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
