Pharmacology Flashcards
why might a woman be on medication during pregnancy, childbirth and lactation?
- hypertension
- migraine
- asthma
- mental health disorders
- epilepsy
- long term anticoagulant therapy
how can pregnancy affect pharmacokinetics of drugs
affects any of the four basic kinetic processes:
- absorption
- distribution
- metabolism and elimination
- excretion
What absorption changes occur via the oral route during pregnancy?
- May be more difficult “morning sickness” nausea/vomiting
- Increase in gastric emptying and gut motility
describe absorption changes during pregnancy
oral route: decrease in gastric emptying and gut motility
intramuscular route: blood flow increased = absorption increased
inhalation: increased cardiac output, decreased tidal volume = absorption increased
describe distribution changes during pregnancy
increased Vd: increase in plasma volume and fat
increased fraction of free drug: greater dilution of plasma will decrease relative amount of plasma proteins.
describe metabolism changes during pregnancy
oestrogen and progestogens can induce or inhibit liver P450 enzymes, increasing or reducing metabolism
eg phenytoin levels reduced due to induction of metabolism or theophylline levels increased due to inhibition of metabolism
describe excretion changes during pregnancy
GFR increased = increased excretion of many drugs
this can reduce the plasma concentration, and can necessitate an increase in dose of medicines cleared by the kidney
how can pregnancy affect pharmacodynamics
site of drug action: metabolites at sites of biological action (changes in blood flow)
receptor response to drugs : mechanism of action (changes in receptors)
describe the exchange of materials across the placenta
What does placental transfer depend on?
- molecular weight (smaller sizes will cross more easily)
- polarity (unionised molecules cross more readily)
- lipid solubility (lipid soluble drugs will cross)
how does foetal distribution differ from adults?
- 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
how does foetal metabolism differ from adults?
- reduced enzyme activity, though increases with gestation
- different p450 isoenzymes to adults
how does foetal excretion differ from adults?
- excretion is into amniotic fluid – this is swallowed and can allow recirculation
- drugs and metabolites can accumulate in amniotic fluid
- placenta not functioning at delivery so can be issues with excretory function
what are some drug associated problems in pregnancy
- teratogenicity: 1st trimester (3-8 weeks organogenesis)
- fetotoxicity: 2nd & 3rd trimester
what problem is there with people who have chronic conditions?
They are often undertreated due to fear that the drugs will affect the pregnancy
What are the mechanisms of teratogenicity?
- folate antagonism
- neural crest cell disruption
- endocrine disruption: sex hormones
- oxidative stress
- vascular disruption
- specific receptor- or enzyme-mediated teratogenesis
describe folate antagonism
key process in DNA formation and new cell production
drugs that affect folate metabolism:
- block conversion of folate to THF by binding irreversibly to enzyme
- block other enzymes in folate pathway
result: neural tube, oro-facial or limb defect
describe neural crest cell disruption
caused by retinoid drugs
results in:
- aortic arch anomalies
- ventricular septal defects
- craniofacial malformations
- oesophageal atresia
- pharyngeal gland abnormalities
describe enzyme mediated teratogenesis?
drugs which inhibit or stimulate enzymes to produce therapeutic effects may also interact with specific receptors and enzymes damaging foetal development
eg NSAIDs cause oro-facial clefts and cardiac septal defects
what is fetotoxicity?
toxic effect on the foetus later in the pregnancy
possible issues:
- growth retardation
- structural malformations
- foetal death
- functional impairment
- carcinogenesis
eg ACEI or ARBs can cause renal dysfunction and growth retardation
how are drugs stages for use in pregnancy?
- A: No foetal risk
- B: Animal studies show no risk but no human studies conducted
- C: No human data
- D: Evidence of foetal risk but benefits outweigh them
- X: Foetal risk outweigh possible benefit
examples of known teratogens to avoid during pregnancy
- anticonvulsants (valproate, carbamazepine, phenytoin): neural tube defects
- anticoagulants (warfrin): haemorrhage, multiple malformations in CNS
- antihypertensives (ACEI): renal damage, restict normal growth patterns
- NSAIDs: premature closure of ductus arteriosus
- alcohol: foetal alcohol syndrome
- retinoids: ear, CNS, cardiovascular, and skeletal disorders
what is the issue with drugs and lactation?
almost all drugs will be present in breast milk (important to know concentration)
what drugs should be avoided when breast feeding?
- cytotoxics
- immunosuppressants
- anti-convulsants (not all)
- drugs of abuse (especially opiates)
- amiodarone
- lithium
- radio-iodine
