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Y3 repro > pharmacology in pregnancy and breastfeeding > Flashcards

pharmacology in pregnancy and breastfeeding Flashcards

1
Q

what % of pregnant women take medicines

A

~50-90% will take a medicine
60% prescribed
90% OTC

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2
Q

what is the implication of unplanned pregnancy

A

many pregnancies are unplanned

80% of women of child bearing age take medication

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3
Q

why may a woman be on medication during pregnancy, birth and lactation

A 
HT
asthma
epilepsy
migraine 
mental health disorders
long term anticoagulation
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4
Q

what 4 processes can the physiological changes during pregnancy effect in relation to medication

A

absorption
distribution
metabolism and elimination
excretion

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5
Q

oral route absorption changes during pregnancy

A

may be more difficult - morning sickness, N+V

decrease in gastric emptying and gut motility - unlikely to be a problem with regular dosing but may affect single doses

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6
Q

IM route absorption changes during pregnancy

A

blood flow may be increased

absorption may also increase using this route

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7
Q

inhalation absorption changes during pregnancy

A

increased cardiac output
decreased tidal volume
increased absorption of inhaled drugs

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8
Q

distribution changes during pregnancy

A

increase in plasma volume and fat will change distribution of drugs - increased volume of distribution
greater dilution of plasma will decrease relative amount of plasma proteins 0 increased fraction of free drug

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9
Q

metabolism changes during pregnancy

A

oestrogen and progestogens can induce/inhibit liver P450 enzymes - increases/decreases metabolism

e.g. phenytoin levels reduced due to induction of metabolism, theophylline levels increased due to inhibition of metabolism

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10
Q

excretion changes during pregnancy

A

GFR increased by 50% in pregnancy - increased excretion of many drugs
this can reduce the plasma concentration and can require an increased dose of the medicines cleared by the kidney

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11
Q

pharmacodynamic changes during pregnancy

A

pregnancy may affect the site of drug action and receptor response to drugs

  • concentration of drug, metabolites at sites of biological action (changes of blood flow)
  • mechanism of action (changes in receptors)

efficacy and adverse effects may be different

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12
Q

what factors affect placental drugs transfer and drug effects on the foetus

A

drug physiochemical properties
rate at which drug crosses placenta and amount reaching the foetus
duration of drug exposure
distribution in different foetal tissues
stage of placental and foetal development
effects of drugs when used in combination

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13
Q

what does placental transfer depend on

A

molecular weight - smaller sizes cross more easily
polarity - unionised molecules cross more readily
lipid solubility - lipid soluble drugs will cross

placenta may also metabolise some drugs

safe to assume all drugs will cross placenta

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14
Q

fetal pharmacokinetics - distribution

A

circulation is different
less protein binding than adults - more free drug available
little fat, distribution different
relatively more blood flow to brain

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15
Q

fetal pharmacokinetics - metabolism

A

reduced enzyme activity - although this increases with gestation
exhibits different P450 isoenzymes to adults

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16
Q

fetal pharmacokinetics - excretion

A

excretion is into amniotic fluid - foetus swallows leading to recirculation
drugs and metabolites can accumulate in amniotic fluid
placenta not functioning at delivery - can be issues with excretory function

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17
Q

issues with PK and PD during pregnancy

A

inadequate data for most drugs so uncertainty around dosing

some information available for some drug groups - anti-convulsants, anti-hypertensives, analgesics, antibacterials

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18
Q

factors of safety of drugs in pregnancy

A

teratorgenicity - 1st trimester

fetotoxicity - 2nd and 3rd trimester

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19
Q

principles of prescribing for women of child bearing age

A

always consider possibility of pregnancy
warn re. possible risks
when treating medical conditions advise women to attend before getting pregnant if planning to - optimise treatment
discuss contraception
if necessary, don’t prescribe w/o contraception

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20
Q

principles of prescribing in pregnancy

A

try non-pharmacological methods first
use the drug with the best safety record, avoid new drugs unless proven safe
check SPC for most up to date info
use lowest effective dose
use the drug for the shortest possible time, intermittently if possible
avoid the first 10wks of pregnancy if possible
consider stopping/reducing dose before delivery
never under treat a disease which may be harmful to the mother/fetus

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21
Q

why is treatment of chronic illness still important during pregnancy

A

under-treatment of maternal illness due to fear of using medicines during pregnancy may cause greater fetal risk

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22
Q

what % of fetal abnormalities are drugs responsible for

A

2%

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23
Q

when is the highest risk of drug caused fetal abnormalities

A

during organogenesis

3-8wks

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24
Q

by what mechanisms can drugs cause fetal abnormalities

A 
folate antagonism 
neural crest cell disruption
endocrine disruption - sex hormones
oxidative stress
vascular disruption
specific receptor/enzyme mediated teratogenesis
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25
Q

what is folate antagonism

A

key process in DNA formation and new cell production

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26
Q

what groups of drugs affect folate metabolism

A

2 groups:

  1. block the conversion of folate –> THF by binding irreversible to the enzyme e.g. methotrexate, trimethoprim
  2. block other enzymes in the folate pathway e.g. phenytoin, carbamazepine, valproate
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27
Q

what types of defects does folate antagonism tend to result in

A

neural tube
oro-facial
limb defects

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28
Q

what drugs cause neural crest cell disruption

A

retinoid drugs e.g. isotretinoin (accutane)

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29
Q

what defects can be caused by neural crest cell disruption

A 
aortic arch anomalies
ventricular septal defects
craniofacial malformations
oesophageal atresia
pharyngeal gland abnormalities
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30
Q

describe enzyme mediated teratogenesis

A

drugs which inhibit/stimulate enzymes to produce therapeutic effects may also interact w/ specific receptors and enzymes damaging fetal development

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31
Q

example of enzyme mediated teratogenesis

A

NSAIDs causing orofacial clefts and cardiac septal defects

32
Q

what is fetotoxicity

A

toxic effect on the fetus later in pregnancy

33
Q

possible issues related to fetotoxicity

A 
growth retardation
structural malformations
fetal death 
functional impairment
carcinogenesis
34
Q

example of fetotoxicity

A

ACE inhibitors/ARBs - renal dysfunction and growth retardation

35
Q

category A drugs

A

controlled human studies - no fetal risks

safest drugs

36
Q

category B drugs

A

animal studies - no risk to fetus but no controlled human studies conducted
OR
animal studies show risk to fetus but well controlled human studies dont

37
Q

category C drugs

A

no adequate animal/human studies have been conducted
OR
adverse fetal effects have been shown in animals but no human data available

38
Q

category D drugs

A

evidence of human fetal risk exists but benefits > risks in certain situations (life threatening disorders, serious disorders for which safer drugs can’t be used/are ineffective)

39
Q

category X drugs

A

proven fetal risks&raquo_space; any possible benefit

40
Q

6 categories of known teratogens to avoid during pregnancy

A 
anticonvulsants
anticoagulants
antihypertensive agents
NSAIDs
alcohol 
retinoids
41
Q

examples of teratogenic anticonvulsants

A

valproate, carbamazepine, phenytoin - neural tube defects

42
Q

examples of teratogenic anticoagulants

A

warfarin - haemorrhage in fetus, multiple malformations in CNS and skeletal system

43
Q

examples of teratogenic antihypertensive agents

A

ACE inhibitors - renal damage, may restrict normal growth patterns in the unborn child

44
Q

examples of teratogenic effects of NSAIDs

A

premature closure of ductus arteriosus

45
Q

examples of teratogenic effects of alcohol

A

fetal alcohol syndrome/effects

46
Q

examples of teratogenic effects of retinoids

A

ear, CNS, CVS and skeletal disorders

47
Q

ACEI - trimester affected, effects

A

all

renal damage

48
Q

TCAs - trimester affected, effects

A

3rd

neonatal withdrawal syndrome

49
Q

barbituates - trimester affected, effects

A

all

chronic use - neonatal dependence

50
Q

carbamazepine - trimester affected, effects

A

1st

neural tube defects

51
Q

cocaine, tamoxifen - trimester affected, effects

A

all

risk of spontaneous abortion

52
Q

ethanol - trimester affected, effects

A

all

fetal alcohol syndrome

53
Q

iodine - trimester affected, effects

A

all
congenital goitre
hypothyroidism

54
Q

lithium - trimester affected, effects

A

1st

increased ICP

55
Q

tobacco - trimester affected, effects

A

all

intrauterine growth retardation

56
Q

tetracycline - trimester affected, effects

A

all

discolouration of teeth, altered bone growth

57
Q

thalidomide - trimester affected, effects

A 
1st 
limb malformation (DES cancer risk increased)
58
Q

warfarin - trimester affected, effects

A

1st - alters resp tract formation
2nd - CNS malformation
3rd - risk of bleeding, IC haemorrhage

59
Q

issues with drugs and lactation

A

almost all drugs the mother takes will be present in breast milk
important to know what the concentration will be in the breast milk
PK are different in the neonate to the fetus

60
Q

minimal exposure during BF - questions to ask

A

is maternal drug therapy necessary?
if yes, what is the safest option for the infant?
possibility of harm –> monitor infant blood levels of drug
MINIMISE INFANT EXPOSURE

61
Q

minimising the infant exposure during BF - steps to take

A

if possible, postpone drug treatment until baby is weaned
use non-pharmacological options where possible
if drug needs to be used, mother should take immediately after feeding baby
avoid BF during peak drug effect
avoid drugs w/ long 1/2 life or active metabolites
drugs that are highly protein bound are preferred
extra caution if baby is severely ill/pre-term

62
Q

which drugs should be avoided during breast feeding

A 
cytotoxics
immunosuppressants
anti-convulsants (not all)
drugs of abuse
amiodarone 
lithium 
radio-iodine
63
Q

tetracycline - effects on infant when used during lactation

A

risk of permanent tooth staining in infant

64
Q

isoniazid - effects on infant when used during lactation

A

risk of pyridoxine deficiency in infant

65
Q

barbituates - effects on infant when used during lactation

A

lethargy, sedation, poor suck reflexes

66
Q

chloral hydrate - effects on infant when used during lactation

A

drowsiness if infant fed at peak

67
Q

diazepam - effects on infant when used during lactation

A

drug accumulation and sedation

68
Q

methadone - effects on infant when used during lactation

A

risk of withdrawal if breastfeeding stops

69
Q

iodine - effects on infant when used during lactation

A

thyroid suppression

risk of cancer

70
Q

propylthiouracil - effects on infant when used during lactation

A

can suppress thyroid function in infant

71
Q

which 2 popular herbal medicine can pose a risk in breast feeding mothers to their children

A

marketed as galactagogues to improve milk supply:
fenugreek
comfrey

72
Q

risk of herbal medicines during pregnancy - when do they occur

A

almost 1/2 of pregnant women

increases potential of teratogenicity when used during 1st trimester and fetotoxcity in 3rd trimester

73
Q

examples of herbal medicines which can pose a risk to the child if the mother is breastfeeding

A 
Bladderwrack
Buckthorn
Chaparral
Coltsfoot (Farfarae folium)
Dong Quai (Angelica Root)
Elecampane
Ephedra / Ephedra sinica / Ma Huang
Ginseng (Panax ginseng)
Indian Snakeroot
Kava-kava (piper methysticum)
Petasites root
Phen-fen, herbal
Rhubarb
Star anise
Tiratricol (TRIAC)
Uva Ursi
Wormwood
74
Q

advice for breastfeeding mothers re. herbal medicines

A

should avoid
lack of info re scientific safety date
contamination of herbal products w/ conventional medicines, pesticides or heavy metals

75
Q

specific risks of herbal medicines in breastfeeding mothers

A

herbs containing pyrrolizidine alkaloids (PAs) can be hepatotoxic
some have hormonal effects
some contain constituents with sedative properties

76
Q

principles of prescribing in breast feeding

A

avoid unnecessary drug use
check on up to date drug info - may be a lack of info
if licensed and safe in paediatric use (esp <2y/o) a drug is likely to be safe in breast feeding
choose drugs w/ pharmacokinetic properties that reduce infant exposure e.g. highly protein bound

Y3 repro (47 decks)

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