Pharmacology in pregnancy and breast feeding Flashcards
in terms of the pregnnant mother: ABSORPTION changes in pregnancy -
Oral route: May be more difficult if there is nausea/vomiting, Increase in gastric emptying and gut motility, Can increase time to peak absorption but reduce overall concentration, This is unlikely to be a problem with regular dosing, but may affect single doses. Intramuscular route: Blood flow may be increased, so absorption may also increase using this route. Inhalation: Increased cardiac output and decreased tidal volume may cause increased absorption of inhaled drugs
DISTRIBUTION CHANGES - in the woman
Changes in total body water and fat will change distribution of drugs, Greater dilution of plasma will decrease relative amount of plasma proteins, These two effects cancel each other out so effectively there is no change seen in the distribution.
METABOLISM CHANGES + - in the woman
Oestrogen and progestogens can induce or inhibit P450 enzymes in the liver – increasing of reducing metabolism, Examples: Phenytoin levels reduced due to induction of metabolism, Theophylline levels increased due to inhibition of metabolism.
EXCRETION CHANGES + - in the woman
GFR is increased during pregnancy by 50%, This leads to increased excretion of many drugs, This can reduce the plasma concentration and may necessitate dose increase
Pharmacodynamic changes - in the woman
Pregnancy may affect site of action & receptor response to drugs, Concentration of drug, metabolites at sites of biological action (changes in blood flow), Mechanism of action (changes in receptors), Efficacy may be different
what does placental transfer depend on inn terms of Fetal Pharmacokinetics and Placental Absorption
Molecular weight (smaller sizes will cross more easily), Polarity (non-polar cross more readily, Lipid solubility (lipid soluble drugs will cross), Placenta may also metabolise some drugs, Safest to assume all drugs will cross placenta. Cross placenta if: small, non-ionized, High lipophilicity
describe fetal pharmacokinetics in terms of its - Distribution
Circulation different, Less protein binding than adults = more ‘free’ drug, Little fat makes distribution different, Relatively more blood flow to the brain
describe fetal pharmacokinetics in terms of its - Metabolism
Less enzyme activity, though increases with gestation, Different isoenzymes to adults
describe fetal pharmacokinetics in terms of its - Excretion
Excretion is into amniotic fluid – this is swallowed and can allow recirculation, Concentration and metabolites can accumulate in amniotic fluid, Placenta not functioning at delivery so can be issues with excretory function.
safety of drugs in pregnancy, when does teratongenicity effect and when does fetotoxicity effect?
terato - 1st tirmester, feto - 2nd and 3rd trimesters
what are the different mechanisms of teratogenicity?
Folate Antagonism, Neural Crest Cell Disruption, Endocrine Disruption: Sex Hormones, Oxidative Stress, Vascular Disruption, Specific Receptor- or Enzyme-mediated Teratogenesis
describe the process of folate antagonism
Key process in DNA formation and new cell production, Two groups of drugs: one blocks the conversion of folate to THF, the other blocks other enzymes in the pathway, Results in neural tube, oro-facial or limb defects
outline the process of neural crest cell disruption
Retinoid drugs – individuals on retinoid are usually given contraception as well, Aortic arch anomalies, Ventricular septal defects, Craniofacial malformations, Oesophageal atresia, Pharyngeal gland abnormalities
outline the process of enzyme-mediated teratogenesis
Drugs which inhibit or stimulate enzymes to produce therapeutic effects may also interact with specific receptors and enzymes damaging fetal development.
E.g. NSAID’s - orofacial clefts anf cardiac septal defects.
what is fetotoxicity?
Toxic effects on the fetus later in pregnancy. Possible issues: Growth retardation, Structural malformations, Fetal death, Functional impairment, Carcinogenesis.
Example = ACEIs/ARBs – renal dysfunction and growth retardation.
outline the FDA’s categorisation of risks
- A = risk not shown in human studies
- B = risk not confirmed in human studies but seen in animal studies
- C = risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
- D = risk shown in humans, only use if benefit outweighs risk
- X = benefit does not outweigh risk = contraindicated
examples of knnown teratogens, other than those below
alcohol, androgens, benzos, carbemazepine, lithium, phenytoin, retinoids, tetracycline, warfarin.
Teratogen
Effect
Anticonvulsants - Sodium Valproate/ Carbamazepine/ Phenytoin
Valproate is associated with neural tube defects, as is carbamazepine and phenytoin
Anticoagulants - Warfarin
Warfarin is associated with haemorrhage in the fetus, as well as multiple malformations in the central nervous system and skeletal system.
Antihypertensive agents - ACEi’s
ACE inhibitors cause renal damage and may restrict normal growth patterns in the unborn child.
NSAID’s
Premature closure of the ductus arteriosus.
Alcohol
Fetal alcohol syndrome/effects
a small head. a smooth ridge between the upper lip and nose, small and wide-set eyes, a very thin upper lip, or other abnormal facial features. below average height and weight. hyperactivity. lack of focus. poor coordination.
Retinoids
Ear, CNS, cardiovascular, and skeletal disorders
issues with using drugs during lactation…
Most drugs given to lactating women are detectable in breast milk, Concentrations are usually low – preventing infants receiving therapeutic amounts, Some drugs do carry serious toxicity and are to be avoided, Recommendations for feeding mothers:
Safe drug = take 30-60 mins after nursing and 3-4 hours before the next feeding.
examples of drugs to avoid when breastfeeding other than those below
Cytotoxics, Immunosuppressants, Anti-convulsants (not all), Drugs of abuse, Amiodarone, Lithium, Radio-iodine
Drug
Comments
Tetracycline
Risk of permanent tooth staining in infant
Isoniazid
Risk of pyridoxine deficiency in the infant
Barbiturates
Lethargy, sedation and poor suck reflexes
Chloral hydrate
Drowsiness if infant fed at peak
Diazepam
Drug accumulation and sedation
Methadone
Risk of withdrawal if breast feeding stops
Iodine
Thyroid suppression and risk of cancer
Propylthiouracil
Can suppress thyroid function in infant
what herbal remedies pose threat to infants?
fenugreek, comfrey
what are the principles of prescribing for women of chiuld-bearinng age?
Always consider possibility of pregnancy (planned or not!)
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
Principles of prescribing in pregnancy
- If you can, try non-pharmacological treatment first
- Use the drug with the best safety record
- 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 use during the first 10 weeks of pregnancy
- Don’t under treat disease which may be harmful to the fetus
Principles of prescribing in breast feeding
- Avoid unnecessary drug use
- If licensed and safe in paediatric use (< 2 years), a drug is likely to be safe in breast feeding
- Choose drugs with pharmacokinetic properties that reduce infant exposure
GOOD DISTRIBUTION, METABOLISM AND EXCRETION
