Pharmacology in pregnancy and breastfeeding Flashcards
What are the physiological changes in pregnancy that alter drug absorption orally?
More difficult due to morning sickness
Decrease in gastric emptying and gut motility
What are the physiological changes in pregnancy that alter drug absorption IM?
Increased blood flow, so may increase absorption
What are the physiological changes in pregnancy that alter drug absorption via inhalation?
Increase CO and increased tidal volume may increase
What are the physiological changes in pregnancy that alter drug distribution?
Increase in plasma volume- greater dilution decreases relative amount of plasma proteins
Increase in fat
What are the physiological changes in pregnancy that alter drug metabolism and elimination?
Increased oestrogen and progesterone can induce or inhibit liver P450 enzymes
What are the physiological changes in pregnancy that alter drug excretion?
GFR increased
What is the overall effect of pregnancy on oral drug absorption, metabolism and excretion?
Absorption decreases
Metabolism increases
Excretion increases
What are the pharmacodynamic changes in pregnancy?
Changes in blood flow alter conc of drug and metabolites at site
Changes in receptors alters mechanism of action
What does placental transfer of drugs depend on?
Molecular weight- small sizes cross more easily
Polarity- non polar cross more easily
Lipid soluble cross more easily
What is the effect of the placenta on drugs?
Placenta will metabolise some drugs but assume all drugs will cross placenta
What ar the aspects to consider with drug distribution in a foetus?
Abnormal circulation
Less protein binding
Little fat
Relatively more flow to brain
What are the aspects to consider wth drug metabolism in a foetus?
Less enzyme activity
Different isoenzyme to adult
What are the aspects to consider with drug excretion in a foetus?
Excreted into amniotic fluid and can be swallowed and reabsorbed
What are the 2 forms of toxicity in pregnancy?
Teratogenicity- first trimester
Fetotoxicity- 2nd and 3rd trimesters
When is teratogenicity the biggest risk?
During organogenesis
What are the mechanisms of teratogenicity?
Folate antagonism Neural crest cell disruption Endocrine disruption Oxidative stress Vascular disruption Specific receptor or enzyme mediated teratogenesis
What are the 2 methods by which drugs can cause folate antagonism?
Block conversion of folate to THF by binding irreversibly to the enzyme
Block other enzymes in the pathway
What drugs can cause folate antagonism by blocking conversion of late?
Methotrexate, trimethoprim
What drugs can cause folate antagonism by blocking other enzymes?
Phenytoin
Carbamazepine
Valproate
What are the causative drugs of neural creat disruption?
Retinoids
What problems can neural creat cell disruption cause?
Aortic arch abnormalities Ventricular septal defect Craniofacial malformation Oesophageal atresia Pharyngeal gland abnormalities
What is enzyme mediated teratogenesis?
Drugs which inhibit or stimulate enzymes o produce therapeutic effects may also interact with specific receptors and enzymes, damaging foetal development
What is an example of enzyme mediated teratogenesis?
NSAIDs can cause orofacial and cardiac septal defects
What are the issues associated with fetotoxicity?
Growth retardation Structural malformations Foetal death Functional impairment Carcinogenesis
What are the 5 categories of a drugs fetotoxicity?
A B C D X
What are class A fetotoxic drugs?
Contolled human studies show no foetal risk
What are class B fetotoxic drugs?
Animal studies show no foetal risk but no controlled human studies OR
Animal studies show a risk but controlled human studies did not
What are class C fetotoxic drugs?
No adequate animal or human studies have been conducted OR
Adverse effects n animal study but no human data
What are class D fetotoxic drugs?
Evidence of foetal risk exists but rbenefit may outweigh risk in certain circumstances
What are class X fetotoxic drugs?
Proven foetal risks outweigh any benefit
What classes of drugs are known teratogens?
Anticonvulsants Anticoagulents Antihypertensives NSAIDs Alcohol Retinoids
What are anticonvulsants associated with?
Valproate, carbamazepine ad phenytoin are associated with neural tube defects
What are anticoagulants associated with?
Warfarin- haemorrhage in foetus and malformations of CNS and skeletal system
What are antihypertensives associated with?
ACEi cause renal damage and restrict growth patterns
What are NSAIDs associated with?
Premature closure of ductus arteriosus
What is alcohol associated wth?
Foetal alcohol syndrome
What are retinoids associated with?
Ear, CNS, CV and skeletal deformities
What drugs should be avoided during lactation?
Cytotoxics Immunosuppressants Most, but not all, anticonvulsants Drugs of abuse Amiodaone Lithium Radio-iodine
What are the principles of prescribing in non pregnant women of child bearing age?
Always consider pregnancy
Warn of possible risks
When treating long term conditions, advise women to attend when planning a pregnancy
If necessary, do not prescribe without contraception
What are the principles of prescribing in pregnant women?
Try non pharm treatment firs where appropriate
Use drug with best safety record
Use lowest effective dose for shortest time possible, intermittently if at all possible
Avoid in 1st 10 weeks if possible
Don’t under treat disease
What are the principles of prescribing in breastfeeding?
Avoid unnecessary drugs
If safe for paediatric use, esp in under 2s, usually safe to give
Choose drugs with pharmacokinetic properties that reduce infant exposure
