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Block 11 > Drugs In Pregancny And The Newborn > Flashcards

Drugs In Pregancny And The Newborn Flashcards

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1
Q

What kind of causes are there for birth defects

A
  • chromosomal aberrations: such as Edward’s and Patau and down’s (3-5%)
  • background risk of congenital malformations 2-3%
  • known genetic transmission 20%
  • infectious accounts = rubella most common agent (2-3%))
  • drugs and chemical (4-6%)
  • maternal metabolic disorders (1-2%)
  • unknown (70%)
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2
Q

What is a teratogen

A

Agent if administered causes directly or indirectly structural or functional abnormalities in the foetus or in child after birth (may not be apparent until later in life)

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3
Q

What can teratogens cause

A

Resorption or abortion of the early embryo

Structural malformations

Intrauterine growth retardation

Mental retardation

Foetal death

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4
Q

What are common teratogens

A

Infections
‘
Physical agents/ chemicals

Medicines

Alcohol, tobacco or cocaine

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5
Q

What is behavioural teratology

A

Effect on the behaviour or functional adaptation of the offspring to its environment

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6
Q

What is transplacental carcinogenicity

A

Has no effect on the mother but results in cancer in the offspring

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7
Q

What causes vaginal/testicular cancer in the offspring

A

Diethylstilboestrol DES

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8
Q

How can mutagenicity result in infertility or cancer

A

Mutations in germ lines = sex cells are defective causing reduced fertility or complete infertility

Mutations of somatic cells can result in cancer induction

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9
Q

How does smoking result in defects

A

Causes hypoxia and vasoconstriction —> spontaneous abortion

Cocaine can cause placental issues indirectly and directly same as above leading to stillbirth

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10
Q

With regard to teratogens having any effect what are the some of the most important considerations

A
  • time of exposure is critical
  • teratogenicity is usually dose dependent
  • susceptibility to some teratogens is genetically determined

However risk may altered through individual metabolism of drug

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11
Q

Behavioural teratology: alcohol use: how does it present

A

Use of alcohol is associated with increased risk of spontaneous abortion and reduced birth weight by 1kg

Foetal alcohol syndrome associated with binge drinking

Facial features: microcephaly, small chin, short nose, low set ears, flat mid face

However above physical features may not be as recognisable so other key indicators include attention span and academic ability as development of brain and CNS hindered

Strong link for children to have secondary comorbidities such as behavioural abnormalities

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12
Q

How is foetal alcohol spectrum disorders FASD different to FAS

A

In FASD not all symptoms of FAS are present

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13
Q

What are patterns of alcohol consumption in women of child-bearing age

A

Overall alcohol consumption has fallen

Younger women are drinking less frequently than older women but are more likely to participate in binge drinking

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14
Q

What are the two types of inheritance and how do they explain recurrence risks

A

Mendelian/ monogenic inheritance = recognisable patterns in inheritance

Multi factorial/ polygenic = degree of sensitivity is variable
Eg spina bifida
For many malformations there is a high recurrence rate and chromosomal abnormalities can result in disease

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15
Q

What is spina bifida

A

Failure of the caudal end of the neural tube to fuse

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16
Q

What are some of the causes of spina bifida

A

Chromosomal abnormalities
Single gene disorders
Teratogenic exposures

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17
Q

What % of spina Bifida can be prevented in mother takes folic acid

A

70%

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18
Q

What are risk factors for spina bifida

A

History of previous affected pregnancy with same partner

Inadequate maternal intake of folic acid

Pre-gestational diabetes

Valproate and carbamazepine use

Maternal obesity

Strong family history

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19
Q

Teratogenic damage is dependent on the dose relationship curve. What would a steep curve indicate

A

Small increments in dose show large increases in effect

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20
Q

What is the concept of synergy in relation to teratogenic damage

A

Work together to increase the harm done to the foetus. For example administering a second drug that enhances the teratogenicity of the first drug

So the general rule is to avoid poly pharmacy when possible

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21
Q

Placental transfer of drugs occurs via which 3 mechanisms

A
  • passive diffusion
  • facilitated diffusion through pores of the chorionic membrane
  • active transport via enzymes or protein carriers
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22
Q

Drug transfer is influenced by which of the 5 factors

A

1) molecular weight

2) lipid solubility

3) ionisation

4) protein binding

5) chemical structure

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23
Q

Large molecular weight drugs such as ____________, _________, _________ do not cross the placenta

A
  • heparin’s
  • insulins
  • iron dextran
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24
Q

Does a drug need to cross the placenta to affect the foetus

A

No! Eg insulin

Th glucose produced during episodes of maternal hyperglycaemia may pass across causing the foetus to produce insulin that it cannot clear

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25
A molecular weight of ________ daltons will allow drug to enter the placenta
1000 or less
26
What is the main determinant of the conc in the foetus
The concentration in the mothers blood
27
How may physiological changes affect drug transfer to the placenta
Can modify blood flow to placenta Can modify placental surface area available for transfer
28
What pharmacokinetic changes occur during pregnancy
- increase in maternal liver function so there is an increase in metabolism - increase in maternal excretion due to increased renal flow eg Li - there is a decrease in albumin which leads to a higher concentration of free unbound drug in the foetal circulation - decrease in GI motility
29
Why is detecting teratogenic effects so difficult
- requires large number of infants exposed in utero to study them But since it is advised to not take drugs in pregnancy and testing is not carried on women of childbearing age = lack of data And most birth defects occur rarely
30
Difference between gestational age and embryonic age
Gestational age = pregnancy is dated from the last menstrual period Embryonic age = post conception so difference of two weeks in dating
31
What is the most critical time period
In the first trimester
32
What major structures form in the first trimester
Spine Head Arms Legs Organ development Lungs Heart Stomach
33
What are the greatest risks in the 2nd trimester
Harmful exposures in the 2nd trimester may result in growth problems and minor birth defects Functional defects such as learning problems Brain and CNS
34
How may the use of androgenic steroids impact development if administered in the first 13 weeks
May masculinise a developing female foetus through clitoromegaly and labial fusion
35
What is transposition of the great vessels
Rare but serious disorder that requires surgical treatment Group of congenital defects in which position of major blood vessels of heart are switched around. Rarely even chambers may be switched around
36
What is a cleft lip
Gap/split in the upper lip or roof of mouth. Occurs because part of the baby’s face did not join together properly Most common facial birth defect
37
What is a ventricular septal defect
Hole in the heart which causes oxygen rich blood to get pumped back to the lungs causing the heart to work harder Small VSDs may repair on own but larger ones may require intervention
38
What is syndactyly
Joined digits May also involve webbing of the skin or fusion of the bones
39
What is hypospadiasis
Congenital birth defect in which the opening of the urethra is on the underside of the penis instead of at the tip. Corrective surgery ensures normal appearance, urination and reproduction
40
1st trimester: what may oestrogens do to the foetus
Feminisation of the male foetus
41
Effects of warfarin in the T1
Nasal hypoplasia Skeletal defects
42
Effects of retinoids in T1
Craniofacial, cardiovascular and CNS defects
43
Effects of diethylstilboestrol in T1
Uterine lesions Transplacental carcinogen (vaginal and testicular cancer in the offspring)
44
Effects of anti-epileptics in T1
Facial defects Mental retardation Neural tube defects
45
Use of narcotics after T1 may result in
Neonatal respiratory depression
46
Use of warfarin after T1:
Foetal haemorrhage CNS abnormalities
47
Use of anti-depressant after T1
Neonatal withdrawal symptoms
48
Use of benzodiazepines after T1
Floppy infant syndrome, Neonatal respiratory depression Withdrawal symptoms
49
Use of ACE inhibitors after T1
Olighydraminous (deficient amniotic fluid —> severe growth restriction) Growth retardation Lung and kidney hypoplasia Hypocalvaria (cranial bones are hypoplastic (incomplete or arrested development) Neonatal convulsions Hypotension Anuria
50
What kind of defects timing is unknown
Neurodevelopmental defects
51
What happens if you take NSAIDS in last 9 weeks of pregnancy
Premature closing of the ductus arteriosus. Is a foetal blood vessel that connects the aorta and pulmonary artery May result in pulmonary hypertension and death
52
Possible paternal exposure to agents may include
Chemotherapeutic agents such as methotrexate Industrial chemicals Metals such as lead pesticides Steroids Recommended if exposed to mutagenic agent should wait 6 months/ 2 sperm cycles before attempting conception As may impact on fertility/chance of getting pregnant and in some cases chromosomal aberrations
53
As a result of the thalidomide scandal post marketing surveillance introduced which regulatory measures
- MHRA yellow card - congenital malformation registries - UK teratology information service UKTIS - UK epilepsy and pregnancy register and other national registers Changes to the packaging and warning labels Congenital disability act 1977
54
What could potentially be a risk to the foetus
- risks from the maternal illness - risks from the treatment - risks from failing to treat the mother
55
What are the critical factors in assessing risk factors to the foetus
Stage of the pregnancy Drug and chemical exposure Clinical condition of the mother or patient Previous obstetric history (history of malformations or recurrent abortions)
56
What are the main principles of prescribing in pregnancy
Only give drug when necessary and make sure to carry out a risk vs benefit assessment Use the lowest effective dose for the shortest amount possible Consider the stage of pregnancy Avoid all drug treatment in the first trimester wherever possible Avoid new drugs Avoid poly-pharmacy
57
Where to seek advice and information when it comes to prescribing in pregnancy
Safety in pregnancy SPS UKMI UK medicines information UKTIS UK teratology information service RCOG royal college of obstetricians and gynaecologists NHS medicines A-Z library NHS evidence/ NICE DoH green book - vaccine information
58
How is pain usually treated in pregnancy
- normally paracetamol or codeine if former not effective - NSAIDS but not after week 20 - risk of opioid use near delivery associated with respiratory depression - prolonged used of opioids related to neonatal withdrawal Non pharmacological treatments - physiotherapy, hot and cold packs, TENS
59
How is nausea and vomiting treated in pregnancy
Step 1 = non pharmacological: small high carb, low fat frequent meals Use of ginger or acupuncture Step 2 = pharmacological 1st choice = cyclizine, promethazine or doxylamine 2nd choice = ondansetron or domperidone
60
Treatment for hyperemesis gravidarum
Hospitalisation Fluid and electrolyte replacement Consider corticosteroids (if severe) Thiamine and pyridoxine if required
61
What are the treatments for constipation in pregnancy
Step 1 = non-pharmacological Increased fibre Increased fluid Increased exercise Step 2: Bulk-forming laxatives isphagol Osmotic laxatives = lactulose or macrogol Senna Glycerol suppository
62
What causes constipation in pregnancy
Affects 40% of women Progesterone induced intestinal smooth muscle relaxation
63
Treatment of hay fever in pregnancy
Non-pharmacological interventions such as allergen avoidance Topical therapy in form of intranasal corticosteroids Non sedating anti-histamines such as certirizine and loratadine Sedating anti-histamines = chhlorphenamine
64
What is the ruling on use of valproate in pregnancy
Valproate must not be given to women and girls of childbearing age and especially not pregnant women unless conditions of pregnancy prevention programme are met
65
What other drugs should be avoided in pregnancy
Anti-seizure medication such as leviteracetum Topiramate Isotretinoin
66
What did the baroness cumberledge report find
Reported on 3 clinical areas where harm has occurred 1) primodos 2) sodium valproate 3) surgical mesh for female incontinence Patient voice is dismissed, parents are living with guilt and failure of informed consent

Block 11 (13 decks)

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