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Reproductive System > Pharmacology in Pregnancy and Breast Feeding > Flashcards

Pharmacology in Pregnancy and Breast Feeding Flashcards

1
Q

Why might a woman be on medication at the start of a pregnancy?

A
  • Hypertension
  • Asthma
  • Epilepsy
  • Migraines
  • Mental health disorder
  • Long-term anticoagulant therapy e.g. for AF
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2
Q

What are the 4 basic kinetic drug processes?

A
  • Absorption
  • Distribution
  • Metabolism and elimination
  • Excretion
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3
Q

What are the changes in the oral route of absorption in pregnancy?

A
  • May be more difficult due to morning sickness

* Decrease in gastric emptying and gut motility - more likely to affect single dose rather than multiple dosing

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4
Q

What are the changes in the intramuscular route of absorption in pregnancy?

A

Blood flow may be increased, so absorption may also increase using this route

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5
Q

What are the changes in the inhalation route of absorption in pregnancy?

A

Increased cardiac output and decreased tidal volume may cause increased absorption of inhaled drugs

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6
Q

Why is distribution different in pregnancy?

A
  • Increase in plasma volume and fat will change distribution of drugs - increased volume distribution (Vd)
  • Greater dilution of plasma will decrease relative amount of plasma proteins - increases fraction of free drug
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7
Q

What metabolism changes occur in pregnancy?

A
  • Oestrogen and progesterone can induce or inhibit liver P450 enzymes
  • This leads to an increase or reduction in metabolism
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8
Q

What are some examples of liver enzyme changes?

A
  • Phenytoin levels reduced - due to induction of metabolism

* Theophylline levels increased - due to inhibition of metabolism

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9
Q

How does excretion change in pregnancy?

A
  • GFR is increased in pregnancy by 50% leading to increased excretion of many drugs
  • This can reduce the plasma concentration, and can necessitate an increase in dose of medicines cleared by the kidney
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10
Q

How well are pregnancy pharmacodynamics understood?

A

Less well understood

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11
Q

How does pregnancy affect pharmacodynamics?

A
  • Pregnancy may affect the site if drug action and the receptor response to drugs
  • Concentration of drug change metabolites at sites of biological action (changes in blood flow)
  • Mechanism of action (changes in receptors)
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12
Q

How does pregnancy affect pharmacodynamics?

A
  • Pregnancy may affect the site of drug action and the receptor response to drugs
  • Concentration of drug change metabolites at sites of biological action (changes in blood flow)
  • Mechanism of action (changes in receptors)
  • Efficacy may be different
  • Adverse effects may be different
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13
Q

What are the material exchanged from mother to foetus across the placenta?

A
  • Oxygen
  • Glucose
  • Amino acids
  • Lipids, fatty acids & glycerol
  • Vitamins
  • Ions; Na, Cl, Ca, Fe
  • Alcohol, nicotine + other drugs
  • Viruses
  • Antibodies
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14
Q

What are the material exchanged from foetus to mother across the placenta?

A
  • Carbon dioxide
  • Urea
  • Other waste products
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15
Q

Can drugs pass the placenta during pregnancy?

A

Yes, most do

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16
Q

What are the factors affecting placental drug transfer and drug effects on the foetes inside?

A
  • Drug physiochemical properties
  • Rate at which drug crosses placenta and amount reaching the fetus
  • Duration of drug exposure
  • Distribution in different fetal tissues
  • Stage of placental and fetal development
  • Effects of drugs when used in combination
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17
Q

What does placental transfer depend on?

A
  • Molecular weight (smaller sizes will cross more easily)
  • Polarity (unionised molecules cross more readily)
  • Lipid solubility (lipid soluble drugs will cross)
  • Placenta may also metabolise some drugs
  • Safest to assume all drugs will cross placenta
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18
Q

What molecular weight (size) of drugs can pas the placenta?

A
  • Most drugs withMW < 500 Da cross the placenta

* MW > 1000 Da do not

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19
Q

How easily do ionised drugs cross the placenta?

A

•Non-ionized drugs cross the placenta more easily than ionized drugs

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20
Q

How does protein-binding affect drugs crossing the placenta?

A

Previously it was believed that protein-bound drugs did not cross the placenta, however as these medications exist in equilibrium with non-bound versions this is not true

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21
Q

How does lipophilicity affect drugs crossing the placenta?

A

High lipophilicity will increase placental transfer

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22
Q

How is distribution different in foetal pharmacokinetics?

A
  • Circulation is different (e.g. Umbilical vein to liver)
  • Less protein binding than adults therefore more “free” drug available
  • Little fat, so distribution different
  • Relatively more blood flow to brain
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23
Q

How is metabolism different in foetal pharmacokinetics?

A
  • Reduced enzyme activity, although this increases with gestation
  • Fetus exhibits different P450 isoenzymes to adults
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24
Q

How is excretion different in foetal pharmacokinetics?

A
  • Excretion is into amniotic fluid – which the fetus swallows leading to recirculation
  • Drugs and metabolites can accumulate in amniotic fluid
  • Placenta not functioning at delivery so can be issues with excretory function
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25
Q

In which drug groups is there actually information available on pregnancy and PK and PD?

A
  • Anti-convulsants
  • Anti-hypertensives
  • Analgesics
  • Antibacterials
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26
Q

When does teratogenicity occur?

A

The first trimester

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27
Q

When does fetotoxicity occur?

A

Second and third trimester

N.B. Under treatment due to fear of using drugs during pregnancy may cause greater foetal risk

28
Q

What are the principles of prescribing for women of a child-bearing age?

A
  • Always consider possibility of pregnancy
  • Warn women of possible risks
  • When treating medical conditions, advise women to attend before getting pregnant if planning to (optimise treatment)
  • Discuss contraception
  • If necessary, do not prescribe without contraception
29
Q

What are the principles when prescribing in pregnancy?

A
  • If you can, try non-pharmacological treatment first
  • Use the drug with the best safety record (avoid new drugs unless proven safe).
  • Check the SPC for the most up to date information
  • Use the lowest effective dose.
  • Use the drug for the shortest possible time, intermittently if possible.
  • Avoid the first 10 weeks of pregnancy if possible.
  • Consider stopping or reducing dose before delivery
  • Never under a treat disease which may be harmful to the mother or fetus
30
Q

Drugs are responsible for what percentage of foetal abnormalities?

A

2%

31
Q

When is the highest risk of teratogenesis?

A

3-8 weeks

32
Q

What mechanisms can cause teratogenicity?

A
  • Folate Antagonism
  • Neural Crest Cell Disruption
  • Endocrine Disruption: Sex Hormones
  • Oxidative Stress
  • Vascular Disruption
  • Specific Receptor- or Enzyme-mediated teratogenesis
33
Q

What is folate antagonism?

A

A key process in DNA formation and new cell production

34
Q

Why is folate essential in pregnancy?

A

Key in DNA formation and new cell production

35
Q

What are the mechanisms of the two groups of drugs that affect folate metabolism?

A
  1. Block the conversion of folate to THF by binding irreversibly to the enzyme (eg methotrexate, trimethoprim)
  2. Block other enzymes in the folate pathway (e.g. phenytoin, carbamazepine, valproate)
36
Q

What happens if folate requirements are not met?

A

Tends to result in neural tube, oro-facial or limb defects

37
Q

Which drugs cause neural crest cell disruption?

A

Retinoid drugs e.g. isotretinoin (Accutane)

38
Q

What are the effects of neural crest cell disruption?

A
  • Aortic arch anomalies
  • Ventricular septal defects
  • Craniofacial malformations
  • Oesophageal atresia
  • Pharyngeal gland
  • Abnormalities
39
Q

How does enzyme-mediated teratogenesis occur?

A
  • Drugs which inhibit or stimulate enzymes to produce therapeutic effects may also interact with specific receptors and enzymes damaging fetal development
  • E.g. NSAIDs causing orofacial clefts and cardiac septal defects
40
Q

What is feototoxicity?

A

Toxic effect on the fetus later in pregnancy

41
Q

What are the possible issues caused by foetotoxicity?

A
  • Growth retardation
  • Structural malformations
  • Fetal death
  • Functional impairment
  • Carcinogenesis

•E.g. ACE inhibitors/ARBs – renal dysfunction and growth retardation

42
Q

How does the FDA categorise teratogenic drugs?

A

From A-X

43
Q

Describe each category of teratogenic drug

A

TERATOGENIC DRUG CLASSIFICATION

44
Q

What is the effect of anticonvulsants in pregnancy?

A

Valproate is associated with neural tube defects, as is carbamazepine and phenytoin

(all anti-seizure)

45
Q

What is the effect of anticoagulants in pregnancy?

A

Warfarin is associated with haemorrhage in the fetus, as well as multiple malformations in the central nervous system and skeletal system

46
Q

What is the effect of antihypertensive agents in pregnancy?

A

ACE inhibitors cause renal damage and may restrict normal growth patterns in the unborn child

47
Q

What is the effect of NSAIDs in pregnancy?

A

Premature closure of the ductus arteriosus

48
Q

What is the effect of alcohol in pregnancy?

A

Fetal alcohol syndrome/effects

49
Q

What is the effect of retinoids in pregnancy?

A

Ear, CNS, cardiovascular, and skeletal disorders

50
Q

What issues do drugs pose to breast feeding?

A
  • Almost all drugs the mother takes will be present in breast milk
  • Important to know what concentration will be in breast milk
  • Remember pharmacokinetics are different in the neonate compared to the fetus
51
Q

How should a possibility of harm to the infant through breast feeding be monitored?

A

Monitor infant blood levels of the drug

52
Q

How else might the issues surrounding drugs and breast feeding be tackled?

A
  • If possible postpone drug treatment until the baby is weaned
  • Use non-pharmacological strategies when possible.
  • If a drug needs to be used, then the mother should take the medication immediately after feeding the baby
  • Avoid breast-feeding during peak drug effect
  • Avoid drugs with long half-life or active metabolites
  • Drugs that are highly protein-bound are preferred
  • Extra caution if baby is severely ill or preterm
53
Q

How else might the issues surrounding drugs and breast feeding be tackled?

A
  • If possible postpone drug treatment until the baby is weaned
  • Use non-pharmacological strategies when possible.
  • If a drug needs to be used, then the mother should take the medication immediately after feeding the baby
  • Avoid breast-feeding during peak drug effect
  • Avoid drugs with long half-life or active metabolites
  • Drugs that are highly protein-bound are preferred
  • Extra caution if baby is severely ill or preterm
54
Q

What are some drugs to avoid when breast-feeding?

A
  • Cytotoxics (chemotherapy)
  • Immunosuppressants
  • Anti-convulsants (not all)
  • Drugs of abuse
  • Amiodarone (anti-arrhythmic)
  • Lithium
  • Radio-iodine
55
Q

What effect does tetracycline have on the infant during lactation?

A

Risk of permanent tooth staining in infant

56
Q

What effect does isoniazid have on the infant during lactation?

A

Risk of pyridoxine (vit B6) deficiency in the infant

TB antibiotic

57
Q

What effect do barbiturates have on the infant during lactation?

A

Lethargy, sedation and poor suck reflexes

58
Q

What effect does chloral hydrate have on the infant during lactation?

A

Drowsiness if infant fed at peak

Sedative

59
Q

What effect does diazepam have on the infant during lactation?

A

Drug accumulation and sedation

60
Q

What effect does methadone have on the infant during lactation?

A

Risk of withdrawal if breast feeding stops

61
Q

What effect does iodine have on the infant during lactation?

A

Thyroid suppression and risk of cancer

62
Q

What effect does propylthiouracil have on the infant during lactation?

A

Can suppress thyroid function in infant

for hyperthyroidism

63
Q

What are the two most popular galactagogues for nursing mothers?

A
  • Fenugreek

* Comfrey

64
Q

Why should breast-feeding mothers avoid herbal remedies?

A
  • This is is due to the lack of information of scientific safety data
  • Contamination of herbal products with conventional medicines, pesticides or heavy metals
  • Herbs containing pyrrolizidine alkaloids (PAs) can be hepatotoxic
  • Some herbal medicines have hormonal effects.
  • Some herbal medicines contain constituents with sedative properties
65
Q

What are the principles of prescribing in breast-feeding?

A
  • Again avoid unnecessary drug use
  • Check on up to date drug information - may be a lack of information
  • If licensed and safe in paediatric use (esp under 2 years), a drug is likely to be safe in breast feeding
  • Choose drugs with pharmacokinetic properties that reduce infant exposure (e.g. highly protein bound)

Reproductive System (31 decks)

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