miscarriage
Pre-eclampsia
Pre-term labour
Induction of labour/caesarean
Diabetic retinopathy may worsen
Birth trauma
42
Q

For diabetes, what is the risks for the baby?

A 
Birth trauma
Perinatal death
Neonatal hypoglycaemia
Obesity
Diabetes developing from childhood
Macrosomia- larger than average baby
43
Q

How should you control diabetes in pregnancy?

A
  • 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
Q

Should you continue ACEis, ARBs and statins during pregnancy?

A

No- stop before conception or as soon as pregnancy is confirmed

45
Q

What is the risk with gestational diabetes?

A

Increased risk of Type 2

46
Q

How do you manage gestational diabetes?

A
  • Diet, exercise
  • Insulin, metformin
  • Glibenclamide (sulphonylurea) if blood glucose targets not achieved, insulin declined or metformin not tolerated
47
Q

What are the risks associated with acei in pregnancy?

A
  • 1st trimester has increased risk of congenital cardiac or CNS malformations
  • 2nd and 3rd trimesters- foetal hypotension and renal failure – risk of death
48
Q

What are the risks associated with beta blockers in pregnancy?

A

Increased risk of growth restriction

49
Q

How would you diagnose pre-eclampsia?

A
  • Hypetension and proteinuria
  • PCR (protein creatinine ratio)
  • 24 hour urine collection
50
Q

How do you treat pre-eclampsia?

A
  • Labetalol
  • Nifedipine
  • Methyldopa
  • Hydralazine
51
Q

How do you prevent pre-eclampsia?

A

75 mg aspirin OD

52
Q

What are the risks associated with anticoagulation treatment options and what would be the treatment of choice in pregnancy?

A
  • 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
Q

What would you use for VTE prophylaxis in pregnancy?

What risk score do you need to have to go on this?

A

LMWH

Score of 3 or more in pregnancy

Score of 2 or more postnatally

54
Q

Elective caesareans decrease the risk of HIV transmission from mother to baby. True or false?

A

True

55
Q

What are the risk factors in pregnancy for mother to baby transmission?

A
  • Viraemia (virus in blood)
  • Mode of delivery
  • Duration of membrane rupture
  • Deliver <32 weeks
56
Q

What is the post exposure prophylaxis regimen for a baby whose mother is HIV positive?

A

Zidovudine (AZT) 4mg/kg BD for 4 weeks

Nevirapine +/- lamivudine (or alternatives if resistance)

57
Q

Is the flu vaccine safe in pregnancy?

A

Yes

58
Q

Can the flu virus cross the placenta?

A

Yes

59
Q

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?

A

Antenatal care

60
Q

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?

A

C - potential placental transfer

Use if potential benefit outweighs risk

Tamiflu has neonatal dosing from 2 months whereas zanamivir has no neonatal dosing

61
Q

What are the PKs of Tamiflu?

A

Pro drug via hepatic metabolism

Renal elimination

Nausea and vomiting side effects

62
Q

What are the PKs of Zanamivir?

What is a disadvantage of its inhaled powder form?

A
  • 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
Q

What is used in the treatment of ectopic pregnancies?

A

Methotrexate

64
Q

What is used in combination for medical termination of pregnancy?

A
  • Mifepristone (antiprogesterone)– yellow, cylindrical 200mg tablets
  • Misoprostol (Prostaglandin E1 analogue) white, hexagonal 200 mcg tablets
65
Q

What sources can we use to see if a drug is safe in pregnancy?

A
  • 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
Q

What are the FDA category risks for pregnancy?

A

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
Q

What does WHO say about babies being breastfed?

A

Infants should be exclusively breast fed for the first 6 months of life to achieve optimal growth, development and health

68
Q

What are the psychological aspects of BF?

A

The thought of “poisoning” baby if they give formula instead, or take drugs during BF, am I a good mum?

69
Q

Codeine is restricted for use as an analgesic in children/BF women.

Why?

What alternatives are there?

What should you monitor in the baby?

A

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
Q

How is codeine metabolised?

A

CYP2D6

71
Q

What are the PKs of beta blockers?

A
  • Water soluble, low protein binding, renally excreted

* Half life 6-7 hours

72
Q

What is the risk of using a beta blocker whilst BF and what is the general advice given?

A
  • 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
Q

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?

A

Captopril, enalapril and quinapril

Ramipril is C/I

BP monitoring due to hypotension risk

74
Q

Can diuretics be given in BF ?

A

No-avoid

75
Q

If the patient is hypertensive, what monitoring should do you when the baby is born?

A

Assess wellbeing of the baby and how well they are being fed daily for the first 2 days after birth

76
Q

What antihypertensives have no known side effects on BF babies?

A
  • Labetolol, atenolol, metoprolol
  • Nifedipine
  • Enalapril, captopril
77
Q

Should statins be given in BF?

A

No information available

Manufacturers advise avoid

78
Q

What is the risk of aspirin in BF?

A

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
Q

How would you manage epilepsy in BF?

A

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
Q

Should you restart any medicines stopped before pregnancy whilst BF?

A

No

81
Q

How should you manage Type 1 diabetes after a woman has given birth?

A

Reduce insulin doses immediately after birth and monitor blood glucose levels to establish an appropriate dose

82
Q

What is the risk of BF in type 1 diabetes?

A

Increased risk of hypoglycaemia especially when breastfeeding so need to have a meal/snacks before feeds

83
Q

How should you manage Type 2 diabetes after a woman has given birth and for BF?

A
  • Resume or continue to take metformin and glibenclamide immediately after birth
  • Avoid any other oral diabetic meds when BF
84
Q

How should you manage gestational diabetes after a woman has given birth?

A

Stop blood glucose lowering therapy immediately after birth

85
Q

What needs to be considered with azathioprine in BF in terms of its PK?

A
  • 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
Q

What medication is used to stimukate breast milk production?

A
  • 10 mg TDS domperidone or metoclopramide for 7 days and review
87
Q

What medication can be used to suppress/prevent breast milk production?

A
  • 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
Q

What does compatible mean in terms of drug and milk?

A

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
Q

What are the Thomas Hale lactation risk strategies?

A

L1- safest (lots of studies)

L2- safer (limited studies)

L3- moderately safe (possible risk)

L4- hazardous (evidence of risk)

L5- contraindicated

90
Q

How is carbamazepine a teratogenic?

A

Neural tube defects

91
Q

How is phenytoin a teratogenic?

A

Growth retardation, CNS defect

92
Q

How is warfarin a teratogenic?

A

Skeletal and CNS defect

Dandy walker syndrome

93
Q

What drug causes dandy walker syndrome?

A

Warfarin

CDM (17 decks)

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