Pharmacology in Pregnancy and Breast Feeding Flashcards
Absorption changes in pregnancy
Oral route
- morning sickness
- increase in gastric emptying and gut motility
IM route
- blood flow increased so absorption may increase also
Inhalation
- CO increased and TV decreases which may cause increased absorption of inhaled drugs
Distribution changes in pregnancy
Increased plasma volume and fat will change distribution of drugs and increase vD
Greater distribution of plasma will decrease the relative amount of plasma proteins and increase the fraction of free drug
Metabolism changes in pregnancy
Oestrogens and progesterones can induce or inhibit P450 enzymes, increase or decrease metabolism
Excretion changes in pregnancy
GFR increased by 50% leading to increased excretion of many drugs
Decreased plasma conc. and therefore can necessitate an increase in dose of renally cleared drugs
Pharmacodynamic changes in pregnancy
May affect site of action and receptor response to drugs
Efficacy may be different
Adverse effects may be different
Functions of the placenta
Attach foetus to uterine wall
Provide nutrients to foetus
Allows foetus to transfer waste products to mothers blood
What materials are exchanged from foetus to the mother?
Carbon dioxide
urea
other waste products
What materials are exchanged from mother to foetus?
Oxygen glucose amino acids lipids, fatty acids and glycerol Vitamins Ions; Na, Cl, Ca, Fe Alcohol, nicotine and drugs Viruses Antibodies
Placental transfer depends on
Molecular weight (smaller sizes will cross more easily) Polarity (non-polar cross more easily) Lipid solubility (lipid soluble drugs will cross)
Foetal distribution features
Circulation different (e.g. umbilical vein to liver)
Less protein binding than adults so more free drug available
Little fat so distribution is different
Relatively more blood flow to the brain
Metabolism of the foetus features
Less enzyme activity, though increases with gestation
Different izoenzymes to adults
Foetal excretion features
Excretion is in amniotic fluid - this can be swallowed and allow recirculation
Drugs and metabolites can accumulate in amniotic fluid
Placenta not functioning at delivery so can be issues with excretory function
Which trimester does teratogenicity affect?
First trimester
Which trimester does fetotoxicity affect?
Second and third trimester
What time is the biggest risk of teratogenicity?
During organogenesis (weeks 3-8)
Mechanisms of teratogenicity
Folate antagonism neural crest cell disruption endocrine disruption; sex hormones oxidative stress vascular disruption specific receptor or enzyme mediated teratogenesis
Folate antagonism drugs
Methotrexate Trimethoprim Phenytoin Carbamazepine Valproate
Folate antagonism drugs tend to result in
Neural tube defects
Oro-facial defects
Limb defects
Neural crest cell disruption is caused by
Retinoid drugs (e.g. isotretinoin)
Drugs causing neural crest cell disruption result in….
Aortic arch anomalies Ventricular septal defects Craniofacial malformations Oesophageal atresia Pharyngeal gland abnormalities
Enzyme mediated teratogenesis is caused by
NSAIDs
Enzyme mediated teratogenesis results in…
Orofacial clefts
Cardiac septal defects
Possible issues caused by fetotoxicity
Growth retardation Structural malformations Foetal death Functional impairment Carcinogenesis
ACEIs and ARBs result in
Renal dysfunction
Growth retardation
Drugs to avoid in breast feeding
cytotoxics immunosuppressants anti-convulsants (not all) drugs of abuse amiodarone lithium radioiodine
Principles of prescribing in breast feeding
Avoid unnecessary drug use
Check on up to date drug info
If licensed and safe in paediatric use (esp < 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)
Which cancers is the COCP protective against?
Ovarian
Endometrial
Which cancers does the COCP increase the risk of?
Breast
Cervical
