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Block 11 > Drugs In Pregancny And The Newborn > Flashcards

Drugs In Pregancny And The Newborn Flashcards

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
Q

A molecular weight of ________ daltons will allow drug to enter the placenta

A

1000 or less

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26
Q

What is the main determinant of the conc in the foetus

A

The concentration in the mothers blood

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27
Q

How may physiological changes affect drug transfer to the placenta

A

Can modify blood flow to placenta

Can modify placental surface area available for transfer

28
Q

What pharmacokinetic changes occur during pregnancy

A
  • 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
Q

Why is detecting teratogenic effects so difficult

A
  • 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
Q

Difference between gestational age and embryonic age

A

Gestational age = pregnancy is dated from the last menstrual period

Embryonic age = post conception so difference of two weeks in dating

31
Q

What is the most critical time period

A

In the first trimester

32
Q

What major structures form in the first trimester

A

Spine
Head
Arms
Legs

Organ development
Lungs
Heart
Stomach

33
Q

What are the greatest risks in the 2nd trimester

A

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
Q

How may the use of androgenic steroids impact development if administered in the first 13 weeks

A

May masculinise a developing female foetus through clitoromegaly and labial fusion

35
Q

What is transposition of the great vessels

A

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
Q

What is a cleft lip

A

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
Q

What is a ventricular septal defect

A

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
Q

What is syndactyly

A

Joined digits
May also involve webbing of the skin or fusion of the bones

39
Q

What is hypospadiasis

A

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
Q

1st trimester: what may oestrogens do to the foetus

A

Feminisation of the male foetus

41
Q

Effects of warfarin in the T1

A

Nasal hypoplasia
Skeletal defects

42
Q

Effects of retinoids in T1

A

Craniofacial, cardiovascular and CNS defects

43
Q

Effects of diethylstilboestrol in T1

A

Uterine lesions
Transplacental carcinogen (vaginal and testicular cancer in the offspring)

44
Q

Effects of anti-epileptics in T1

A

Facial defects
Mental retardation
Neural tube defects

45
Q

Use of narcotics after T1 may result in

A

Neonatal respiratory depression

46
Q

Use of warfarin after T1:

A

Foetal haemorrhage
CNS abnormalities

47
Q

Use of anti-depressant after T1

A

Neonatal withdrawal symptoms

48
Q

Use of benzodiazepines after T1

A

Floppy infant syndrome,
Neonatal respiratory depression
Withdrawal symptoms

49
Q

Use of ACE inhibitors after T1

A

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
Q

What kind of defects timing is unknown

A

Neurodevelopmental defects

51
Q

What happens if you take NSAIDS in last 9 weeks of pregnancy

A

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
Q

Possible paternal exposure to agents may include

A

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
Q

As a result of the thalidomide scandal post marketing surveillance introduced which regulatory measures

A
  • 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
Q

What could potentially be a risk to the foetus

A
  • risks from the maternal illness
  • risks from the treatment
  • risks from failing to treat the mother
55
Q

What are the critical factors in assessing risk factors to the foetus

A

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
Q

What are the main principles of prescribing in pregnancy

A

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
Q

Where to seek advice and information when it comes to prescribing in pregnancy

A

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
Q

How is pain usually treated in pregnancy

A
  • 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
Q

How is nausea and vomiting treated in pregnancy

A

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
Q

Treatment for hyperemesis gravidarum

A

Hospitalisation
Fluid and electrolyte replacement
Consider corticosteroids (if severe)
Thiamine and pyridoxine if required

61
Q

What are the treatments for constipation in pregnancy

A

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
Q

What causes constipation in pregnancy

A

Affects 40% of women

Progesterone induced intestinal smooth muscle relaxation

63
Q

Treatment of hay fever in pregnancy

A

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
Q

What is the ruling on use of valproate in pregnancy

A

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
Q

What other drugs should be avoided in pregnancy

A

Anti-seizure medication such as leviteracetum

Topiramate

Isotretinoin

66
Q

What did the baroness cumberledge report find

A

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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